Search

Background: Autoimmune thyroid disease (AITD) is induced by various factors, including inheritability, which regulates gene expression. Multiple loci correlated with AITD have been discovered utilizing genome-wide association studies (GWASs). Nevertheless, demonstrating the biological relevance and function of these genetic loci is difficult. Methods: The FUSION software was utilized to define genes that were expressed differentially in AITD using a transcriptome-wide association study (TWAS) method in accordance with GWAS summary statistics from the largest genome-wide association study of 755,406 AITD individuals (30,234 cases and 725,172 controls) and levels of gene expression from two tissue datasets (blood and thyroid). Further analyses were performed such as colocalization, conditional, and fine-mapping analyses to extensively characterize the identified associations, using functional mapping and annotation (FUMA) to conduct functional annotation of the summary statistics of 23329 significant risk SNPs (P < 5 × 10−8) recognized by GWAS, together with summary-databased mendelian randomization (SMR) for identifying functionally related genes at the loci in GWAS. Results: There were 330 genes with transcriptome-wide significant differences between cases and controls, and the majority of these genes were new. 9 of the 94 unique significant genes had strong, colocalized, and potentially causal correlations with AITD. Such strong associations included CD247, TPO, KIAA1524, PDE8B, BACH2, FYN, FOXK1, NKX2-3, and SPATA13. Subsequently, applying the FUMA approach, novel putative AITD susceptibility genes and involved gene sets were detected. Furthermore, we detected 95 probes that showed strong pleiotropic association with AITD through SMR analysis, such as CYP21A2, TPO, BRD7, and FCRL3. Lastly, we selected 26 genes by integrating the result of TWAS, FUMA, and SMR analysis. A phenome-wide association study (pheWAS) was then carried out to determine the risk of other related or comorbid phenotypes for AITD-related genes. Conclusions: The current work provides further insight into widespread changes in AITD at the transcriptomic level, as well as characterized the genetic component of gene expression in AITD by validating identified genes, establishing new correlations, and uncovering novel susceptibility genes. Our findings indicate that the genetic component of gene expression plays a significant part in AITD. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy and safety of 6-weekly and 12-weekly intravenous methylprednisolone (IVMP) regimens in moderate-to-severe, active thyroid-associated orbitopathy (TAO) patients. Basic Procedures: Retrospective comparative study of patients who received IVMP between January 2011 and July 2021 at the Thyroid Eye Clinic, the Chinese University of Hong Kong. Outcome measures included the 7-item clinical activity score (CAS), exophthalmos, extraocular muscle motility (EOMy), marginal reflex distance (MRD), best corrected visual acuity (BCVA), intraocular pressure (IOP), the requirement of additional treatment, and complications. Main findings: A total of 65 (63% (41/65) females) moderate-to-severe, active TAO patients aged 50 ± 13 (25–74) years received 6-weekly (n = 22) or 12-weekly (n = 43) IVMP. Sex, age, smoking status, and Graves' disease status were comparable in the two groups (all p > 0.05). CAS at week 6 (p = 0.0279), 12 (p = 0.00228), and 52 (p = 0.0228) were lower at each time for the 12-weekly group. Exophthalmos improved more at week 6 (p = 0.0453) and 12 (p = 0.0347) in the 12-weekly group. The improvement of diplopia, MRD1, MRD2, and EOMy were comparable between the two groups. More patients in the 6-weekly group (p = 0.00169) required additional treatments including IVMP+/−ORT. Patients in the 6-weekly group who did not require additional treatment had a lower presenting CAS (p = 0.0193) than those who required additional treatment. The total numbers of adverse events were comparable between the two groups. [ABSTRACT FROM AUTHOR]

