Metrics details one of the most common autoimmune diseases and the leading cause of hypothyroidism is linked to metabolic and cellular dysfunctions that contribute to disease aetiopathogenesis This case-control study aimed to identify potent metabolic biomarkers of HT employing machine learning techniques 62 euthyroid patients with HT and 58 healthy individuals were included from the metabolic biomarkers in Hashimoto’s thyroiditis and psoriasis (METHAP) clinical trial Quantification of 73 metabolites was performed using gas-chromatography/mass spectrometry in plasma and urine samples of fasted participants microbiome and lipid metabolism were identified in the HT group Ordinary least squares and beta regression modeling associated the presence of HT with methylmalonic acid myristoleic acid and total saturated fatty acids Artificial neural network analysis had good predictive accuracy with an AUC of 0.8 while debiased sparse partial correlation network analysis identified metabolite-metabolite interactions distinct for HT These findings provide insights into novel biomarkers associated with HT and we discuss their biological relevance and clinical significance Hashimoto’s thyroiditis is associated with mitochondrial dysfunction and carbohydrate and fatty acids dysfunctional metabolism Considering the large number of studies demonstrating distinct metabolic imbalances and cellular dysfunctions in HT this study aimed to define the metabolic imprint of HT using a comprehensive panel of metabolites as markers There is a pressing need to seek sensitive biomarkers that capture the metabolic state of patients with HT and reflect the underlying metabolic disturbances Metabolism is a complex network of thousands of metabolites that might be a marker of specific metabolic blocks we analyzed the changes of metabolites participating in key cellular metabolism and function pathways we measured the levels of urine organic acids and plasma fatty acids in human samples of patients with HT and compared them to age and sex-matched healthy individuals a total of 200 individuals were recruited at the Heraklion University Hospital in Crete and the Health Clinic for Autoimmune and Chronic Diseases in Athens with the contribution from private practices in Athens to reach the required number of participants For the purpose of this case-control study 62 patients with HT and 58 age and sex-matched healthy individuals were included Potential participants were first screened by an endocrinologist to assess whether the patients met the following criteria: Inclusion criteria for all participants: 18–60 years old non-lactating or pregnant women and non-athletes Inclusion criteria for Hashimoto’s thyroiditis: Presence of anti-thyroid antibodies and gray-scale findings Exclusion criteria for Hashimoto’s thyroiditis: Individuals having undergone complete thyroidectomy with malignant or congenital goiter Exclusion criteria for the control group: Participants with acute or chronic disease receiving medication Participants were verbally informed of the study objectives they were requested to read and sign the informed consent Baseline measurements include TSH levels for both groups and FT3 participants were requested to fill in a form to record demographic data alcohol consumption (number of glasses/week) while their dietary habits were recorded through the Mediterranean Diet Score (MDS) Metabolomic profiling was performed in both groups using targeted metabolomics and the study conformed to the EU General Data Protection Regulation (GDPR) Research was performed in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards The present study has received approval by the Research Ethics Committee of the University of Crete (AP 147/10072020) An informed consent was obtained from all participants.This research received no external funding Fasted participants were requested to collect urine samples in a sterilized container Peripheral blood was collected on the same day and time to ensure minimal day-to-day or daytime metabolite fluctuations using a K2-ethylene diamino tetra-acetic EDTA-containing vacuum blood collection tube Plasma isolation was performed by centrifuge at 1500×g at 4 °C Urine and plasma samples were aliquoted and then stored at − 80 °C and − 20 °C until analysis and up to 24 h to ensure minimal metabolite degradation Concentrations of organic acids are reported in relation to creatinine levels we estimated the ratio of product metabolite to reactant metabolite to assess the function of specific enzymes The ANN model employed was a feed-forward neural network trained using the error backpropagation algorithm The receiver operating characteristic (ROC) curve was utilized to evaluate the model’s accuracy which aligns with established methods for assessing model performance a Debiased sparse partial correlation (DSPC) network analysis was employed in both groups DSPC enables the computation of partial correlation coefficients and their p values while facilitating the identification of underlying connectivity patterns among numerous metabolic features Main central tendency measures were also estimated such as the degree of centrality and the betweenness In the present study, 120 participants were analyzed, including 62 patients with Hashimoto’s thyroiditis and 58 individuals in the control group who were matched for age and gender. The population characteristics are summarized in Table 1 The two groups exhibited similar characteristics in terms of demographics TSH levels were within the normal range for both groups with no statistical significance between them Differential metabolite expression in HT patients: Up: fold change analysis of the organic acid metabolic compounds Corrected false discovery rate (Wilcoxon test Colored dots indicate significantly different variables which estimates the group variable and age as statistically significant factors at 90% and 95% levels of significance It has to be noted that the interpretation of coefficients within the beta regression framework diverges from that of a conventional linear model the exponentiation of coefficients in this context yields the odds ratios for a one-unit increase in a given predictor variable All the models used had a slight positive autocorrelation (DW < 2) but the collinearity diagnostics revealed a lack of multicollinearity The graphical examination of the standardized residuals revealed that the hypothesis of normality and homoscedasticity was held in all the models above Receiver operating characteristics (ROC) curve for the ability of a specific combination of biomarkers to identify patients with Hashimoto’s disease. “0” represents the control group; “1” represents the HT cases. Neural network architecture used as a predictive model A debiased sparse partial correlation (DSPC) network of OA and TFA metabolites of Hashimoto's disease while the edges symbolize the association measures between them The thickness of the edges corresponds to the strength of these associations providing a visual indication of their relative importance The network employs color coding to differentiate between positive (red lines) and negative (blue lines) there is an increasing need to define the metabolic imbalances of HT to provide early detection and targeted treatment in addition to thyroid hormone replacement therapy The present study identified differentially expressed urine organic acids and plasma fatty acids in euthyroid patients with HT compared to healthy individuals 3-hydroxybutyric acid and fumaric: succinic ratio were markedly different between case and control groups adjusting for confounding variables dihomo-gamma-linolenic acid (C20:3n6) and total saturated fatty acids (SFA) were all higher in the HT group compared to control we discuss our findings by grouping the tested metabolites according to their biological relevance given the underlying metabolic interconnections the present study validates these findings in the population of euthyroid patients with HT using MMA which is regarded as a more sensitive biomarker for functional vitamin B12 insufficiency preliminary findings indicated a possible change in 4-hydroxyphenylpyruvic acid (4-HPPA) levels among individuals with HT the statistical significance of this hypothesis was not confirmed in the regression model potentially due to the limited sample size Further research with a larger sample size is needed to investigate the relationship between 4-HPPA and HT more comprehensively and determine its clinical significance considering the central role of antioxidants in the fine-tuning of the immune system and the findings of this study attention should be given to the marginal micronutrient deficiencies of HT patients and the use of sensitive biomarkers for their detection we assessed SDH activity by measuring the fumaric acid: succinic acid ratio and found it was significantly lower in the HT group indicating a reduced enzymatic activity and accumulation of the reactant succinic acid Riboflavin (vitamin B2) acts as an important cofactor for ETC and the function of SDH in particular suggesting a potential role of marginal vitamin B2 deficiency in HT the two groups had similar adherence scores to the Mediterranean Diet suggesting a disrupted metabolism of endogenous fatty acids in the HT group rather than an increased intake of SFA reduced sensitivity in capturing inter-individual differences Another parameter to assess the non-difference in fatty acids intake was the levels of the essential fatty acids linoleic acid and a-linoleic acid which are exclusively obtained through diet and were similar between the two groups (p = 0.248 and 0.475 respectively) indicating that more sophisticated techniques could be employed without compromising the primary results’ generality Factors such as patient heterogeneity and variability in other parameters influence these estimations studies often include 30–50 patients per treatment group which aligns closely with the sample size utilized in the present investigation the implementation of ANN analytical techniques in this study demonstrates their applicability to targeted metabolomics data careful consideration of sample size and strategies to address overfitting are essential to optimize their effectiveness in medical research contexts this study provides a detailed report of the differences between organic and fatty acids between Hashimoto and healthy individuals generating a novel hypothesis that needs further exploration we applied more stringent approaches in predictive modeling and regression analysis to explore the potency of certain metabolites as predictive biomarkers and identified an improved combination that reached fairly good predictive accuracy the present study identified certain borderline significant metabolites participating in central metabolic pathways A possible explanation for the mild differences observed is that these metabolic networks are supplied by numerous metabolic pathways to maintain cellular function and counterbalance metabolic dysfunctions at different stages the interpretation of metabolomic findings needs to be done with caution assessing them within the context of metabolic networks rather than as single markers such as DSPC and others employed in the present and previous studies are expected to shed light on these borderline significance differences and especially their association with related phenotypical traits such as dysfunctional TCA with fatigue in Hashimoto although patients’ medical history was obtained and individuals with severe acute or chronic disease were excluded routine biochemical and blood count testing would clarify potential clusters within the group Age and BMI were different in females with HT compared to control and although these variables did not affect the detected association between HT and the selected metabolic biomarkers subgroup analysis using a larger sample size would provide in-depth insight into these associations An in-depth subgroup analysis could reveal essential heterogeneities within the analyzed dataset a comprehensive separate subgroup analysis was not conducted in this study OLS regression with age and gender as predictors was performed to provide preliminary insights into potential subgroup effects a complete subgroup analysis would necessitate either separate data analysis for each gender and age group or the generation of a regression model with interaction terms (age_group x Gender) An additional limitation of this study is the absence of analyses pertaining to population differences across regions or ethnic groups which may restrict the generalizability of our findings to broader populations it is suggested that a more comprehensive population-specific analysis for distinct groups (Caucasians people of African descent etc.) could be the focus of future research the above points limit the generalizability of the present study’s findings to other populations Hashimoto’s thyroiditis is characterized by metabolic complications affect the patient’s overall health and quality of life we identified markers of mitochondrial dysfunction carbohydrate and fatty acids metabolism malfunction and microbiome imbalance in HT Early detection and monitoring of the underlying metabolic dysfunctions are critical in the decision-making process to achieve low levels of thyroid destruction and hormonal regulation targeted strategies can significantly contribute to the alleviation of the pro-inflammatory status and the metabolic burden of HT The dataset is available upon reasonable request from the corresponding authors Is a normal TSH synonymous with ‘euthyroidism’ in levothyroxine monotherapy? 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Immunomodulatory actions of vitamin D in various immune-related disorders: A comprehensive review Immunomodulatory function of vitamin D and its role in autoimmune thyroid disease Five serum fatty acids are associated with subclinical hypothyroidism in a Chinese pregnant population Serum metabolomic patterns in patients with autoimmune thyroid disease Metabolic profiling of organic and fatty acids in chronic and autoimmune diseases Targeted metabolomic analysis of serum fatty acids for the prediction of autoimmune diseases Prediction of autoimmune diseases by targeted metabolomic assay of urinary organic acids Classification of some test of normality techniques into UMP and LMP using Monte Carlo simulation technique James-Stein type estimators in beta regression model: Simulation and application Autoimmune comorbidities in Hashimoto’s thyroiditis: Different patterns of association in adulthood and childhood/adolescence Autoimmune mechanisms in pernicious anaemia and thyroid disease Relationship of tobacco smoking with serum vitamin B12 folic acid and haematological indices in healthy adults Exploring the impact of cigarette smoke extracts on vitamin B12: Insights into the transformation of methylcobalamin and hydroxycobalamin to cyanocobalamin through in vitro evaluation Mechanism of enzymic formation of homogentisate from p-hydroxyphenylpyruvate Metabolomic profile overlap in prototypical autoimmune humoral disease: A comparison of myasthenia gravis and rheumatoid arthritis and zinc in benign thyroid diseases and of selenium in malignant thyroid diseases: Low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma Effect of micronutrients on thyroid parameters Assessment of vitamin concentrations in patients with Hashimoto’s thyroiditis and their relationships with thyroid function and anthropometric parameters—A preliminary study Martínez-Reyes, I. & Chandel, N. S. Mitochondrial TCA cycle metabolites control physiology and disease. Nat. Commun. 11(1), 1–11. https://doi.org/10.1038/s41467-019-13668-3 (2020) “Ferrocrinology”—Iron Is an important factor involved in gluco- and lipocrinology Mechanisms of insulin resistance in humans and possible links with inflammation Succinate-to-fumarate ratio as a new metabolic marker to detect the presence of SDHB/D-related paraganglioma: Initial experimental and ex vivo findings Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages Structure and function of biotin-dependent carboxylases Influence of intestinal flora on the elimination of phenylacetic acid in urine Intestinal microbiota regulates the gut-thyroid axis: The new dawn of improving Hashimoto thyroiditis Serotonin: A potent immune cell modulator in autoimmune diseases The dopaminergic system in autoimmune diseases Mitochondrial functions modulate neuroendocrine and transcriptional responses to acute psychological stress Effects of thyroid hormones on lipid metabolism pathologies in non-alcoholic fatty liver disease Fatty acid status in infancy is associated with the risk of type 1 diabetes-associated autoimmunity The association between serum palmitic acid and thyroid function ER stress contributes to high-fat diet-induced decrease of thyroglobulin and hypothyroidism Palmitic acid downregulates thyroglobulin (Tg) and thyroperoxidase (TPO) in human primary thyrocytes: A potential mechanism by which lipotoxicity affects thyroid? The influence of nutritional intervention in the treatment of Hashimoto’s thyroiditis—A systematic review Logistic regression and artificial neural network classification models: A methodology review Artificial neural networks for small dataset analysis MetSizeR: Selecting the optimal sample size for metabolomic studies using an analysis based approach Trivedi, D. K., Hollywood, K. A. & Goodacre, R. Metabolomics for the masses: The future of metabolomics in a personalized world. New Horiz. Transl. Med. 3(6), 294–305. https://doi.org/10.1016/j.nhtm.2017.06.001 (2017) Multiple-testing correction in metabolome-wide association studies and transformations: Improving the biological information content of metabolomics data Critical evaluation of the questionnaires assessing adherence to the Mediterranean diet that are based on servings Download references The authors would like to thank all the administrative technical and medical staff of the Laboratory of Toxicology of the University of Crete the University Hospital of Heraklion and the Metabolomic Medicine health clinic for their dedicated involvement in this study The study was supported by Metabolomic Medicine and European Institute of Molecular Medicine Laboratory of Toxicology and Forensic Sciences Evangelia Sarandi & Aristidis Tsatsakis Health Clinics for Autoimmune and Chronic Diseases Evangelia Sarandi & Dimitris Tsoukalas Clinic of Endocrinology and Metabolic Disorders Laboratory of Health Economics and Management (LabHEM) National and Kapodistrian University of Athens Efstathia Paramera & Evangelos Papakonstantinou SK and AT conceived and designed the present study as part of a PhD ES and CL collected patient data and samples of the participants EvP and AT were responsible for the methodological and experimental procedures statistical analysis and preparation of figures and tables were performed by ES and VF DT and GR and was critically reviewed by CL All authors have read and reviewed the final manuscript is the scientific director at Metabolomic Medicine There is no further financial relationship between the study investigators The rest of the authors declare no competing interest Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Below is the link to the electronic supplementary material Download citation DOI: https://doi.org/10.1038/s41598-025-89600-1 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology MLS sides won both age groups at the Generation adidas Cup MLS NEXT announced individual award winners from the competition Real Salt Lake earned two of the three individual awards who scored two goals in the 4-0 final victory over LA Galaxy An all-action attacking midfielder who played out wide or centrally Hashimoto made things happen all week in Florida with five goals Teammate Konstantinos Kyriazis was named Best Goalkeeper presented by Allstate He started every game for RSL as they conceded just once during the competition PSV Eindhoven were led by the top scorer in the age group Obama Appiah finished with five goals and edged out Hashimoto via the tiebreaker Two players crucial to Orlando’s triumph deservedly walked away with individual honors who scored both goals in the 2-1 final win over Colorado Having recently signed a homegrown contract in March the attacking midfielder scored twice in the 3-0 semifinal win against Santos Laguna as well finishing with five goals in the competition Orlando City B forward Justin Ellis excelled playing with the U18s this past week His six goals in Generation adidas Cup play were most in the competition Rapids goalkeeper Kendall Starks made several quality saves during the seven games played and was named Best Goalkeeper presented by Allstate He produced a shutout in each of his first five matches and helped Colorado reach the final with a pair of saves in the semifinal shootout win over Atlanta United New evidence highlights how the Mediterranean diet’s anti-inflammatory nutrients like extra-virgin olive oil and omega-3-rich fish can help manage both joint and thyroid autoimmune disorders offering a low-cost lifestyle intervention with clinical benefits Study: Unlocking the Power of the Mediterranean Diet: Two in One—Dual Benefits for Rheumatic and Thyroid Autoimmune Diseases Image Credit: monticello / Shutterstock.com A recent study published in the journal Nutrients reviews the effects of the Mediterranean diet (MD) on both systemic and organ-specific autoimmune disorders particularly rheumatic and thyroid diseases Autoimmune diseases are systemic or organ-specific diseases that are associated with the development of anomalous immune responses against self-antigens. Systemic autoimmune diseases may include rheumatoid arthritis (RA), seronegative spondyloarthritis (SpA), and autoimmune connective tissue diseases (CTDs), whereas Hashimoto’s thyroiditis (HT), type 1 diabetes mellitus (T1D) and Graves’ disease (GD) are considered organ-specific diseases Autoimmune diseases are triggered by genetic and environmental factors that activate the immune system through various mechanisms including the production of interferon type I post-translational modification of proteins T- and B-lymphocytes are involved in the manifestation of autoimmune diseases as demonstrated by the synthesis of autoantibodies against self-antigens also damage tissues through the synthesis of pro-inflammatory cytokines the MD recommends a moderate consumption of red meat Previous studies have highlighted the potential of MD in modulating inflammation due to its antioxidant and anti-inflammatory properties The MD has also been shown to promote the growth of beneficial bacteria Several studies have reported the beneficial effects of various MD components on rheumatoid arthritis (RA) the intake of oily fish rich in ω-3 polyunsaturated fatty acids (PUFAs) as well as various fruits and vegetables containing different classes of bioactive compounds has been shown to mitigate the effects of certain autoimmune diseases The high intake of fiber enhances the proliferation of fermenting bacteria which produce short-chain fatty acids (SCFAs) such as butyrate Multiple studies have confirmed the anti-inflammatory properties of SCFAs and their ability to alleviate oxidative stress and chemotaxis of immune cells by enhancing the number of Treg cells and the release of interleukin-10 (IL-10) a recent clinical trial also revealed that ω-3 PUFA supplementation could positively impact the progression of RA by suppressing the levels of inflammatory cytokines and reducing the production of leukotriene B4 (LTB4) by neutrophils Extra virgin olive oil (EVOO) contains a wide range of bioactive compounds Several preclinical studies have investigated the potential anti-inflammatory properties of extra-virgin olive oil (EVOO) and its components a typical phenolic component of extra-virgin olive oil (EVOO) exhibits preventive effects against rheumatoid arthritis (RA). Likewise a mouse model of pristane-induced systemic lupus erythematosus (SLE) showed that EVOO consumption inhibited the release of nitric oxide (NO) and the production of pro-inflammatory cytokines The National Health and Nutrition Examination Survey (NHANES) recently reported that individuals who consume a pro-inflammatory diet had higher levels of total T4 and total T3 HT patients adhering to an anti-inflammatory diet exhibited lower TSH levels Higher adherence to MD also improved thyroid autoimmunity and related dysfunction a randomized clinical trial (RCT) revealed that patients with RA who underwent the MD intervention for 12 weeks exhibited a significant reduction in their disease activity score on 28 joints (DAS28) compared to controls These patients also experienced improvements in cardiometabolic parameters Encouraging adherence to the MD could serve as an effective cost-efficient lifestyle approach to reduce the burden of autoimmune disorders in modern societies.” The synergistic effect of individual MD components may be sufficient to mitigate the inflammatory processes that occur during autoimmune conditions thus supporting the incorporation of this dietary approach into the management of autoimmune diseases and their complications have confirmed the potential of MD as a complementary tool for managing rheumatic and thyroid autoimmune diseases; however combining MD with exercise has the potential to provide more robust and durable improvements Posted in: Men's Health News | Medical Science News | Medical Research News | Medical Condition News | Women's Health News in Plant Biology and Biotechnology from the University of Madras She is an active researcher and an experienced science writer Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals She is also an avid reader and an amateur photographer Please use one of the following formats to cite this article in your essay Mediterranean diet helps manage rheumatoid arthritis and Hashimoto’s 2025 from https://www.news-medical.net/news/20250423/Mediterranean-diet-helps-manage-rheumatoid-arthritis-and-Hashimotoe28099s-study-shows.aspx "Mediterranean diet helps manage rheumatoid arthritis and Hashimoto’s <https://www.news-medical.net/news/20250423/Mediterranean-diet-helps-manage-rheumatoid-arthritis-and-Hashimotoe28099s-study-shows.aspx> https://www.news-medical.net/news/20250423/Mediterranean-diet-helps-manage-rheumatoid-arthritis-and-Hashimotoe28099s-study-shows.aspx Cancel reply to comment Learn how experts are advancing benzodiazepine analysis and detection using insights from the lab discusses how he is addressing today’s medical challenges using the technology of the future Explore how the Radian ASAP mass spectrometer is being used to streamline and enhance seized drug screening you can trust me to find commercial scientific answers from News-Medical.net please log into your AZoProfile account first Registered members can chat with Azthena, request quotations, download pdf's, brochures and subscribe to our related newsletter content A few things you need to know before we start Read the full Terms & Conditions. Volume 15 - 2024 | https://doi.org/10.3389/fendo.2024.1445878 Clinicians often consider the use of dietary supplements to assist in lowering thyroid autoantibody titres in patients with Hashimoto’s thyroiditis (HT) different supplements differ in their ability to reduce autoantibody levels The purpose of this article is to compare the ability of different supplements to lower autoantibody titres and restore TSH levels through a systematic literature review as well as the China National Knowledge Infrastructure (CNKI) Selected studies included those using selenium and Myo-inositol in combination with selenium for the treatment of HT patients with euthyroidism These data were combined using standardised mean differences (SMDs) and assessed using a random effects model A total of 10 quantitative meta-analyses of case-control studies were selected for this meta-analysis the use of selenium supplements was able to significantly reduce the levels of thyroid peroxidase autoantibodies (TPOAb) (SMD: -2.44 -0.69) and thyroglobulin autoantibodies (TgAb) (SMD: -2.76 and Myo-inositol did not effectively reduce TPOAb (Myo-inositol: SMD:-1.94 95% CI: -6.51,1.42; Se+Myo-inositol: SMD: -3.01 95% CI: -8.96,2.93) or TgAb (Myo-inositol: SMD:-2.02 95% CI: -6.44,0.98; Se+Myo-inositol: SMD: -3.64 we recommend that patients with HT(Hashimoto’s Thyroiditis) be given an appropriate amount of selenium as an auxiliary treatment during standard-of-care treatment In addition to selenium and Vitamin D supplementation in HT patients, Krysiak et al. recently used selenium and Vitamin D in combination with inositol (35) This combination was effective in lowering autoantibody levels but due to the reduced sample size of the study these findings warrant validation across larger patient cohorts the effects of supplementation with selenium A systematic review and network meta-analysis was performed to assess the effects of these supplements on TPOAb based on recently published randomised controlled trials A systematic literature search was performed using the PubMed as well as the China National Knowledge Infrastructure (CNKI) in December 2023 using the following search terms: (Hashimoto Disease[MeSH Terms]) OR (Disease Hashimoto[Other Term]) OR (Chronic Lymphocytic Thyroiditis[Other Term]) OR (Chronic Lymphocytic Thyroiditides[Other Term]) OR (Lymphocytic Thyroiditides Chronic[Other Term]) OR (Lymphocytic Thyroiditis Chronic Lymphocytic[Other Term]) OR (Thyroiditis Chronic Lymphocytic[Other Term]) OR (Hashimoto Struma[Other Term]) OR (Hashimoto’s Struma[Other Term]) OR (Hashimoto’s Syndrome[Other Term]) OR (Hashimoto Syndrome[Other Term]) OR (Hashimoto’s Syndromes[Other Term]) OR (Hashimotos Syndrome[Other Term]) OR (Syndrome Hashimoto’s[Other Term]) OR (Syndromes Hashimoto’s[Other Term]) OR (Hashimoto’s Disease[Other Term]) OR (Disease Hashimoto’s[Other Term]) OR (Hashimotos Disease[Other Term]) OR (Hashimoto Thyroiditis[Other Term]) OR (Hashimoto Thyroiditides[Other Term]) OR (Thyroiditides Hashimoto[Other Term]) AND (selenium[MeSH Terms]) OR (Vitamin d[MeSH Terms]) OR (Myo-inositol[MeSH Terms]) Relevant literature was selected in PubMed and the article language was restricted to English The words or technical terms used for the search were related to “Autoimmune thyroiditis” “Hashimoto’s thyroiditis” Studies included in this meta-analysis had to meet the following criteria: (I)Participants were diagnosed with HT; (II) Patients enrolled in the study did not use levothyroxine sodium tablets throughout the study; (III) Patients did not suffer from other autoimmune or metabolic disease; (IV) Patients in experimental and control groups did not take any supplements within six months (particularly inositol and selenium); (V) Patients with increased TPOAb or TgAb titres; (VII) Patients did not suffer from congestive heart failure Wang Ping and Gu Qing Ling reviewed and quality-assessed each article’s title and/or full text retrieved from the literature search to determine eligibility for the meta-analysis Data extraction was performed using an extraction table that focussed on study characteristics (first author Two reviewers completed quality assessment of the selected studies using the Jadad scale This included assessment of whether the studies were blinded and whether subjects withdrew from the study or were lost to follow-up with higher scores representing a higher assessment quality All discrepancies or conflicting assessments were resolved via a consensus discussion with a third reviewer Mean differences with a 95% CI(Confidential intervals) were used to evaluate the impact of each supplement on HT-related and representative metrics To account for the heterogeneity among studies the data were pooled using a random-effects method Heterogeneity was assessed using the I² statistic and I² > 50% was considered a level of high heterogeneity Subgroup analysis was performed according to the time and dose of the supplements used All analyses were performed using STATA (version 17.0 and a P<0.05 was considered statistically significant TgAb and TSH before and after supplementation Flowchart of the search strategy and study selection process for this meta-analysis Characteristics of the studies included in the meta-analysis Clinical parameters and microbiology assessment of selected studies In 7 of these articles, interventions lasted 6 months, while in 3 articles, interventions lasted 3 months. Of these 10 studies, 1 was an open trial, which was considered of moderate quality, and the remaining studies were randomised controlled trials, all of high quality (Table 2) Figure 1 shows a network diagram of trials that tested the effectiveness of different interventions (placebo Vitamin D + inositol) and direct comparisons of these interventions Node size is the sample size for each type of intervention and line thickness is proportional to the number of trials for that comparison the majority of HT patients who received vitamin D supplementation exhibited significant hypothyroidism which raises concerns about the reliability of the findings While inositol alone may not significantly reduce antibody titres its combination with selenium or vitamin D may enhance the function of these supplements further research is needed to clarify its role in clinical practice Forest plots of TPOAb and TgAb levels during supplement use (A) Forest plot of TPOAb levels when using Se (B) Forest plot of TgAb levels when using Se (C) Forest plot of TSH levels when using Se Due to inconsistencies in the treatment duration of the included trials a separate subgroup analysis was conducted for trials that included treatment supplementation for a period of 6 months The use of selenium supplements was still found to be effective in reducing TPOAb(SMD: -2.98 Furthermore, Myo-inositol used in combination with selenium was able to reduce TSH levels (SMD: -1.53, 95%CI: -2.99, -0.08) (Figure 2C). However these results were not significant when subgroup analyses were performed for studies using treatment supplements for 6 months (Figure 3C) Forest plot of TPOAb and TgAb levels during supplement use for 6 months Because many of the articles on selenium supplementation came from CNKI we conducted a publication bias test on the included articles The results of Egger’s test indicated the presence of publication bias and the results did not reverse after using the trim and fill method indicating that the results are stable and publication bias does not affect this result Each article was successively excluded and a meta-analysis was performed on the remaining literature and we found that the results did not change significantly which means that the results are stable and reasonable In this network meta-analysis, selenium supplementation during the treatment of HT patients effectively reduced TPOAb (SMD:-2.44, 95% CI:-4.19, -0.69) and TgAb (SMD: -2.76, 95% CI:-4.50, -1.02) levels. If patients have vitamin D deficiency or insufficiency(<20 ng/mL) or low selenium levels(20-30 ng/mL) (41) and still have high autoantibodies after long-term regular treatment we can consider adding selenium or vitamin D or a combination of the two If a single supplement does not significantly reduce antibody levels a combination of supplements is more likely to be recommended it is recommended that patient levels of selenium and vitamin D be monitored throughout the course of treatment with adjustments to supplement dosages made as necessary supplementation should be moderate and tailored to the individual further clinical trials and mechanistic studies are required to provide additional support for these findings The combination of multiple supplements is likely to become a future trend in clinical practive for the reduction of HT-specific autoantibody titres this is the meta-analysis to compare the efficacy of divers dietary supplements as an adjunctive therapy for the management of HT patients treated with levothyroxine were excluded from this analysis avoiding drug influences on the assessed measures including a stendency towards a higher number of included selenium-related articles which has been proposed as a dietary supplement for HT patients in recent years and differences in drugs administration may also influence the reported experimental outcomes this meta-analysis revealed a statistically significant reduction in autoantitody titres when selenium was administered Further research is required to investigate the efficacy of other supplements in this clinical setting the results of this study demonstrated that selenium supplementation has a significant role in lowering thyroid autoantibody titres in patients with HT large multicentre randomised controlled studies are required to ascertain whether other supplement-assisted treatments for HT can prove beneficial for these patients The author(s) declare financial support was received for the research This study was supported by the National Natural Science Foundation of China (Grant Number: 82270836) The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher Efficacy and safety of long-term universal salt iodization on thyroid disorders: epidemiological evidence from 31 provinces of Mainland China Hashimoto thyroiditis: