Hashimoto's Thyroiditis Research Articles

The Gut Microbiota and Its Metabolites and Their Association with the Risk of Autoimmune Thyroid Disease: A Mendelian Randomization Study

Objectives: Observational research shows associations of the gut microbiota and its metabolites with autoimmune thyroid disease (AITD), but the causality is undetermined. Methods: Two-sample Mendelian randomization (MR) was employed to analyze the association of the gut microbiota and its metabolites with AITD. A total of 119 gut microbiotas and nine fecal/circulating metabolites were the exposures. AITD, Graves’ disease (GD), and Hashimoto’s thyroiditis (HT) were the outcomes. Inverse-variance weighting (IVW) was primarily used to assess causality; Cochran’s Q was used to assess heterogeneity. Sensitivity analyses (weighted median, MRPRESSO regression, MRPRESSO intercept, MRPRESSO global, Steiger filtering, leave-one-out) were conducted to assess causal estimate robustness. Multivariable MR (MVMR) was used to estimate the effects of body mass index (BMI) and alcohol consumption frequency on causality. Results: The outcomes were potentially causally associated with 22 gut microbiotas and three metabolites. After multiple-test correction, 3-indoleglyoxylic acid retained significant causality with AITD (IVW: odds ratio [OR] = 1.09, 95% confidence interval [CI] = 1.05–1.14, p = 2.43 × 10−5, FDR = 0.009). The sensitivity analyses were confirmatory (weighted median: OR = 1.06, 95% CI = 1.01–1.12, p = 0.025; MRPRESSO: OR = 1.09, 95% CI = 1.15–1.14, p = 0.001). MVMR revealed no confounding effects on this association (BMI: OR = 1.21, 95% CI =1.08–1.35, p = 0.001; drinks/week: OR = 1.22, 95% CI = 1.04–1.43, p = 0.014). Conclusions: MR revealed no significant causal effects of the gut microbiota on the outcomes. However, MR revealed the causal effects of 3-indoleglyoxylic acid on the risk of AITD.

Association Between Hashimoto’s Thyroiditis and Periodontal Disease: A Narrative Review

Objective: This review aims to elucidate the link between Hashimoto’s thyroiditis (HT) and periodontal disease (PD) and to substantiate whether the autoimmune mechanisms involved in the pathogenesis of HT influence the integrity of oral tissues, eventually inducing the development of PD. Methods: The present article is a narrative review that has been composed conforming to the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines on the topic ‘Association between HT and PD’. Results: Eight studies, including four case–control studies, one cross-sectional study, two case reports, and one bidirectional Mendelian randomization study, were cited. These studies were filtered by language (all in English) and relevance to the topic and were sourced from the Google Scholar and PubMed databases. The results suggest a potential link between HT and PD, indicating that HT may have a direct impact on oral tissues. Conclusion: Existing research shows limited but probable evidence associating HT with PD; nevertheless, further large-scale studies with refined methodologies are required to assess this hypothesis and elucidate the precise mechanisms by which HT may contribute to PD pathogenesis.

Thyroid antibodies in Hashimoto's thyroiditis patients are positively associated with inflammation and multiple symptoms.

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. In the present study, 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, respectively. Compared with healthy controls, multiple extrathyroidal symptoms were significantly more serious in HT patients despite euthyroid status, mainly including that related to digestive system (abdominal distension, constipation and diarrhea), endocrine system (chilliness, gain weight and facial edema), neuropsychiatric system (forgetfulness, anxiety, depressed, fatigue, insomnia, irritability, and indifferent) and mucocutaneous system (dry skin, pruritus, and hair loss). Furthermore, 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, diarrhea, chilliness, forgetfulness and fatigue. Moreover, TG-Ab level was positively associated with depressed, insomnia and indifferent. 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.

Association between total vitamin C intake and hypothyroidism among Hashimoto thyroiditis: National Health and Nutrition Examination Survey, 2007-2012.