Background—Purpose: Randomized controlled trials (RCTs) are the cornerstone of evidence-based medicine, yet their quality is often suboptimal. The Consolidated Standards of Reporting Trials (CONSORT) statement is a list of advice to upgrade the quality of RCTs. The aim of this study was the assessment of the quality of RCTs for vitamin D supplements in thyroid autoimmunity according to the revised CONSORT 2010 checklist. Methods: Databases were searched for RCTs involving patients with autoimmune thyroid disorders (AITDs) who received vitamin D supplements published from 2011 to 2021. A list of 37-items was used and adherence ≥75% was considered of optimal quality. The primary outcome was the mean CONSORT adherence of studies. Secondary outcomes were the estimation of compliance per CONSORT item and the examination for possible determinants of the reporting quality. Results: Thirteen eligible trials were finally included. The mean compliance was 61.15% ± 14.86%. Only threeof the studies (23%) achieved a good reporting quality (≥75%), while ten (77%) were presented with inadequate reporting (<75%). Randomization and blinding were mainly poorly reported. Impact Factor (IF) of journal was associated with the reporting quality in the univariate analysis [p = 0.033, OR = 1.65, 95%CI = (1316, 1773)]. Sample size (p = 0.067), number of authors (p = 0.118) and number of citations (p = 0.125) were marginally not significant. None of the factors showed significant results in multivariate analysis. Reporting quality and IF were strongly positively correlated [Pearson's r = 0.740, p = 0.04]. Conclusion: This study shows that mean CONSORT adherence of RCTs for Vitamin D supplementation in AITDs is moderate, reflecting that study quality and transparency could be improved with better adherence to CONSORT rules. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA) genes are associated with more diseases than any other region of the genome. Highly polymorphic HLA genes produce variable haplotypes that are specifically correlated with pathogenically different autoimmunities. Despite differing etiologies, however, many autoimmune disorders share the same risk-associated HLA haplotypes often resulting in comorbidity. This shared risk remains an unanswered question in the field. Yet, several groups have revealed links between gut microbial community composition and autoimmune diseases. Autoimmunity is frequently associated with dysbiosis, resulting in loss of barrier function and permeability of tight junctions, which increases HLA class II expression levels and thus further influences the composition of the gut microbiome. However, autoimmune-risk-associated HLA haplotypes are connected to gut dysbiosis long before autoimmunity even begins. This review evaluates current research on the HLA-microbiome-autoimmunity triplex and proposes that pre-autoimmune bacterial dysbiosis in the gut is an important determinant between autoimmune comorbidities with systemic inflammation as a common denominator.

Introduction: Vulvar lichen sclerosus (VLS), a chronic inflammatory skin disorder, often coexists with autoimmune thyroid disease (AITD). VLS presents with subtle symptoms including vulvar itching and discomfort. Clinically, a “Figure 8” pattern involving the labia minora, clitoral hood, and perianal region is often observed. It is prevalent both in pre-pubertal girls and women aged 40–60, and the link between VLS and AITD remains unclear, with proposed causes including autoimmune, hormonal or genetic factors, and environmental triggers. This study addresses the lack of research on the association in children, aiming to investigate the largest group of underage girls to date. Aim: This study aimed to investigate the coexistence of thyroid autoimmune diseases in girls diagnosed with vulvar lichen sclerosus (VLS) and to assess the presence of antibodies for specific thyroid autoimmune diseases. Materials and Methods: Our study was conducted from July 2020 to February 2021, involving a sample of 55 girls aged 2–18 years old, all free from systemic diseases. The study group comprised 20 girls previously diagnosed with vulvar lichen sclerosus (VLS), while the control group included 35 girls without VLS. Legal guardians completed questionnaires detailing the medical history of their children. Blood samples were collected from all participants and subjected to biochemical analysis. The presence of human IgG antibodies against thyroid peroxidase and IgG antibodies against thyroglobulin was assessed using the immunoenzymatic method with commercially available ELISA kits. Results: In the study group, common symptoms included itching, soreness, burning sensation, excoriation, and erythema or pallor of the skin and perineal mucosa. An evaluation of anti-thyroglobulin and anti-thyroid peroxidase antibodies revealed no statistical significance between the study and control groups (anti-TG p = 0.379, anti-TPO p = 0.96). Family history of autoimmune diseases showed no significant correlation with anti-thyroid antibodies in girls. Although no significant relation between VLS occurrence and antibody levels was found, it emphasizes the need for multidisciplinary medical care. Further research with larger patient groups is necessary.