clinical and diagnostic criteria PubMed Abstract | Crossref Full Text | Google Scholar Limited genetic overlap between overt Hashimoto's thyroiditis and Graves' Disease in twins: A population-based study Changing iodine status and the incidence of thyroid disease in mainland 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thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in myo-inositol-treated and myo-inositol-naive women with autoimmune thyroiditis: A pilot study Protective effects of myo-inositol and selenium on cadmium-induced thyroid toxicity in mice Teng W and Shan Z (2024) Effects of different supplements on Hashimoto’s thyroiditis: a systematic review and network meta-analysis Received: 08 June 2024; Accepted: 19 November 2024;Published: 04 December 2024 Copyright © 2024 Peng, Wang, Gu, Wang, Teng and Shan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Zhongyan Shan, Y211c2hhbnpob25neWFuQDE2My5jb20= †These authors have contributed equally to this work and share first authorship Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish Unlock discounted publishing that highlights your organization and the peer-reviewed research and clinical experiences it produces Find out how channels are organized and operated including details on the roles and responsibilities of channel editors Offering a variety of advertising and sponsorship options for reaching influential specialists from targeted demographic splits efficient publishing and peer reviewing experience without sacrificing publication times Generate broad awareness and deliver relevant peer-reviewed clinical experiences directly to potential customers Dedicated Cranial Radiosurgery: Clinical Experience with New & Innovative SRS Technologies Real-Time Adaptive Motion Management on Helical and Robotic RT Platforms Please note that by doing so you agree to be added to our monthly email newsletter distribution list and Empower Millions Affected by Hashimoto's an autoimmune condition that affects millions yet remains misunderstood Hashimoto's is often overlooked—we're raising awareness to ensure patients get the diagnosis and care they deserve By raising awareness, the Clayman Thyroid Center hopes to improve early detection and connect patients with the resources they need to manage their condition Hashimoto's Disease: A Widespread but Overlooked Condition Hashimoto's thyroiditis is the leading cause of hypothyroidism yet many individuals suffering from the disease face years of uncertainty before receiving a diagnosis The condition occurs when the immune system mistakenly attacks the thyroid and eventual underproduction of thyroid hormones "Too many people struggle with symptoms for years only to be dismissed by doctors who don't check for Hashimoto's or fail to order the right tests," said Dr a senior thyroid surgeon at the Clayman Thyroid Center and empower patients so they can get the care they deserve." Why Hashimoto's Disease Awareness Day Matters This new awareness day was established to: "There's so much misinformation about Hashimoto's science-backed education to those who need it most," said Dr "This initiative is about ensuring patients have access to accurate information so they no longer have to struggle with unanswered questions about their health." Anyone can participate in Hashimoto's Disease Awareness Day by: Expanding Resources for Hashimoto's Patients In addition to launching Hashimoto's Disease Awareness Day the Clayman Thyroid Center is dedicated to providing long-term resources for those affected "Raising awareness isn't just about one day—it's about creating lasting change for the millions living with Hashimoto's disease," said Dr "We hope this initiative will give patients the information and confidence they need to take control of their health." Media Contact:Julie Canan, Director of Marketing941.468.3002 | [email protected] The Clayman Thyroid Center at the Hospital for Endocrine Surgery is proud to celebrate Thyroid Cancer Survivor's Day In recognition of Thyroid Cancer Awareness Month in partnership with the Hospital for Endocrine Surgery Health Care & Hospitals Medical Pharmaceuticals New Products & Services Do not sell or share my personal information: But how are these two specific conditions linked to each other A new study from China has attempted to find the answer leading to ulcers on the inner lining of your large intestine and symptoms such as diarrhea The study authors concluded that there’s a one-way connection between the two diseases. “The data seems to suggest that there is an increased risk for UC in patients with Hashimoto’s thyroiditis that is statistically significant,” says Mitali Agarwal, M.D. a gastroenterologist at Orlando Health Digestive Health Institute Center for Inflammatory Bowel Disease in Florida “The statistical data also suggests that the reverse is not true.” Translation: Having Hashimoto’s is a risk factor for developing UC The increase in risk for developing UC with Hashimoto’s was about nine to 10-fold How commonly does one person have both diseases? That’s unclear. The study authors write that UC and Hashimoto’s occur together frequently. However, the authors of a 2024 case report published in the Journal of Translational Autoimmunity call their co-occurrence “relatively rare.” Our experts say they see it infrequently or not at all in their practices Experts don’t know for sure why having one autoimmune condition may predispose you to another “The reason this occurs in not fully understood as the interrelationship between autoimmune diseases is complex and involves multiple factors: the immune system researchers say the connection between UC and Hashimoto’s may be due to what they refer to as a T-cell imbalance “T-cells are cells that help the body fight off a perceived threat,” says Jakob Saidman a gastroenterology fellow at Northwell Lenox Hill Hospital in New York City Saidman explains that when your immune system functions normally the threat the T-cells perceive is an infection in auto-immune diseases such as ulcerative colitis or Hashimoto’s the perceived threat is the colon or thyroid gland,” he says “When this system is perturbed or overwhelmed by a perceived threat the chemicals that activate or deactivate these T-cells are unregulated leading to the T-cells attacking the body.” The study authors suggest that the T-cell imbalance that occurs in Hashimoto’s subsequently leads to UC by triggering inflammation and impacting the immune system The study authors zeroed in on a proinflammatory cell called interleukin-21 (IL-21) as a potential link between the two conditions IL-21 may be involved in the development of UC IL-21 plays a role in intestinal inflammation by stimulating immune system activity They also note that its activity is related to another proinflammatory marker called Th17 which may contribute to the development of Hashimoto’s “IL-21 may be the key to finding a cure,” the authors write also propose that early diagnosis and treatment of Hashimoto’s may help treat people who also have UC treating thyroid disease will have an impact on the progression of UC.” Saidman wants to see more research on the connection: He says that UC is associated with at least 100 gene loci which are specific places on a chromosome where a certain gene or genes are located “The association seen in this study may be more associated with the fact that UC is involved with multiple genes as opposed to a direct link between the two disease processes,” he says I would like to see future studies showing a closer link to these two auto-immune diseases.” Link between Hashimoto’s Thyroiditis and Ulcerative Colitis (1): BMC Gastroenterology. (2024.) “Causal relationship between hypothyroidism and ulcerative colitis: a bidirectional Mendelian randomization study.” https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-024-03461-y Link between Hashimoto’s Thyroiditis and Ulcerative Colitis (2): Journal of Translational Autoimmunity. (2024.) “Ulcerative colitis with autoimmune thyroid disease results in bilateral auricular ossificans：a case.” https://www.sciencedirect.com/science/article/pii/S2589909023000382 Ulcerative Colitis (1): Cleveland Clinic. (2023.) “Ulcerative Colitis.” https://my.clevelandclinic.org/health/diseases/10351-ulcerative-colitis Ulcerative Colitis (2): Mayo Clinic. (2024.) “Ulcerative colitis.” https://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/symptoms-causes/syc-20353326 Hashimoto’s Thyroiditis (1): National Institute of Diabetes and Digestive and Kidney Diseases. (2021.) “Hashimoto’s Disease.” https://www.niddk.nih.gov/health-information/endocrine-diseases/hashimotos-disease Hashimoto’s Thyroiditis (2): Cleveland Clinic. (2023.) “Hashimoto’s Disease.” https://my.clevelandclinic.org/health/diseases/17665-hashimotos-disease Rezapour's clinical interests include inflammatory bowel disease.Visit Our Ulcerative Colitis Community Thanks for visiting The use of software that blocks ads hinders our ability to serve you the content you came here to enjoy We ask that you consider turning off your ad blocker so we can deliver you the best experience possible while you are here Metrics details Hashimoto’s thyroiditis (HT) is an autoimmune disease characterized by abnormal elevation in thyroid peroxidase antibody (TPO-Ab) and/or thyroglobulin antibody (TG-Ab) Patients have multiple symptoms despite adequate hormone substitution we aimed to quantify the relationship between thyroid antibodies and multiple symptoms inflammation and health-related life quality A total of 108 HT patients with clinical euthyroid status and 57 heathy controls were recruited Clinical parameters were determined by laboratory examination and the symptoms burden and life quality were obtained by a Hashimoto’s Thyroiditis Symptom Questionnaire and a SF-36 Questionnaire multiple extrathyroidal symptoms were significantly more serious in HT patients despite euthyroid status mainly including that related to digestive system (abdominal distension and indifferent) and mucocutaneous system (dry skin serum TPO-Ab and TG-Ab were both inversely correlated with health-related life quality of general health and vitality parameters and positively correlated with pro-inflammatory factors of TNF-α and IFN-γ as well as severity of abdominal distension TG-Ab level was positively associated with depressed HT patients suffered from a variety of symptoms and the elevated thyroid antibodies were inversely associated with health-related life quality and positively associated with inflammation and multiple extrathyroidal symptoms no specific treatment exits to improve the immune dysfunction in HT patients and prevent further development of Hashimoto disease the evidences directly demonstrating the association between abnormally elevated thyroid antibodies in HT patients and their extrathyroidal manifestations are still limited multiple symptoms and life quality were determined in HT patients who were kept in euthyroid status the association between thyroid antibodies (TPO-Ab and TG-Ab) and inflammatory factors multiple symptoms and life quality was analyzed to investigate the influence of elevated thyroid antibodies on HT patients A total of 108 patients with Hashimoto’s thyroiditis and 57 healthy subjects were enrolled for the present study 51 HT patients and 22 healthy participants were recruited at Affiliated Hospital of Qingdao University in northern China and the others were recruited at Zhejiang Chinese Medical University in southern China The study protocol was approved by the Ethics Committee of Qingdao University (Approval Number: QDU-20201107-1) All methods were performed in accordance with relevant guidelines and regulations Written informed consent has been provided by each participant Key inclusion criteria for HT patients were as follows: (a) age between 18–60 years old; (b) diagnosed by at least one endocrinologist according to clinical parameters and color ultrasonography; (c) positive TG-Ab or positive TPO-Ab while in euthyroid status without hormone substitution The healthy controls were recruited at the physical examination centers of Zhejiang Hospital and Affiliated Hospital of Qingdao University through a health-check program The main inclusion criteria for the control group were: (a) do not suffer from any type of thyroid disease hypothyroidism and thyroid tumor; (b) match the age and gender with the patients included: (a) pregnancy or lactation; (b) alcohol addiction; (c) with other kind of autoimmune disease such as rheumatoid arthritis or multiple sclerosis; (d) with serious chronic diseases such as cancer or heart disease; (e) use of anti-inflammatories or immunosuppressant drugs Demographic data of patients and healthy subjects were obtained with a face-to-face interview Each participant provided written informed consent and received no financial compensation or gifts Fasting blood from participants were centrifuged with 3000 rpm in 4 °C for 10 min to separate serum and erythrocytes FT3 and FT4 were determined by chemiluminescent immunoassays (Siemens Healthcare Diagnostics tumor necrosis factor (TNF)-α and interferon (IFN)-γ were determined by a flow cytometer (BD Biosciences Serum biomarkers of liver and kidney function and lipid profiles were measured with an automatic analyzer (HITACHI 7020 T lymphocyte subpopulations were measured with blood samples by a flow cytometry (BD Laboratory assays were performed in duplicate to minimize analytical errors and the presented values are the average of two measurements All measurements were performed at the end of the study to minimize variability Severity of multiple extrathyroidal manifestations was determined with the Hashimoto’s Thyroiditis Symptom Questionnaire each of which need to be answered with score from 0 to 10 (0 means no symptom 10 means the symptom seriously affect life quality) Data are described as means ± standard deviations for normally distributed variables as medians (interquartile ranges) for non-normally distributed variables and as counts (percentages) for categorical variables The difference between groups was analyzed by unpaired t test The correlation between thyroid antibodies and various symptoms as well as health-related quality of life was analyzed using Spearman’s correlation test To control for potential Type I errors due to multiple comparisons the Benjamini–Hochberg procedure was applied to adjust the p-values thereby controlling the false discovery rate P < 0.05 was considered statistically significant and all analyses were performed with the SPSS version 27.0 at least 106 patients with Hashimoto’s thyroiditis were required Healthy subjects were matched to cases using a 2:1 case-to-control ratio Demographic data of participants are shown in Table 1 There was no significant difference between HT patients and healthy subjects in age The proportion of married people in HT group was significantly higher than that in healthy controls Subjects with family history of HT in HT group were more than that in control group Clinical parameters of participants are shown in Table 2 parameters related to thyroid function (FT3 FT4 and TSH) of HT patients were similar with healthy controls only TPO-Ab and TG-Ab in HT group were remarkably higher than that in control group lipid metabolism biomarkers (TC and LDL-C) pro-inflammatory factors (TNF-α and IFN-γ) TP and ALB) and hsCRP levels were significantly increased in HT patients compared with healthy controls while all of them were still within normal ranges The correlation between thyroid antibodies and the 36-Item Short Form Health Survey scores. (A, B): Serum TPO-Ab levels and general health and vitality scores. (C-F): Serum TG-Ab levels and bodily pain, general health, vitality, and social functioning scores. Abbreviations: TPO-Ab, thyroid peroxidase antibody; TG-Ab, thyroglobulin antibody. The correlation between thyroid antibodies and inflammatory factors. (A, B): Serum TPO-Ab levels and TNF-α and IFN-γ. (C, D): Serum TG-Ab levels and TNF-α and IFN-γ. Abbreviations: TPO-Ab, thyroid peroxidase antibody; TG-Ab, thyroglobulin antibody; IFN-γ, interferon-γ; TNF-α, tumor necrosis factor-α. The correlation between thyroid antibodies and systematic symptom scores. (A-C): Serum TPO-Ab levels and endocrine system symptom scores, neuropsychiatric system symptom scores, and movement system symptom scores. (D-H): Serum TG-Ab levels and endocrine system symptom scores, neuropsychiatric system symptom scores, mucocutaneous system symptom scores, digestive system scores, movement system scores. Abbreviations: TPO-Ab, thyroid peroxidase antibody; TG-Ab, thyroglobulin antibody. The correlation between TPO-Ab and multiple symptom scores Serum TPO-Ab levels and abdominal distension (A) The correlation between TG-Ab and multiple symptom scores Serum TG-Ab levels and abdominal distension (A) this is the first study to quantify the relationship between thyroid antibodies (TPO-Ab and TG-Ab) and inflammatory factors as well as multiple symptoms in Hashimoto’s thyroiditis patients We found that both serum TPO-Ab and TG-Ab were inversely associated with life quality and positively associated with various extrathyroidal symptoms and inflammation even though all the patients were in euthyroid status without hormone substitution there are still many other symptoms reported by HT patients their relationships with Hashimoto disease have not been confirmed we used the Hashimoto’s Thyroiditis Symptom Questionnaire containing 49 items which included more detailed symptoms related to digestive The results showed that symptoms of abdominal distension constipation and diarrhea that related to digestive system irritability and indifferent that related to neuropsychiatric system were significantly more serious than healthy controls These findings provided us more comprehensive information about symptoms of HT patients and also provided guidance for clinician to diagnose the etiology of these extrathyroidal symptoms due to the euthyroid status of all enrolled participants these findings also confirmed that these symptoms were caused by autoimmune disease TNF-α and hsCRP were higher in HT patients than in healthy controls and increase of IFN-γ and TNF-α were both associated with higher TPO-Ab the reduction in serum TPO-Ab is probably a surrogate marker for the modification of the systemic inflammation and extrathyroidal symptoms our results also showed that TG-Ab was comparable with TPO-Ab when it come to their relationship with aforementioned proinflammatory factors even though TG-Ab has been known to be associated with HT its potential function as a predictive marker for inflammation and extrathyroidal symptoms is relatively unexplored limited study has given attention to intestinal symptoms in HT patients The present study firstly found that abdominal distension constipation and diarrhea were more serious in HT patients and both TPO-Ab and TG-Ab were positively associated with severity of abdominal distension and diarrhea indicating a possibility that reducing serum TPO-Ab and TG-Ab may be an effective way to modify these intestinal symptoms abdominal distension and diarrhea seemed to be unescapable symptoms of Hashimoto disease their close relationship has always been overlooked The serious intestinal symptoms reported by HT patients in the present study confirmed the assumption and raised a possibility that both the intestinal symptoms and HT could be cured from the perspective of improving the leaky gut we also found that TPO-Ab and TG-Ab were positively associated with severity of multiple other symptoms related to neuropsychiatric system the relationship between the other symptoms and thyroid antibodies were reported for the first time in this study the mechanisms were uncertain and warranted further investigation As the heavy symptom load in HT patients and its positive correlation with thyroid antibodies it is not a surprise that higher levels of TPO-Ab and TG-Ab were also associated with decreased health-related life quality For various health parameters in SF-36 questionnaire social functioning and mental health were significantly affected by the HT disease TPO-Ab and TG-Ab were both inversely associated with general health and vitality scores these results reflected an altered health perception of HT patients and may be due to the higher symptom burden Strengths of the present study include the study design where all cases are kept at euthyroid status thus the observed difference was free of hypothyroidism which has been known to be associated with HT but was seldom involved in other relevant studies the present study cannot demonstrate the causal relationship between increased thyroid antibodies and pro-inflammatory factors we observed multiple symptoms related to neuropsychiatric system in HT patients but not sure whether these symptoms were the cause or result of HT disease the sample size in the study was relatively small which represented participants from both northern and southern China Future prospective studies with large sample size are still needed the use of a Likert scale to evaluate specific symptoms may potentially overstate the significance of certain findings as the ordinal nature of Likert data may not accurately capture the true intensity of symptoms results from symptom ratings should be interpreted with caution considering these potential sources of inaccuracy the present study demonstrated that HT patients were accompanied with multiple symptoms especially those related to intestine and mood even though they were in a euthyroid state TPO-Ab and TG-Ab levels were inversely associated with general health and vitality scores and positively associated with pro-inflammatory factors as well as severity of several intestinal and psychiatric symptoms These results highlight the symptoms burden that HT patients are suffering from and are of great significance as they shed light on the clinical picture of HT Future research that aiming to explore the causes of Hashimoto disease or develop treatment strategies to decrease antibodies of HT patients is sorely needed The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request The incidence and prevalence of thyroid autoimmunity Relation of anti-TPO autoantibody titre and T-lymphocyte cytokine production patterns in Hashimoto’s thyroiditis Automatic levothyroxine dosing algorithm for patients suffering from Hashimoto’s thyroiditis Thyroidectomy versus medical management for euthyroid patients with Hashimoto disease and persisting symptoms: A randomized trial Hashimoto’s thyroiditis affects symptom load and quality of life unrelated to hypothyroidism: A prospective case-control study in women undergoing thyroidectomy for benign goiter Thyroidectomy for persistent Hashimoto disease symptoms Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance Disease-specific as well as generic quality of life is widely impacted in autoimmune hypothyroidism and improves during the first six months of levothyroxine therapy Effect of thyroid-related symptoms on long-term quality of life in patients with differentiated thyroid carcinoma: A population-based study in Sweden Sample size estimation in clinical research: From randomized controlled trials to observational studies Global prevalence and epidemiological trends of Hashimoto’s thyroiditis in adults: A systematic review and meta-analysis Local symptoms of Hashimoto’s thyroiditis: A systematic review and perceived quality of life in patients with Hashimoto’s thyroiditis Associations of elevated antithyroperoxidase antibodies with thyroid function and depressive symptoms in the oldest old: The Leiden 85-plus study The role of the immune system and cytokines involved in the pathogenesis of autoimmune thyroid disease (AITD) Regulatory B and T cell responses in patients with autoimmune thyroid disease and healthy controls The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto’s thyroiditis Persisting symptoms in patients with Hashimoto’s disease despite normal thyroid hormone levels: Does thyroid autoimmunity play a role Selenium supplementation for Hashimoto’s thyroiditis Polymeric immunoglobulin receptor deficiency exacerbates autoimmune hepatitis by inducing intestinal dysbiosis and barrier dysfunction measurement and clinical implications in humans Zonulin and its regulation of intestinal barrier function: The biological door to inflammation The potential of gut commensals in reinforcing intestinal barrier function and alleviating inflammation A Global regulatory network for dysregulated gene expression and abnormal metabolic signaling in immune cells in the microenvironment of graves’ disease and Hashimoto’s thyroiditis Intestinal inflammation and the enterocyte transportome Download references This work was supported by the National Natural Science Foundation of China (NSFC: 82103843 82273625 & 81973041); Natural Science Foundation of Zhejiang Province (ZCLY24H2602) and Zhejiang Provincial Xinmiao Talents Program (2024R410B062) These authors contributed equally: Jiaomei Li and Qingling Huang the Second Affiliated Hospital of Zhejiang Chinese Medical University collected the blood samples in hospital; Q.H. critically reviewed the manuscript; and all authors approved the final manuscript The authors declare no competing interests Download citation DOI: https://doi.org/10.1038/s41598-024-78938-7 Sign up for the Nature Briefing newsletter — what matters in science There are no statistics available for this player Thanks for visiting Metrics details Hashimoto’s thyroiditis is the most common endocrine disorder with diagnosis primarily relying on serum thyroid autoantibodies and ultrasound feature the diagnostic accuracy of serum thyroid autoantibodies and ultrasound for Hashimoto’s thyroiditis remains unclear including 6,195 (25.8%) patients diagnosed with Hashimoto’s thyroiditis The diagnostic performance of ultrasound and serum thyroid autoantibodies was assessed against histopathological findings Both serum thyroid autoantibodies and ultrasound demonstrated high overall specificity (91.8% respectively) and negative predictive value (87.4% respectively) for diagnosing Hashimoto’s thyroiditis thyroid autoantibodies level was strongly correlated with the risk of Hashimoto’s thyroiditis these methods demonstrated low independent sensitivity (30.5% respectively) and positive predictive value (43.7% the combined use of these methods resulted in a notably low sensitivity of 33.6% despite a relatively low false positive rate of 11.9% Elevated thyroid autoantibodies strongly correlate with Hashimoto’s thyroiditis risk While both autoantibodies and ultrasound demonstrate high specificity and negative predictive value their low independent sensitivity and positive predictive value limit reliability Combined use reduces false positives but further diminishes sensitivity accurate assessment and diagnosis of HT are crucial for early monitoring and intervention in affected patients the diagnostic efficacy of ultrasound and serum autoantibodies for HT remains ambiguous to investigate the diagnosis accuracy of these markers for HT we conducted a multicenter cross-sectional study including 24,014 cases The aim was to comprehensively analyze the overall and independent diagnostic efficacy of ultrasound and serum autoantibodies in diagnosing HT We conducted a multicenter cross-sectional study and retrospectively collected electronic medical records of 28,986 individuals from three medical centers in the central province of China: (1) Xiangya Hospital The participants’ data spanned from 2010 to 2023 This study was reviewed and approved by the Institutional Review Board of Xiangya Hospital and adhered to the ethical standards of the Declaration of Helsinki The requirement for informed consent was formally waived by the Institutional Review Board of Xiangya Hospital Central South University due to the retrospective design all methods were performed in accordance with the reporting guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement Selection and exclusion of participants and the flow of study design and 9.01–19.05 pmol/L for fT4 using the chemiluminescent assay from Abbott A result was considered positive if the thyroid autoantibodies titers exceeded the normal range for the respective assay Ultrasound images are generated using various device models from 11 manufacturers employing two-dimensional grayscale ultrasound and color Doppler flow imaging The ultrasound results were assessed and reported by an ultrasound physician with at least 3 years of experience and expertise in the field Ultrasound feature suggestive of Hashimoto’s thyroiditis (HT) included diffuse heterogeneous or raster-like changes in the thyroid parenchyma Feature of diffuse thyroid enlargement with abundant blood flow signals presenting a “sea of fire,” were not considered diagnostic of HT Hashimoto’s thyroiditis (HT) was diagnosed based on histopathological findings from postoperative paraffin-embedded tissue specimens obtained from the three medical centers Histopathological diagnosis of thyroid tissue was made independently and without reference to ultrasound imaging results or biochemical data on thyroid hormones and autoantibodies The diagnostic efficacy of ultrasound and serum autoantibodies for HT was calculated based on histologic findings we assessed both the overall diagnostic efficacy combined diagnostic efficacy and independent diagnostic efficacy of these indicators for HT The overall diagnostic efficacy was calculated without considering the status of other diagnostic indicators The parallel diagnostic efficacy was calculated when any one of indicators the sequential diagnostic efficacy was calculated when all other diagnostic indicators while the independent diagnostic efficacy was calculated assuming all other diagnostic indicators were negative 22,813 participants with thyroid autoantibodies measurements taken using the electrochemiluminescence immunoassay were selected to investigate the non-linear relationship between serum thyroid autoantibodies titers and the risk of HT using restricted cubic splines Qualitative data are presented as counts and percentages (%) and quantitative data are presented as medians with interquartile ranges (IQR) The chi-square test was used to compare the diagnostic efficacy (sensitivity FNR) of ultrasound and serum autoantibodies for HT across different groups All statistical analyses were performed using SPSS 26.0 for Windows (IBM SPSS USA) and R version 4.2.4 for Windows (R Foundation for Statistical Computing) A P-value < 0.05 was considered statistically significant A total of 24,014 participants were enrolled in this study of whom 77.0% (18,494/24,014) were women and 23.0% (5,520/24,014) were men resulting in a female-to-male ratio of 3.3:1 with an interquartile range (IQR) of 35–54 years The overall prevalence of HT was 25.8% (6,195/24,014) with a female-to-male ratio of approximately 2:1 HT was predominantly observed in middle-aged and younger individuals with prevalence rates ranging from 24.9 to 29.6% Association of serum thyroid autoantibodies level with risk of Hashimoto’s thyroiditis As summarized in Table 2 we evaluated the overall diagnostic efficacy of ultrasound for HT and accuracy of ultrasound for diagnosing HT were found to be 56.3% This study is the first to comprehensively assess the diagnostic efficacy of ultrasound and serum autoantibodies for HT based on a multicenter Our results indicate that thyroid autoantibodies level is closely associated with the risk for HT the independent diagnostic performance of ultrasound and serum autoantibodies in diagnosing HT is limited with both exhibiting high rates of false positive and false negative the combined diagnostic approach using both ultrasound and serum autoantibodies demonstrates lower sensitivity although it shows reduced false positive and false negative rates large-scale data evaluating the practical application of both serum thyroid autoantibodies and ultrasound for clinical HT diagnosis though none of these studies comprehensively evaluated the independent diagnostic performance of both serum thyroid autoantibodies and ultrasound for HT elevated level of thyroid autoantibodies is frequently observed in clinical practice especially when they are only slightly above the normal physiological range This may complicate the diagnosis of HT for clinicians our results show a strong correlation between thyroid autoantibodies level and the risk of HT TPOAb level were significantly positively associated with HT risk the relationship between TGAb level and HT risk appeared to be nonlinear and presenting an inverted V-shape on the restricted cubic spline plot This phenomenon may be attributed to the fewer number of patients with high TGAb level These data suggest that higher TPOAb and TGAb level correspond to an increased risk of HT we assessed the independent diagnostic performance of serum thyroid autoantibodies and ultrasound for HT Our findings revealed relatively low sensitivity (30.5% respectively) when these tools were used independently These results suggest that the clinical utility of serum thyroid autoantibodies and ultrasound alone for diagnosing HT is limited with a significant risk of missed diagnoses the false positive rates of these tests are high (56.3% highlighting the risk of misdiagnosis when relying solely on these methods for HT diagnosis although the combination of thyroid autoantibodies and ultrasound demonstrated higher diagnostic specificity (98.4%) and positive predictive value (88.1%) along with lower false positive rate (11.9%) and false negative rate (19.1%) this combination also showed reduced sensitivity (33.6%) This suggests that while the combination of ultrasound and thyroid autoantibodies may improve diagnostic accuracy in the detection of HT especially in detecting sensitivity to the disease these findings highlight the fact that both ultrasound and serum autoantibodies whether used independently or in combination There are several limitations in this study that should be noted While patients with toxic nodular goiter and Graves’ disease were excluded other types of autoimmune thyroiditis could not be definitively diagnosed and excluded which may introduce some error into our results the study participants were all undergoing surgery for thyroid malignancy or large thyroid nodules rather than participating in a general health screening This difference in study population may impact the accuracy and generalizability of the findings Another limitation is the potential observer bias in the thyroid ultrasound assessments which were conducted by different operators Although our results indicate that serum thyroid autoantibodies and ultrasound alone are not sufficient for diagnosing Hashimoto’s thyroiditis we have not yet explored more effective diagnostic methods such as artificial intelligence or biological diagnostic kits our next research direction will focus on developing a more accurate clinical diagnostic model These limitations highlight the inadequacy of current methods for conclusive diagnosis and underscore the urgent need for more accurate diagnostic strategies The datasets generated and/or analyzed during the current study are not publicly available due to participant information privacy but are available from the corresponding author on reasonable request Caturegli, P., De Remigis, A. & Rose, N. 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Thyroid 6, 445–450. https://doi.org/10.1089/thy.1996.6.445 (1996) Download references We wish to thank all the patients who participated in this study This work was supported by the National Natural Science Foundation of China (82371602 and 82300884); the Natural Science Foundation of Hunan Province (2023JJ40990); the Graduate Research and Innovation Projects of Hunan Province (CX20230361) Hai-Long Tan and Huan Ge contributed equally to this work Clinical Research Center for Respiratory Disease Hunan Provincial Clinical Medical Research Centre for Thyroid Diseases Hunan Engineering Research Center for Thyroid and Related Diseases Diagnosis and Treatment Technology National Clinical Research Center for Geriatric Disorders National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology Quality control of data and algorithms (H-L T The requirement for informed consent was formally waived by the Institutional Review Board of Xiangya Hospital All authors gave consent for the publication of this study Download citation DOI: https://doi.org/10.1038/s41598-025-97299-3 Sorry, a shareable link is not currently available for this article. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. This study aims to explore the correlation between patients with Hashimoto’s thyroiditis and food intolerance. A total of 172 subjects who visited Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2020 and March 2023 were selected and tested for 90 food-specific IgG antibodies. The study group composed 85 individuals diagnosed with Hashimoto’s thyroiditis, while the control group consisted of 87 healthy individuals. Data were analyzed to determine the correlation between Hashimoto’s thyroiditis and food intolerance. Volume 11 - 2024 | https://doi.org/10.3389/fnut.2024.1452371 Objective: This study aims to explore the correlation between patients with Hashimoto’s thyroiditis and food intolerance Methods: A total of 172 subjects who visited Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2020 and March 2023 were selected and tested for 90 food-specific IgG antibodies The study group composed 85 individuals diagnosed with Hashimoto’s thyroiditis while the control group consisted of 87 healthy individuals Data were analyzed to determine the correlation between Hashimoto’s thyroiditis and food intolerance Results: Among the 85 patients with Hashimoto’s thyroiditis with an average of 15.76 ± 10.61 types of food intolerances The most common intolerances were to eggs (75.29%) In the control group of 87 healthy individuals with an average of 9.57 ± 8.90 types of food intolerances The most prevalent intolerances in the control group were to bok choy (54.02%) and eggs (52.87%) Conclusion: The findings suggest that patients with Hashimoto’s thyroiditis are more likely to develop food intolerance compared to the healthy population which may indicate a correlation between Hashimoto’s thyroiditis and food intolerance Different dietary patterns may affect the activity of the thyroid axis and may even be the cause of autoimmune thyroid disease The technique of detecting food intolerance IgG antibodies has the potential to be an important reference for dietary interventions in patients with Hashimoto’s thyroiditis and persistent thyroid function abnormalities including pronounced fluctuations in TSH levels (fluctuating between hyperthyroidism and hypothyroidism) These cases present significant clinical challenges as conventional treatments often fail to maintain normal thyroid function and reduce thyroid-associated antibodies highlighting the urgent need for innovative diagnostic and therapeutic approaches They concluded that food intolerance is common in HT patients The aim of this study was to investigate the relationship between Hashimoto’s thyroiditis and food intolerance (specific IgG antibody test for 90 foods) A total of 172 subjects who visited Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2020 and March 2023 were selected and tested for 90 food-specific IgG antibodies 85 were diagnosed with Hashimoto’s thyroiditis (HT group) and 87 were included in a healthy control group (Non-HT group) In conjunction with the 2008 Chinese Guidelines for the Diagnosis and Treatment of Thyroid Diseases-Thyroiditis (9) and the American Thyroid Association’s (10) manual on Hashimoto’s thyroiditis: Any patient with diffuse thyroid enlargement especially with an enlarged pyramidal lobe Diagnosis can be confirmed if serum TPOAb and TgAb are positive Fine Needle Aspiration Cytology (FNAC) has diagnostic value Clinical or subclinical hypothyroidism further supports the diagnosis the diagnosis of HT was mainly made by thyroid ultrasound presenting changes characteristic of HT (e.g. The healthy control group (Non-HT group) was defined as people whose thyroid-related antibody (TPOAb and TgAb) tests were suggestive of negativity and whose thyroid ultrasound did not show Hashimoto’s thyroiditis-specific changes in order to minimize the interference of other autoimmune diseases with the results of this study we excluded subjects with a clear diagnosis of other autoimmune diseases Sensitized subjects with multiple allergies were also excluded (mainly to multiple IgE antibodies) We meticulously recorded data concerning the subjects’ age and levels of thyroid-related antibodies (TgAb Blood samples were collected from all subjects and quality control was conducted by the Laboratory Department of Guangdong Provincial Hospital of Traditional Chinese Medicine and thyroid-stimulating hormone (TSH) levels were measured using chemiluminescence while TgAb and TPOAb levels were measured using electrochemiluminescence The normal reference ranges are as follows: FT3: 3.5–6.5 pmol/L Blood samples were collected from all subjects after fasting for 12 h and were sent to the Guangzhou JingYu Center for Clinical Laboratory Food-specific IgG antibody test kits (HOB Biotech Group) were used to measure serum concentrations of 90 food-specific antibodies and to perform grading The grading standards were as follows: < 50 U/mL as negative; ≥ 50 U/mL as positive; under the positive result the antibody titer level was graded as follows: 50–100 U/mL as level I intolerance; 100–200 U/mL as level II intolerance; ≥ 200 U/mL as level III intolerance The 90 food items total include: Cheddar cheese Data were analyzed using IBM Statistical Package for the Social Sciences The level of significance for tests was set at α = 0.05 Count data were expressed as frequencies and percentages Comparisons between groups were made using the Chi-square test or Fisher’s exact test with P < 0.05 indicating statistical significance Among the 85 patients with Hashimoto’s thyroiditis TgAb levels averaged (391.42 ± 528.82) U/mL and TPOAb levels averaged (864.41 ± 518.45) U/mL The average age was (35.94 ± 14.10) years the average age was (44.39 ± 13.47) years Food intolerance profile of 172 subjects for 90 food-specific IgG antibody tests A total of 85 patients with HT were included in the study 83 of whom exhibited elevated food-specific IgG antibodies resulting in a positive detection rate of 97.65% The average number of intolerances per patient was (15.76 ± 10.61) the top fourteen with the highest positive rates were: eggs (75.29%) The highest rates of intolerance were primarily to eggs and dairy products (including cow’s milk Proportion of severity levels for the top three foods with the highest positive intolerance rates in the HT group (a) For eggs: 26 patients (41%) exhibited level I intolerance 21 patients (33%) exhibited level II intolerance and 17 patients (26%) exhibited level III intolerance (b) For bok choy: 50 patients (82%) exhibited level I intolerance 10 patients (16%) exhibited level II intolerance and 1 patient (2%) exhibited level III intolerance (c) For milk: 14 patients (25%) exhibited level I intolerance 17 patients (30%) exhibited level II intolerance and 25 patients (45%) exhibited level III intolerance An analysis comparing the food intolerance rates of the top 14 items among different genders within the HT group revealed that only potatoes showed significant differences between genders (see Table 2) Food intolerance among different genders in the HT group The analysis of food intolerance rates for the top 14 items among different age groups within the HT group revealed significant variations in the positive rates for eggs, cow’s milk, soft white cheese, yogurt, goat’s milk, and cheddar cheese across different age brackets (see Table 3) Food intolerance among different age in the HT group This study included 87 healthy individuals 83 of whom showed elevated levels of food-specific IgG antibodies resulting in a positive detection rate of 95.40% The average number of food intolerances per individual was (9.57 ± 8.90) with a range from none to as many as 41 different types the fourteen with the highest positive rates were bok choy (54.02%) Proportion of severity levels for the top three foods with the highest positive intolerance rates in the non-HT group (a) For bok choy: 40 individuals (85%) exhibited level I intolerance 7 individuals (15%) exhibited level II intolerance and none (0%) exhibited level III intolerance (b) For eggs: 27 individuals(59%) exhibited level I intolerance 10 individuals (22%) exhibited level II intolerance and 9 individuals (19%) exhibited level III intolerance (c) For milk: 13 individuals (42%) exhibited level I intolerance 9 individuals (29%) exhibited level II intolerance and 9 individuals (29%) exhibited level III intolerance Xue (11) and Zhao et al. (12) analyzed the serum specific IgE and IgG of nearly 100 children with allergic purpura inhalant allergens sIgE and tIgE were closely related to the development of the disease in the children and concluded that avoiding contact with allergens in the clinic could play a therapeutic and preventive role in the disease the results showed that the positive rates of food-specific IgG antibodies were higher than those of inhalant allergen IgE which led some scholars to suggest that “food intolerance-specific IgG antibodies can be a powerful complement to the detection of allergen IgE antibodies.” The rapid onset of IgE-mediated food allergy with onset of symptoms within minutes to hours and severe anaphylactic shock is a far cry from the chronic onset of Hashimoto’s thyroiditis Compared to IgE-mediated allergies, IgG-mediated food intolerances align more closely with the characteristics of Hashimoto’s thyroiditis. Recent research indicates that food intolerances are not limited to gastrointestinal disorders but are also associated with the development of various diseases, such as psoriasis (13), systemic lupus erythematosus (14), chronic urticaria (15) increasing their resistance to digestive breakdown and enhancing their allergenic potential the composition of the food matrix and processing techniques may also play a critical role in sensitization involving a questionnaire survey of 81 HT patients and 119 healthy individuals revealed that HT patients consumed higher amounts of animal-based foods (especially red meat and processed products) whereas the healthy group consumed more plant-based foods Their findings indicated that food intolerance is a risk factor for abnormal thyroid function as intolerance to these four foods correlated with thyroid function abnormalities 24.77% exhibited at least one of the seven thyroid function abnormalities The highest abnormality rate was observed in TSH levels all of which were statistically significant we consider that food intolerance is associated with thyroid dysfunction in the immune state rather than being a specific factor that leads to hyperthyroidism or hypothyroidism so we did not clearly distinguish between combined hyperthyroidism or combined hypothyroidism in our study we did not perform it on all patients with Hashimoto’s thyroiditis and significant fluctuations in thyroid-stimulating hormone (alternating between hyperthyroidism and hypothyroidism) which may have contributed to the increased positivity rate The use of a 90-food test in the present study compared to previous studies that tested 7 or 14 foods also contributed to the higher overall positive rate of intolerance observed This study demonstrates a close correlation between Hashimoto’s thyroiditis and food intolerance patients with Hashimoto’s thyroiditis are intolerant to a broader array of foods significant differences in intolerance rates between the two groups were noted for cheddar cheese HT patients showed particularly high intolerance rates to eggs and dairy products predominantly at levels II and III of intolerance; interestingly bok choy had a very high intolerance rate (HT group: 71.76% but the difference between the two groups was not statistically significant (χ2 = 6.534 which may be related to dietary habits in the Guangdong region Mei et al. (15) employed a treatment regimen combining medication with dietary restrictions (mainly including “alternate diet” “No-Eat” and “Absolute No-Eat”) based on food intolerance test results in 180 patients with chronic urticaria Their study found that compared to the control group the quality of life of the treatment group improved and the duration and frequency of outbreaks decreased future prospective studies could enhance the clinical value of this research there are few studies on the correlation between food intolerance and Hashimoto’s thyroiditis and no observational studies have been conducted in China regarding dietary management changes the limitations of this study include a small sample size and a relatively narrow range of tested foods indicating the need for further in-depth research in the future HuW: Writing – review & editing The authors declare that financial support was received for the research This study was supported by grants from the Guangdong Famous Chinese Medicine Workshop: Shusen Li Workshop Foundation Program the Guangdong Famous Chinese Medicine Workshop: Zhizheng Lu Workshop Foundation Program (E43710) and State Key Laboratory of Dampness Syndrome of Chinese Medicine (SZ2021ZZ3203) Shusen Li for his invaluable guidance and support His insights into my research topic were crucial in shaping my understanding and direction The impact of gut microbiota on autoimmune thyroiditis and relationship with pregnancy outcomes: a review Clinical effect of wenyang xiaoying formula on Hashimoto’s Thyroiditis and lts influence on TPOAb and TGAb titers Transition from Hashimoto thyroiditis to Graves’s disease: an unpredictable change Patients with Hashimoto’s thyroiditis present higher immune response to COVID-19 mRNA vaccine compared to normal individuals Analysis of T follicular and T peripheral helper lymphocytes in autoimmune thyroid disease Intestinal microbiota regulates the gut-thyroid axis: the new dawn of improving Hashimoto thyroiditis Google Scholar Study on the relationship between food specific lgG antibody and Hashimoto’s thyroiditis doi: 10.3760/cma.j.issn.1673-4394.2021.06.005 Organization of the Endocrinology Branch of the Chinese Medical Association Guidelines for the Diagnosis and Treatment of Thyroid Diseases in China (2008) Google Scholar Hashimoto’s Thyroiditis (Chronic Lymphocytic Thyroiditis or Autoimmune Thyroiditis Google Scholar The Study on the Relationship Between Food intolerance lgG and Serum Specific lgE in Abdominal type Henoch-SchönleinPurpura in children [D] Google Scholar Analysis of serum specific immunoglobulin E and immunoglobulin G in children with allergic purpura Crossref Full Text | Google Scholar Detection and analysis of food intolerance in patients with psoriasis Google Scholar A Preliminary Study on the Relationship between Systemic Lupus Erythematosus and Food Intolerance Guangzhou: Medical University of the South (MUMSouth) Google Scholar Patients with chronic urticaria triggered by food intolerance were treated with a combination of drug food avoidance therapy in patients with chronic urticaria caused by food intolerance Google Scholar Current Status of IgG Antibody Detection of 14 Food Intolerances in Health Checkup Population and its Relationship with Related Diseases Google Scholar Study on the prevalence of food intolerance and related factors in health checkup population J Preventive Med Chin Peopte’s Liberatton Army Google Scholar Digestibility and Potential Allergenicity of Gluten Proteins Inseventeen Wheat Varieties Google Scholar The effects of roasting on the allergenic properties of peanut proteins Identification and Quantification Study of Major Allergenic Proteins in Milk Egg and Soybean by Liquid Phase Tandem High Resolution Mass Spectrometry (Master’s Degree) [D] Google Scholar Excess iodine and high-fat diet combination modulates lipid profile and hepatic LDLr expression values in mice Effect of combined excess iodine and low-protein diet on thyroid hormones and ultrastructure in wistar rats Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats Effects of dietary protein on thyroid axis activity A high-fat diet rich in saturated and mono-unsaturated fatty acids induces disturbance of thyroid lipid profile and hypothyroxinemia in male rats Dietary self-management using mobile health technology for adults with type 2 diabetes: A scoping review Thyroid-gut-axis: how does the microbiota influence thyroid function Influence of dietary habits on oxidative stress markers in Hashimoto’s Thyroiditis Evaluation of correlations between food-specific antibodies and clinical aspects of Hashimoto’s thyroiditis Relationshipbetweentheblood test results of thyroid function and intoleranceto14 kinds of foods in physical examination population Google Scholar Wang Y and Wei H (2024) Analysis of the correlation between Hashimoto’s thyroiditis and food intolerance Copyright © 2024 Yan, Wu, Zhang, Gong, Wang and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Hua Wei, MTM4Mjk3MDExNjhAMTYzLmNvbQ== Metrics details Atherosclerosis (AS) is a chronic vascular disease characterized by inflammation of the arterial wall and the formation of cholesterol plaques Hashimoto’s thyroiditis (HT) is an autoimmune disorder marked by chronic inflammation and destruction of thyroid tissue Although previous studies have identified common risk factors between AS and HT the specific etiology and pathogenic mechanisms underlying these associations remain unclear We obtained relevant datasets for AS and HT from the Gene Expression Omnibus (GEO) we pinpointed common differentially expressed genes (DEGs) and discerned co-expression modules linked to AS and HT via Weighted Gene Co-expression Network Analysis (WGCNA) We elucidated gene functions and regulatory networks across various biological scenarios through enrichment and pathway analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Core genes were identified using Cytoscape software and further validated with external datasets We also conducted immune infiltration analysis on these core genes utilizing the CIBERSORT method Single-cell analysis was instrumental in uncovering common diagnostic markers we identified 119 candidate genes within the cohorts for AS and HT KEGG and GO enrichment analyses indicate that these genes are significantly involved in antigen processing and presentation along with various immune-inflammatory pathways were identified using five algorithms from the cytoHubba plugin Validation through external datasets confirmed their substantial diagnostic value for AS and HT the results of Gene Set Enrichment Analysis (GSEA) indicated that these core genes are significantly enriched in various receptor interactions and signaling pathways Immune infiltration analysis revealed a strong association of lymphocytes and macrophages with the pathogenesis of AS and HT Single-cell analysis demonstrated predominant expression of the core genes in macrophages T cells and Common Myeloid Progenitor (CMP) This study proposes that an aberrant immune response might represent a shared pathogenic mechanism in AS and HT The genes PTPRC and TYROBP are identified as critical potential biomarkers and therapeutic targets for these comorbid conditions the core genes and their interactions with immune cells could serve as promising targets for future diagnostic and therapeutic strategies delineating the interrelationship between HT and AS is essential for the effective prevention and management of cardiovascular diseases This shared characteristic of immune-inflammatory response enhances our understanding of the interaction mechanisms between diseases and supports the development of new therapeutic approaches thereby potentially improving treatment efficacy comprehensive research into these common pathological features is vital for devising broad-spectrum therapeutic strategies We sourced transcriptome datasets (GSE100927 and GSE29315) and a single-cell dataset (GSE155512) from the GEO database the dataset GSE100927 (platform: GPL17077) comprised 69 atherosclerotic and 35 healthy arterial samples GSE28829 (platform: GPL570) included 16 late-stage and 13 early-stage atherosclerotic plaque samples GSE155512 (platform: GPL24676) encompassed 3 atherosclerotic samples dataset GSE138198 (platform: GPL6244) contained 13 HT and 3 normal thyroid samples while GSE29315 (platform: GPL8300) included 6 HT and 8 thyroid hyperplasia samples We performed gene expression analysis on datasets GSE28829 and GSE138198 for AS and HT DEGs were identified using the Limma package in R (Version 4.4.0 adhering to criteria of Log2|fold change (FC)|> 1 and adjusted p value < 0.05 We generated volcano plots and heatmaps for the top 20 ranked DEGs using the ‘ggplot’ package The ‘VennDiagram’ package was then employed to identify common DEGs between AS and HT we selected the upper quartile of genes displaying the greatest median absolute deviation (MAD) we computed the Pearson correlation matrix for all gene pairings and crafted a weighted adjacency matrix using average linkage along with weighted correlation coefficients The adjacency matrix was established by applying a ‘soft’ thresholding power (b) which was then converted into a topological overlap matrix (TOM) For clustering genes with analogous expression patterns we implemented average linkage hierarchical clustering based on TOM-derived dissimilarity setting a threshold for the minimum module size at 60 we examined the similarity among genes within these modules defined a threshold for cutting the module dendrogram The WGCNA analysis enabled us to pinpoint significant modules related to AS and HT and to create visual representations of characteristic gene networks We performed these analyses using the ‘clusterProfiler’ package in R identifying significant pathways at a threshold of P < 0.05 The results were visualized using the ‘ggplot2’ package The defined parameters for this analysis were a degree cutoff of 2 datasets GSE100927 and GSE29315 were used for AS and HT with the expression of core genes confirmed using the ‘ggpubr’ R package we conducted Receiver Operating Characteristic (ROC) curve analysis using the ‘pROC’ R package utilizing the Area Under the Curve (AUC) as a measure of reliability GSEA was utilized for AS and HT employing the ‘clusterProfiler’ package Patients diagnosed with AS or HT were categorized into groups with high and low gene expression determined by the median expression levels of the central genes GSEA was then applied to compute enrichment scores for gene sets which illuminated differing functional phenotypes GSEA facilitated the comparison of biological pathways between the two expression groups referencing the c5.go.bp.v7.5.1.entrez.gmt gene set a normalized enrichment score (NES) > 1 and a false positive rate (FDR) q-value < 0.05 were deemed significantly enriched Enrichment plots prominently displayed the top five activating and inhibiting pathways for each essential gene in both conditions Pearson correlation analysis was then used to elucidate the relationships between various immune cell phenotypes and critical genes which were visually represented in lollipop plots we created a Seurat object from the read single-cell expression data and conducted quality control excluding cells with fewer than 50 expressed genes and those with a mitochondrial gene expression ratio exceeding 5% The data underwent normalization via the LogNormalize technique followed by the identification of 1500 highly variable genes through the ‘FindVariableFeatures’ function Principal Component Analysis (PCA) was then executed along with cluster analysis using Seurat’s ‘FindClusters’ function t-distributed stochastic neighbor embedding (t-SNE) was utilized for nonlinear dimensionality reduction facilitating the visualization of the data in t-SNE plots Volcano plot and Heatmap of the DEGs identified from GSE28829 and GSE138198. (A,B) Volcano map of DEGs fromGSE28829 and GSE138198. (C,D) Heatmap of DEGs from GSE28829 and GSE138198. Venn plot of common DEGs between AS and HT Screening of genes in the GSE28829 and GSE138198 datasets using the WGCNA algorithm. (A,B) The Cluster dendrogram in GSE28829 and GSE138198. (C,D) Heatmap illustrating the module-trait relationships in GSE28829 and GSE138198. WGCNA, weighted gene coexpression network analysis. Venn plot of common genes between AS and HT and the PPI network of the merged genes (A) The overlapped genes between the key modules in GSE28829 and GSE138198 Enrichment analysis of merged genes. (A,B) Circle plot and bubble plot of GO enrichment analysis includes biological process, cellular component and molecular function. (C) Bubble plot of KEGG enrichment analysis. (D) Venn diagram of core genes. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes. Validation of the expression level and diagnostic efficacy of PTPRC gene. The violin plots of PTPRC gene in GSE28829 (A), GSE100927 (B), GSE138198 (C) and GSE29315 (D). The ROC curves of PTPRC gene in GSE28829 (E), GSE100927 (F), GSE138198 (G) and GSE29315 (H). *p < 0.05; **p < 0.01;***p < 0.001; ****p < 0.0001. Validation of the expression level and diagnostic efficacy of TYROBP gene The violin plots of TYROBP gene in GSE28829 (A) The ROC curves of TYROBP gene in GSE28829 (E) *p < 0.05; **p < 0.01;***p < 0.001; ****p < 0.0001 GSEA analysis of core genes (PTPRC and TYROBP) in AS. GSEA Gene set enrichment analysis. GSEA analysis of core genes (PTPRC and TYROBP) in AS Immune infiltration analysis of AS. (A) Histogram of proportion of immune cells. (B) Comparison of immune cell proportion between AS and controls (Willcoxon’s test). (C) Correlation between PTPRC and immune cells content in AS. (D) Correlation between TYROBP and immune cells content in AS. *p < 0.05; **p < 0.01;***p < 0.001. (A) Histogram of proportion of immune cells (B) Comparison of immune cell proportion between HT and controls (Willcoxon’s test) (C) Correlation between TYROBP and immune cells content in HT (D) Correlation between TYROBP and immune cells content in HT *p < 0.05; **p < 0.01;***p < 0.001 Quality control results for single-cell data are presented as follows: the number of genes (C) Scatter plot of the expression of PTPRC and TYROBP macrophages and T-cells play a fundamental role in the pathogenesis of AS and HT driving disease progression through their involvement in inflammatory processes and immune regulation Future research is directed towards elucidating the mechanisms of action of these cells with the aim of developing targeted therapies such as modulating specific receptor activities or enhancing regulatory T-cell functions These advancements aim to effectively control inflammatory responses and pioneer new strategies for disease management Such progress not only has the potential to enhance patient quality of life but also offers significant theoretical and practical insights for the clinical treatment of cardiovascular and autoimmune diseases The precise mechanisms underlying AS and HT remain elusive which has prompted this study to undertake a comprehensive bioinformatics analysis aimed at elucidating the shared mechanisms and immune infiltration characteristics of AS and HT Results of the GSEA demonstrate a significant association between the elevated expression of specific genes and enhanced interactions with numerous receptors alongside involvement in various receptor signaling pathways Further examination of immune infiltration has uncovered a notable correlation between the expression of these genes and the prevalence of macrophages and lymphocytes in the development of AS and HT Single-cell analysis showed that PTPRC and TYROBP are predominantly expressed in macrophages immune profiles from patients with AS and HT demonstrated increased levels of memory B cells in affected individuals we propose that there may be shared pathogenic processes between AS and HT leveraging advanced gene editing technologies to precisely regulate specific gene expression in B cells may represent an effective treatment method The development of these therapeutic strategies necessitates a profound understanding of the role of B cells in these diseases and a comprehensive grasp of the intricate interactions within the immune system This connection opens new avenues for future research that could clarify the specific pathogenesis of HT and identify potential therapeutic targets the roles of PTPRC in studies on HT and AS mutually reinforce its broad applications in immune regulation a deeper exploration of the interactions between PTPRC and other immune regulatory molecules could uncover the complex networks involved in pathological states setting the stage for the development of more comprehensive treatment approaches TYROBP is likely to serve as a biomarker for patients with AS and HT This study boasts several significant strengths We implemented a comprehensive and intricate bioinformatics analysis approach to investigate the interactions between AS and HT By examining the shared molecular mechanisms and pathways of AS and HT we pinpointed crucial genes and immune infiltration characteristics These were corroborated through external datasets Our findings potentially illuminate the shared mechanisms underpinning AS and HT it is important to acknowledge the limitations of this study the data were sourced from the GEO database which could have inconsistencies in collection and processing methods potentially affecting the accuracy and reliability of our analyses Variations in processing methods and technical platforms across laboratories could introduce biases our analysis primarily focused on gene expression changes without directly measuring protein expression and activity Considering that gene expression levels do not always correlate with protein functions our findings necessitate further validation at the protein level future research should prioritize multidimensional data integration and experimentally validate the functions of identified genes and proteins Such approaches will foster a more comprehensive understanding of the pathogenic mechanisms of AS and HT and identify more precise clinical treatment targets and elucidated shared regulatory pathways and common immune characteristics This led to the development of an effective diagnostic model Further analysis using CIBERSORT revealed a significant correlation between the expression of these core genes and immune cell infiltration single-cell sequencing analysis demonstrated that these genes are primarily expressed in macrophages Our findings enhance the understanding of the molecular mechanisms underlying both diseases by highlighting key genes and immune regulatory pathways These achievements not only deepen our knowledge of the pathologies of AS and HT but also set the stage for further clinical research and therapeutic development The datasets GSE100927, GSE28829, GSE155512, GSE138198, and GSE29315 for this study can be found in the https://www.ncbi.nlm.nih.gov/geo/ The data supporting the findings of this study are available from the corresponding author upon a reasonable request t-distributed stochastic neighbor embedding Immunity and inflammation in atherosclerosis Mortality due to low-quality health systems in the universal health coverage era: A systematic analysis of amenable deaths in 137 countries Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease and risk factors for carotid atherosclerosis: A systematic review Global burden of cardiovascular diseases and risk factors Hashimoto’s thyroiditis: An update on pathogenic mechanisms The association of other autoimmune diseases in patients with Graves’ disease (with or without ophthalmopathy): Review of the literature and report 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acetylated low-density lipoproteins and generation of reactive oxygen species are regulated by linear stiffness of the growth surface TREM2 promotes cholesterol uptake and foam cell formation in atherosclerosis The role of natural killer cells in autoimmune diseases Natural killer cells in human autoimmune disorders Causal role of immune cells in Hashimoto’s thyroiditis: Mendelian randomization study Genetics and functional genetics of autoimmune diseases Download references The authors wish to thank GEO for providing open access to the database This work was supported by National Construction Project for Traditional Chinese Medicine Specialties with Advantages (Gan Cai She Zhi [2024] No 39) (Translated name); NATCM’s Project of High-level Construction of Key TCM Disciplines (zyyzdxk-2023113); Jiangxi Province Key Laboratory of Traditional Chinese Medicine for Cardiovascular Diseases (2024SSY06301); National Natural Science Foundation of China (82374367); Natural Science Foundation of Jiangxi Province (20242BAB26163 Affiliated Hospital of Jiangxi University of Chinese Medicine Jiangxi Province Hospital of Integrated Chinese & Western Medicine All authors have read and approved the final manuscript led the entire research project and reviewed and approved the final version of the paper Download citation DOI: https://doi.org/10.1038/s41598-025-85112-0 Metrics details Hashimoto’s thyroiditis (HT) is a prevalent autoimmune disorder yet the metabolic abnormalities associated with HT and their relationship to antibody positivity remain poorly understood This study aimed to characterize the distinct metabolic profiles associated with thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) positivity in female patients with HT Serum metabolomic analysis was performed on 14 TPOAb-positive patients Partial least squares discriminant analysis (PLS-DA) revealed significant metabolic differences among the groups 13 metabolites showed significant differences between the TPOAb-positive group and healthy controls while 23 metabolites exhibited marked differences between the TgAb-positive group and controls Further correlation analysis revealed a moderate positive association between TgAb and phenylacetyl-L-glutamine while TPOAb was strongly correlated with LPC 16:0 sn-1 metabolic pathway analysis showed significant activation of glycine and threonine metabolism in the TPOAb-positive group whereas the TgAb-positive group exhibited enhanced activity in galactose metabolism These findings suggest that TPOAb and TgAb positivity are associated with distinct metabolic profiles reflecting their differential roles in metabolic pathways linked to Hashimoto’s thyroiditis This study provides valuable exploratory evidence of metabolic abnormalities in HT under different antibody-positive states laying the foundation for future large-scale investigations to elucidate the underlying mechanisms most research has predominantly focused on the effects of thyroid hormones on glucose and lipid metabolism leaving the relationship between thyroid autoantibody positivity and metabolic disturbances largely unexplored These findings highlight the significant association between thyroid autoantibody expression and systemic metabolic disturbances the specific mechanisms underlying the distinct roles of TPOAb and TgAb remain unclear and require further investigation While these findings underscore the relationship between thyroid antibodies and metabolic disturbances the specific association between isolated TgAb or TPOAb positivity and small-molecule metabolites remains unclear These findings underscore the potential of metabolite profiling in distinguishing disease states and offer valuable insights for clinical diagnosis and disease management studies exploring the relationship between small-molecule metabolites and isolated TgAb or TPOAb positivity in female patients with Hashimoto’s thyroiditis remain scarce our study employs serum metabolomic profiling to preliminarily investigate abnormalities in serum metabolites associated with different antibody states in HT and their correlations with thyroid antibodies This work aims to provide foundational data for future large-scale longitudinal studies that will further elucidate the underlying mechanisms we seek to validate and clarify the distinct roles of TPOAb and TgAb in the progression of Hashimoto’s thyroiditis The study protocol was approved by the Ethics Committee of the Second Hospital of Dalian Medical University (Approval Number: 2021 NO.073) All procedures were performed in accordance with the principles outlined in the Declaration of Helsinki were included and divided into three groups for the study The experimental group consisted of eighteen patients with Hashimoto’s thyroiditis from the Department of Endocrinology at Dalian Medical University fourteen patients were assigned to the HT group with positive thyroid peroxidase antibodies (TPOAb (+)) and four were assigned to the HT group with positive thyroglobulin antibodies (TgAb (+)) Fourteen healthy individuals were recruited from the medical examination center of the Second Hospital of Dalian Medical University and assigned to the control group The inclusion and exclusion criteria were as follows: The TPOAb (+) group met the following criteria: (a) Female gender (b) Diffuse swelling of the thyroid gland with surface roughness and nodularity (c) Positive thyroid peroxidase antibodies (TPOAb) and normal thyroglobulin antibodies (TgAb) The TgAb (+) group met the following criteria: (a) Female gender (c) Positive thyroglobulin antibodies (TgAb) and normal thyroid peroxidase antibodies (TPOAb) Any participant who meets any of the following criteria will be excluded: (a) Patients with other autoimmune diseases (b) P Patients with concurrent acute or chronic infectious diseases such as acute or chronic hepatitis and pneumonia (c) Patients taking both non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids (d) Patients with concurrent malignant tumors or immune deficiency Under sterile conditions and in a calm environment 2 to 3 mL of peripheral blood is drawn from the antecubital fossa of the study participants and promptly sent to the central laboratory for analysis Thyroid function is assessed using the Siemens ADVIA Centaur XP fully automated chemiluminescent immunoassay system Metabolites were detected using the LC-MS full-component data system with chromatographic separations performed in both positive and negative ion modes Chromatographic column: Waters BEH C8 column (50 mm × 2.1 mm Mobile phases: water with 0.1% formic acid and acetonitrile with 0.1% formic acid Gradient: The initial gradient was set to 5% B followed by a linear increase to 40% B within 1.5 min a further linear increase to 100% B occurred over 6 min then returned to the initial gradient of 5% B at 10.1 min Chromatographic column: ACQUITY UPLC HSS T3 (50 mm × 2.1 mm Mobile phase: Phase A consisted of water with 6.5 mM NH₄HCO₃ while Phase B comprised an aqueous solution containing 95% methanol and 6.5 mM NH₄HCO₃ Gradient: The initial gradient was set to 2% B followed by a linear increase to 100% B within 6 min and then returned to the initial gradient of 2% B at 10.1 min The statistical analyses were conducted using the Statistical Package for the Social Sciences (SPSS Normally distributed data were expressed as mean ± standard deviation (SD) whereas non-normally distributed data were presented as median with interquartile range For comparisons among three or more groups analysis of variance (ANOVA) or Kruskal-Wallis tests were employed the significance threshold was adjusted using the Bonferroni method with the adjusted p-value threshold set at 0.017 (0.05/3) A p-value of less than 0.017 was considered statistically significant Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) were performed using SIMCA version 14.1 (Umetrics AB Serum metabolites with a Variable Importance in Projection (VIP) score greater than 1.5 in the OPLS-DA model were subjected to statistical significance evaluation using either a t-test or a non-parametric test The data were normalized using MetaboAnalyst 5.0 (https://www.metaboanalyst.ca/) to minimize systematic bias and enhance consistency Features with more than 25% missing values were excluded and any remaining missing values were imputed with the mean of the original data and scaled by dividing each variable by the square root of its standard deviation Enrichment analysis and heatmap generation of differential metabolites were conducted using MetaboAnalyst Correlation analysis was performed using Origin 2021 The receiver operating characteristic (ROC) curve was generated using SPSS and metabolite point plotting was carried out using GraphPad Prism 9.0 The baseline parameters of the control, TPOAb (+), and TgAb (+) groups are presented in Table 1 Significant differences were observed in the levels of thyroid peroxidase antibody (TPOAb) between the control and TPOAb (+) groups no statistically significant differences were found in the levels of thyroglobulin antibody (TgAb) significant differences were observed only in TgAb levels Both TPOAb and TgAb levels exhibited significant differences between the TPOAb (+) and TgAb (+) groups with no other significant differences in the remaining parameters The PLS-DA score plot comparing the control group to the TPOAb (+) and TgAb (+) groups (a) PLS-DA score plot of three groups (R2X = 0.195 (b) OPLS-DA score plot comparing the Control group to the TPOAb (+) group (R2X = 0.262 (c) OPLS-DA score plot comparing the Control group to the TgAb (+) group (R2X = 0.203 The t [1] and t [2] values in the figures represent the scores of each sample in principal components 1 and 2 Each dot on the plot represents a sample in the corresponding group Based on the criteria of VIP > 1.5 and P < 0.05, a total of 36 differential metabolites were identified. Thirteen differential metabolites were identified in the comparison between the Control and TPOAb (+) groups, while 23 differential metabolites were identified in the comparison between the Control and TgAb (+) groups (Table 2) (a) Differential metabolites from the comparison between the Control group and the TPOAb (+) group (b) Differential metabolites from the comparison between the Control group and the TgAb (+) group (a) Heatmap of differential metabolites comparing the Control group and the TPOAb (+) group (b) Heatmap of differential metabolites comparing the Control group and the TgAb (+) group (c,d) Pearson correlation coefficients between clinical variables and differential metabolites displayed by Correlograms Enrichment analysis was performed to identify the significantly altered metabolic pathways based on the Kyoto Encyclopedia of Genes and Genomes database through Metaboanalyst (a,b) Comparison between the Control group and the TPOAb (+) group (c,d) Comparison between the Control group and the TgAb (+) group alterations in serum TPOAb levels in TPOAb-positive patients can impact thyroid hormone levels modifying bile acid metabolism and its related metabolite products potentially influencing disease progression subsequently regulating amino acid levels in the body abnormal levels of phospholipid metabolites such as SM Correlation analysis suggests a relationship between TPOAb and LPC Since TPOAb inhibits thyroid hormone synthesis the overall phospholipid metabolism decreases leading to changes in phospholipid metabolites These changes may lead to the abnormal secretion of inflammatory factors and immune disorders ultimately resulting in inflammatory abnormalities and immune dysfunction TgAb is one of the most common autoantibodies found in the thyroid gland and is often used to diagnose and identify autoimmune thyroiditis Previous studies have suggested that TgAb positivity alone suppresses the development of hypertriglyceridemia in women and reduces the risk of impaired fasting glucose regulation (IFG) in men and PC in female patients in the TgAb (+) group we found a significant correlation between TgAb levels and serum glutamate due to the lack of literature on the mechanisms underlying the association between serum TgAb levels and suppressed lipid metabolism further research is needed to elucidate how TgAb influences metabolism Our study indicates that female patients with Hashimoto’s thyroiditis exhibit abnormal levels of small molecule metabolites depending on TPOAb or TgAb positivity TPOAb affects metabolic levels by modulating thyroid hormones while the mechanisms through which TgAb affects metabolism require further investigation This research provides insights into potential biomarkers for disease monitoring and treatment longitudinal studies involving larger populations are needed to confirm these results and further research is needed to elucidate the underlying mechanisms There are several limitations to our study it did not include metabolomic analysis of male patients with Hashimoto’s thyroiditis future research will involve expanding the sample size and adopting more stringent diagnostic criteria as inclusion criteria for thyroiditis patients we plan to conduct further studies in larger and more diverse populations to improve statistical power and more robustly validate our findings The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request Partial Least Squares-Discriminant Analysis Orthogonal projections to latent structures discriminant analysis Antibody-dependent cell-mediated cytotoxicity Detection of At-Risk pregnancy by means of highly sensitive assays for thyroid autoantibodies The spectrum of thyroid disease in a community: the Whickham survey Hashimoto’s Thyroiditis: similar and dissimilar characteristics in neighboring areas Possible implications for the epidemiology of thyroid Cancer Longitudinal change in thyroid-stimulating hormone and risk of nonalcoholic fatty liver disease Are thyroid autoimmune diseases associated with cardiometabolic risks in a population with normal thyroid-stimulating hormone Elevated TPOAb is a strong predictor of Autoimmune Development in patients of type 2 diabetes Mellitus and non-alcoholic fatty liver disease: a case-control study The Presence of serum TgAb suggests lower risks for glucose and lipid metabolic disorders in Euthyroid General Population from a National Survey Crystal structure of the TSH receptor bound to a blocking type TSHR autoantibody Thyrotropin stimulation of polyamine biosynthesis in the rat thyroid Serum polyamine metabolic profile in autoimmune thyroid disease patients The correlation between metabolic disorders and Tpoab/Tgab: A Cross-sectional Population-based study Physiological and metabolic changes during the transition from hyperthyroidism to Euthyroidism in Graves’ Disease Deciphering the metabolomics-based intervention of Yanghe Decoction on Hashimoto’s thyroiditis Targeting bile-acid signalling for metabolic diseases Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells thyroid hormone induction of human cholesterol 7 alpha-hydroxylase (Cyp7a1) in vitro Hypothyroidism increases cholesterol gallstone prevalence in mice by elevated hydrophobicity of primary bile acids Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes Serum bile acid profile in thyroid dysfunction and effect of medical treatment Amino assets: how amino acids support immunity Thyroid hormone regulates glutamine metabolism and anaplerotic fluxes by inducing mitochondrial glutamate aminotransferase GPT2 Thyroid hormones stimulate L-arginine transport in human endothelial cells Preferential hydrolysis of truncated oxidized glycerophospholipids by lysosomal phospholipase A2 Dihydroxyacetone phosphate signals glucose availability to mTORC1 Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4 + T cell subsets PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation Metabolomic basis for response to high dose vitamin D in critical illness Migration to apoptotic find-me signals is mediated via the phagocyte receptor G2A Attraction of phagocytes by apoptotic cells is mediated by lysophosphatidylcholine T lymphocyte-derived extracellular vesicles aggravate abdominal aortic aneurysm by promoting macrophage lipid peroxidation and migration via pyruvate kinase muscle isozyme 2 Effect of amiodarone on phospholipid content and composition in heart kidney and skeletal muscle: relationship to alteration of thyroid function Download references We gratefully acknowledge the approval from the Second Hospital of Dalian Medical University and the support provided by the Dalian Institute of Chemical Physics This study was supported by the following grants: the “Xingliao Talent Plan” of Liaoning Province China (YXMJ-QN-05); the Dalian Science and Technology Innovation Fund Dalian Science and Technology Bureau (2022JJ12SN048); and the “1 + X” Program for Clinical Competency Enhancement – Clinical Research Incubation Project The Second Hospital of Dalian Medical University (2022LCYJZD03) Xinyu Zhao and Xiao Jiang contributed equally to this work The Second Affiliated Hospital of Dalian Medical University Xiao Jiang and Haixia Liu; methodology and validation Pengqian Li and Xiaotong Gu; writing—original draf preparation Xinyu Zhao and Xiao Jiang; writing—review and editing Pengqian Li and Xingjie Xie; funding acquisition All authors have reviewed and approved the final version of the manuscript for publication This study protocol was approved by the Ethics Committee of the Second Hospital of Dalian Medical University (Approval No Informed consent was obtained from all participants According to national regulations and institutional requirements written informed consent was not required for this study Download citation DOI: https://doi.org/10.1038/s41598-025-90467-5 Hashimoto’s thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid. In recent years, metformin has been proven to be effective in a variety of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. This study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model, in vitro cell culture and differentiation, mRNA sequencing and 16S rRNA sequencing. These experiments provided a preliminary theoretical basis for the clinical application of metformin in the treatment of HT. Volume 9 - 2021 | https://doi.org/10.3389/fcell.2021.685522 Background: Hashimoto’s thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid metformin has been proven to be effective in a variety of autoimmune diseases rheumatoid arthritis and multiple sclerosis Methods: This study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model Findings: We found that metformin indeed had a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue metformin also significantly suppressed the number and function of Th17 cells and M1 macrophages polarization in HT mice metformin can inhibit the differentiation and function of Th17 in vitro The results of mRNA sequencing of thyroid tissue illustrated that the therapeutic effect of metformin on HT was mainly achieved by regulating immune pathways 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differs significantly from that of the normal mice and also were altered by metformin treatment Interpretation: These experiments provided a preliminary theoretical basis for the clinical application of metformin in the treatment of HT We have previously performed a meta-analysis of 75 patients with HT and 100 patients with subclinical thyroiditis (SH) and found that metformin effectively reduced the levels of TPOAb and TgAb in both HT and SH patients, and significantly inhibited thyroid stimulating hormone (TSH) level (Jia et al., 2020) we hypothesized that metformin may have a potential therapeutic effect on HT via pleiotropic mechanisms which need to be verified from multiple perspectives (C) TGAb expression in plasma and spleen index comparison Three fields of view of each sample were observed and the average was taken as the final score A total of 1–1.5 ml of whole blood was collected using retrobulbar bleeding method under anesthesia in an ethylenediaminetetraacetic acid anticoagulant EP tube and centrifuged at 2,000 rpm for 5 min at 4°C to obtain plasma The expression levels of TgAb (Cat # CSB-E09543m R&D) in mouse plasma were determined using ELISA according to the manufacturer’s recommended protocols The entire spleen of each mouse was obtained and placed on a 200-mesh sterile cell sieve After slowly mixed with 20 ml of RPMI 1640 cell culture medium (containing 10% inactivated fetal bovine serum) each spleen was ground and meshed into very fine parts cell pellets were resuspended in red blood cell lysis buffer to obtain single splenic cell suspension The spleen lymphocyte mononuclear cells were counted after trypan blue staining and adjusted to 5 × 106/test The cells were cultured for 5 h in 6-well plates with each well containing 2 ml of RPMI 1640 cell culture medium supplemented with 10% inactivated fetal bovine serum and 1% penicillin + streptomycin as well as 2 μl of cytokine stimulating agent the resulting spleen cells were labeled with CD3 antibodies (Cat # 145-2C11 We also detected macrophage polarization by labeling M1 macrophage as CD45+CD11b+Ly6G–F4/F80+CD206– and M2 macrophage as CD45+CD11b+ Ly6G–F4/F80+CD206+ (Misharin et al., 2013) cells samples were labeled with antibodies CD45-APC-Cy7 (Cat # 565853 cells were mixed first with lysis buffer then with antibody CD206-PE (Cat # 141706 CA) at 4°C for 25 min in the dark for intracellular staining The prepared cell suspension was filtered through a sterile 300 mesh filter to remove cell pellets and then subjected to flow cytometric analysis (Beckman CytoFlex) Mouse thyroid tissues were prepared as 4 μm paraffin sections each section was treated with 100 μL of 3% H2O2 for 10 min at room temperature and blocked with 100 μL of 2.5% goat serum blocking solution for 30 min at room temperature each section was incubated first for 1 h with 100 μL of diluted primary antibodies (IL-17A antibody Novus) then with 100 μL of secondary antibody for 30 min at room temperature The positive cells were revealed by incubating with 100 μL of freshly prepared 3,3’-diaminobenzidine (DAB) solution each section was incubated first with 100 μL of diluted primary antibody (IL-17A antibody Novus) overnight at 4°C then with 100 μL of secondary antibody for 2 h at room temperature in the dark Cells were counterstained with 100 μL 4′,6-diamidino-2-phenylindole (DAPI) for 10 min in the dark The phycoerythrin-labeled IL-17-secreting cells were sorted by flow cytometry In the above Th17 cells inducing process, metformin (0, 0.5, and 5 mmol/L; Cat # 317240, Sigma-Aldrich, Germany) was added at the beginning and its effects on Th17 cells differentiation in each group was analyzed by flow cytometry. The setting of the dose gradient of metformin referred to a previous study (Limagne et al., 2017) Th17 cells obtained without metformin intervention were collected by flow cytometry sorting and cultured in a 48-well plate IL-17 secreting cells obtained from same mouse were equally divided into two groups and cultured for 1 day without intervention cells were treated with metformin (0 and 5 mmol/L) cells were collected and used for flow cytometry and mRNA transcriptome sequencing (method described above) Upon establishment of Hashimoto’s thyroiditis animal model and completion of metformin intervention (within 30 min before sacrifice) mice were grabbed and their abdomens were gently massaged to stimulate defecation A total of 4 fresh feces per mouse were collected in a sterile cryopreservation tube and snap frozen in liquid nitrogen for future use Continuous variables were calculated as mean ± standard error (SE) and analyzed using independent sample t-test to identify significant differences between groups Non-normal distribution data were analyzed using Mann-Whitney U-test Statistical analysis of data was performed using GraphPad Prism (8.0 United States) with P-values < 0.05 being considered to have significant statistical differences All flow cytometry experimental data were analyzed using CytExpert (2.0 United States) and mRNA-sequencing results were analyzed using R software (version 3.5.1) Flow cytometry and statistics of mouse spleen T cells; (A) Flow cytometry diagram (A) IL-17 Immunohistochemistry and immunofluorescence of thyroid tissue (B) The expression level of IL-17 in thyroid tissue and plasma (a) the immunohistochemical score of IL-17 in thyroid tissue (b) the immunofluorescence score of IL-17 in thyroid tissue (c) the expression level of IL-17 in plasma detected by ELISA The effect of metformin on the differentiation of Naive T cells into Th17 cells (A) Flow cytometry diagram of Naïve T cells (C) Proportion of Th17 cell differentiation under different metformin concentrations (D) Differences in the mRNA transcriptome of Th17 cells before and after metformin treatment The percentages shown in (A,B) were the mean value of the corresponding groups Flow cytometry and statistics of mouse spleen neutrophils and macrophages; (A) Flow cytometry diagram Differences in intestinal flora detected by 16s-RNA sequencing Simpson’ diversity and Good’s coverage between groups due to strict control of interference factors in our experiment the HT group and the metformin treatment group were considered in similar stages of disease course it can still reflect the therapeutic effect of metformin on HT significant inhibitory effect of metformin on M1 macrophages was only observed in spleen cells but not in thyroid In order to further explore the local immunity changes in thyroid tissue mRNA sequencing of mouse thyroid tissue was conducted and the results proved that the therapeutic effect of metformin on HT was mainly achieved by regulating immune pathways immunofluorescence and mRNA sequencing of thyroid tissue were used to study local immune changes in the thyroid how the immune cells infiltrating the thyroid tissue were inhibited by metformin has still not been fully revealed more researches are needed to further study the effect of metformin on the local infiltrating macrophages and lymphocytes of the thyroid was not significantly different in HT mice and metformin treated mice our study has verified that metformin has a therapeutic effect on HT from multiple perspectives such as animal model our study still has some shortcomings and needs to be further improved The major limitation of the present research comes from the usage of only one animal model while the large sample size of each group may partially compensate for this shortcoming our results could be more robust if clinical data were available to support the therapeutic effect of metformin on HT The datasets presented in this study can be found in online repositories The names of the repository/repositories and accession number(s) can be found below: NCBI SRA (BioProject ID: PRJNA723153) The studies involving human participants were reviewed and approved by Ethical Committees of Zhoupu Hospital The patients/participants provided their written informed consent to participate in this study The animal study was reviewed and approved by Ethical Committees of Zhoupu Hospital operation and data analysis of the experiment and CQ: breeding and management of the experimental animals J-AZ and QQ: overall direction of the research All authors contributed to the article and approved the submitted version The present work was supported by Grants from the National Natural Science Foundation of China (Nos Pudong New Area Health Commission key sub-specialty (No Clinical Research Center of thyroid diseases of Shanghai Health Medical College (No 20MC20200002) and The Project of Shanghai Medical Key Specialty (No The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcell.2021.685522/full#supplementary-material Supplementary Figure 1 | mRNA sequencing of mice thyroid tissue (A) Thyroid tissue differential gene volcano map (a) different genes of mice in NC group vs (b) different genes of mice in HT group vs Met treatment group; 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Jin-an Zhang, emhhbmdqaW5hbkBob3RtYWlsLmNvbQ==; Qiaohui Qian, MTg5MTc2ODQwMjlAMTg5LmNvbQ== †These authors have contributed equally to this work all the way to Paris 2024A year on from Tokyo 2020 the reigning Olympic men's gymnastics all-around champion is determined to defend his title and bring the team gold back to Japan The process starts at the world championships in Liverpool this autumn Picture by 2021 Getty ImagesBy Shintaro Kano“I see the path” True words of enlightenment from a soon-to-be 21-year-old Olympic champion The Olympic champion is Hashimoto Daiki, who one year ago on Thursday (28 July), was crowned the new Olympic men’s all-around champion at Tokyo 2020 who only competed on the horizontal bar due to the wear and tear on his once superhuman body The torch, officially, had been passed on and since, Hashimoto has been using it to light his way down the path to Paris 2024 “Even after the Tokyo Olympics, there were a slew of competitions. I kept busy and a year was gone before I knew it. Hashimoto Daiki exclusive: Trying to be a better version of meWhere do you go when you are already on top of the world Just ask Olympic all-around champion Hashimoto Daiki who told us his philosophy "I learned that if I perform to my potential the results will take care of themselves," said the Japanese "Also just because I won gold I can’t get complacent He says to this day, he still watches his performances from last summer when he was in “a zone” like he had never been in before. The show he put on in Tokyo has become the gold standard to him, one that was so well executed that it even caught Hashimoto himself off guard. “I now know how locked in I was at the time”, the Chiba Prefecture native said at the state-of-the-art gymnasium of his school, Juntendo University. “I watch it, quite a lot actually. At Tokyo, my body moved really well. I had full control of my body and when that happens, it naturally leads to good results. “I don’t think I made a single mistake at the Olympics and that’s something I’d never done at any competition. “I’m still surprised with the performance I had at the Games”. Hashimoto said being able to turn confidence into conviction has set himself up well for Paris, mentally. “My goal was to win an Olympic gold medal. I knew I could do it - and I did it”, he said. “I felt my own strength, my own powers which made me No. 1 in the world. “It gave me the confidence to fight with my whole career ahead of me. “I learned that if I perform to potential, the results will take care of themselves. “Also just because I won gold I can’t get complacent. I have to keep working to get better. That’s what I figured out”. View this post on Instagram A post shared by 橋本 大輝/Daiki Hashimoto (@hasshii_807) Hashimoto puts a lot of thought into his words which he doesn’t mince and are usually straight as an arrow He has a direct way of getting his point across similar to the way Uchimura used to when he did media where he became the youngest-ever Olympic male all-around champion His gold on the high bar was Japan’s first in 37 years The following October at the world championships in Kitakyushu he competed at the national collegiate championships - Hashimoto was runner-up in both the all-around and the horizontal bar a perfectly respectable result all things considered The individual accolades are starting to pile up and should continue to do so for Hashimoto over the years But ask him what his upcoming goals are and he doesn’t hesitate Winning the team event - one of the most popular Olympic events across all sports in Japan - is hugely important to Hashimoto There is a maturity and selflessness about Hashimoto that are beyond his years “At the world championships in Liverpool this year “I want us to win the team gold and ride that to the all-around gold “We’ve missed out on the team gold the last few years We need to come together and perform well as a team Hashimoto will forever be grateful that Tokyo 2020 took place from a lot of people who didn’t gain a thing He realises they made Tokyo 2020 a possibility Yet not much has changed with Hashimoto in the last year He hasn’t gone on a splurge as someone his age might When Hashimoto turned 20 last year on 7 August The legacy of Tokyo 2020 for Hashimoto is indescribable because it’s intangible and ever-lasting he can visualise himself in Paris two years from now - on top of the podium “My biggest goal is to outdo my performance from Tokyo I’m convinced I can win both the team and the all-around in Paris But the focus is to perform to the best of my ability “Then I will have shown a better version of me” Relive the Men's All-Around Final from #Tokyo 2020 where 19-year-old Japanese Daiki Hashimoto extended his country's winning ways by capturing Japan's third straight men's gymnastics all-around title in a row and following up on Kōhei Uchimura's back-to-back wins in London 2012 and Rio 2016 Daiki Hashimoto (88.465)/ Ruoteng Xiao (8.065)/ Nikita Nagornyy (88.031) Thanks for visiting Yuu-U (“Loy”) Hashimoto — the URECA researcher of the month for October — is a junior majoring in biology with a minor in applied mathematics and statistics she has been working under the mentorship of Eugene Serebryany assistant professor in the Department of Physiology and Biophysics to investigate protein aggregation in the eye lens and a potential non-surgical treatment involving a metabolite in the human eye lens known as myo-inositol Based on her URECA application and proposal to study “The mechanism of myo-inositol in HgD-NtD crystallin aggregation,” Hashimoto was one of two students from the pool of 2024 URECA summer applicants to be awarded the prestigious Chhabra-URECA Fellowship which provides summer undergraduate research funding and recognizes students with a passion for research Hashimoto explains that her motivation has always been deeply personal: “Growing up as the daughter of a blind mother has influenced me to always hold a deep interest in anything eye-related I was particularly invested in conducting research that would benefit individuals with visual impairments and would like to pursue it more seriously moving forward.” Hashimoto’s strong interest in research was nurtured by joining the laboratory of Natasha Vitek assistant professor in the Department of Ecology and Evolution in January 2023 and being selected as a participant for the inaugural 2023 SUNY SOAR summer research program Hashimoto’s research focused on measuring the thickness of dentine and enamel in more than 50 mice teeth work she presented at the 2023 Summer Symposium on campus she plans to pursue a PhD in biomedical sciences Hashimoto serves as president of the Japanese Student Organization and is participating in an externship for the Diversity Professional Leadership Network She is also a participant in the AAPI mentoring program for Asian American and Pacific Islanders and in the Women’s Leadership Council Read the full interview with URECA Director Karen Kernan and website in this browser for the next time I comment Δdocument.getElementById( "ak_js_1" ).setAttribute( "value" This site uses Akismet to reduce spam. 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Stony Brook University Libraries is hosting The Human Library on November 20 to challenge stereotypes and prejudice through open dialogue with real people The Stony Brook community mourns the loss of Dorothy Lichtenstein a longtime supporter of Stony Brook Southampton arts programs and member of the Stony Brook Foundation Board of Trustees since 2008 Financial expert recognized for outstanding contributions to New York’s small business community Willa Smith advanced certified small business advisor at Stony Brook University’s Small Business Development.. © 2024 Stony Brook University Metrics details The management of papillary thyroid carcinoma (PTC) concurrent with Hashimoto’s thyroiditis (HT) lacks standardized guidelines This study aimed to compare unilateral thyroidectomy (UT) with total thyroidectomy (TT) in PTC-HT patients to optimize clinical management and improve postoperative outcomes This retrospective study included PTC-HT patients undergoing thyroid surgery at a tertiary academic medical institution from January 2018 to August 2023 The patients were grouped according to the quartiles of preoperative thyroid peroxidase antibody (TPOAB) levels at the last follow-up patients were divided into UT and TT groups with propensity score matching (PSM) to ensure comparability Patients were also stratified by TPOAB levels (L: 100–400 were compared between UT and TT groups within each TPOAB subgroup (ΔPROMs = UT-TT) Those with higher TPOAB levels at the last follow-up reported increased physical fatigue scores there were no significant demographic differences between UT and TT groups During a median follow-up of 16 months for UT and 20 months for TT the TT group exhibited lower TPOAB levels at the last follow-up (65.7 ± 78 vs and lower physical fatigue scores (3.6 ± 2.5 vs TT was associated with a higher incidence of transient hypoparathyroidism (7.8% vs Stratified analysis by preoperative TPOAB levels revealed significant differences in ΔPROMs (Physical fatigue) between L and H groups (0.2 ± 3.5 vs p = 0.004) and between M and H groups (0.6 ± 4.5 vs ΔPROMs (Mental fatigue) also significantly differed between L and H groups (0 ± 1.8 vs particularly those with high preoperative TPOAB levels TT offers advantages in alleviating fatigue symptoms but carries a higher risk of complications clinical decision-making should consider patient-specific factors to determine the optimal surgical approach Trial registration: Chinese Clinical Trial Registry further in-depth research is needed to develop more precise and personalized treatment strategies for this patient population with the goal of improving both their quality of life and long-term prognosis This study aims to evaluate the differences in postoperative outcomes between UT and TT in PTC-HT patients By thoroughly understanding the impact of different surgical approaches on these patients we hope to provide scientific evidence to further optimize clinical management ultimately enhancing their quality of life and long-term prognosis retrospective study conducted at a tertiary academic medical institution We retrospectively collected data on all patients who underwent thyroid surgery between January 2018 and August 2023 All the surgeries were performed by the same surgeon the patients were grouped according to the quartiles of TPOAB levels at the last follow-up This decision was made through multidisciplinary team(MDT) discussions at our institution following a comprehensive evaluation of tumor characteristics and other relevant factors preoperative discussions were held with patients to ensure they fully understood the benefits The final decision regarding the extent of surgery was made after thorough communication and consideration of the patient’s preferences The surgical approach (conventional open surgery or transoral endoscopic thyroidectomy vestibular approach) was decided upon through thorough communication between the chief surgeon and the patient patients were stratified by preoperative TPOAB levels (L: 100–400 Intraoperative neuromonitoring was performed for all patients Vocal fold function was assessed by laryngoscopy before discharge all PTC patients are recommended to undergo TSH suppression therapy postoperatively ensuring that their TSH levels were maintained within the recommended range Outpatient follow-up was performed at 1-month the patients were followed up every 6 months These items reflect the severity of fatigue from different aspects and can be divided into two categories representing physical fatigue and mental fatigue respectively Independent sample t test was used to analyze whether there were differences in PROMs between groups with different TPOAB levels (≤ P50 Spearman correlation analysis was conducted to further investigate the correlation between them Then propensity score-matched (PSM) analysis was done using a multivariable logistic regression model six factors that may affect postoperative health-related quality of life and fatigue degree follow-up time and surgical method were selected as covariables Pairs of patients receiving UT or TT were derive using 1:1 greedy nearest neighbor matching within propensity score of 0.02 Quantitative data are expressed as mean (SD) classification data are expressed as n (%) independent sample t test was used for quantitative data paired t test was used for quantitative data Statistical significance was accepted at a p value < 0.05 Flow chart of inclusion, exclusion and propensity score matching. The relationship between PROMs and TPOAB levels Physical fatigue between groups with different TPOAB levels (≤ P50 Mental fatigue Figure between groups with different TPOAB levels (≤ P50 Total score of THYCA-QOL between groups with different TPOAB levels (≤ P50 > P50) at the last follow-up.D: Spearman correlation analysis showed that physical fatigue scores were positively correlated with the TPOAB levels After PSM, 90 pairs of patients remained in the study population. There were no statistically significant differences between the two groups in terms of age, gender, BMI, preoperative TPOAB levels, follow-up duration, and surgical approach (Table 1) The PROMs differences are related to different preoperative TPOAB levels the impact of surgical extent selection on prognosis remains unstudied in PTC-HT patients although the TT group underwent more extensive CND and retrieved a higher number of lymph nodes than the UT group there was no significant difference in the number of metastatic lymph nodes between the two groups patients with multifocal tumors were more likely to undergo TT which explains the higher proportion of multifocality observed in the TT group we found that neither group experienced postoperative recurrence or metastasis which may be attributed to the favorable impact of HT on the prognosis of PTC the benefits of TT for PTC-HT patients may be less pronounced we found a positive correlation between physical fatigue scores and TPOAB levels at the last follow-up This suggests that higher TPOAB levels may lead to more severe physical fatigue If alleviating fatigue in HT patients is a priority targeted treatments addressing TPOAB might be more effective whether UT can significantly or partially reduce TPOAB levels has not yet been reported in studies the residual thyroid tissue continued to produce antigens sustaining the immune system’s attack and failing to significantly alleviate the patients’ physical fatigue symptoms there was no significant difference between the two groups We speculate that this may be due to the persistent autoimmune reaction caused by the residual thyroid tissue in the UT group which offsets the potential benefits of preserving the thyroid tissue UT does not significantly improve quality of life TT may be a better choice for PTC patients with higher preoperative TPOAB levels and more severe clinical symptoms surgeons must consider not only the efficacy of recurrence prevention and the surgical risks but also the impact of HT on the quality of life when determining the extent of surgery This holistic approach will help devise the optimal individualized treatment plan This study has several limitations that should be acknowledged it was unable to assess patients’ preoperative PROMs which limits the accuracy of evaluating the impact of surgery on these parameters this cross-sectional design prevented us from analyzing the time-dependent pattern of TPOAB changes and its impact on PROMs we did not systematically collect data on other metabolic disorders (e.g. elevated glucose levels) that could have impacted postoperative fatigue the relatively small sample size and the retrospective design of the study limits our ability to control for individual variations in thyroid function parameters Despite adhering to the CSCO guideline recommendations for TSH suppression therapy individual differences in hormone levels may have influenced postoperative outcomes only short-term postoperative effects could be observed The lack of long-term follow-up data may limit a comprehensive assessment of the effectiveness of surgical choices we plan to address these limitations by incorporating a longitudinal design implementing stricter control measures for thyroid hormone levels and systematically collecting data on metabolic impacts to provide a more rigorous and comprehensive assessment of the factors influencing postoperative fatigue and overall outcomes the choice of surgical extent for patients with PTC coexisting with HT requires comprehensive consideration of multiple factors Despite the higher risk associated with TT it significantly mitigates postoperative fatigue particularly in patients with elevated preoperative TPOAB levels where the benefits of TT are more pronounced it is crucial to assess the patient’s specific circumstances particularly focusing on preoperative TPOAB levels and carefully weigh the advantages and disadvantages of TT versus UT to determine the most appropriate surgical approach The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid Cancer: the American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid Cancer and disability-adjusted life-years for 32 Cancer groups 1990 to 2015: a systematic analysis for the global burden of Disease Study Increased annual frequency of Hashimoto’s thyroiditis between years 1988 and 2007 at a cytological unit of Sicily The impact of Coexistent Hashimoto’s Thyroiditis on Central Compartment Lymph Node Metastasis in Papillary thyroid carcinoma Hashimoto’s thyroiditis as a risk factor for thyroid cancer High prevalence of papillary thyroid carcinoma in nodular Hashimoto’s thyroiditis at the first diagnosis and during the follow-up Immunological changes of T 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strengthening the reporting of cohort cross-sectional and case-control studies in surgery Guidelines Working Committee of Chinese Society of Clinical Oncology Guidelines of Chinese Society of Clinical Oncology (CSCO) differentiated thyroid Cancer[J] Recurrent laryngeal nerve injury in thyroid surgery: a review Thyroglobulin levels as a predictor of Papillary Cancer recurrence after thyroid lobectomy Thyroglobulin for monitoring for thyroid Cancer recurrence Development of a disease-specific health-related quality of life questionnaire (THYCA-QoL) for thyroid cancer survivors Thyroid Cancer-specific quality of life and Health-Related Quality of Life in young adult thyroid Cancer survivors Quality of life in patients with low-risk papillary thyroid microcarcinoma: active surveillance Versus Immediate surgery Chronic fatigue syndrome treated by the traditional Chinese procedure abdominal tuina: a randomized controlled clinical trial Dose-effect of long-snake-like moxibustion for chronic 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rheumatic manifestations Anti-thyroid microsomal antibody in synovial fluid as a revealing feature of seronegative autoimmune thyroiditis Antithyroid-antibody activity in the snyovial fluid of patients with various arthritides Thyroid antibodies are produced by thyroid-derived lymphocytes Selenium supplementation in patients with Hashimoto Thyroiditis: a systematic review and Meta-analysis of Randomized clinical trials Reassessing selenium for the management of Hashimoto’s Thyroiditis: the Selini shines Bright for Autoimmune Thyroiditis patients Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients Association of total thyroidectomy or thyroid lobectomy with the quality of life in patients with differentiated thyroid Cancer with Low to Intermediate Risk of Recurrence Total thyroidectomy versus thyroid lobectomy for papillary thyroid cancer: comparative analysis after propensity score matching: a multicenter study Total thyroidectomy is associated with increased risk of complications for low- and high-volume surgeons Download references This study was supported by the Hunan Provincial Natural Science Foundation of China (Grant No Hunan Cancer Hospital Climb Plan (Grant No Health Research Project of Hunan Provincial Health Commission (Grant No W20243236 and R2023115) and Changsha Municipal Natural Science Foundation (Grant No Xiaoyong Wen and Shiwei Zhou contributed equally The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University/Hunan Cancer Hospital and SXH participated in the postoperative follow-up.MY and CGJ participated in data collection.All authors reviewed the manuscript The study was approved by the Medical Ethics Committee of Hunan Cancer Hospital Written informed consent was obtained from all individual patients included in this study All participants provided written informed consent before participating in the study which included consent to publish anonymous quotes from individual participants Download citation DOI: https://doi.org/10.1038/s41598-024-82626-x Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research “Through the first four events I felt great but I hadn’t really worked on the stamina to get through the two days which I was a little bit concerned about. “I think that’s the takeaway for the NHK Trophy. But I was happy with how I felt.” 