Oxidative stress may be involved in the progression of hypothyroidism in patients with Hashimoto thyroiditis (HT). Vitamin C is a well-known powerful antioxidant. To our knowledge, whether vitamin C intake relates to hypothyroidism in patients with HT remains unclear. In this cross-sectional study based on the National Health and Nutrition Examination Survey, 2007-2012, we aimed to explore the relationship between total vitamin C intake and hypothyroidism in patients with HT, using multivariate logistic regression models and restricted cubic spline analyses. Our results showed a significant negative linear association between total vitamin C intake (log10-transformed data) and hypothyroidism in HT. Compared with those with the lowest quartile of total vitamin C intake (log10-transformed), participants with the highest quartile were at lower odds of having hypothyroidism (adjusted OR 0·40, 95 % CI: 0·18, 0·88, Ptrend = 0·027). This association was consistent in subgroups stratified by sex (Pfor interaction = 0·084) and age (≥ 60 years and < 60 years, Pfor interaction = 0·330). This study revealed that total vitamin C intake was inversely associated with hypothyroidism among individuals with HT, indicating that higher vitamin C intakes (4·57-1258·9 mg/d) may be associated with a lower likelihood of hypothyroidism among HT participants.

Warthin-like Papillary Thyroid Carcinoma: A Case Report and Review of the Literature.

Warthin-like subtype of papillary thyroid carcinoma (WLPTC) is a rare subtype of papillary thyroid carcinoma. This PTC subtype shows some pattern resemblance to Warthin tumors of the salivary gland, which confers its name but is a not genetically similar to salivary Warthin tumor, with the most frequent genetic change in WLPTC being BRAF p.V600E, the most frequent genetic driver of PTC. Warthin-like subtype of papillary thyroid carcinoma is found to have a favorable prognosis. We report a 44-year-old woman who presented with anterior neck swelling and elevated levels of antithyroid peroxidase antibodies. Fine-needle aspiration cytology showed features of papillary thyroid carcinoma and lymphocytic thyroiditis. On histopathological examination, thyroid follicular cells have oncocytic cytoplasm with infiltration of the tumor and fibrovascular cores by a dense lymphoplasmacytic infiltrate. Numerous multinucleated giant cells in the tumor are a notable feature. The final diagnosis is Warthin-like papillary thyroid carcinoma arising in association with chronic lymphocytic (Hashimoto) thyroiditis. Along with this case report, we perform a literature review of WLPTC between 2010 and 2024.

Predicting lymph node metastasis in papillary thyroid carcinoma with Hashimoto's thyroiditis using regression and network analysis.

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, from January 2020 to December 2021. 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.The regression model indicated that age, calcification, free triiodothyronine (FT3), 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, respectively, 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.

Does Epstein-Barr virus and intracellular Toll-like receptors affect the course of Hashimoto's disease? Findings from studies on newly diagnosed patients.

Epstein-Barr virus (EBV) reactivation is increasingly recognized as a potential exacerbator of autoimmune diseases, including Hashimoto's thyroiditis (HT). This study examined the association between EBV reactivation and intracellular Toll-like receptors (TLRs) expression in newly diagnosed, untreated HT patients. The aim was to determine whether EBV reactivation and specific TLRs (TLR3, TLR7, TLR8, and TLR9) contribute to the pathogenesis and progression of HT. A cohort was 54 newly diagnosed, untreated patients with HT and 20 healthy volunteers (HV). Also, the HV were similarin age and gender. Blood samples were collected to assess EBV viral load and intracellular expression levels of TLR3, TLR7, TLR8, and TLR9 using flow cytometry. Specific anti-EBV antibodies (e.g., VCA IgM, VCA IgG, EBNA-1 IgM, EBNA-1 IgG) were measured to identify signs of EBV reactivation, while soluble TLRs (sTLR3, sTLR7, sTLR8, and sTLR9) were quantified in serum using ELISA. Notably, this study's patients with Hashimoto's thyroiditiswere not euthyroid, as they exhibited significantly lower TSH levels and elevated fT3 and fT4 levels compared to healthy controls. Results showed a significant increase in EBV reactivation among HT patients, with 26 of 54 (48.1%) testing positive for EBV DNA, compared to none in the control group. HT patients with reactivated EBV showed significantly higher levels of intracellular expression of TLR3, TLR7, and TLR9, with TLR3+ cells constituting an average of 4.72% of CD4+ lymphocytes compared to 0.69% in the control group, suggesting a potential synergistic effect. In addition, soluble TLR levels were increased in HT patients with reactivated EBV, suggesting a potential role in potentiating autoimmune responses. These findings highlight the importance of considering both viral reactivation and TLR activity in the treatment of HT. Understanding the interplay between EBV and intracellular TLRs may lead to the development of new therapeutic approaches to mitigate the impact of these factors on disease progression. Further research is warranted to investigate the mechanisms underlying this interaction and its implications for treatment strategies.