There is limited data on hypotheses linking autoimmune thyroid diseases (AITD) and hypothyroidism with pulmonary hypertension (PH). Moreover, the prevalence of this coincidence, as well as the possible common pathogenic mechanisms, are even less explicit in paediatric population. We present a review of recently published articles regarding relatively large cohorts of children with PH, coming from paediatric PH registries, aiming to clarify the coincidence of PH and AITD, especially hypothyroidism, and discuss its possible mutual impact. Although thyroid disorders have been excluded from the latest PH classification, it is still important to remember the possibility of this coincidence as it may significantly influence patients’ clinical outcome. Moreover, children with PH may need multidisciplinary care due to the relatively frequent coexistence with not only hormonal abnormalities but also growth impairment, genetic disorders, and mental delay. Further specific paediatric studies are needed to improve the care in this rare disease, especially in patients with other comorbidities present.

Background: Autoimmune thyroid disease (AITD) is an inflammatory condition that primarily affects women between the ages of 30 and 50. It has been hypothesised that AITD causes salivary glands to produce less saliva due to its endocrine effects. Studies showing the effect of AITD on salivary glands are very scarce. The aim of this study was to compare AITD patients with controls who were of a similar age and gender in terms of salivary metrics and the prevalence of dental caries. Methods: 200 subjects in Bangalore city (100 AITD subjects and 100 healthy subjects as controls) participated in a cross-sectional study. Subjective oral dryness was assessed using Farsi’s criteria. Salivary parameters and caries were assessed using GC Saliva-Check BUFFER kit and WHO caries criteria respectively. Descriptive and analytical statistics were done. Significant data was defined as a p value of Results: When compared to controls, the AITD group had substantially more subjective mouth dryness and dental caries. Unstimulated (USFR) and stimulated salivary flow rate (SFR), pH and buffering capacity were reduced in AITD group whereas viscosity was high. There was a significant negative correlation between USFR, SFR, subjective oral dryness and dental caries. In a linear regression, there was no association between age, gender, socioeconomic status (SES), thyroid stimulating hormone (TSH), salivary viscosity, pH, buffering capacity and dental caries. Dental caries, USFR and SFR demonstrated a substantial relationship. Conclusions: The present research may indicate an underlying association between thyroid and salivary gland dysfunction resulting in oral dryness and high dental caries experience.

Abstract Background Rheumatoid arthritis (RA) is one of the most common chronic non-organ-specific autoimmune diseases; meanwhile, autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disease that can lead to hypo or hyperthyroidism. Although the etiology of both diseases is complex with a combination of genetic and environmental factors, there are overlaps in genes contributing to the pathogenesis of both diseases. Numerous studies found a correlation between thyroid abnormality and RA in different populations, yet some didn’t. This study is aimed to evaluate the prevalence of thyroid dysfunction, AITD, and anti-thyroid peroxidase (anti-TPO) positively in Iranian patients with RA. Methods A total of 250 RA patients and 248 patients with non-inflammatory rheumatologic disease were included in this case–control study. All participants underwent complete clinical and laboratory assessments. Participants were also assessed for thyroid function testing, including anti-TPO antibodies. Results Thyroid dysfunction was twice as common in RA patients as in controls (OR = 2.16; P-value > 0.001). Overt hypothyroidism was the most common thyroid dysfunction among RA patients (58 out of 84). Anti-TPO positivity was also significantly more common in RA compared with controls (OR = 2.65; P-value > 0.001). The proportion of controls and RA patients with AITD were 9 and 21.5%, respectively. AITD was found 2.8 times more common in RA group than controls (OR = 2.77; P-value > 0.001). Conclusion It was demonstrated that RA was an independent factor associated with thyroid dysfunction and AITD.