🥇","event":null,"destination_url":"","entry_point_tag":"base","entry_point_type":"instory_campaign"}" data-tracking="click" href="https://www.olympics.com/en/sign-in?entry_point_type=instory_campaign&entry_point_tag=base&template=base&origin=https%3A%2F%2Folympics.com%2Fen%2Folympic-channel" target="_blank" rel="noopener noreferrer">Olympic Membership - Free Live Stream Sports & Original Series - join now Picture by The Yomiuri ShimbunHashimoto Daiki has looked like an Olympic medallist on the pommel horse in 2024 in total control of mind and body - until he hit the parallel bars on Sunday Hashimoto immediately clutched his arms in pain Hashimoto was rubbed down and went back out for the horizontal bar but the cramps returned as soon as he started his routine the 22-year-old held on and made it to the finish although he almost stumbled off the safety mats on the landing which resulted in a very pedestrian 13.800 by his standards While the crowd sighed in relief after it was revealed that Hashimoto simply cramped up and was not hurt it was a shame he couldn’t sustain his level of performance through all six events 15.133 on the pommel horse and 15.100 on the vault “Zhang scored an 89.2, I think, so if I can score 89 overseas I definitely think I can win (Paris),” Hashimoto said. “It’s hard to tell from domestic competitions alone but I want a performance that will translate well overseas. “I managed to get through the two days without an injury. The NHK Trophy will be the last competition before Paris. I want to compete there with confidence so I hope I figure out whatever I need to figure out physically.” *As National Olympic Committees have the exclusive authority for the representation of their respective countries at the Olympic Games, athletes' participation at the Paris Games depends on their NOC selecting them to represent their delegation at Paris 2024. Get to know the Men's Artistic Gymnastics teams and athletes who qualified for Paris 2024 at the FIG World Championships in Antwerp! Recent studies have indicated a potential association of hypertension with Hashimoto’s thyroiditis (HT) and other autoimmune diseases, yet the impact of antihypertensive drugs on HT risk is not well understood. The study suggests that CCBs and diuretics could potentially reduce the risk of HT in different populations. Additional research is needed to assess the feasibility of repurposing antihypertensive medications for the prevention of HT. Volume 15 - 2024 | https://doi.org/10.3389/fendo.2024.1419346 Introduction and objectives: Recent studies have indicated a potential association of hypertension with Hashimoto’s thyroiditis (HT) and other autoimmune diseases yet the impact of antihypertensive drugs on HT risk is not well understood Methods: We employed a drug-target Mendelian randomization approach to investigate the prolonged impact of 9 classes of antihypertensive medications on HT susceptibility in European and Asian populations Genetic variants close to or within genes associated with the drug targets and systolic blood pressure (SBP) were utilized to mimic the effects of antihypertensive medications We focused on drugs linked to a lower risk of coronary artery disease for our main analysis We gathered genetic data on SBP and HT risk from comprehensive genome-wide association studies available for European and Asian groups we used expression quantitative trait loci (eQTLs) related to drug target genes as proxies Results: Our analysis revealed that the use of calcium channel blockers (CCBs) is linked to a reduced risk of HT in both European (OR [95% CI]: 0.96 [0.95 to 0.98] per 1 mmHg decrease in SBP; p = 3.51×10-5) and Asian populations (OR [95% CI]: 0.28 [0.12 genetically mimicking the use of loop diuretics (OR [95% CI]: 0.94 [0.91 0.97]; p = 3.57×10-5) and thiazide diuretics (0.98 [0.96 0.99]; p = 3.83×10-3) showed a significant association with a decreased risk of HT only in European population These outcomes were confirmed when eQTLs were employed to represent the effects of antihypertensive medications Conclusion: The study suggests that CCBs and diuretics could potentially reduce the risk of HT in different populations Additional research is needed to assess the feasibility of repurposing antihypertensive medications for the prevention of HT the appropriate selection of antihypertensive drugs not only helps manage cardiovascular risk but may also play a key role in the prevention and management of HT ongoing systemic inflammation in HT may influence hypertension likelihood the impact of antihypertensive medication on HT remains minimally explored in epidemiological studies with traditional pharmaco-epidemiological research vulnerable to biases compromising validity and reliability Mendelian randomization (MR) evaluates causal relationships between modifiable exposures or risk factors and clinically meaningful outcomes using genetic variations (29). The resultant estimate is consistent even in cases of reverse causation and unmeasured confounding if the instrumental variable conditions are met (30) MR reduces bias for confounding variables in observational research being more practical than randomized controlled trials Drug-target MR predicts treatment outcomes and side effects before clinical trials It uses genetic variants as proxies for drug target effects enabling investigation of protein functions and drug target alterations This technique assessed long-term effects of nine antihypertensive medications on HT in European and Asian populations to determine their causal relationships with the disease Figure 1 illustrates the workflow of our current drug-target Mendelian Randomization (MR) investigation we consulted the British National Formulary to compile a comprehensive list of antihypertensive medication categories then utilized the DrugBank database to pinpoint the specific target genes for each category we employed genetic markers to represent 8 categories of antihypertensive medications These genetic markers were derived from two separate Genome-Wide Association Studies (GWAS) focusing on systolic blood pressure (SBP) from a European consortium we conducted an MR analysis to explore the relationship between genetically inferred antihypertensive medication use and the incidence of coronary artery disease (CAD) thus evaluating the efficacy of our genetic markers across different cohort Antihypertensive medications that showed no correlation with CAD risk were omitted from further analysis The concluding phase entailed examining the influence of genetically inferred antihypertensive medication categories on the risk of HT in both European and Asian populations Institutional Review Board (IRB) Approval (or Waiver) Statement: This study utilized summary statistics data exclusively without any individual-level data involvement Study design of the MR study of the associations between genetically proxied antihypertensive drugs and the risk of Hashimoto thyroiditis This selection strategy aimed to enhance the explained variance for each antihypertensive drug class through the genetic markers and to strengthen the instruments’ effectiveness it was deemed acceptable to utilize SNPs with an r2 < 0.1 as proxies to represent the various classes of antihypertensive medications We assessed the F-statistics for each single nucleotide polymorphism (SNP) related to genetically mimicked antihypertensive medications SNPs exhibiting F-statistics less than 10 were removed to mitigate the risk of weak instrument bias as F-statistics equal to or above 10 suggest a robust instrument In instances where an SNP from the genetic proxy was absent in the outcome genome-wide association study (GWAS) we sought a substitute SNP that was in strong linkage disequilibrium (r2 > 0.80) via LDlink (LDlink) To ensure consistency between the exposure and outcome data aligning them with the same effect allele across both datasets SNPs that were ambiguous or palindromic (with a minor allele frequency > 0.42) were systematically omitted In this study, coronary artery disease (CAD) served as the control outcome, reflecting the pivotal role of antihypertensive medications in decreasing CAD morbidity. For Europeans, summary-level CAD data were derived from a combined analysis of genome-wide association studies (GWAS) conducted by the CARDIoGRAMplusC4D consortium and the UK Biobank, encompassing 122,733 CAD cases and 424,528 controls (34) The primary focus of the research was HT. Summary-level HT data were obtained from a GWAS involving 395,640 individuals of European descent, which included 15,654 HT cases and 379,986 controls. HT was classified according to the International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10), with codes 245.2 and E06.3 respectively for each revision (35) The GWAS utilized the BOLT-LMM method for analysis were converted into log odds ratios using a standardized transformation process In the case of Asian population, summary-level HT data came from the same study of 173,193 individuals, which recorded 537 HT cases and 172,656 controls. The original research of GWAS was a multi-institutional, hospital-based registry that compiled DNA, serum, and clinical data, genotyped with Illumina HumanOmniExpressExome BeadChip or a combination of the Illumina HumanOmniExpress and HumanExome BeadChip. Diagnosis of HT cases was conducted by attending physicians (35) we assessed the validity of SNPs for genetically mimicking 9 antihypertensive drug classes by setting these classes as exposures and using CAD as a reference outcome the inverse-variance weighted (IVW) approach was utilized to determine the impact of these genetically mimicked antihypertensive drug classes on CAD Any class of genetically mimicked antihypertensive drugs not showing an inverse relationship with CAD risk at a nominally significant level (p ≥ 0.05) was removed to affirm the legitimacy of the genetically mimicked drugs The primary findings were expressed as odds ratios (ORs) for disease occurrence per 1 mmHg decrease in SBP attributed to the antihypertensive drug class The Bonferroni correction method was applied to adjust for multiple comparisons setting a p-value threshold of < 0.0056 (0.05/9 considering 9 classes of antihypertensive drugs and one cancer outcome) to denote “strongly significant” Results falling between a p-value of ≥ 0.0056 and < 0.05 were classified as “suggestively significant” In the final stage of our analysis, we employed cis-expression quantitative trait loci (cis-eQTLs) as genetic surrogates to measure exposure to each antihypertensive drug class in European populations, using data from previous studies (31) These studies identified SNPs that regulate the expression of drug target genes based on data from the Genotype-Tissue Expression (GTEx) consortium The selected SNPs demonstrated an impact on systolic blood pressure (SBP) according to summary statistics from the UK Biobank we excluded trans-eQTLs and SNPs with linkage disequilibrium (r2 > 0.1) based on the 1000 Genomes Project Phase 3 European reference panel to maintain specificity we assessed the relationship between eQTLs that mimic antihypertensive drug exposure and SBP utilizing summary statistics from the International Consortium for Blood Pressure (ICBP) and the UK Biobank The inverse-variance weighted (IVW) method was used to estimate the effect size representing the change in SBP per standard deviation decrease in the gene expression level we applied the IVW method to investigate the causal links between the expression levels of drug target genes and the risk of HT in European populations The outcomes were articulated as odds ratios (ORs) for HT per 1 mmHg reduction in SBP which is influenced by the expression of antihypertensive drug target genes This approach aimed to elucidate the potential genetic basis of antihypertensive drug efficacy in reducing HT risk through blood pressure modulation To assess the potential for horizontal pleiotropy, we also performed the MR-Egger regression and the MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) test (37, 38). The average pleiotropic effect of IVs is indicated by the intercept term in the MR-Egger regression (38) we employed MR-egger regression and Cochran’s Q statistic the robustness and consistency of the findings were evaluated using the leave-one-out method The packages “TwosampleMR” and “MRPRESSO” in R version 4.2.2 were used for all of the analyses Although the observed effect sizes are relatively small their clinical significance should not be overlooked In the context of a multifactorial disease like Hashimoto’s thyroiditis (HT) even modest reductions in risk can have a substantial impact on public health the cumulative effect of reducing multiple small risks may significantly lower the overall incidence of HT Associations between genetic proxies for 9 classes of antihypertensive drugs and the risk of CAD Primary results for MR of Genetic proxies for 9 antihypertensive drugs with Hashimoto thyroiditis Associations between genetic proxies for 9 classes of antihypertensive drugs and the risk of Hashimoto thyroiditis in European Associations between genetic proxies for 9 classes of antihypertensive drugs and the risk of Hashimoto thyroiditis in Asian Sources of heterogeneity may include differences in the frequency of genetic variants across populations and the interaction of environmental factors These differences can lead to variations in drug mechanisms across populations affecting the interpretability of study results Future research could incorporate stratified analyses and introduce interaction terms to identify and quantify potential factors contributing to heterogeneity These analytical methods would help us better understand the sources of these differences and increase our confidence in the results Upon refining the cis-expression quantitative trait loci (cis-eQTLs) from previous research by clumping (r2 < 0.1), we identified eQTLs for the 9 classes of antihypertensive drugs, detailed in Supplementary Table S5 reduced expression levels of the target genes for these antihypertensive drug classes correlated with lower systolic blood pressure (SBP) across the board (all p < 0.001) This MR investigation provides substantial evidence for the beneficial role of genetically inferred CCBs and thiazides and related diuretics in reducing the risk of HT across different study with results corroborated by MR analyses and eQTL analyses linking the expression of target genes for classes of antihypertensive drugs with HT due to their potentially favorable safety profiles as antihypertensive treatments could be considered for HT prevention strategies the study does not provide definitive evidence linking genetic proxies for primary antihypertensive treatments such as ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs) Our Mendelian randomization study provides groundbreaking insights into the potential role of antihypertensive medications specifically CCBs and two types of diuretics This finding is particularly significant given the current scarcity of observational studies examining the relationship between antihypertensive drugs and HT Our research not only fills this gap but also opens new avenues for therapeutic interventions Calcium channel blockers (CCBs) might reduce the risk of Hashimoto thyroiditis Although the above hypotheses are not yet supported by experimental evidence these preliminary findings highlight the need for further research to validate the observed associations and elucidate the mechanisms by which CCBs and diuretics may reduce the risk of Hashimoto’s thyroiditis Future investigations should include larger more diverse cohorts to strengthen the evidence base clinical trials are crucial to assess the efficacy and optimal dosing of these antihypertensive drugs when repurposed as treatments for HT while research exploring the association between antihypertensive medications and HT remains limited there is emerging evidence to suggest that certain antihypertensive drugs may be linked to other autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus HT has been identified as a potential risk factor for these conditions or often co-occurs with them This interconnection underscores the complexity of autoimmune diseases and highlights the potential systemic impact of antihypertensive medications beyond their primary cardiovascular effects suggesting that such immunomodulatory effects may also apply to Hashimoto’s thyroiditis genetic polymorphisms related to drug metabolism in the Asian population may result in different metabolic responses to these drugs compared to the European population factors such as dietary habits and environmental exposures may contribute to varying drug responses among different populations These differences remind us that even when drug treatment strategies show population-wide consistency population-specific factors should be considered when applying them across different groups the possibility that HT may serve as a risk factor or a comorbid condition for other autoimmune diseases further emphasizes the need for a comprehensive approach in the research and treatment of women’s health Understanding the potential dual benefits of antihypertensive medications could lead to more holistic treatment strategies addressing both cardiovascular and immune system health simultaneously There are several benefits to our research the study employed genetic variants that simulate the effects of antihypertensive medications to assess drug impacts on HT via MR addressing challenges such as reverse causation and confounding factors inherent in observational studies and circumventing the extensive time and resources required for randomized controlled trials (RCTs) it capitalized on GWAS data from the most comprehensive genetic studies available bolstering the statistical robustness and credibility of its findings the investigation meticulously selected genetic variants within drug target genes linked to systolic blood pressure as surrogates for antihypertensive treatments incorporating a positive control analysis to confirm the appropriateness of these genetic proxies a series of sensitivity analyses were executed to ensure the findings’ reliability and consistency The use of summary-level data may obscure individual-level variability and introduce bias in the presence of population heterogeneity our approach of selecting SNPs within a ±100 kb region around the target genes may limit the comprehensiveness of the analysis our study did not consider certain factors such as environmental and inflammatory influences which may affect the drug targets and potentially lead to adverse effects and long-term health consequences The relatively small sample size in the Asian database may have reduced the statistical power especially in assessing the effects of certain drugs which could impact the robustness and generalizability of our findings Future research should not only integrate individual-level data more diverse populations to strengthen the evidence base but also pay particular attention to high-risk groups or subgroups with specific biomarker characteristics as these populations may benefit more from targeted interventions it is necessary to explore the mechanisms behind the differential responses to different drug categories across various genetic backgrounds as well as the interactions between environmental and genetic factors that may influence drug efficacy To effectively translate these findings into clinical practice future studies should validate the efficacy of these drugs through RCTs in diverse populations using real-world data to assess long-term outcomes and safety will provide critical support for clinical practice our study highlights the potential association between the use of CCBs and thiazide diuretics and a reduced risk of Hashimoto’s thyroiditis These findings suggest a potential immunomodulatory role for these antihypertensive medications offering new insights into the prevention and management of autoimmune thyroid disorders Further research is warranted to explore the mechanisms underlying these associations and to evaluate the clinical implications of our findings we not only contribute to the understanding of HT pathophysiology but also pave the way for innovative treatment strategies The original contributions presented in the study are included in the article/Supplementary Material Further inquiries can be directed to the corresponding author All the data for this study were publicly available summary statistics ethical approval and consent to participate were not required CX is supported by Zhenjiang City 169 Project (YLJ202114); Guiding Science and Technology Plan Project for Social Development in Zhenjiang City (FZ2022084) The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fendo.2024.1419346/full#supplementary-material Supplementary Figure 1 | Associations of expressions 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Asian subpopulations and impacts on commonly prescribed medications Genetic variation in human drug-related genes Mao C and Chen Y (2024) Causal relationship between antihypertensive drugs and Hashimoto’s thyroiditis: a drug-target Mendelian randomization study Received: 18 April 2024; Accepted: 17 September 2024;Published: 07 October 2024 Copyright © 2024 Cui, Chen, Xu, Mao and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Chengcheng Xu, MTAwMDAxMjIwOEB1anMuZWR1LmNu The dates displayed for an article provide information on when various publication milestones were reached at the journal that has published the article activities on preceding journals at which the article was previously under consideration are not shown (for instance submission All content on this site: Copyright © 2025 Elsevier B.V., its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies. For all open access content, the relevant licensing terms apply. Volume 15 - 2024 | https://doi.org/10.3389/fneur.2024.1360222 This article is part of the Research TopicCase Reports in Multiple Sclerosis and Neuroimaging, volume III - 2023View all 15 articles Stiff-person syndrome (SPS) is a rare neurological disorder characterized by chronic and progressive axial muscle rigidity and paroxysmal painful muscle spasms The present case study described an SPS patient (increased anti-GAD65 antibody in serum and cerebrospinal fluid) with co-occurring Hashimoto’s thyroiditis and decreased C3 complement levels and treatment employed for this unique case were comprehensively described in detail we comprehensively presented a case of SPS with co-occurring Hashimoto’s thyroiditis and an associated decrease in serum C3 complement as well as a discussion on the current data on this topic Given the low incidence of SPS and limited reports on its concurrent occurrence with Hashimoto’s thyroiditis along with decreased serum C3 complement levels there may be a gap in the clinical understanding of SPS we comprehensively presented a case of SPS with co-occurring Hashimoto’s thyroiditis and an associated decrease in serum C3 complement levels as well as a discussion on the current data on this topic The patient is a 36-year-old right-handed Chinese married woman The patient presented with initial symptoms of bilateral leg fatigue the patient’s symptoms gradually progressed to limb rigidity and intermittent difficulty initiating movements both walking and standing functions were affected the patient was diagnosed with a “somatic symptom disorder” at a major medical center according to the physical symptoms at the time the patient’s condition evolved and progressed with the manifestations of mental and psychological symptoms the patient was examined at a local neurology specialist hospital Considering increased autoimmune thyroid antibody levels and the physical clinical symptoms the patient was diagnosed with “Hashimoto’s thyroiditis and Hashimoto’s encephalopathy.” The patient’s symptoms improved with steroid treatment; however discontinuation of steroids led to the recurrence of gait disturbance The representative ultrasonographic image of the thyroid of the patient The representative chest computed tomography (CT) images of the patient The representative images of brain magnetic resonance imaging (MRI) of the patient These findings strongly suggested a neuromuscular inhibitory effect induced by diazepam Electromyography (EMG) before and after intravenous administration of diazepam (10 mg) (A) Large numbers of motor unit-like units were seen in both the tibialis anterior muscles and the right vastus medialis muscle the duration and amplitude of the motor units in the examined muscles were all within the normal range the right tibialis anterior muscle exhibited electrical silence with no evidence of fibrillation potentials or positive sharp waves we cannot definitively conclude that C3 complement alone contributes to the development of SPS the decrease in C3 complement levels may also be a concurrent manifestation of Hashimoto’s thyroiditis This limitation should be acknowledged in our report we will deeply focus on the alterations in C3 complement levels and Hashimoto’s thyroiditis remission or relapse The treatment options for SPS are diverse, with immunomodulatory therapy being the foremost and pivotal approach (21) High-dose corticosteroid pulse therapy is considered a potentially effective treatment for SPS The patient exhibited significant symptom improvement following the administration of high-dose corticosteroid pulse therapy thereby further substantiating the autoimmune etiology of SPS The incidence of SPS in the population is relatively low yet it poses significant health risks to patients SPS is closely associated with autoimmunity and the presence of anti-GAD65 antibodies is frequently detected in serum and cerebrospinal fluid The present case study described a patient with SPS (increased anti-GAD65 antibody in serum and cerebrospinal fluid) co-occurring Hashimoto’s thyroiditis accompanied by a decrease in C3 complement levels The association between complement C3 and SPS requires further longitudinal observation in the future The data supporting the findings of this study are available from the corresponding author upon reasonable request The study involving a human was approved by the Ethics Review Committee of Yancheng Third People’s Hospital (Review-2023-59) The study was conducted in accordance with the local legislation and institutional requirements The human samples used in this study were acquired from a by-product of routine care or industry Written informed consent was obtained from the individual for the publication of any potentially identifiable images or data included in this article The author(s) declare that no financial support was received for the research The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2024.1360222/full#supplementary-material Antineutrophil cytoplasmic antibody; VitB12 Google Scholar Crossref Full Text | Google Scholar Stiff-person syndrome: insights into a complex autoimmune disorder Quantitative clinical and autoimmune assessments in stiff person syndrome: evidence for a progressive disorder Crossref Full Text | Google Scholar Increased spontaneous activity of a network of hippocampal neurons in culture caused by suppression of inhibitory potentials mediated by anti-gad antibodies Presynaptic impairment of cerebellar inhibitory synapses by an autoantibody to glutamate decarboxylase Stiff person syndrome with eye movement abnormality Crossref Full Text | Google Scholar Crossref Full Text | Google Scholar C3aR inhibition reduces neurodegeneration in experimental lupus Crossref Full Text | Google Scholar Increased in vitro uptake of the complement C3b in the serum of patients with Guillain-Barré syndrome Anti-MAG IgM penetration into myelinated fibers correlates with the extent of myelin widening doi: 10.1002/(SICI)1097-4598(199908)22:8<1030::AID-MUS4>3.0.CO;2-H Crossref Full Text | Google Scholar Complement C3 aggravates post-epileptic neuronal injury via activation of TRPV1 Complement activation by direct C4 binding to Thyroperoxidase in Hashimoto’s thyroiditis Movement disorders with neuronal antibodies: syndromic approach Wen C and Shen Y (2024) Stiff-person syndrome in association with Hashimoto’s thyroiditis: a case report Received: 22 December 2023; Accepted: 19 June 2024; Published: 17 July 2024 Copyright © 2024 Chen, Hong, Shi, Wen and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Yuan Shen, c2hlbi55dWFuMDA4QDE2My5jb20= Courtney Southwick is a writer focusing on health She holds a Master of Science in Health Science from the University of Texas at Tyler and a Bachelor of Science in Biological Anthropology with an emphasis in health from the University of Utah She blogs about the history of medical science on her personal website Maria Laura is EatingWell's Editorial Manager for Nutrition & News she edits and assigns nutrition-related content and provides nutrition reviews for articles experience and clinical hours from Mexico are equivalent to that of a U.S food enthusiast and has over seven years of experience in nutrition counseling MedlinePlus. Hashimoto’s Disease Duntas L. Nutrition and Thyroid Disease Hu Y, Feng W, Chen H, et al. Effect of selenium on thyroid autoimmunity and regulatory T cells in patients with Hashimoto’s thyroiditis: A prospective randomized-controlled trial National Institutes of Health, Office of Dietary Supplements. Fact Sheet for Consumers. Selenium USDA FoodData Central. Fish, tuna, light, canned in water, drained solids Dupuis M, Pagano M, Pierdominici M, Ortona E. The role of vitamin D in autoimmune diseases: could sex make the difference? MedlinePlus. Vitamin D USDA FoodData Central. Milk, whole, 3.25% milkfat, with added vitamin D Metrics details A Publisher Correction to this article was published on 14 February 2025 This article has been updated While ultrasonography effectively diagnoses Hashimoto’s thyroiditis (HT) exploring its transcriptomic landscape could reveal valuable insights into disease mechanisms This study aimed to identify HT-associated RNA signatures and investigate their potential for enhanced molecular characterization Samples comprising 31 HT patients and 30 healthy controls underwent RNA sequencing of peripheral blood Differential expression analysis identified transcriptomic features which were integrated using multi-omics factor analysis and regulatory network analyses were performed A novel machine-learning model was developed for HT molecular characterization using stacking techniques HT patients exhibited increased thyroid volume and higher antibody levels despite being in the early subclinical stage Analysis identified 79 HT-associated transcriptomic features (3 mRNA 45 edges) networks revealed significant hub genes and modules associated with HT Enrichment analysis highlighted dysregulation in immune system The novel stacking-model achieved 95% accuracy and 97% AUC for HT molecular characterization This study demonstrates the value of transcriptome analysis in uncovering HT-associated signatures providing insights into molecular changes and potentially guiding future research on disease mechanisms and therapeutic strategies posing challenges in molecular characterization identifying expression patterns and regulatory network changes in HT remains challenging with implications for understanding disease mechanisms and potential therapeutic strategies Integrating differential expression analysis and machine learning to identify RNA signatures and transcriptional regulatory networks in HT requires further research This study aims to analyze whole-transcriptome sequencing data from HT patients By integrating differential expression analysis and MOFA models we seek to identify transcriptomic signatures for characterizing HT and potential regulatory mechanisms Co-expression and regulatory networks will be