Occupational Physical Activity and Regular Exercise Are Inversely Correlated with Thyroid Function in Patients with Hashimoto’s Thyroiditis

Objective: We evaluated correlations of occupational physical activity (OPA) and recreational exercise (RE), respectively, with thyroid function in patients with Hashimoto’s thyroiditis (HT). Methods: We included 438 individuals with clinically diagnosed HT. Information on OPA and RE were collected through a self-report questionnaire. We assessed correlations between clinical phenotypes (TSH, T3, T4, fT4, TgAb, TPOAb, thyroid volume, vitamin D) and physical activities (OPA and RE) in all HT patients (ALL) and in two severity-based subgroups of patients (MILD and OVERT). Results: The main novel findings are significant correlations between increase in OPA and (i) a decrease in fT4 (OVERT, r = −0.265, p = 0.0002 and ALL, r = −0.138, p = 0.006); (ii) an increase in TSH (ALL, r = 0.124, p = 0.014 and OVERT, r = 0.183, p = 0.013) and (iii) an increase in TPOAb antibodies (ALL, r = 0.101, p = 0.045). In contrast, we observed correlations between increase in RE and: (i) a decrease in TSH (OVERT, r = −0.238, p = 0.001); (ii) a decrease in TgAb antibodies (OVERT, r = −0.194, p = 0.01) and (iii) an increase in vitamin D levels (ALL, r = 0.146, p = 0.005 and OVERT, r = 0.173, p = 0.023). Conclusions: Our results suggest that, unlike RE, OPA correlates with decreased thyroid function and increased thyroid autoimmunity. Our study proposes that the PA health paradox also applies for the thyroid health.

Clinicopathological and molecular markers for the identification of Hashimoto’s thyroiditis as a possible predisposing and prognostic factor of papillary thyroid carcinoma

Background: The papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, while Hashimoto’s thyroiditis (HT) is the most common inflam¬matory thyroid disease. The coincidental coexistence or the possible predisposing, protective or aggravating role of HT in the development of PTC have been repeatedly examined. Aim: The aim of the present study was to eval¬uate histopathological and clinical data obtained from pa¬tients with HT, PTC, and PTC+HT so as to investigate the possible association of HT with PTC. Methodology: The study’s cohort consisted of 114 patients (67 PTC, 29 PTC+HT, and 18 HT patients). A full record of their clini¬copathological and clinical laboratory data was followed by extensive statistical analysis in order to reveal possi¬ble correlations between the existence of each disease and various clinicopathological parameters. The study was conducted from 2019 to 2023 at the Hippokration General Hospital of Athens (Greece). Results: A signifi¬cant increase in the levels of thyroid-stimulating hormone (TSH; p=0.031), anti-thyroglobulin antibodies (Anti-Tg; p&lt;0.001), and anti-thyroid peroxidase antibodies (Anti-TPO; p&lt;0.001) was observed in the PTC+HT group. These patients also have smaller tumors (p=0.015) and a younger age of disease onset (p&lt;0.001), while the ma¬jority of PTC+HT patients were women (p=0.023) and had infiltrated lymph nodes (p=0.002). Furthermore, the majority of patients with infiltration of the capsule be¬longed to the PTC+HT group (57.1%; p=0.032). Conclu¬sion: PTC+HT represents a less aggressive clinical state, as good prognostic markers of PTC correlate with the presence of HT. In PTC+HT patients, the PTC tends to have early onset age and the primary tumor is often small, while the majority of PTC+HT patients are women.