Abstract Background Autoimmune thyroiditis (AIT) is the most common thyroid pathology in pediatric patients among which Hashimoto’s thyroiditis has the highest prevalence. Along with size, measuring mechano-acoustic tissue elasticity is evolving as an important parameter in the evaluation of diffuse thyroid pathology. This study aims to investigate the role of shear wave elastography (SWE) in the diagnosis of autoimmune thyroid disease (AITD) in the pediatric population and also compare the elasticity between them and healthy individuals. Results This case–control analytical study was carried out on 64 pediatric subjects ranging in age from 7 to 17 years. All the cases were diagnosed as AIT by anti-thyroid antibodies, and their thyroid function was evaluated by thyroid hormones. We performed thyroid Ultrasonography and Shear wave elastography. Patients with AIT had significantly higher elasticity values (35.6 kPa, IQR 8.43–103.7 kPa) than the control group (9.35 kPa, IQR 5.73–13.21 kPa). There was no correlation of elasticity values of thyroid gland in patients with AIT with autoantibodies and thyroid function test, respectively. The cutoff value for elasticity was 12.317 kPa with sensitivity and specificity of 96.9% and 100%, respectively. Conclusions SWE is a highly sensitive imaging method integrating routine ultrasonography in the diagnosis of AITD which estimates the extent of fibrosis in numerical value.

A large body of evidence indicates that women with polycystic ovary syndrome (PCOS) have a higher risk of developing Hashimoto’s thyroiditis (HT) than healthy individuals. Given the strong genetic impact on both diseases, common predisposing genetic factors are possibly involved but are not fully understood. Here, we performed whole-exome sequencing (WES) for 250 women with sporadic PCOS, HT, combined PCOS and HT (PCOS+HT), and healthy controls to explore the genetic background of the joint occurrence of PCOS and HT. Based on relevant comparative analyses, multivariate logistic regression prediction modeling, and the most informative feature selection using the Monte Carlo feature selection and interdependency discovery algorithm, 77 variants were selected for further validation by TaqMan genotyping in a group of 533 patients. In the allele frequency test, variants in RAB6A, GBP3, and FNDC7 genes were found to significantly (padjusted < 0.05) differentiated the PCOS+HT and PCOS groups, variant in HIF3A differentiated the PCOS+HT and HT groups, whereas variants in CDK20 and CCDC71 differentiated the PCOS+HT and both single disorder groups. TaqMan genotyping data were used to create final prediction models, which differentiated between PCOS+HT and PCOS or HT with a prediction accuracy of AUC = 0.78. Using a 70% cutoff of the prediction score improved the model parameters, increasing the AUC value to 0.87. In summary, we demonstrated the polygenic burden of both PCOS and HT, and many common and intersecting signaling pathways and biological processes whose disorders mutually predispose patients to the development of both diseases.

Background: Autoimmune thyroid disease (AITD) is an inflammatory condition that primarily affects women between the ages of 30 and 50. It has been hypothesised that AITD causes salivary glands to produce less saliva due to its endocrine effects. Studies showing the effect of AITD on salivary glands are very scarce. The aim of this study was to compare AITD patients with controls who were of a similar age and gender in terms of salivary metrics and the prevalence of dental caries. Methods: 200 subjects in Bangalore city (100 AITD subjects and 100 healthy subjects as controls) participated in a cross-sectional study. Subjective oral dryness was assessed using Farsi’s criteria. Salivary parameters and caries were assessed using GC Saliva-Check BUFFER kit and WHO caries criteria respectively. Descriptive and analytical statistics were done. Significant data was defined as a p value of

IntroductionVitamin D insufficiency is a global health problem affecting healthy and diseased individuals, including patients with Hashimoto’s thyroiditis (HT). Identifying dietary factors that may affect vitamin D levels and providing dietary guidelines accordingly can alleviate this problem. We therefore aimed to identify still unknown associations of dietary patterns, assessed through the Food Frequency Questionnaire (FFQ) with vitamin D blood levels.Materials and methodsFFQ was collected from 459 patients from Croatian Biobank of Patients with Hashimoto’s thyroiditis (CROHT), while total 25(OH)D was measured from their stored serum samples. We performed linear regression analysis between vitamin D levels and weekly intake of 24 food groups in 459 patients with HT (ALL), and in two disease-severity groups (MILD and OVERT).ResultsThe main results of our study are observations of: (1) an inverse association between vitamin D levels and coffee consumption (ALL: β = −0.433, p = 0.005; OVERT: β = −0.62, p = 0.008); (2) an inverse association between vitamin D levels and sweets consumption (ALL: β = −0.195, p = 0.034; OVERT: β = −0.431, p = 0.006); (3) positive association between vitamin D levels and vegetable consumption (ALL: β = 0.182, p = 0.019; OVERT, β = 0.311, p = 0.009). Importantly, effect sizes of all three associations were more prominent in HT patients with prolonged and more severe disease (OVERT).ConclusionFurther research into the functional and causal relationships of the observed associations is important to provide guidance regarding coffee/sugar intake on vitamin D status. A well-balanced diet can help prevent vitamin D deficiency and improve the quality of life of patients with HT, especially those in later stages of disease characterized by greater metabolic imbalance.