constructed to reveal changes in gene regulation a novel machine learning stacking model will be developed to assess the potential of these signatures for enhanced molecular characterization of HT This comprehensive approach aims to provide valuable insights into HT molecular mechanisms and identify potential targets for future research and therapeutic strategies This study involved two distinct cohorts from different medical centers a total of 31 early HT patients and 30 healthy controls (HC) were recruited from Qilu Hospital of Shandong University and the Second Affiliated Hospital of Xi’an Jiaotong University The diagnosis of HT was based on specific criteria such as thyroid enlargement with no clinical or biochemical evidence of thyroid dysfunction a longitudinal assessment was conducted over a period of six months with evaluations performed every two months to observe the development of autoantibodies and ultrasound changes If subjects experience thyroid dysfunction during the assessment period they are considered to be in a stage other than early HT and excluded from this study Participants with prior history of thyroid diseases The healthy control group exhibited normal thyroid function and tested negative for thyroid autoantibodies Exclusion criteria included the presence of cardiovascular Thyroid function tests were conducted using the Roche Cobas 6000 E601 module immunoassay analyzer Demographic information was collected through a questionnaire The study was ethically approved by the Medical Ethics Committee of Xi’an Jiaotong University and conducted following the Helsinki Declaration guidelines (NO Written informed consent was obtained from all participants transcripts were classified through a systematic pipeline transcripts were mapped to the human reference genome (GRCh38) and annotated based on RefSeq database using StringTie miRNAs were identified through alignment to miRBase (v22) using Bowtie and quantified with miRDeep2 we first excluded known protein-coding transcripts and small RNAs then selected transcripts longer than 200 nucleotides and assessed their coding potential using CPC2 and CNCI tools circRNAs were identified by detecting back-spliced junction reads using find_circ and CIRI2 algorithms with at least two unique back-spliced reads required for circRNA annotation All identified transcripts were further filtered based on expression level (FPKM > 0.1) to ensure reliable quantification The resulting gene expression matrices for mRNA and circRNA were utilized for subsequent analysis The parallel implementation of both limma and edgeR packages for identifying DEGs was strategically chosen to leverage their complementary strengths Limma excels in handling complex experimental designs through its sophisticated linear modeling framework and empirical Bayes methods which are particularly effective for controlling false discovery rates in multi-factor analyses edgeR specifically addresses the challenges of RNA-seq count data through its negative binomial distribution-based statistical framework making it especially robust for analyzing genes with low expression levels This dual-package approach enhances the reliability of our differential expression analysis by combining limma’s statistical power in handling experimental complexity with edgeR’s specialized capabilities for RNA-seq data characteristics The intersection of results from both methods provides a more stringent and confident set of differentially expressed genes Differentially expressed RNAs meeting the significance criteria were identified (P-value < 0.05&|log2FC| > 1) The intersection of differentially expressed RNA lists obtained from both packages was used for further analysis z-score normalization was applied to eliminate biases caused by library size discrepancies The normalization was performed using the formula: Where xij represents the expression value of RNA j in sample i µi represents the mean expression value of sample i and σi represents the standard deviation of sample i A 15-factor MOFA model was generated using 10,000 iterations in ‘slow’ convergence mode The sample factor matrix was extracted to examine correlations between factors and clinical variables Factors showing significant differences between the HT and control groups were identified High-contributing weight features meeting the criteria (weight ≥ mean + 2 * standard deviation & weight ≤ mean − 2 * standard deviation) under these factors were selected as the characteristic RNA signatures Enrichment information for cellular components and KEGG pathways with P-value < 0.05 was considered statistically significant This analysis aimed to provide insights into the biological processes and pathways potentially involved in HT pathogenesis To identify potential regulatory relationships we conducted a co-expression network analysis for the characteristic RNA signatures Pearson correlation coefficient was used to examine the correlation between RNA pairs RNA pairs with a statistical significance (P-value < 0.05) and meaningful correlation strength (|r| > 0.2) were included to construct the co-expression network where RNAs represented nodes and significant correlations were depicted as edges Visualization of the co-expression network was performed using Cytoscape we employed CytoHubba with five attribute-ranking methods: Betweenness The shared top 5 ranking nodes in attributes were considered as hub RNAs in the co-expression network To identify modules with potential similar expression patterns we utilized ClusterONE with the following parameters: Minimum size = 3 Self-interactions and duplicate records were removed for data quality assurance regulatory networks were constructed for characteristic RNA signatures and CytoHubba and clusterONE software were used to identify hub RNAs and modules in these networks we concatenated the predictions from the first layer with the original training set as input The second-layer models included the ten ML models from the first layer and the final model was a logistic regression model The selection of logistic regression as the final model was based on several key considerations logistic regression excels in binary classification tasks and is particularly effective when combining predictions from multiple models making it ideal for our stacking architecture its linear nature helps prevent overfitting when integrating diverse predictions from the double-layer models the model provides interpretable probability outputs and clear insights into the contribution of each base model which is crucial for understanding the relative importance of different RNA signatures in HT characterization logistic regression demonstrated stable performance in handling the transformed feature space created by the double-layer predictions while maintaining computational efficiency Hyperparameter optimization and fine-tuning of the models were performed using the Tree-structured Parzen Estimator Approach (TPE)-based Bayesian optimization algorithm Model performance and reliability were assessed using accuracy (ACC) and area under the curve (AUC) metrics on the testing set Differential expression analysis of RNA signatures in Hashimoto’s thyroiditis (A-D) Volcano plots depicting the results of differential expression analysis based on limma for four RNA-seq datasets Significantly differentially expressed RNAs were identified: 1743 mRNAs (342 Up (E-H) Volcano plots showing the results of differential expression analysis based on edgeR for the same four RNA-seq datasets Significantly differentially expressed RNAs were identified: 1919 mRNAs (71 Up (I-L) Venn diagrams illustrating the intersection of upregulated differentially expressed RNAs identified by both limma and edgeR for the four RNA-seq datasets (M-P) Venn diagrams displaying the intersection of downregulated differentially expressed RNAs identified by both limma and edgeR for the four RNA-seq datasets Intersection analysis of the two methods resulted in a final set of preliminary RNA signature candidates: 1279 mRNAs (52 Up ENSEMBL IDs are shown only for transcripts without officially assigned gene symbols primarily novel lncRNAs; all other transcripts are displayed using their HGNC gene symbols Multi-omic factor analysis of RNA signatures in Hashimoto’s thyroiditis (A) Bar plot demonstrating the total variance explanation of the model for the four RNA-seq datasets (B) Heatmap representing the correlation between factors (C) Heatmap displaying the variance explanation for each factor across the four RNA types E) Violin plots indicating the values of Factor 3 and Factor 10 across Hashimoto’s thyroiditis and healthy control samples (F) Expression heatmap visualizing the characteristic RNA signatures identified through multi-omic factor analysis (G) Bar plot presenting the results of GO and KEGG enrichment analysis for the mRNAs included in the characteristic RNA signatures Results of co-expression network analysis in Hashimoto’s thyroiditis (A) Visualization of the co-expression network and lines between nodes represent interactions This module consisted of 5 RNA signatures (MARCHF1 (C–H) Expression correlation plots for molecular pairs within Module 1 purple points represent the healthy control group and the gray interval represents the confidence interval This module comprised 5 RNA signatures (ENSG00000272372 (J–P) Expression correlation plots for molecular pairs within Module 2 Regulatory network analysis of RNA signatures in Hashimoto’s thyroiditis (A) Visualization of the regulatory network yellow diamond-shaped nodes represent lncRNAs (B–F) Visualization of four modules within the regulatory network highlighting potential functional RNA signature clusters (G) Bar plot presenting the results of GO and KEGG enrichment analysis for the regulatory network providing insights into the biological processes and pathways associated with the identified RNA signatures Stacking model construction and performance evaluation for molecular characterization of Hashimoto’s thyroiditis (A) Overview of the proposed stacking model integrating multiple machine learning algorithms for enhanced molecular characterization of HT (B) Comparison of various machine learning models demonstrating the performance in distinguishing Hashimoto’s thyroiditis from healthy controls based on the identified RNA signatures performed a comprehensive transcriptomic analysis of HT patients and healthy individuals identifying 79 characteristic RNA signatures We constructed co-expression and regulatory networks based on these signatures and developed a Stacking model for enhanced molecular characterization of HT Our model demonstrated excellent performance on an independent testing set highlighting its potential for improving HT molecular profiling These findings provide valuable insights into HT’s molecular mechanisms and may contribute to the development of more precise diagnostic and therapeutic strategies The widespread down-regulation observed across different RNA types provides important insights into HT pathogenesis The down-regulated mRNAs were primarily enriched in pathways related to thyroid hormone synthesis and metabolism particularly the up-regulated hsa-miR-144-3p and hsa-miR-374a-5p may contribute to immune dysregulation through their targeting of immune-related genes The extensive down-regulation of lncRNAs implies altered transcriptional regulation potentially affecting thyroid-specific gene expression programs These regulatory patterns align with the progressive nature of HT and may represent early molecular events in disease development This strategy significantly mitigates model fluctuations caused by data changes and enhances performance for the complex task of molecularly characterizing HT This combination of known immune regulators and novel HT-associated RNAs suggests both the biological relevance of our findings and their potential to reveal previously unknown aspects of HT pathogenesis These findings suggest common expression patterns and regulatory changes among autoimmune diseases and HIF1A-AS3 potentially playing significant roles in HT pathogenesis Our enrichment analysis supports these findings indicating the involvement of immune system processes and RNA/protein regulation in HT pathogenesis the characteristic RNA signature co-expression network resembles the regulatory network but contains more nodes and edges suggesting additional molecules and relationships worth exploring further While our study provides valuable insights into HT’s molecular landscape which may limit the generalizability of our findings Although we implemented several strategies to maximize reliability including rigorous patient selection with longitudinal assessment external validation using larger and more diverse cohorts remains essential This validation should include independent cohorts from different populations and testing across various disease stages and subtypes Further research is necessary to functionally characterize the identified RNA signatures and explore their potential as therapeutic targets Cellular and animal models can help elucidate their mechanisms in HT pathogenesis will further enhance our understanding of HT’s molecular features Addressing these limitations through additional investigations will advance our understanding of HT and potentially uncover novel therapeutic targets Our study has yielded several novel and significant findings in HT research we identified a unique set of 79 characteristic RNA signatures specific to early-stage HT including previously unreported associations such as hsa-miR-548aq-3p we constructed the first comprehensive experimental non-coding RNA interactome (ENCI) for HT integrating data from ten databases and revealing novel regulatory networks with 18 nodes and 45 edges we discovered two distinct co-expression modules and four regulatory modules that provide new insights into potential HT pathogenic mechanisms our innovative stacking model achieved superior performance (95% accuracy 97% AUC) in molecular characterization of early HT demonstrating the potential of machine learning in disease diagnosis These computational findings establish a foundation for future experimental validation and potential therapeutic development this study performed a comprehensive transcriptomic analysis of peripheral blood from HT patients identifying 79 characteristic RNA signatures through the integration of differential expression analysis and MOFA Our co-expression and regulatory network analyses revealed key molecular interactions including previously unreported RNA relationships and functional modules in HT The constructed stacking model achieved promising performance in molecular characterization suggesting the potential utility of RNA signatures in HT diagnosis our findings provide new insights into the complex RNA regulatory networks in HT and establish a foundation for future mechanistic studies and potential therapeutic developments This computational framework also demonstrates the value of integrative approaches in understanding autoimmune disease pathogenesis The datasets generated and/or analysed during the current study are available in the GitHub repository (https://github.com/zefenglee/HT) A Correction to this paper has been published: https://doi.org/10.1038/s41598-025-89653-2 Fragments per kilobase of exon model per million reads mapped Rapoport, B. 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Commun. 8(1), 35. https://doi.org/10.1186/s40478-020-00903-y (2020) Download references We would like to express our sincere gratitude to the patients and their families for their understanding and willingness to participate in this study We are also grateful to the investigators and site staff for their dedicated efforts and contributions this research would not have been possible This work was supported by the Natural Science Foundation of China (82071952 82030058) and Shandong Provincial Natural Science Foundation (ZR2022ZD14) The funding sources had no role in the design and conduct of the study; collection and interpretation of the data; preparation or approval of the manuscript; and decision to submit the manuscript for publication Key Laboratory of National Health Commission for Forensic Sciences Xi’an Jiaotong University Health Science Center Department of Endocrinology and Metabolism participated in part of the sequencing work wrote the manuscript with input from co-authors All authors reviewed and approved the manuscript before submission The original online version of this Article was revised: In the original version of this Article Miao Li was omitted as a corresponding author Correspondence and requests for materials should also be addressed to limiaodr@xjtu.edu.cn Download citation DOI: https://doi.org/10.1038/s41598-024-80728-0 Daiki Hashimoto won his fifth straight artistic gymnastics national championships on Sunday after coming out on top in a battle between the last two Olympic men's individual all-around gold medalists the 23-year-old winner of the 2021 Tokyo Games was second after Friday's qualification round behind Paris Olympics gold medalist Shinnosuke Oka But 85.464 points from six apparatuses in Sunday's final lifted him to 169.695 in total He has become the first gymnast to win the title five times in a row since Kohei Uchimura whose dominance lasted for a decade from 2008 through 2017 Trailing Oka by 0.667 heading into the final horizontal bar Hashimoto showed immense character by nailing both his difficult release techniques before landing perfectly to score 15.033 It was the only performance that earned a point north of 15.000 by anyone across all apparatus over the two days "I suppose it was a fun competition for those who were watching I have a sense of satisfaction," said Hashimoto who settled for sixth and without an individual medal in Paris Taking this season off was an idea but Hashimoto decided against it after Oka with whom he won the team gold together last summer for Japan "Would you not want to compete in the Olympics again with these five members?" "These sorts of competitions will continue for the next few years It almost ties my stomach in knots but it also makes me happy," Hashimoto said expressing gratitude to his younger rival for spurring him on Oka lost his balance in the horizontal bar and finished runner-up for the second successive year but his execution scores were above Hashimoto's in all the other apparatuses tense feeling was fun," Oka said after an exciting matchup ended with him missing out on his maiden national title Tomoharu Tsunogai and Tsuyoshi Hasegawa tied for third for their first podium finishes 17-year-old Paris Olympian Rina Kishi won the women's national title for the first time on 108.431 Figure skating: U.S. holds on to win World Team Trophy, Japan 2nd Golf: Akie Iwai surges into tie for lead at LPGA event in LA Baseball: Shohei Ohtani announces birth of daughter on Instagram To have the latest news and stories delivered to your inbox, subscribe here. Simply enter your email address below and an email will be sent through which to complete your subscription. Please check your inbox for a confirmation email. If you wish to change your message, press 'Cancel' to go back and edit. Thank you for reaching out to us.We will get back to you as soon as possible. Hashimoto’s thyroiditis (HT) is a significant public health concern, particularly among females. While existing studies have explored the correlation between serum iron levels and HT, limited research has specifically focused on this association in reproductive-age females. Our study aims to investigate the relationship between serum iron and HT. Using data from the National Health and Nutrition Examination Survey (NHANES) database (2007–2012), we employed weighted multivariate logistic regression models, an XGBoost model, and smooth curve fitting. We assessed the correlation between serum iron and HT and examined linear and non-linear relationships with thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb). Our study reveals that in reproductive-age women, every unit increase in serum iron is associated with a 43% lower risk of HT, demonstrating an inverse relationship. Additionally, serum iron exhibits a negative correlation with TPOAb and a non-linear association with TgAb. Volume 11 - 2024 | https://doi.org/10.3389/fnut.2024.1410538 This article is part of the Research TopicNutrition, Inflammation and Oxidative Stress in Obstetrics and GynecologyView all 12 articles Purpose: Hashimoto’s thyroiditis (HT) is a significant public health concern While existing studies have explored the correlation between serum iron levels and HT limited research has specifically focused on this association in reproductive-age females Our study aims to investigate the relationship between serum iron and HT Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) database (2007–2012) we employed weighted multivariate logistic regression models We assessed the correlation between serum iron and HT and examined linear and non-linear relationships with thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) each unit increase in serum iron was associated with a 43% reduced risk of HT (Odds Ratios (OR) 0.574; 95% Confidence Interval (CI) 0.572 The XGBoost model identified serum iron as the most significant variable correlated with HT Smooth curves revealed a linear association between log2-transformed serum iron and HT log2-transformed serum iron inversely correlated with TPOAb levels (β −15.47; 95% CI -25.01 while a non-linear relationship was observed with TgAb Conclusion: Our study reveals that in reproductive-age women every unit increase in serum iron is associated with a 43% lower risk of HT serum iron exhibits a negative correlation with TPOAb and a non-linear association with TgAb HT has become a significant public health concern the association between serum iron levels and HT in females is under-researched in cross-sectional studies the aim of this research is to further investigate the correlation between serum iron levels and HT in females of reproductive age we have selected the age range of 15 to 44 years as a representative sample Understanding this correlation could potentially lead to new strategies for managing HT in this demographic Our objective is to gain a more comprehensive understanding of this intricate interaction Through the execution of a comprehensive cross-sectional study utilizing the National Health and Nutrition Examination Survey (NHANES) database (2007–2012) our aim is to provide further insights into this intricate relationship the study was conducted in compliance with the revised 2013 Declaration of Helsinki Flow chart of the studying participants’ selection from the NHANES 2007–2012 Serum samples in the NHANES studies underwent processing and storage before being sent to the Collaborative Laboratory Services for examination in accordance with the guidelines in the NHANES Laboratory/Medical Technologists Procedures Manual (LPM) The vials were kept in suitable frozen conditions (−30°C) until they were dispatched to the National Center for Environmental Health for testing both the LX20 and DcX800 timed-endpoint methods were employed for the measurement and complexed with the FerroZine Iron Reagent The alteration in absorbance at 560 nm which is in direct proportion to the iron concentration HT, identified as the outcome variable, is diagnosed by the presence of thyroid autoantibodies. The titers of TgAb and TPOAb are determined using a sequential two-step immunoenzymatic ‘sandwich’ assay. Individuals with a TgAb titer of 115.0 IU/mL or higher and/or a TPOAb titer of 9.0 IU/mL or higher are considered positive (31) Based on previous similar studies and clinical experience we identified the following variables as potential confounders in this study because they may affect our statistical results: age Laboratory data included thyroid-stimulating hormone (TSH high-density lipoprotein cholesterol (HDL-C low-density lipoprotein cholesterol (LDL-C The extracted questionnaire data encompassed aspects such as alcohol intake Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS version 26.0) and R software (version 4.4.2) The analysis was performed in line with the survey methods and the guidelines stipulated by NHANES Continuous variables with normal distribution are expressed as weighted mean ± standard deviation (Mean ± SD) with differences analyzed using the independent t-test continuous variables are presented as weighted median with interquartile range (IQR) and differences between groups are analyzed using the Kruskal-Wallis rank sum test Categorical variables are represented as percentages with differences analyzed using the chi-squared test Serum iron concentrations were transformed using a logarithm base 2 (Log2) for subsequent analyses due to their skewed distribution Serum iron concentrations were also divided into four quartiles The objective of the study was to delve into the relationship between serum iron and the onset of HT in a specific population A multivariate logistic regression model was built to evaluate the odds ratios (OR) and 95% Confidence Interval (CI) between serum iron and HT This model was split into three parts: Unadjusted Model (Model 1): Adjusted for none Minimally Adjusted Model (Model 2): Adjusted for age and race/ethnicity Fully Adjusted Model (Model 3): Included the variables from Model 2 and was further adjusted for education level Subgroup analyses were carried out on variables including age and diabetes to assess potential effect modification Generalized Additive Models (GAMs) were utilized to test potential non-linear relationships of serum iron with HT adjusting the GAMs for the same covariates as linear regression models Statistical significance was set at p < 0.05 Table 1 showcases the characteristics of the NHANES participants included in our analysis. The study cohort is composed of females of reproductive age with an average age of 29.65 years. Table 1 provides a comprehensive overview of sociodemographic data physical activity data derived from questionnaires and comorbidity statistics for the participants those diagnosed with HT are typically older and have a higher poverty-income ratio (p < 0.05) HT patients exhibited elevated levels of TSH alongside reduced serum iron and urinary iodine levels when compared to their non-HT counterparts (p < 0.05) A greater prevalence of diabetes mellitus was noted among HT patients (p < 0.05) While race/ethnicity and marital status initially indicated significant differences further analysis between the two groups revealed no significant disparities We constructed a multivariate logistic regression model to delve into the relationship between log2-transformed serum iron levels and HT, as depicted in Table 2 it was observed that each unit increment in serum iron was associated with a 35% decrease in the risk of HT (OR 0.652; 95% CI 0.650 When adjusted for age and race/ethnicity (Model 2) each unit increment in serum iron corresponded to a 39% reduction in HT risk (OR 0.606; 95% CI 0.605 with the p-value for trend remaining below 0.05 each unit increment in serum iron was linked to a 43% lower risk of HT (OR 0.574; 95% CI 0.572 with the p-value for trend still less than 0.05 These findings suggest a robust inverse association between serum iron levels and the risk of HT consistent across various levels of adjustment Stratified associations between Serum Iron and HT serum iron levels were used as the most relevant variable for constructing a smoothing curve model The relative importance was calculated for each variables using the XGBoost model These findings indicate an inverse relationship between serum iron levels and the risk of HT The correlation between serum iron (log2-transformed) and Hashimoto’s thyroiditis The dark blue line represents the smooth curve fit between variables The light blue area represents the 95% CI of the fit HT is marked by the generation of antibodies that target antigens in the thyroid, and iron plays a crucial role in TPO function. Accordingly, an examination was also conducted on the association between serum iron and both TPOAb and TgAb (Table 3) Participants with higher serum iron levels showed a decrease in TPOAb levels serum iron (log2-transformed) was found to have a negative correlation with TPOAb levels (β = −15.47; 95% CI -25.01 but no significant association was observed with TgAb levels (β = −3.52; 95% CI -9.35 we transformed the continuous variable into quartiles Compared to participants in the lowest quartile (Q1) those in the highest quartile (Q4) were significantly associated with lower TPOAb levels across all models while no such association was found for TgAb levels We utilized smooth curve fitting to delve into potential non-linear associations between serum iron and the levels of TPOAb and TgAb. Smooth curves were formulated based on the fully adjusted model. The results indicated that serum iron has a linear negative association with TPOAb levels. Conversely, a curvilinear association was observed between serum iron and TgAb levels (Figure 5) Log2-Transformed Serum Iron’s Correlation with Thyroid Autoimmunity Markers (A) The correlation between serum iron (log2-transformed) and thyroid peroxidase antibodies (B) The correlation between serum iron (log2-transformed) and thyroglobulin antibodies Our findings reinforce the biological plausibility that lower serum iron levels may be associated with HT emphasizing that adequate iron is essential for optimal thyroid function These mechanisms underscore the importance of maintaining adequate iron levels to prevent or mitigate the risk of HT who are more prone to iron deficiency and thyroid autoimmunity Our findings underscore the importance of comprehensive nutritional assessments in HT management and suggest that monitoring and managing iron levels can be beneficial Incorporating iron management into clinical guidelines for HT could enhance treatment outcomes Our study contributes by specifically examining this relationship in reproductive-aged women offering valuable insights into the complex interaction between iron status and thyroid autoimmunity future studies should explore these factors to better understand the relationship between serum iron levels and HT Further prospective studies and clinical trials are needed to explore the mechanisms linking iron deficiency to HT Longitudinal data focusing on this demographic will help clarify the temporal relationship between iron status and thyroid autoimmunity providing insights into how these interactions influence HT development and progression Understanding these relationships in this specific population will guide targeted prevention and treatment strategies ultimately improving clinical care for women of reproductive age who are vulnerable to iron deficiency and thyroid dysfunction we can better address the unique needs of reproductive-aged women with HT our study uncovers an inverse association between serum iron levels and HT in females of reproductive age Serum iron levels were found to be negatively correlated with TPOAb levels and exhibited a non-linear relationship with TgAb levels These findings emphasize the potential role of serum iron in HT pathogenesis and underscore the need for future prospective studies to validate and further explore these relationships The names of the repository/repositories and accession number(s) can be found in the article/supplementary material The studies involving humans were approved by Nhanes-Nchs Research Ethics Review Board (Erb) Approval. Available at: https://www.cdc.gov/nchs/nhanes/irba98.htm The studies were conducted in accordance with the local legislation and institutional requirements The human samples used in this study were acquired from a by- product of routine care or industry Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements Crossref Full Text | Google Scholar Crossref Full Text | Google Scholar Hashimoto's thyroiditis and papillary thyroid cancer: polyglandular hints Crossref Full Text | Google Scholar Crossref Full Text | Google Scholar Crossref Full Text | Google Scholar The etiology of autoimmune thyroid disease: a story of genes and environment PubMed Abstract | Crossref Full Text | Google Scholar Crossref Full Text | Google Scholar Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence Crossref Full Text | Google Scholar Multiple nutritional factors and the risk of Hashimoto's thyroiditis PubMed Abstract | Crossref Full Text | Google Scholar Update on intrathyroidal iodine metabolism PubMed Abstract | Crossref Full Text | Google Scholar PubMed Abstract | Crossref Full Text | Google Scholar Crossref Full Text | Google Scholar Occurrence and risk factors for autoimmune thyroid disease in patients with atrophic body gastritis Prevalence of parietal cell antibodies in a large cohort of patients with autoimmune thyroiditis Crossref Full Text | Google Scholar Crossref Full Text | Google Scholar Autoimmune gastritis: Pathologist's viewpoint Trace element levels in Hashimoto thyroiditis patients with subclinical hypothyroidism Google Scholar Urinary iodine and genetic predisposition to Hashimoto's thyroiditis in a Chinese Han population: a case-control study Joint effect of 25-hydroxyvitamin D and secondhand smoke exposure on hypertension in non-smoking women of childbearing age: NHANES 2007-2014 The relationship between thyroid antibodies and vitamin D level in primary hypothyroidism FT3/FT4 ratio is correlated with all-cause mortality and cardiovascular disease risk: NHANES 2007-2012 The association between dietary selenium intake and Hashimoto's thyroiditis among US adults: National Health and nutrition examination survey (NHANES) Selenomethionine and Myo-inositol: a pilot study Relationship between Iron deficiency and thyroid function: a systematic review and Meta-analysis Crossref Full Text | Google Scholar Prevalence of thyroid autoimmunity and dysfunction in women with iron deficiency during early pregnancy: is it altered PubMed Abstract | Crossref Full Text | Google Scholar Hepcidin and the Management of Iron Deficiency Anemia in chronic kidney disease Crossref Full Text | Google Scholar Treatment of mild non-chemotherapy-induced iron deficiency anemia in cancer patients: comparison between oral ferrous bisglycinate chelate and ferrous sulfate National trends in nine key minerals intake (quantity and source) among U.S and vitamin D deficiency among Egyptian female patients: associations and possible causalities a risk factor for thyroid autoimmunity during second trimester of pregnancy in China The relation between serum ferritin and goiter urinary iodine and thyroid hormone concentration The relationship between iron status and thyroid hormones in adolescents living in an iodine deficient area Thyroid-gut-Axis: how does the microbiota influence thyroid function Crossref Full Text | Google Scholar PubMed Abstract | Crossref Full Text | Google Scholar Crossref Full Text | Google Scholar Crossref Full Text | Google Scholar Nutritional iron turned inside out: intestinal stress from a gut microbial perspective Iron supplements modulate Colon microbiota composition and potentiate the protective effects of probiotics in dextran sodium sulfate-induced colitis Immune cells and microbiota response to Iron starvation PubMed Abstract | Crossref Full Text | Google Scholar Ren F and Hu T (2024) Inverse association between serum iron levels and Hashimoto’s thyroiditis in United States females of reproductive age: analysis of the NHANES 2007–2012 Received: 14 June 2024; Accepted: 18 September 2024; Published: 01 October 2024 Copyright © 2024 Zhang, Li, Yang, Luo, Wu, Wang, Qin, Ren and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Tianyuan Hu, aHV0aWFueXVhbjI3QGdtYWlsLmNvbQ== Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish. Some 14 years since he founded his first gallery the easygoing multihyphenate now juggles an impressive array of projects without seeming to break a sweat These include both the contemporary art project Spoke Art Gallery, specializing in pop culture–inspired art and illustration, and the tastemaking gallery Hashimoto Contemporary—spanning New York, Los Angeles, and San Francisco. Harman also finds the time to lead the nomadic Harman Projects and his publishing company Paragon Books all while maintaining various film and art curatorial projects Harman’s mission has always been straightforward: Supporting his friends and community has fueled the art world dynamo for the past 14 years Portrait of Dasha Matsuura and Jennifer Rizzo “[San Francisco] was just a chance for me to give my friends shows,” Harman said “New York was a chance for me to give my friends shows in New York and Los Angeles was very much the same thing—opening the L.A space was to sort of get more opportunities for our artists.” Jeffrey CheungAt Night, 2021Hashimoto ContemporaryPrice on request Seonna HongMurmurations, 2023Hashimoto ContemporarySold At 18 Harman graduated from high school and started working at Whole Foods in 2007 It was during this time that he became captivated by street artists who were creating work dedicated to a young junior senator from Chicago by the name of Barack Obama Inspired by the political and creative fervor at the