Epidemiological, Clinical, Laboratory, and Radiological Characteristics of Children and Adolescents Diagnosed with Hashimoto's Thyroiditis: A Single-Center Experience.

This study aimed to investigate the epidemiological, clinical, laboratory, and radiological characteristics of children diagnosed with Hashimoto's thyroiditis and to present the experiences of a referral center. This study included 200 pediatric patients diagnosed with Hashimoto's thyroiditis between January 2020 and May 2024 at a single center. The data were extracted and compiled from the participants' medical records, including clinical information, physical examination findings, laboratory test results, and radiological imaging. Mean age of the study population was 11.3 ± 3.2 years at diagnosis, with a female predominance. At the time of clinical presentation, 8.5% of the study participants were 6 years of age or younger. The majority of patients, comprising 39.5% of the cohort, exhibited euthyroid thyroid function. Additionally, 33.5% of the patients were classified as having subclinical hypothyroidism, 22% demonstrated overt hypothyroidism, and 5% presented with hyperthyroidism. Approximately one-third of the study participants were referred for further evaluation due to the identification of abnormal thyroid function test results during routine screening examinations. 48% of the patients had a documented family history of thyroid disease. At diagnosis, 39.5% were prepubertal. The rate of overt hypothyroidism was higher in prepubertal patients compared to pubertal patients (41.8% vs. 9.1%, P < .005). Mean gland volume SDS was 2.61 ± 3.69, and 45.5% had goiter. Thyroid nodular lesions were identified in 5.5% of the study participants. Fine-needle aspiration biopsy was performed on five patients, revealing benign findings in three cases and atypia of undetermined significance in the remaining two cases. Patints with subclinical hypothyroidism who have a baseline TSH level exceeding 8.5 mIU/L at initial presentation and do not receive treatment are likely to progress to overt hypothyroidism during subsequent follow-up. Prepubertal cases were more frequently observed compared to previous reports, and the course of hypothyroidism was more severe in prepubertal patients. These findings suggest a potential shift towards earlier onset of autoimmunity in children. Further studies are warranted to substantiate this observation.

Sex-Based Differences in Thyroid Plasma B Cell Infiltration: Implications for Autoimmune Disease Susceptibility.

Thyroid autoimmune diseases, such as Hashimoto's thyroiditis and Graves' disease, are significantly more prevalent in women than in men, suggesting underlying biological differences in immune system function and regulation between sexes. Plasma B cells are crucial in autoimmunity due to their role in producing antibodies targeting self-antigens, but their presence in the thyroids of women without clinical autoimmune diseases remains largely unexplored. This study investigates the infiltration of plasma B cells in female thyroids specifically excluding those with any clinical signs of autoimmune diseases. Using bulk RNA-seq analysis, we identified significant sex differences in gene expression profiles, particularly in genes associated with plasma B cells. Single-cell RNA-seq and spatial transcriptomic analyses further revealed that the CXCL13-CXCR5 signaling axis plays a pivotal role in recruiting and organizing plasma B cells within the thyroid tissue. These findings suggest that the inherent presence of plasma B cells in the female thyroid, driven by CXCL13, may contribute to the higher risk of developing autoimmune thyroid diseases in women. Our study provides new insights into the immune landscape of the thyroid and underscores the importance of understanding sex-specific differences in immune cell distribution and function.

From Phenotype to Molecules: Unveiling the Genetic and Immunological Bridges Between Autoimmune Diseases and Vitiligo.