Autoimmune thyroid disease (AITD) is typified by Graves' disease (GD) and Hashimoto's thyroiditis (HT) at both ends of the disease spectrum with subclinical thyroid dysfunctions in between. Genetic associations have been described in the pathogenesis of AITD. We describe a case each of GD and HT occurring in two siblings.

Background: Autoimmune thyroid disease (AITD) is the commonest autoimmune disease. Although viewed as a classic form of single-organ autoimmunity, AITD is increasingly associated with non-thyroid sequelae including musculoskeletal manifestations and chronic pain syndromes. However, large population-based studies are needed. Objectives: To examine the relationships between chronic hand pain and the AITD autoantibodies, anti-thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb), in the Third National Health and Nutrition Examination Survey (NHANES III). Design: This is a cross-sectional study. Methods: We examined data from NHANES III on 4820 persons aged 60 years or older with respect to hand pain and its association with TPOAb and TgAb. Log-binomial regressions were fit to examine the associations between the anti-thyroid autoantibodies and hand pain. Results: Positive TPOAb was associated with a higher prevalence of hand pain than negative TPOAb [prevalence ratio (PR) = 1.158, p = 0.048] in the unadjusted model. This association was no longer significant after controlling for age, body mass index, gender, and diabetes (p = 0.313). When positive TPOAb was considered as a categorical variable with four levels, the highest quartile was associated with hand pain in the unadjusted (PR = 1.489, p = 0.005) and adjusted models (PR = 1.325, p = 0.042). There was no significant association between TgAb and hand pain when covariates were controlled for. Conclusion: TPOAb may be associated with the presence of chronic hand pain in persons aged over 60 years, especially at higher serum levels. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is a dermatological disorder characterized by functional melanocyte loss, affecting 1% of the global population. The prevalence and impact of thyroid hormone and autoantibody levels on pediatric patients with vitiligo remain unclear. Aim: This study aims to assess the incidence of autoimmune thyroid disorder in pediatric vitiligo patients and investigate the impact of thyroid hormone and autoantibody levels on vitiligo activity. Subjects and Methods: A total of 68 children with vitiligo participated in this cross-sectional study, which included measurements of thyroid function, autoantibody tests, and examinations of the patients' vitiligo type, duration, activity, and onset. Results: Autoimmune thyroiditis was detected in 33.8% of patients. Positive anti-thyroglobulin antibodies were significantly associated with a family history, duration, and activity of vitiligo. Positive anti-thyroid peroxidase antibodies were significantly related to active vitiligo, sudden onset, and higher TSH levels. Anti-thyroglobulin antibodies correlated positively with age, duration, and TSH levels but negatively with T3 and T4 levels. Anti-thyroid peroxidase antibodies were positively correlated with TSH. Positive anti-thyroglobulin antibodies extended disease duration. Active vitiligo and rapid onset were more frequent with positive anti-thyroid peroxidase antibodies. Conclusions: This study concluded that pediatric vitiligo patients, particularly females and those with a family history of autoimmune diseases, have a higher frequency of thyroid dysfunction and autoantibodies. Moreover, regular monitoring of thyroid function and autoantibodies among pediatric patients with vitiligo is important to detect progression to overt hypothyroidism. Consequently, practitioners should recognize and treat thyroid-related conditions early and be aware of the relationship between vitiligo and autoimmune thyroid disease. [ABSTRACT FROM AUTHOR]