time where he interviewed artists and wrote about the artwork he encountered This initiative led to significant recognition including being flown to New York for a live on-air interview for MSNBC along with several other interviews by the Wall Street Journal and NPR While continuing to write about art for Hi Fructose Magazine and working in the restaurant industry—“I’ve done everything there is to do in a restaurant,” he underscored—Harman founded Spoke Art Gallery in 2010 The concept for his breakthrough (and second-ever) show “Bad Dads,” originated from a movie night at the restaurant where he worked Harman adapted the idea to focus on art inspired by Wes Anderson’s filmmaking notable for the father figures in films such as The Royal Tenenbaums and Fantastic Mr The exhibition struck such a note that it was reiterated in subsequent years as well as his regular castmember Jason Schwartzman As his reputation grew, Harman seized an opportunity to pivot, opening Hashimoto Contemporary, a physical gallery in lower Nob Hill, bordering the Tenderloin neighborhood. The gallery opened with a pair of shows in March 2014: a solo exhibition by Crystal Wagner and a two-person exhibition featuring Jessica Hess and GATS His early experiences in San Francisco were undoubtedly shaped by the local gallery community influenced by its strong female gallerists and community-oriented mindset one thing that I’ve always loved about the Bay is all of the best dealers are women,” Harman said people are just a lot more supportive,” he added installation view of “Murmurations” at Hashimoto Contemporary in New York Harman made the decision to open a branch in New York “My artists weren’t getting shows in New York because there was very much a West Coast/East Coast divide in the art scene,” said Harman “There were very few galleries in New York championing Bay Area artists so I opened the space in New York so that our San Francisco artists could have New York shows for example—the first New York show—was with me.” Harman aims to make his galleries as welcoming as possible This authenticity manifested in the programs’ focus on showcasing artists whose voices are otherwise marginalized “So much of our early experiences as a gallery involved showcasing queer artists and artists of color,” the gallerist said Angela Fang ZirbesWhite Christmas Revisited, 2024Hashimoto ContemporarySold “I didn’t get into this to make money,” Harman said “My aim was always to provide a platform for artists If I can manage a barely livable wage while doing so Continuing this mission—to uplift and support artists—is what truly matters.” Hashimoto Contemporary is extremely active on the international stage establishing a presence during Miami Art Week at Context: Art Miami and Miami Art Project since the very beginning and maintaining a steady art fair schedule ever since “My view on art fairs is that they’re a really expensive business card,” Harman said The point of the art fair is to get my artists out there and to get them an opportunity to show work Over the years, the gallery has participated in ZONA MACO in Mexico City, Future Fair in New York, and more. Most recently, the gallery participated in Taipei Dangdai Art & Ideas, where it featured works by artist Bianca Nemelc. At this year’s Future Fair in New York, one of the artists in the gallery’s three-person booth, Angela Fang Zirbes awarding her a spot at the Virreina Artist Residency “I have so much faith and confidence in her and in the future of her career,” Harman said Installation view of the inaugural group exhibition at Hashimoto Contemporary in the Minnesota Street Project I always want to see what’s best for my artists The sad reality of our position in this middle tier is if I’m good at my job It’s bittersweet because I want to see them succeed I take comfort in knowing that it simply means I did my job well.” And a time when the mid-size and emerging tiers of the gallery world are facing pressures—particularly around him in downtown New York—Harman remains committed to his career-long mission: “As long as we can continue to provide talented artists with the shows they need and the platform they deserve Metrics details The comprehensive study of the relationship between lymph node metastasis (LNM) and its associated factors in patients with concurrent papillary thyroid carcinoma (PTC) and Hashimoto’s thyroiditis (HT) remains insufficient Building upon the initial investigation of factors associated with LNM in patients with concurrent PTC and HT we further analyzed the complex relationships between different severity indicators of LNM and these associated factors This study included patients confirmed PTC with HT who underwent total thyroidectomy at Xiangya Hospital A total of 271 patients from 2020 were used as the training set and 300 patients from 2021 as the validation set Univariate analysis and regression modeling were used to identify key factors associated with LNM Model reliability was assessed using the area under the receiver operating characteristic curve (AUC) Network analysis was employed to explore associations between LNM severity and its related factors and tumor maximum diameter (TMD) are independent factors for LNM The severity model showed free thyroxine (FT4) and hemoglobin (Hb) are independent protective factors for the region and quantity of LNM while TMD is an independent risk factor for both Network analysis revealed TMD has a closer relationship with LNM severity compared to other associated factors This study innovatively combined regression models and network analysis to investigate factors related to LNM in patients with PTC and HT providing a theoretical basis for predicting preoperative LNM in future clinical practice • Innovative Methods: First to combine regression models and network analysis for LNM study • Risk Factor Identification:Identified 4 independent risk factors for LNM in PTC with HT • Detailed Subgroup Analysis:Uncovered specific risk factors for LNM severity and regional spread investigating the factors contributing to LNM and constructing predictive models is crucial for improving the accuracy of preoperative diagnosis in this patient population these studies have failed to conduct an in-depth exploration of the mutual influences between the key outcome variable and the risk factors building upon the risk factors for LNM in patients with HT and PTC revealed by regression models this study aims to further investigate the intricate interplay between the severity of LNM and the associated risk factors among patients with concurrent HT and PTC who exhibit LNM through the employment of robust data-driven analytical methodologies The emerging paradigm of symptom network analysis presents an opportune avenue to address this inquiry symptom network analysis not only allows for the visualization of complex interrelationships among variables but also facilitates the detection of clustering communities within the network further elucidating the clustering preferences among variables By leveraging the novel capabilities of symptom network analysis and other data-driven techniques we aim to unravel the intricate interdependencies between the extent of LNM and the pertinent associated factors in the clinical cohort we systematically gathered data encompassing age and the presence of the BRAFV600E mutation The primary objective was to elucidate the integrated clinical and pathological features of PTC combined with HT and to explore their correlation with LNM we employed emerging network analysis methods to further investigate the complex relationships between the severity of LNM and its associated factors This study received approval from the Ethics Review Committee of Xiangya Hospital All procedures were conducted in accordance with relevant guidelines and regulations Written informed consent was obtained at the time of surgery for general use of clinical information in future studies The strobe flow of the inclusion and exclusion criteria for the study The clinicopathological characteristics including age results of thyroid function tests [free triiodothyronine (FT3); free thyroxine (FT4); thyroid-stimulating hormone (TSH)] preoperative level of antithyroglobulin antibodies (TgAb) and thyroid peroxidase antibody (TPOAb) extrathyroidal extension and vascular invasion were determined from postoperative pathological findings The reference TgAb and TPOAb ranges were less than 115 IU/mL and less than 34 IU/mL Ultrasound characteristics of thyroid nodules such as tumor maximum diameter (TMD) aspect ratio (the anteroposterior dimension/the transverse diameter: ≤1 or > 1) and calcification To ensure the reliability of ultrasound assessments all examinations were performed by experienced thyroid radiologists utilizing high-resolution ultrasound systems with reports subsequently reviewed and verified by both junior and senior radiologists preoperative evaluations commonly included follow-up imaging at multiple time points allowing for comparison of findings to enhance diagnostic accuracy and reliability HT coexistence was ascertained through postoperative sectioning and examination of paraffin-embedded thyroid tissue specimens A positive determination entailed the identification of diffuse lymphocytic and plasma cell infiltrate and the presence of reactive germinal centers All acquired surgical specimens were examined by two or more board-certified pathologists from the department of pathology of the Xiangya Hospital Continuous variables were expressed as mean ± standard deviation (SD) while categorical variables were presented as frequencies and percentages (%) Clinicopathologic characteristics were compared among groups using the t-test for continuous variables and the Pearson χ2 test (for expected values > 5) or Fisher’s exact χ2 test (for expected values ≤ 5) for categorical variables Stepwise logistic regression was used to identify independent factors associated with LNM: Initially an analysis was conducted across all patients to determine the factors that influence LNM in individuals with concurrent HT and PTC the investigation was focused on identifying the factors that affect the quantity and regions of lymph node metastases in this specific patient cohort A two-tailed P-value of < 0.05 was considered statistically significant for variable inclusion Receiver operating characteristic (ROC) curves were constructed and area under the curve (AUC) values were calculated to assess the predictive performance of the regression model with higher AUC values indicating better predictive accuracy The severity of LNM (regions and quantity of metastases) and their independent associated factors were utilized in the network construction to explore the complex interrelationships among them This study employed the Least Absolute Shrinkage and Selection Operator (LASSO) combined with the Extended Bayesian Information Criterion (EBIC) to eliminate spurious correlations among variables thereby making the network easily analyzable and comprehensible The detailed process and parameter settings for the network analysis can be found in Method S1 identifying communities within the network model through the simulation of random walks the igraph R package was employed to perform the aforementioned steps A non-parametric bootstrap method was employed to construct 95% confidence intervals which were used to assess edge weight accuracy with narrower intervals indicating higher reliability to determine statistical differences between pairwise edge weights a bootstrap difference test was conducted using confidence intervals The presence of statistically significant differences between compared edges was inferred if the confidence intervals did not contain zero for any pairwise comparisons Procedures above were completed with the bootnet (version 1.5) R package there was no significant correlation between age and quantity of LNM in this cohort As demonstrated in Table 2 Significant differences were observed in the TMD (P = 0.031) and serum Ca2+ (P = 0.049) among groups divided by regions of LNM ROC curve of multivariate logistic regression analysis in papillary thyroid cancer patients with Hashimoto thyroiditis (A) ROC forpresence or absence of lymph node metastasis (LNM); (B) ROC for the quantity of LNM; (C) ROC for the regions of LNM ROC Curve for External Validation of Logistic Regression Model Model 1for the presence of LNM; Model 2for the quantity of LNM; Model 3 for the regions of LNM Network structure and community clustering results of lymph node metastasis severity and associated factors (A) Network structure of lymph node metastasis severity and associated factors (B) Community clustering results of lymph node metastasis severity and associated factors The results of the community clustering are presented in Fig The Walktrap algorithm identified two communities: one comprising TMD The community clustering results suggest that despite all being independent associated factors the association between TMD and both RM and QG may be closer than the association between FT4 and Hb with RM and QG The evaluation of edge weight accuracy revealed that the 95% confidence intervals produced by the non-parametric bootstrap tests were of average width. Additionally, the analysis of edge weight differences showed that the edge weights were statistically robust. Further details can be found in Figure S1-2 this study is the first to employ both regression models and network analysis—two reliable data-driven approaches—to thoroughly investigate LNM in patients with coexistent PTC and HT Not only did this study construct and externally validate three predictive models for LNM in patients with coexistent PTC and HT but it also delved into the complex interrelations of the severity of LNM and its risk factors We identified four key characteristics associated with LNM in patients with HT and PTC: age ≤ 47 years and tumor size are confirmed independent risk factors for predicting LNM in patients with HT and PTC or PTC alone This study firstly demonstrated a positive correlation between FT3 levels and LNM in patients with both HT and PTC although further verification in larger samples and exploration of the molecular basis are needed The regression model identified distinct independent risk factors in two subgroups of LNM severity TMD > 1.75 cm and Hb < 121.5 g/L are indicators of a higher number of LN metastases (> 5 nodes); while in the regional subgroup TMD > 1.85 cm and serum FT4 < 18.25 pmol/L were associated with LLNM we propose a higher cutoff value specifically to assess whether patients with HT combined with PTC experience more severe lymph node metastases reduced hemoglobin levels are correlated with increased malignancy severity and poorer prognoses across diverse cancer types This association might suggest similar implications for TC where systemic manifestations like anemia could indicate advanced or more aggressive disease states although our study did not find significant TSH differences Further clinical and molecular investigations are needed to understand these hormone interactions and their effects on LNM This study is subject to certain limitations it only reflects the disease characteristics of patients from one institution the data collection was not exhaustive regarding variables that might influence LNM in patients with HT combined with PTC future research should include multicenter larger-scale cohort studies to validate and extend the findings presented herein This study innovatively employs both regression models and network analysis to explore potential factors related to LNM in patients with coexisting PTC and HT as well as the complex associations between these factors and the severity of LNM and TMD are all associated with LNM in patients with PTC and HT FT4 and Hb correlate with the regions and quantity of LNM while TMD shows a significant association with both exhibiting a stronger correlation than either FT4 or Hb our results provide a theoretical basis for predicting preoperative LNM in patients with PTC and HT in future clinical practice The data that support the findings of this study are available on request from the corresponding author The data are not publicly available due to privacy or ethical restrictions Pizzato, M. et al. 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J Clin Endocrinol Metabol. 97(4), 1134–45. https://doi.org/10.1210/jc.2011-2735 (2012) Download references The authors would like to thank all participants in this study This study was supported by grant 81902729 (S.C.) and 82300884 (N.T.) from the National Natural Science Foundation of China grant 2020SK4003 (S.C.) from the Special Funding for the Construction of Innovative Provinces in Hunan grant 2023JJ40990 (N.T.) from the Natural Science Foundation of Hunan Province and grant 2021KFJJ03 (S.C.) from the Project Program of National Clinical Research Center for Geriatric Disorders National Clinical Research Center for Mental Disorders The Second Xiangya Hospital of Central South University This study is part of the "Ultrasound and Clinical Big Data Research on Thyroid Diseases" project conducted by the Department of General Surgery (Hepatic and Thyroid Surgery) at Xiangya Hospital The project has been approved by the Ethics Committee of Xiangya Hospital All methods were performed in accordance with the relevant guidelines and regulations Given that minors typically do not possess the legal capacity and maturity to fully understand the nature the written informed consent for minors in this research will be confirmed by their parents or guardians to ensure the protection of their rights I would like to declare on behalf of my co-authors that our paper is new and neither the entire manuscript nor any part of its content has been published or has been accepted elsewhere It is not in submission at any other journal All authors have approved of the final version of this manuscript Download citation DOI: https://doi.org/10.1038/s41598-024-78179-8 Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly. Volume 15 - 2024 | https://doi.org/10.3389/fendo.2024.1339473 This study investigates the impact of Hashimoto’s thyroiditis (HT) on the papillary thyroid cancer (PTC) microenvironment using a dataset of 140,456 cells from 11 patients By comparing PTC cases with and without HT we identify HT-specific cell populations (HASCs) and their role in creating a TSH-suppressive environment via mTE3 These cells facilitate intricate immune–stromal communication through the MIF–(CD74+CXCR4) axis emphasizing immune regulation in the TSH context our HASC-focused analysis within the TCGA-THCA dataset validates the utility of HASC profiling for guiding tailored therapies objective method to determine K-means clustering coefficients in copy number variation inference from bulk RNA-seq data mitigating the arbitrariness in conventional coefficient selection our research presents a detailed single-cell atlas illustrating HT–PTC interactions deepening our understanding of HT’s modulatory effects on PTC microenvironments It contributes to our understanding of autoimmunity–carcinogenesis dynamics and charts a course for discovering new therapeutic targets in PTC advancing cancer genomics and immunotherapy research This indicates that the role of HT in the formation of the tumor immune microenvironment of PTC is still unclear this research will focus on HT development to promote or inhibit PTC the inferCNV algorithm was usually used to distinguish malignant epithelial cells from non-malignant epithelial cells which is an effective method and widely used the existing problem is how to screen the results obtained by the inferCNV algorithm The usual selection of the clustering coefficient K with copy number variation is subjective we proposed a method to determine the best clustering coefficient K based on TCGA data which can effectively solve the problem of subjectivity in coefficient selection and provide a new strategy for the clustering coefficient selection of the inference results of single-cell copy number variation in the future To explore whether HT promotes or inhibits the generation and development of PTC we conducted a comprehensive analysis of the paratumors and distant metastasis sites of 11 PTC patients and systematically compared the differences in tumor microenvironments of PTC patients with and without HT The developmental trajectories of malignant thyroid epithelial cells (mTEs) and non-malignant thyroid epithelial cells (nTEs) and their interaction with HASCs were indicated This discovery can help us better understand how HT inhibits the development of PTC by affecting its tumor microenvironment we found the relationship between HASCs and prognosis at the single-cell level and clinical features in TCGA-THCA were further investigated to find the value of HASCs in clinical application studies have identified unique genomic and drug sensitivity profiles of different molecular subtypes and this provides a new idea for the personalized treatment of PTC We obtained the number GSE184362 from the Gene Expression Omnibus (GEO) database (22) (https://www.ncbi.nlm.nih.gov/geo/), and a total of 23 samples (6 paratumors, 7 primary tumors, and 10 metastatic tumors), which consisted of 8 samples with HT and 15 samples without HT, were used for analysis via the Seurat R package (23) genes were retained with detected expression in more than three cells Cells with less than 200 detected genes were excluded we used the NormalizeData() function in Seurat to normalize the raw gene expression value by the global-scaling normalization method “Log-Normalize”: To distinguish malignant thyroid epithelial cells (mTEs) from non-malignant thyroid epithelial cells (nTEs), we used the inferCNV R package to predict the copy-number alterations (CNAs) of cells and compared them to the reference “normal” cells (this refers to paratumor cells) from scRNA-seq data (25) By setting the cutoff parameter of the inferCNV package’s run function to 0.1 According to the CNA scores of cells on 22 chromosomes and metastatic tumors) were clustered using K-means clustering and the number of clustering K values ranged from 6 to 15 The Monocle2 R package was used to perform the trajectory analysis for mTEs and nTEs (26) Function newCellDataSet() converted the Seurat object to CellDataSet object and function estimateSizeFactors() and function estimateDispersions() were used to standardize and normalize the gene expression data of cells The genes with average log2 fold change greater than 0.5 and adjusted P-values less than 0.05 between HT and non-HT of T/NK cells were used as ordering genes in the trajectory analysis The DDRTree method of the reduceDimension function was used for dimension reduction the differentially expressed genes (DEGs) (average log2 fold change >1 and q-value<0.01) that changed along with the pseudotime were identified by the differentialGeneTest() function The BEAM function was used to find genes that are regulated in a branching way expression levels were calculated relative to the total read map of the same set of coding genes in all transcriptomes Expression values were averaged across each single-cell cluster/cell sample All statistical analyses were performed using the R tool (v.4.1.1) The Wilcoxon test was applied to compare the differences between two groups and the Kruskal–Wallis test was used to compare differences between multiple groups of samples P<0.05 indicates a significant difference The Kaplan–Meier survival analysis was carried out using the R packages survival and survminer The workflow of this study was divided into four steps as follows (Figure 1): the first step is the processing of single-cell data the second part is the copy-number variation analysis based on the inferCNV algorithm to distinguish malignant and non-malignant epithelial cells the third step is the acquisition of HASCs and the fourth step is the molecular typing of TCGA-THCA samples based on HASCs Workflow of the effect of HT on the PTC tumor microenvironment at the single-cell level the content of immune cells was higher in patients with HT although T/NK cells were excluded which may be due to the low content of T/NK cells in the HT samples of paratumor tissues it is clear that the immune systems of the HT samples were better activated Overview of scRNA-seq analysis across 11 PTC patients (A) t-SNE plot visualizing 14 distinct clusters encompassing 140,456 cells from all samples (n = 23) (B) Bubble plots showing the expression levels of marker genes for each cell type (C) t-SNE plot visualizing cell clusters colored by tissue of origin (D) t-SNE plot visualizing cell clusters colored by HT and non-HT (E) t-SNE plot visualizing cell clusters colored by samples (F) Horizontal bar charts showing the relative abundance of various cell types between HT and non-HT in each tissue of origin (G) Post-hoc analysis of each cell between HT and non-HT; *P< 0.05 and 701 primary tumor mTE cells classified as paratumor nTEs there were 346 paratumor nTE cells classified as primary tumor mTEs The copy number variation (CNV) profile analysis distinguishing malignant thyroid epithelial cells (mTEs) and non-malignant thyroid epithelial cells (nTEs) (A) The differentially expressed genes of mTEs and nTEs obtained at different K values were used as the ssGSEA results of the gene set in TCGA-THCA tumor and paratumor samples (B) Chromosomal CNV plots of thyroid epithelial cells (C) Clustering heatmap of CNV on 22 chromosomes at K = 11 The above results indicate that the TSH-inhibiting environment formed by a high proportion of mTE3 and nTE2 clusters in HT patients has an inhibitory effect on PTC These results indicate that in HT patients nTE0 and nTE2 clusters may differentiate into mTE3 clusters but some cells transform into other nTE clusters which does not affect the environment of TSH inhibition because mTE10 clusters will differentiate into mTE3 clusters making up for the increase of TSH caused by the decrease of nTE0 and nTE2 This dynamic transformation creates a TSH-inhibiting microenvironment that effectively inhibits PTC in HT patients mTE3 was from mTE10 and nTE0 and nTE2 were divided into nTE8 (C) Heatmap showing two-gene clusters of mTE3 marker genes with different expression signatures at pseudotime point 1 (D) Heatmap showing three-gene clusters of mTE3 marker genes with different expression signatures at pseudotime point 2 (E) Heatmap showing three-gene clusters of nTE0 marker genes with different expression signatures at pseudotime point 1 (F) Heatmap showing three-gene clusters of nTE0 marker genes with different expression signatures at pseudotime point 2 (G) Heatmap showing four-gene clusters of nTE2 marker genes with different expression signatures at pseudotime point 1 (H) Heatmap showing four-gene clusters of nTE2 marker genes with different expression signatures at pseudotime point 2 The above proportion of immune cells indicates that HT patients can better activate their own immune system and the presence of PTC prevents excessive activation of the immune system to reach homeostasis which forms a dynamic balance between autoimmune diseases and cancer This finding enables us to clearly see that HT inhibits the development of PTC by mobilizing CD4_Tn_Treg (A) t-SNE plot visualizing 28 distinct clusters of T/NK cells (C) Horizontal bar charts showing the relative abundance of various cell types between HT and non-HT (D) Post-hoc analysis of each cell type between HT and non-HT (E) t-SNE plot visualizing 20 distinct clusters of B cells (F) Bubble plots showing the expression levels of marker genes for each cell type (G) Horizontal bar charts showing the relative abundance of various cell types between HT and non-HT (H) Post-hoc analysis of each cell type between HT and non-HT (I) t-SNE plot visualizing 20 distinct clusters of myeloid cells (J) Bubble plots showing the expression levels of marker genes for each cell type (K) Horizontal bar charts showing the relative abundance of various cell types between HT and non-HT (L) Post-hoc analysis of each cell type between HT and non-HT a high proportion of fibroblast cluster 4 and endothelial cell cluster 13 in stromal cells is a major feature of HT patients which will better inhibit the development of PTC (A) t-SNE plot visualizing 11 distinct clusters of fibroblasts (E) t-SNE plot showing endothelial cells colored by clusters (n = 15) (F) Horizontal bar charts showing the relative abundance of various clusters between HT and non-HT (G) Post-hoc analysis of each cluster between HT and non-HT (H) GO enrichment analysis of the top 50 marker genes in 15 clusters There was no doubt that nTE0 and mTE3 were the senders of the signal; Intermediate_B and fibroblast cluster 4 were the receivers of the signal; CD4_Tn_Treg and CD8_Tex_Teff were both the sender and the receiver; and nTE2 was almost neither the sender nor the receiver Cell–cell communication analysis of HASCs the greater the number of interactions and the greater the weight/intensity of interactions between the two cell types (B) The significantly related ligand–receptor interactions from the main thyroid epithelial cells to other immune and stromal cells (C) Hierarchy plot of interactions between selected target cells and other cells in the MIF signaling pathway network (D) Relative contribution of each ligand–receptor pair to the overall communication network of signaling pathways which is the ratio of the total communication probability of the inferred network of each ligand–receptor pair to that of the signaling pathways (E) Hierarchy plot of interactions between selected target cells and other cells in the MIF–(CD74+CXCR4) signaling network (F) Violin plot showing the expression patterns of signaling genes involved in the inferred signaling network (G) The network centrality index of each cell population was calculated to identify the role of each type of cell in the MIF signaling pathway (H) Scatter plot visualizing the dominant sender (source) and receiver (target) in the MIF signaling pathway in 2D space (A–I) Kaplan–Meier curve of OS according to CD4_Tn_Treg (log-rank test: P = 0.14) (A) CD8_Tex_Teff (log-rank test: P = 0.057) (B) endothelial cell cluster 13 (log-rank test: P = 0.047) (D) fibroblast cluster 4 (log-rank test: P = 0.013) (E) Intermediate_B (log-rank test: P = 0.00043) (F) and cluster 1 showed a stronger drug sensitivity to these drugs indicating that this cluster had a better response to drug treatment which was consistent with the previous results of higher TMB The classification of molecular subtypes in TCGA-THCA samples allows us to more precisely target drug therapy and this new finding will help in the treatment of PTC patients Identification of different molecular subtypes based on HASCs (A) Consensus clustering matrix when K = 2 (B) Consensus clustering CDF with K values of 2 to 9 (C) Relative change in area under the CDF curve for K = 2 (D) Box plot of the HASC content between cluster 1 and cluster 2 F) Box plot of the difference between immune scores (E) and stromal scores (F) in subtypes based on the ESTIMATE algorithm H) SNV waterfall of the top 20 (mutation frequency) genes in cluster 1 (n = 148) (G) and cluster 2 (n = 126) (H) Variations in drug sensitivity between cluster 1 and cluster 2 (A–I) IC50 box diagram of the nine drugs with significant difference in drug sensitivity in cluster 1 and cluster 2 in which red indicated cluster 1 and brown indicated cluster 2 Our work innovates in the approach to distinguish malignant from non-malignant cells, a challenge traditionally addressed through inferential CNV analyses in cancer research (25, 43–48) To overcome the impediment of low CNV variability in PTC we employed K-means clustering informed by the statistical significance of differential enrichment scores derived from TCGA data This novel methodology optimizes CNV-based classification contributing a robust tool for future scRNA-seq studies A pivotal discovery lies in the identification of HT-associated specific cell populations (HASCs). Our findings resonate with the therapeutic efficacy of TSH suppression in PTC management (49), revealing that HASC subsets—marked by mTE3, nTE0, and nTE2 cells enriched in thyroid hormone pathways—are conducive to a TSH-suppressive milieu, thereby affirming HT’s positive influence on PTC progression through these cell clusters (50) molecular stratification emerges as the premier strategy consensus clustering was employed to segregate TCGA-THCA cases into two distinct clusters (cluster 1 and cluster 2) where cluster 1 displayed heightened HASC enrichment an observation corroborated by the ESTIMATE algorithm our investigation of drug responsiveness revealed cluster 1 to be more susceptible to chemotherapeutic agents like sunitinib reinforcing the hypothesis that cluster 1 represents HT-positive PTC with its enriched immune landscape enhancing sensitivity to anticancer therapies a pivotal insight for therapeutic strategies our research constitutes a comprehensive exploration of cellular subset disparities between HT-positive and HT-negative PTC patients at the single-cell resolution By isolating HASCs from differential cell populations we facilitated an in-depth examination of intercellular communication dynamics we quantified HASC abundance in bulk transcriptomic datasets and conducted cluster analysis on TCGA samples This work underscores the significance of HT in modulating PTC progression and identifies the MIF–(CD74+CXCR4) axis as a potential therapeutic target our study undeniably illuminates the favorable influence of HT on PTC outcomes thereby furnishing a fresh perspective and theoretical foundation for subsequent inquiries Further inquiries can be directed to the corresponding authors This research was funded by the National Natural Science Foundation of China (grant numbers 61971166 and 62072144) and the Post-Doctoral Foundation of Heilongjiang Province (grant numbers LBH-Z22207 and LBH-Q20159) Pan Byron Fei from the United States for his help in revising the English language of the article The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fendo.2024.1339473/full#supplementary-material Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries Dual priming oligonucleotide-based multiplex PCR analysis for detection of BRAFV600E mutation in FNAB samples of thyroid nodules in BRAFV600E mutation-prevalent area Therapeutic breakthroughs for metastatic thyroid cancer PubMed Abstract | Crossref Full Text | Google Scholar Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced PD-L1-positive papillary or follicular thyroid cancer The prevalence and prognostic value of BRAF mutation in thyroid cancer The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with 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Single cell RNA-seq reveals the CCL5/SDC1 receptor-ligand interaction between T cells and tumor cells in pancreatic cancer Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma Multikinase inhibitors: a new option for the treatment of thyroid cancer Hashimoto's thyroiditis: A "Double-edged sword" in thyroid carcinoma Correction: miR-451a is underexpressed and targets AKT/mTOR pathway in papillary thyroid carcinoma Zhang D and Chen X (2024) Impact of Hashimoto’s thyroiditis on the tumor microenvironment in papillary thyroid cancer: insights from single-cell analysis Received: 05 December 2023; Accepted: 05 July 2024;Published: 16 September 2024 Copyright © 2024 Ma, Li, Huo, Su, Jin, Lu, Sun, Zhang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Yanyan Sun, NjAxNTg5QGhyYm11LmVkdS5jbg==; Denan Zhang, emhhbmdkZW5hbkBlbXMuaHJibXUuZWR1LmNu; Xiujie Chen, Y2hlbnhpdWppZUBlbXMuaHJibXUuZWR1LmNu This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page MedlinePlus. Thyroid diseases MedlinePlus. Hashimoto thyroiditis National Institute of Diabetes and Digestive and Kidney Diseases. Graves' disease Wu K, Zhou Y, Ke S, et al. Lifestyle is associated with thyroid function in subclinical hypothyroidism: A cross-sectional study Ihnatowicz P, Drywień M, Wątor P, Wojsiat J. The importance of nutritional factors and dietary management of Hashimoto's thyroiditis MedlinePlus. Levothyroxine National Institute of Diabetes and Digestive and Kidney Diseases. Thyroid tests Top Page > Press Release 2024 > MOL President & CEO Hashimoto Welcomes New Employees at Company's Entrance Ceremony - Becoming a Resilient Global Enterprise by Balancing Growth and Stable Management - (MOL; President & CEO: Takeshi Hashimoto) today announced that on October 1 it welcomed 69 new employees (new graduates at sea: 22; career recruits on land: 47) President & CEO Hashimoto delivered the following message at the entrance ceremony Back in May, injury had forced him to suddenly pull out of the NHK Trophy -- the sport's marquee tournament in Japan -- that he hoped would be his chance to dress-rehearse his routines ahead of the Paris Games. Still nursing a far-from-healed finger injury, he joined other Olympic-bound athletes at the team's training camp even though he wondered whether he would be able to lead the five-man team to the gold medal that his nation expected. "To be honest, I was starting to lose confidence," Hashimoto told reporters on Monday. "When the camp ended, I still couldn't