Vitiligo is an autoimmune disease characterized by the loss of skin pigmentation. This study aims to explore genetic associations between vitiligo and 21 autoimmune diseases using Mendelian randomization (MR) analysis, with a focus on identifying potential risk and protective factors. We performed univariable and multivariable Mendelian randomization analyses to assess the causal associations between 21 autoimmune diseases and vitiligo. Confounding factors, including smoking, alcohol consumption, and Body Mass Index (BMI), were integrated into the multivariable analysis. Strongly associated single nucleotide polymorphisms (SNPs) were mapped to genes, followed by Summary-data-based Mendelian Randomization (SMR) analysis with expression Quantitative Trait Loci (eQTL) and methylation Quantitative Trait Loci (mQTL) data. Risk and protective factors were further identified by evaluating inflammatory mediators and immune cell phenotypes. The MR analysis identified seven autoimmune diseases with potential causal associations with vitiligo. However, after accounting for confounding factors, only Hashimoto's thyroiditis and type 1 diabetes maintained genetic associations with vitiligo. Gene mapping revealed 25 intersecting genes between these two diseases and vitiligo. SMR analysis confirmed Sulfite Oxidase (SUOX) as a protective gene across multiple tissues. Furthermore, several inflammatory factors were identified as risk factors, including C-X-C motif chemokine ligand 9 (CXCL9), C-X-C motif chemokine ligand 10 (CXCL10), Tumor Necrosis Factor (TNF), and Signaling Lymphocytic Activation Molecule (SLAM). In contrast, Osteoprotegerin (OPG) was identified as a protective factor. This study provides novel insights into the shared molecular mechanisms linking vitiligo with other autoimmune diseases. The identification of SUOX as a common protective gene and the discovery of specific inflammatory and immune-related factors may facilitate future therapeutic strategies.

Circulating Autoantibodies in Adults with Hashimoto's Thyroiditis: New Insights from a Single-Center, Cross-Sectional Study.

Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. A cross-sectional study was conducted at the University Hospital "R. Dulbecco" in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients.

Predictors for thyroid dysfunction after discontinuation of levothyroxine in children and adolescents with Hashimoto thyroiditis.

Few data on the clinical course after levothyroxine (L-T4) discontinuation in pediatric patients with Hashimoto thyroiditis (HT) are available. We investigated outcomes and predictors for successful withdrawal from L-T4 among children with HT. Among 168 patients diagnosed with HT between January 2000 and March 2021 at Seoul National University Children's Hospital and in whom L-T4 therapy was initiated during childhood, we attempted to discontinue this therapy in 47, 3 boys and 44 girls. L-T4 was restarted when patients developed overt or subclinical hypothyroidism (thyroid-stimulating hormone [TSH] levels≥10 mIU/L) after L-T4 discontinuation. Median age at discontinuation was 15.4 years (12.7-18.4 years) with a median duration of L-T4 therapy of 47 months (20.3-80.3 months). During the median 30 months of follow-up (10.6-61.0 months) after L-T4 discontinuation, 33 (70.2%) developed thyroid dysfunction. Among these patients, 17 were eventually restarted on L-T4. TSH levels over 50 mIU/L at L-T4 initiation (hazard ratio, HR 3.5, P=0.002), age under 12 years at L-T4 discontinuation (HR 11.1, P=0.0001), and TSH levels higher than the upper 50% of normal (above 2.25 mIU/L in the present study) at L-T4 discontinuation (HR 2.7, P=0.014) were significantly predictive for overt hypothyroidism or subclinical hypothyroidism after L-T4 discontinuation. In addition, age under 12 years at L-T4 discontinuation was only predictive factor for restarting L-T4 medication (HR 4.3, P=0.012). L-T4 discontinuation in pediatric patients with HT resulted in thyroid dysfunction in 70.2% of cases; 36.2% of patients who attempted discontinuation required resumption of L-T4. Older age and lower TSH levels at L-T4 discontinuation were advantageous for successful withdrawal.

The Influence of an Anti-Inflammatory Gluten-Free Diet with EPA and DHA on the Involvement of Maresin and Resolvins in Hashimoto's Disease.