visualise how I was going to win that gold." That sense of doubt seemed to have disappeared two days ago when Hashimoto stepped into the Bercy Arena in Paris, beaming and waving to the adoring fans. On the high bar, Hashimoto botched his dismount by landing on his hands and feet, dashing his chance of reaching the final to defend the title in the apparatus. "I became a drag on the team and that felt really heavy again," he said. Japan had been hoping to top the qualifying standings to underline their title credentials but they had to settle for second place behind China. Through the difficult moments, it was his teammates' unwavering determination and constant encouragement that carried him through, Hashimoto said. "Every time I opened the doors to the training grounds, all of them would talk about how they wanted to win the gold medal. Seeing that, I really felt from the bottom of my heart that I wanted to fight for this team." On Monday, with that medal at stake, Hashimoto needed one more lift from his teammates. In an error that drew a collective gasp from the arena, Hashimoto fell off the pommel horse, setting Japan back against a formidable Chinese side. In fact Hashimoto's lowly score of 13.100 left his country trailing in fifth place at the halfway point of the final. "The moment I fell I thought to myself, 'Oh no, we're going to lose the gold again because of me'," said Hashimoto, who was part of the Japanese team that finished second behind Russia at the Tokyo Games. "But when I finished, (teammates Takaaki) Sugino and (Kazuma) Kaya said to me, 'Don't give up. We can still do it.'" With only one of the six apparatuses left to go, China's gold medal seemed all but certain as Japan trailed by more than three points -- a massive deficit that could only be overcome provided the Japanese executed a series of near-flawless routines and also required Chinese gymnasts to suffer some major mishaps. Fortunately for Japan, that is exactly what happened on the horizontal bar. Xiao Ruoteng completely botched his dismount by landing on both knees to earn his lowest score of the day of 13.433. Minutes later his Chinese teammate Su Weide suffered two crash landings from the bar, giving Hashimoto a chance at redemption and his team a shot at gold. The last of his team to compete, Hashimoto put in a solid 14.566 performance to give his team a total of 259.594 points. It left the final Chinese competitor requiring an improbable 15.265 just to tie with Japan. Zhang Boheng fell well short of that target. "I'm so incredibly happy. It's different from an individual medal," Hashimoto said. "Everyone's hugging each other like crazy, and then hugging again even though we just hugged. I feel like this medal has deepened our strong bond even more." Please enable JS and disable any ad blocker Connecting decision makers to a dynamic network of information, people and ideas, Bloomberg quickly and accurately delivers business and financial information, news and insight around the world Takeshi Hashimoto, MOL President & CEO speaks with Bloomberg TV's Haslinda Amin on the sidelines of the 2025 World Economic Forum in Davos, Switzerland. (Source: Bloomberg) Hashimoto’s thyroiditis (HT) is one of the most commonly encountered types of autoimmune thyroid disorders (AITDs), influenced by environmental factors, genetics, and the immune system. Previous research has shown a correlation between gut microbiota and HT, as well as the involvement of immune cells in its onset and progression. We aimed to investigate whether immune cells act as intermediaries in the causal relationship between gut microbiota and HT. In conclusion, we presented causal associations between the EM CD4 + T cell-mediated gut microbiota and HT, as inferred from the MR findings derived from extensive aggregated GWAS data. Our research offers guidance and direction for treating and preventing HT. Microorganisms in Vertebrate Digestive Systems Volume 15 - 2024 | https://doi.org/10.3389/fmicb.2024.1463394 Purpose: Hashimoto’s thyroiditis (HT) is one of the most commonly encountered types of autoimmune thyroid disorders (AITDs) Previous research has shown a correlation between gut microbiota and HT as well as the involvement of immune cells in its onset and progression We aimed to investigate whether immune cells act as intermediaries in the causal relationship between gut microbiota and HT we conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the relationship between gut microbiota and HT using data from genome-wide association studies (GWAS) and the MiBioGen study MR analyses were performed to investigate the interactions between 731 immune cells and gut microbiota an MR analysis was performed to examine the association between HT and these 731 immune cells using a GWAS dataset that included 3,757 European subjects This approach provided insights into the impact of 22 million genetic variants on 731 immune cell signatures Results: There was a causal relationship between the increase in the number of 15 gut microbiota and HT and genus Coprococcus3 were negatively correlated with HT and genus Anaerostipes were positively correlated with HT We identified EM CD4 + T cells as a mediator between the gut microbiota and HT we presented causal associations between the EM CD4 + T cell-mediated gut microbiota and HT as inferred from the MR findings derived from extensive aggregated GWAS data Our research offers guidance and direction for treating and preventing HT due to the susceptibility of previous studies to confounding factors and reverse causality bias it has remained unclear whether there is a causal relationship between gut microbiota and HT It is also uncertain whether immune cells play an intermediary role between the two Mendelian randomization (MR) uses genetic variants to investigate the causal relationships between exposure and disease onset (Li et al., 2022). In this study, we utilized the MR method to investigate the causal relationship between gut microbiota and HT, while also exploring the mediating role of immune cells to eventually help offer fresh insights into strategies for both preventing and treating Hashimoto’s thyroiditis (Long et al., 2023) which enabled us to estimate the direct impact of the gut microbiota on HT and calculate the proportion of the immune cells’ influence on HT The flowchart of this study illustrating the approach taken to investigate the link between the gut microbiota and Hashimoto’s thyroiditis to determine the causal relationships Mediation analysis additionally assessed the potential impact of immune cell traits on the gut microbiota—Hashimoto’s thyroiditis association Summary genetic data for HT were acquired from a genome-wide association study (GWAS) available at https://gwas.mrcieu.ac.uk/ (ebi-a-GCST90018855), which included 15,654 cases and 3,79,986 controls of European ancestry (Sakaue et al., 2021) The study sourced summary statistics for gut microbiota from the MiBioGen study, available at https://mibiogen.gcc.rug.nl/menu/main/home/. This extensive research coordinated 18,340 individuals from 24 cohorts, utilizing 16S rRNA gene sequencing profiles (Kurilshikov et al., 2021) Full GWAS summary statistics for each immune trait are publicly accessible via the GWAS Catalog server at https://www.ebi.ac.uk/gwas/home The GWAS dataset comprises 3,757 European subjects providing insights into the impact of 22 million variants on 731 immune cell signatures We extracted relevant information to calculate F-statistics and R2 to assess the instrument strength of the selected SNPs. R2 = (2 × beta2)/((2 × beta2) + (2 × N × SE2)), F = (R2 × (N−2))/(1−R2) (Palmer et al., 2012; Kamat et al., 2019) Various methods were employed to investigate the potential causal relationship between HT and gut microbiota including the MR pleiotropy residual sum and outlier (MR-PRESSO) test the inverse-variance weighted (IVW) method We excluded gut microbiota exhibiting pleiotropy and linkage disequilibrium. We removed significant outliers by performing the MR-PRESSO test to acquire a revised association outcome, thereby reducing bias introduced by pleiotropy (Verbanck et al., 2018) we utilized the LD trait tool to analyze confounding factors and removed SNPs that might directly influence HT The associations between the risk of HT and the gut microbiota were expressed as odds ratios (ORs) A p-value<0.05 was considered indicative evidence of a potential causal link Forest plots demonstrating the causal associations between the gut microbiota and Hashimoto’s thyroiditis using different methods Briefly, the results from multiple methods regarding the connections between all 196 bacterial traits and the risk of HT are shown in Supplementary Table S3 and Figure 3A (A) Circular heatmap illustrating the relationship between the gut microbiota and Hashimoto’s thyroiditis (B) circular heatmap depicting the relationship between the gut microbiota and immune cells and (C) circular heatmap showing the relationship between Hashimoto’s thyroiditis and the immune cells the genus Akkermansia and the genus Ruminococcus torques group showed odds ratios (OR) of 0.7123 (p = 9.9304E-14) and 0.8781 (p = 0.0001) in the IVW method Among the gut microbiota in the IVW method the family Alcaligenaceae showed an OR of 0.7749(p = 0.0017) class Alphaproteobacteria showed an OR of 0.8550 (p = 0.0075) genus Butyrivibrio showed an OR of 0.9066 (p = 0.0135) genus Turicibacter showed an OR of 1.1618 (p = 0.0203) family Verrucomicrobiaceae showed an OR of 0.8380 (p = 0.0209) order Verrucomicrobiales showed an OR of 0.8381 (p = 0.0209) class Verrucomicrobiae showed an OR of 0.8381 (p = 0.0209) phylum Verrucomicrobia showed an OR of 0.8387 (p = 0.0211) genus Anaerostipes showed an OR of 1.1963 (p = 0.0340) and family Desulfovibrionaceae showed an OR of 0.8245 (p = 0.0436) The MR-PRESSO analysis did not identify any statistically significant outliers (Supplementary Table S4). However, potential outliers were observed upon visual inspection of scatter plots (Supplementary Figure S1) and leave-one-out plots (Supplementary Figure S2) the OR for the gut microbiota in the weighted median method showed that order Desulfovibrionales exhibited an OR of 0.7624 (p = 0.0485) genus Coprococcus1 exhibited an OR of 0.7931 (p = 0.0423) and genus Intestinimonas exhibited an OR of 1.1980 (p = 0.0350) We genetically predicted that specific constituents of the gut microbiota were associated with the risk of HT further solidifying the association between HT and the gut microbiota The MR-Egger regression showed all intercepts with p > 0.05 In the reverse MR analysis, HT did not significantly affect gut microbiota composition, as shown in Supplementary Table S5 Our MR analyses strongly support a causal link between gut microbiota and HT genera such as EM CD4 + T cells become a key mediator in this relationship The genus Akkermansia is one of the most common gut microbiota genera, which plays a pivotal role in the development of HT. The current study found that this genus comprises a single member, designated as Akkermansia muciniphila, which is notably abundant in patients with HT. Furthermore, research has shown that the relative abundance of the genus Akkermansia is higher in patients with HT compared to the control group (Liu et al., 2022) a possible explanation for this might be that CD34+ cells and Treg cells may represent potential mechanisms underlying the reduction in EM CD4 + T cell numbers caused by the genus Akkermansia we conclude that EMCD4 + T cells play a certain role in the occurrence and development of HT through the inflammatory factor IFN-g the gut microbiota genus Turicibacter and genus Anaerostipe potentially influence the occurrence of HT through bile acids and lipid metabolism We explored HT from the perspectives of gut microbiota and immune cells providing the first comprehensive validation and exposition of the interrelations among them The MR-PRESSO approach was used to identify and correct for outlier pleiotropic instruments by detecting and removing anomalous instrumental variables thereby reducing bias introduced by pleiotropy Although our study has revealed important discoveries thus it cannot be directly inferred whether similar causal relationships exist in other regions animal and clinical studies were not conducted to directly establish the causal connection between immune cell-mediated HT and gut microbiota measurement bias might have arisen from the technical factors This could have affected the measurement of the exposure variables and led to bias in the MR analysis results the 16S rRNA sequencing used in the MiBioGen consortium’s GWAS data on gut microbiota can only detect genetic information at the genus to phylum level with no data available at the species level such as whole genome sequencing or nanopore technology we presented causal associations between the immune cell-mediated gut microbiota and HT Our research offers guidance and direction for the clinical treatment and prevention of HT we aim to contribute to the advancement of knowledge in the field of HT The original contributions presented in the study are included in the article/Supplementary material further inquiries can be directed to the corresponding authors All packages for data analysis used in this study were open source in R software (version 4.3.1; R Development Core Team) Z-DZ: Writing – review & editing The author(s) declare that financial support was received for the research This study was supported by the Natural Science Research Foundation of Shandong province (ZR2023QH508 and ZR2023MH002) and the 2022 Research Incubation Fund Project of Shandong Provincial Hospital Affiliated to Shandong First Medical University (2022FY121) The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2024.1463394/full#supplementary-material MR pleiotropy residual sum and outlier; ORs The pathogenesis of Hashimoto's thyroiditis: further developments in our understanding Crossref Full Text | Google Scholar The combination of ınterleukin-10 −1082 and tumor necrosis factor α −308 or ınterleukin-6 −174 genes polymorphisms suggests an association with susceptibility to Hashimoto's thyroiditis Comprehensive network map of interferon gamma signaling Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms Crossref Full Text | Google Scholar Saikosaponin-d attenuates Hashimoto's thyroiditis by regulating macrophage polarization Serum metabolomic analysis in patients with Hashimoto’s thyroiditis PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations Akkermansia muciniphila extracellular vesicles have a protective effect against hypertension Kurilshikov Large-scale association analyses identify host factors influencing human gut microbiome composition Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study Analysis of gut microbiota diversity in Hashimoto's thyroiditis patients Th17/Treg cells imbalance and GITRL profile in patients with Hashimoto's thyroiditis a butyrate-producing bacterium capable of metabolizing 5-fluorouracil Causal relationship between gut microbiota and cancers: a two-sample Mendelian randomisation study Gut microbiota Turicibacter strains differentially modify bile acids and host lipids PubMed Abstract | Crossref Full Text | Google Scholar The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα Prevalence of depression among hypothyroid patients attending the primary healthcare and endocrine clinics of king Fahad Hospital of the University (KFHU) Molaaghaee-Rouzbahani Akkermansia muciniphila exerts immunomodulatory and anti-inflammatory effects on gliadin-stimulated THP-1 derived macrophages and TNFα+ multifunctional memory T cells coexpress GM-CSF A mouse model of irradiation and spleen-thymus lymphocyte infusion induced aplastic anemia Using multiple genetic variants as instrumental variables for modifiable risk factors Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin Hashimotos’ thyroiditis: epidemiology Hashimoto's thyroiditis: an update on pathogenic mechanisms Siemińska and interleukin-6 in postmenopausal women with Hashimoto's thyroiditis Gut microbiota and Hashimoto's thyroiditis Crossref Full Text | Google Scholar Zhao Z-D and Zhang H-W (2024) Role of immune cells in mediating the effect of gut microbiota on Hashimoto’s thyroiditis: a 2-sample Mendelian randomization study Received: 11 July 2024; Accepted: 27 September 2024; Published: 14 October 2024 Copyright © 2024 Pei, Wang, Gao, Zhang, Liu, Zhao and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Zhen-Dan Zhao, enpkc2x5eUAxMjYuY29t; Hua-Wei Zhang, c2x5eXpod0AxNjMuY29t Why publish in Cureus? Click below to find out. Unlock discounted publishing that highlights your organization and the peer-reviewed research and clinical experiences it produces. Find out how channels are organized and operated, including details on the roles and responsibilities of channel editors. Offering a variety of advertising and sponsorship options for reaching influential specialists from targeted demographic splits. Cureus provides an equitable, efficient publishing and peer reviewing experience without sacrificing publication times. Generate broad awareness and deliver relevant, peer-reviewed clinical experiences directly to potential customers. Please note that by doing so you agree to be added to our monthly email newsletter distribution list. Arjun Kapoor revealed that he suffers from Hashimoto’s disease. What is Hashimoto Thyroiditis?Hashimoto's Thyroiditis is a condition where the body's own immunity attacks the thyroid gland, causing malfunction and death of cells. Initially, there may be hyperfunction of the thyroid, but due to the ongoing antibody attack and inflammation in thyroid, it leads to a reduction in thyroid function and hypothyroidism. “It is important to do our periodic, timely check of the thyroid hormone status and adjust the dosages as needed. Taking either too little or too much of the hormone can lead to symptoms. However, if a patient maintains normal thyroid hormone levels, which is easily achievable with regular check-ups and dose adjustments, they can live a normal life,” says Dr. Himika Chawla, Senior Consultant Endocrinology, PSRI Hospital, New Delhi. The diagnosis of Hashimoto thyroiditis is primarily based on physical findings suggestive of hypothyroidism in the patient, along with thyroid profile testing and anti-thyroid antibody tests. Additional blood tests and a thyroid ultrasound may also be necessary to assess for autoimmune processes in the thyroid gland. Management typically involves lifelong thyroid replacement therapy with levothyroxine," says Dr Kadam Nagpa, Head, Neuroimmunology and Senior Neurologist Salubritas Medcentre Volume 9 - 2021 | https://doi.org/10.3389/fcell.2021.758339 The tumor microenvironment heterogeneity of papillary thyroid cancer (PTC) is poorly characterized The relationship between PTC and Hashimoto thyroiditis (HT) is also in doubt we used single-cell RNA sequencing to map the transcriptome landscape of PTC from eight PTC patients Predicted copy number variation in epithelial cells and mesenchymal cells revealed the distinct molecular signatures of carcinoma cells Carcinoma cells demonstrated intertumoral heterogeneity based on BRAF V600E mutation or lymph node metastasis and some altered genes were identified to be correlated with disease-free survival in The Cancer Genome Atlas datasets transcription factor regulons of follicular epithelial cells unveil the different transcription activation state in PTC patients with or without concurrent HT The immune cells in tumors exhibited distinct transcriptional states and the presence of tumor-infiltrating B lymphocytes was predominantly linked to concurrent HT origin Trajectory analysis of B cells and plasma cells suggested their migration potential from HT adjacent tissues to tumor tissues we revealed diverse ligand–receptor pairs between non-immune cells Our results provided a single-cell landscape of human PTC These data would deepen the understanding of PTC as well as the immunological link between PTC and HT Although PTC is generally indolent and shows a favorable prognosis some metastasized lesions are not treatable with radioactive iodine or surgery therapy it is important to characterize tumor cells as well as immune cells to clarify their property in PTC In PTC patients with or without concurrent HT whether tumor-infiltration lymphocytes are attracted by an antitumor immune response or influenced by a preexisting autoimmune process remains unknown an immunological link between PTC and HT could not be excluded but the role of HT in shaping the PTC immune milieu is still unclear we constructed the single-cell transcriptome landscape of human papillary thyroid carcinoma The systemic single-cell transcriptome data provided novel insights to understand the TME of PTC was included in this study to investigate the dynamic relationship of immunocytes the precise characterization of PTC and its microenvironment in combination with the immunological crosstalk with HT facilitates in-depth understanding of the PTC molecular characteristics These results would also help in the identification of potential molecular targets for PTC diagnosis and treatment This study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital and carried out in accordance with the principles of the Declaration of Helsinki diagnosed with PTC were recruited in our study and all the patients signed the informed written consent for each subject and agreed to donate the specimens A total of 10 fresh tissue samples (five samples from PTC patients without concurrent HT three samples from PTC patients with concurrent HT and two paired adjacent tissues of two PTC patients with concurrent HT) were collected from Chinese PTC patients undergoing thyroidectomy at the Department of Thyroid Surgery of the hospital Paired adjacent tissues were collected by curettage at the same time as tumor tissue collection The patients did not receive any other forms of therapy Diagnosis of PTC and HT cases was histologically confirmed by two independent pathologists and all of the tumor tissues were assessed by hematoxylin-eosin staining Fresh and sterile tumor tissue fragments were initially divided into segments after two washings with 1 × phosphate-buffered saline the tumor pieces were dissociated into single-cell suspensions through Human Tumor Dissociation Kit (Miltenyi Biotec GmbH Digested tumor pieces were teased through a 40-μm sieve the dissociated single cells were centrifuged and cell pellets were resuspended in PRIM1640 (Thermo Fisher Scientific) plus 0.04% bovine serum albumin (Sigma–Aldrich) Viability was confirmed to be >90% in all samples via trypan blue (Thermo Fisher Scientific) staining and the cell suspensions were kept on ice for the scRNA-seq Standard Microwell-seq protocol was performed to treat single-cell suspensions from different samples single-cell suspensions and barcode beads were loaded on agarose Microwell array Beads and cells were trapped in separated Microwells Transcripts from lysed cell were captured by barcode oligodT bead Beads were collected in a 1.5-mL tube to do template switch Purified cDNA libraries were tagmented using a customized transposase to enrich 3’ ends of transcripts (TruePrep DNA Library Prep Kit V2 for Illumina Libraries were sequenced on Illumina Hiseq Xten (PE150 mode) by Novogene Co. Drop-seq core computational tool (version 1.12) was used to preprocess the Microwell-seq raw data. As described in Drop-seq computational cookbook1. Online R packages of data preprocessing and detailed parameters are available at Github2 Filtered reads were used to extract cellular barcode and unique molecular identifier (UMI) We discarded the paired reads if the quality of any base in the barcode was below 10 STAR (version 2.5.2a) with default parameters was used for mapping Reads were aligned to the Homo sapiens GRCh38 reference genome and GTF annotation files from GENCODE were used to tag aligned reads molecular barcodes with one edit distance were merged to one within a gene We excluded cells in which there were fewer than 500 UMIs All the R packages were loaded in R (version 3.6.3) and plots were mapped using R package ggplot2 (version 3.3.5) Transcriptome data from The Cancer Genome Atlas (TCGA) THCA datasets were downloaded from UCSC XENA5 Genes with average logFC > 1 were used as marker genes of each cell type We used Spearman correlation analysis to estimate correlation between immune cell types A total of 568 cases with gene expression data (HTSeq-counts and HTSeq-FPKM) in THCA projects were collected from TCGA those with clinical information were included counts and FPKM data were transformed into TPM for the following analyses The TPM data for 500 patients were used for further analyses All statistical analysis and plots in this validation part were produced using R (v4.0.3) Wilcoxon rank sum test and signed rank test were used to analyze the expression of selected genes in PTC samples and PTC combined with HT samples To determine the best cutoff value of selected genes to predict disease recurrence in PTC patients the 500 samples were divided into two groups high-expression group and low-expression group according to the best cutoff value Kaplan–Meier method was applied to conduct the survival analysis and plot the survival curves of selected genes p < 0.05 was considered statistically significant CIBERSORT computational method was applied for estimating the tumor-infiltrating immune cells abundance profile in all 500 samples The profile of 21 types of immune cells was displayed by boxplot Velocyte (version 0.17) was used to calculate RNA velocity of B cell in samples from PTC patients with HT and adjacent tissue samples from PTC patients with HT. The rates of transcriptional changes of each cell were estimated using the ration of spliced and unspliced reads6 with default parameters The plot was visualized with UMAP embedding The differentiation start and end points were estimated using a Markov process with default parameters We selected differentially expressed genes (DEGs) of immune cells (B cells We use monocle2 R package (version 2.4.0) to treat genes expressed in at least three cells in single-cell data Default settings of DEGs were adopted to construct pseudotime trajectory and heatmap We used CellPhoneDB (version 2.1.3) for the analysis of potential receptor–ligand pairings We aggregated the gene expression levels of all clusters in samples from PTC patients with HT and adjacent tissue from PTC patients with HT Receptors and ligands expressed in more than 10% of the cells in each cluster were considered The cutoff was set with the mean expression greater than 0.05 and p values smaller than 0.05 We used the sum of the number of receptor–ligand pairs in each cell–cell pairing to indicate the strength of the cell–cell interactions The interaction network was visualized using Cytoscape (version 3.7.0) and ggplot2 (version 3.3.5) an R package pheatmap was applied to visualize the gene importance in prediction of the source of follicular epithelial cells Immunohistochemistry (IHC) staining was performed on 4-μm-thick paraffin-embedded sections using an Opal multiplex IHC system (NEL811001KT PerkinElmer) according to the manufacturer’s instructions tissue sections were subjected to antigen retrieval in an induction cooker for 25 min in EDTA buffer (pH 9.0) Followed by treatment with goat serum at 37°C for 40 min tissue sections were incubated with the following antibodies: TG (ab151539) and CD3D (ab109531) at 4°C overnight Images were recorded with Metamorph software v7.5.6.0 (Molecular Device) on an Olympus IX81 inverted microscope The images were evaluated by two independent pathologists who were blinded to the patients’ clinical information Single-cell transcriptome landscape of papillary thyroid cancer (B) UMAP plot of subclusters in PTC cell landscape (C) Heatmap of specific marker genes of paired clusters in (B) (D) The fractions of samples in each cell subcluster (E) The fractions of sample types in each cell subcluster (F) UMAP plot of cells colored by PTC patients samples from PTC patients without concurrent HT; HT_PTC samples from PTC patients with concurrent HT (G) UMAP plot of single cells colored by PTC types These results unveiled an activated EMT state in tumor cell microenvironment of PTC while immunogenicity of those tumor cells was inhibited Reclustering of parenchymal cells and identification of malignant cells (A) UMAP plot of parenchymal cell subclusters colored by cell types (C) Fractions of predicted tumor cells in each cell subcluster (D) Volcano plots show DEGs of follicular epithelial cells based on BRAF V600E mutation and LNM highly expressed genes in patients with BRAF V600E mutation; BRAF V600E– highly expressed genes in patients without BRAF V600E mutation; LNM+ highly expressed genes in patients with LNM; LNM- highly expressed genes in patients without LNM; NS genes with no significant expression patterns (E) GSVA pathway enrichment of different group based on CNV level (F) Expression level of TACSTD2 and CLDN3 between different mutation groups and DFS analysis in the TCGA-THCA cohort (G) DFS analysis of CTSC and B2M in the TCGA-THCA cohort Enriched expression of TFF3 suggested a stronger invasion ability of cluster 4 which may contribute to LNM in PTC patients without concurrent HT Identifying transcriptome signatures of follicular epithelial cells (A) UMAP plot of follicular epithelial cell subclusters and FeaturePlot of marker genes in two types of PTC (B) UMAP plot of follicular epithelial cells colored by PTC types (C) Density plots of TG expression levels and cell number distribution in follicular epithelial cell subclusters (D) Volcano plot shows DEGs of epithelial cells from two types of PTC highly expressed genes in patients without concurrent HT; PTC_HT highly expressed genes in patients with concurrent HT; NS (E) Rank of the cell type specific regulons in follicular epithelial cell subclusters (F) Gene ontology enrichment of the top 20 genes in follicular epithelial cells from PTC patients without concurrent HT (G) Gene ontology enrichment of the top 20 genes in follicular epithelial cells from PTC patients with concurrent HT (H) t-SNE plot of follicular epithelial cells clustering patterns using metric learning model (I) MALAT1 expression level in the TCGA-THCA cohort based on PTC types PTC patients without concurrent HT; PTC + HT (J) Heatmap of genes contributed to the classification in metric learning model Those immune responses suggested a potential cell network between follicular epithelial cells and myeloid cells in HT microenvironment that could affect tumor progression The metric learning results suggested MALAT1 as a potential biomarker to evaluate the malignancy of PTC in diagnosis Reclustering of tumor-infiltrating immune cells (A) UMAP plots of immune cell subclusters in PTC colored by cell types (B) Cell–cell Spearman correlation network of immune cell subclusters (C) Pie charts of cell-type fractions for each patient’s tumor-infiltrating immune cells (D) Correlation between myeloid cells and lymphocytes subsets in the TCGA-THCA cohort Coefficient was calculated with Spearman correlation analysis (E) Rank of the cell type–specific regulons in immune cells from PTC patients without concurrent HT (F) Rank of the cell type specific regulon in immune cells from PTC patients with concurrent HT (G) Violin plot of marker genes in T-cell subclusters (H) Violin plot of marker genes in B-cell subclusters (I) Violin plot of marker genes in myeloid cell subclusters (J) Pseudotime trajectory of B-cell subclusters using monocle2 (K) Color-coded pseudotime of B-cell subclusters; the start point is dark blue (L) Heatmap of the top DEGs expression levels in three divided clusters from pseudotime trajectory Cluster 1 enriched the cycling B cell marker Function analysis of enriched genes suggested B cell proliferation Cluster 3 contains up-regulated genes related to the secreting of autoantibodies Gene function enrichment analysis indicated immunoglobulin receptor binding Reclustering of single cells in samples from two types of PTC (A) UMAP plot of single cells in samples from two types of PTC (B) FeaturePlot of selected marker genes in two types of PTC (C) Immunostaining of CD79A/B in two types of samples from PTC patients (a: sample from PTC patient without concurrent HT b: sample from PTC patient with concurrent HT) (D) The fractions of cell types in samples from two types of PTC (E) The expression levels of B cell marker genes in the TCGA-THCA cohort based on PTC types (F) Dot plot of marker genes in samples from PTC patients without concurrent HT Columns represent the selected marker genes (G) Dot plot of marker genes in samples from PTC patients with concurrent HT (H) Density of canonical immune cells in the TCGA-THCA cohort PTC patients with concurrent HT; Thyroiditis No and DCs enriched most ligand–receptor pairs with lymphocytes These findings highlight myeloid cells as a potential signal transition hub to regulate the B cell recruitment from adjacent tissues to tumor tissues Comparison of adjacent tissues and tumor tissues from PTC patients with concurrent HT (A) UMAP plot of cell types in adjacent tissues and tumor tissues from PTC patients with concurrent HT (B) UMAP plot shows RNA velocities of B cell subsets in adjacent tissues and tumor tissues (C) Cell–cell interaction network of ligand–receptor pairs in adjacent tissues of PTC patients with concurrent HT The size of the circle represents the total ligand–receptor pairs of each cell type The line weight represents the ligand–receptor pairs between two linked cell types (D) Cell–cell interaction network of ligand–receptor pairs in tumor tissues of PTC patients with concurrent HT (E) Selected ligand–receptor pairs of follicular epithelial cells from adjacent tissue samples in PTC patients with concurrent HT ligand–receptor pairs (expression level is color-coded) (F) Selected ligand–receptor pairs of follicular epithelial cells from tumor samples in PTC patients with concurrent HT (G) Calculated ligand–receptor pairs of follicular epithelial cells from adjacent tissue samples in PTC patients with concurrent HT (H) Calculated ligand–receptor pairs of follicular epithelial cells from tumor samples in PTC patients with concurrent HT These potential antitumor interaction networks were constructed by plasma cells Reclustering of follicular epithelial cells defined epithelial cells high expressed TFF3 in samples from PTC patients without concurrent HT and epithelial cells high expressed CCDC80 in samples from PTC patients with concurrent HT Machine learning model predicted MALAT1 as a potential biomarker in PTC patients without concurrent HT A great number of ligand–receptor interactions were observed between B cells Precursor–progeny relationship supported by RNA velocity unveiled the migration potential of infiltrating B cells from adjacent tissues to tumor tissues PTC is always accompanied by the synchronous appearance of HT more complicated cell–cell interaction networks of ligands and receptors between endothelial cells and myeloid cells in samples from PTC patients with concurrent HT suggested a controlled homeostasis microenvironment of tumor progress regulation The analyses of PTC and adjacent HT tissues implied that the cellular TME was reshaped by the B lymphocytes derived from adjacent HT tissues we hypothesized that B lymphocyte–related immune response was a possible reason for the better prognosis of PTC patients with concurrent HT But detailed mechanisms need further investigation and verification limited number of cases in our study could not cover all the clinical features of PTC our work is a comprehensive systematic single-cell transcriptome survey of human primary PTC We revealed detailed molecular characteristics of PTC cells as well as their clustering Our analysis uncovered B cells infiltrating in tumor tissues as a distinctive feature for PTC patients with concurrent HT Our findings are potentially valuable in not only serving as a resource for deeper understanding of PTC in general but also elucidating the immunological correlation between PTC and HT The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/ The studies involving human participants were reviewed and approved by Clinical Research Ethics Committee of The first affiliated hospital Zhejiang university (IIT consent: NO.700,2020) and FY conceived and designed the experiments and YZ collected the patients’ samples All authors read and approved the final manuscript This study was supported by grant from Zhejiang Provincial Natural Science Foundation of China (LQ18H180003 and LQ18H050003) the National Natural Science Foundation of China (81800658) and Zhejiang Medical Science and Technology Projects (2019330597 and 2019330585) The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcell.2021.758339/full#supplementary-material epithelial–mesenchymal transition; GSVA Uniform Manifold Approximation and Projection Clinical relationship between Hashimoto’s 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Jun Pan, cGFuanVuMTkyOEBhbGl5dW4uY29t; Fang Ye, eWUtZmFuZ0B6anUuZWR1LmNu; Guoji Guo, Z2dqQHpqdS5lZHUuY24=; Yijun Wu, d3V3dTU5MjVAemp1LmVkdS5jbg==