The potential modulation of thyroid inflammatory conditions via a gluten-free diet has been suggested after establishing a link between Hashimoto's thyroiditis (HT) and celiac disease. However, the majority of targeted studies in this field do not support the general recommendation of prescribing a gluten-free diet (GFD) for all HT patients. This study aims to analyze data regarding the impact of a GFD supplemented with eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), along with vegetables, on the course of inflammation involving long-chain fatty acid mediators. The study cohort consisted of 39 Caucasian female patients with autoimmune HT. Metabolite separations were performed using a liquid chromatograph with a DAD detector. Absorption peaks were read at 210 nm for resolvin E1, protectin DX, and maresin 1 and at 302 nm for resolvin D1. The introduction of a gluten-free diet completed with omega-3, including EPA and DHA, may contribute to a reduction in the inflammatory state in HT patients. This effect is supported by the elevation in the levels of anti-inflammatory mediators derived from long-chain fatty acids with anti-inflammatory properties but not by eliminating gluten. Significant statistical changes in the levels of all derivatives were observed before and after the implementation of the diet. It is worth noting that this effect was not observed in anti-TPO and anti-TG levels. The induction of anti-inflammatory changes can be achieved by supplementing the diet with EPA, DHA and vegetables with increased anti-inflammatory potential.

Causal relationship between hypothyroidism and ulcerative colitis: a bidirectional Mendelian randomization study.

Ulcerative colitis (UC) and Hashimoto's thyroiditis frequently cooccur in patients with multiple autoimmune conditions, but the specific association between UC and hypothyroidism is unknown. We used Mendelian randomization (MR) methods to determine the causal relationship between UC and hypothyroidism. We obtained single nucleotide polymorphisms (SNPs) related to ulcerative colitis (UC) and hypothyroidism from genome-wide association studies (GWAS) available in the public database of the Integrated Epidemiology Unit (IEU). To assess the causal relationship between UC and hypothyroidism, we employed MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode methods. Sensitivity analyses were performed using Cochran's Q test, the horizontal pleiotropy test, and the leave-one-out (LOO) method to assess the reliability of the MR data. The genes corresponding to instrumental variables (IVs) were subjected to Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of the Genome (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis to explore the mechanisms behind the causal relationships at the gene level. Forward MR analysis indicated that hypothyroidism was associated with an increased risk of UC (IVW: P = 0.02, OR = 9.71, 95% confidence interval (CI) = 1.36-69.46). In contrast, reverse MR did not demonstrate a causal relationship between UC and hypothyroidism (IVW: P = 0.53). Sensitivity analysis proved the reliability of the results. The PPI network revealed CD247, CD80, and STAT4 as central genes. GO and KEGG analyses revealed significant enrichment of the T cell, gamma interferon (IFN-γ), and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways. Hypothyroidism was a risk factor for UC. The balance of T-cell differentiation played an important role in the process of hypothyroidism-induced UC, and IL-21 might be the key to finding a cure. Enrichment of PD-1/PD-L1 might attenuate inflammation by suppressing the immune action of T cells.

A Real-Life Study in Patients Newly Diagnosed with Autoimmune Hashimoto’s Thyroiditis: Analysis of Asthenia as Admission Complaint

Background: Amid the large panel of autoimmune thyroid diseases, Hashimoto’s thyroiditis (HT) represents a major point across multidisciplinary daily practice. When it comes to the clinical picture, particularly in regard to asthenia (also described as “fatigue” or “decreased energy”), the differential diagnosis is challenging, and a meticulous anamnesis should be backed up by focused lab investigations. Our objective was to analyze the thyroid panel in newly diagnosed patients with HT in relationship with the presence of asthenia as an admission complaint. Methods: This was a retrospective, multi-centric, real-life study conducted in secondary endocrine units (university hospitals) from July 2022 to July 2023. The exclusion criteria were COVID-19 infection; an active malignancy, etc. Results: The cohort (N = 120) included an asthenia group (AS, 49.2%) and a non-AS group of a similar age (49.3 ± 14.7 vs. 47.1 ± 14.8 y, p = 0.426). Headache was more frequent in the AS group (35.6% vs. 18%, p = 0.03). Thyroid function and HT-related antibodies assays were similar between the groups and show no correlation with serum total cholesterol and triglycerides, respectively. TSH levels did not vary among the age sub-groups (p = 0.701). One third of the studied population was affected by hypothyroidism (TSH &gt; 4.5 μIU/mL), being seen at a higher rate in the AS (39%) vs. non-AS group (23%). Total cholesterol positively correlated with the patients’ age (r = 0.180, p = 0.049) and triglycerides (N = 120; r = 0.324, p &lt; 0.001), as found only in the non-AS group (r = 0.246, p = 0.006, respectively, r = 0.319, p &lt; 0.001). Conclusions: The analysis of the AS vs. non-AS group pinpointed the fact that, in regard to daily practice, asthenia as an admission complaint seems less of an indicator of an underlying thyroid dysfunction or a higher level of serum antibodies against thyroid in patients without a full clinical picture of thyrotoxicosis or myxoedema.

Evaluation of spexin levels in euthyroid patients with Hashimoto thyroiditis and its relation to autoimmunity.

Hashimoto thyroiditis (HT) is chronic lymphocytic thyroiditis. Cytokines and chemokines such as tumor necrosis factor-alpha, interferon-gamma, and interleukin-1 beta originating from immune cells are involved in the etiopathogenesis of HT. Spexin (SPX) is a recently identified novel peptide hormone consisting of 14 amino acids and has been demonstrated in follicle epithelial cells in thyroid tissue. SPX has been shown to affect the inflammatory response and play a role in its regulation in various diseases. There is a need for markers for diagnosis and treatment of HT patients with negative antibody levels. We found that there is no study in the literature that investigates the HT and the role of spexin in this inflammatory process. Forty-five patients aged 18 to 70 years with HT or newly diagnosed HT and 42 healthy subjects as the control group were included in the study. Patients in the HT group were divided into 3 categories according to ultrasound findings. Mild heterogeneity was called grade 1 (G1), moderate heterogeneity was called grade 2 (G2), and high heterogeneity was called grade 3 (G3). Laboratory parameters and anthropometric measurements of all patients participating in the study were performed, and SPX was measured by the ELISA method. There was no significant difference between the HT and control groups in terms of SPX levels (P = .27). In HT subgroup analysis, SPX levels were found to be borderline statistically significantly higher in the G2 group, where antibody levels were higher compared to other groups (P = .061). In our study, we evaluated SPX levels in HT patients, which has never been done before in the literature. We found high SPX levels in HT patients with high antibody levels. Multicenter studies with high case series, especially at the tissue level, are needed to fully explain the role of SPX in HT immunoetiopathogenesis and to understand immune-checkpoint pathways more clearly.

Coexistence of Acute Cerebral Infarction and Reversible Posterior Encephalopathy Syndrome in a Patient with Hashimoto's Thyroiditis.

Coexistence of Acute Cerebral Infarction and Reversible Posterior Encephalopathy Syndrome in a Patient with Hashimoto's Thyroiditis.

Low Serum Fibroblast Growth Factor 21 Level and Its Altered Regulation by Thyroid Hormones in Patients with Hashimoto's Thyroiditis on Levothyroxine Substitution.

Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism exerting protection against atherosclerosis by multiple actions on the blood vessels, liver, and adipose tissues. We aimed to investigate serum FGF21 level and its relation to thyroid hormones and metabolic parameters among patients with Hashimoto's thyroiditis (HT). Eighty patients with HT on levothyroxine treatment and eighty-two age- and BMI-matched adults without thyroid disease serving as controls were enrolled. Serum FGF21 concentrations were determined with an enzyme-linked immunosorbent assay. Median serum FGF21 level was significantly lower in HT patients compared with controls (74.2 (33.4-148.3) pg/mL vs. 131.9 (44.8-236.3) pg/mL; p = 0.03). We found a positive correlation between FGF21 and age, triglyceride, total cholesterol, and low-density lipoprotein cholesterol in both groups, while thyroid stimulating hormone and C-reactive protein showed a positive correlation, and thyroxine had an inverse correlation with FGF21 only in control subjects. According to multiple regression analyses, thyroid status is the main predictor of FGF21 in healthy controls, while it is not a significant predictor of FGF21 among HT patients on levothyroxine supplementation therapy. Our results indicate that the physiological role of thyroid function in the regulation of FGF21 synthesis is impaired in HT patients, which may contribute to the metabolic alterations characteristic of HT patients.