Context: Occurrence of Graves' disease (GD) has been reported following SARS-CoV-2 vaccine administration, but little is known about thyroid eye disease (TED) after SARS-CoV-2 vaccination. Objective: We describe 2 cases of TED activation following mRNA SARS-CoV-2 vaccination and review additional cases reported in the literature. Methods: We report 2 cases of TED activation following SARS-CoV-2 vaccination: 1 case of TED worsening in a patient with GD, and 1 of de novo active TED progressing to dysthyroid optic neuropathy in a patient with a history of Hashimoto hypothyroidism. Our literature search revealed 8 additional reported TED cases associated with SARS-CoV-2 vaccination until June 2022. We review the characteristics, duration, and management of TED following SARS-CoV-2 vaccination in these cases. Results: Of all 10 reported TED cases following SARS-CoV-2 vaccination, 4 developed new-onset TED and 6 previously stable TED cases experienced significant deterioration. Six patients had known GD and 2 patients had Hashimoto thyroiditis. Two cases progressed to dysthyroid optic neuropathy, 6 had moderate/severe active disease, and 2 had mild disease that did not require treatment. Seven TED cases received teprotumumab and had a favorable response, 2 of whom had prior limited response to initial prednisone or methylprednisolone and tocilizumab therapy. Conclusion: New diagnosis or deterioration of TED after mRNA SARS-CoV-2 vaccination can occur, with most cases described in patients with underlying autoimmune thyroid disease. Our report raises awareness to this potential complication to promote early recognition and prompt management of TED associated with mRNA SARS-CoV-2 vaccines. Further studies are needed to explore the mechanism, risk factors, prevention, and treatment of TED following mRNA SARS-CoV-2 vaccination. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid dysfunctions associated with SARS-CoV-2 acute infection have been extensively described since the beginning of COVID-19 pandemics. Conversely, few data are available on the occurrence of thyroid autoimmunity after COVID-19 resolution. We assessed the prevalence of autoimmune thyroid disease (ATD) and thyroid dysfunctions in COVID-19 survivors three months after hospital admission. Design and methods: Single-center, prospective, observational, cohort study performed at ASST Papa Giovanni XXIII Hospital, Bergamo, Italy. 599 COVID-19 survivors were prospectively evaluated for thyroid function and autoimmunity thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb). When a positive antibody concentration was detected, thyroid ultrasound was performed. Multiple logistic regression model was used to estimate the association between autoimmunity and demographic characteristics, respiratory support, and comorbidities. Autoimmunity results were compared to a cohort of 498 controls referred to our Institution for non-thyroid diseases before the pandemic onset. A sensitivity analysis comparing 330 COVID-19 patients with 330 age and sex-matched controls was performed. Results: Univariate and multivariate analysis found that female sex was positively associated (OR 2.01, SE 0.48, p = 0.003), and type 2 diabetes (T2DM) was negatively associated (OR 0.36, SE 0.16, p = 0.025) with thyroid autoimmunity; hospitalization, ICU admission, respiratory support, or COVID-19 treatment were not associated with thyroid autoimmunity (p > 0.05). TPOAb prevalence was greater in COVID-19 survivors than in controls: 15.7% vs 7.7%, p = 0.002. Ultrasonographic features of thyroiditis were present in 94.9% of the evaluated patients with positive antibodies. TSH was within the normal range in 95% of patients. Conclusions: Autoimmune thyroid disease prevalence in COVID-19 survivors was doubled as compared to age and sex-matched controls, suggesting a role of SARS-CoV-2 in eliciting thyroid autoimmunity. [ABSTRACT FROM AUTHOR]

The role of vitamin D (VD) in the etiopathogenesis of autoimmune diseases (AI) is extensively studied. However, its association with autoimmune thyroid disease (AITD) is still controversial. AIM of this study was to assess the relationship between the vitamin D status and thyroid autoimmunity in Slovak premenopausal women with newly diagnosed AITD. SUBJECTS AND METHODS: This prospective case-control study included 57 women with AITD and 41 age- and BMI-matched controls. All subjects were examined for summer and winter serum 25(OH)D, thyroid autoantibodies (a-TPO, a-TG), freeT4 and TSH concentrations. Thyroid volume was measured by ultrasound. RESULTS: There were no significant differences in serum 25(OH)D between AITD and control groups. No significant correlation between 25(OH)D and thyroid autoantibodies was found either in the whole cohort or in AITD women. The prevalence of vitamin D insufficiency was 60.31 % in AITD women and 52.5 % in the control group. No significant association between VD and thyroid autoantibodies, thyroid hormones and thyroid volume was detected in this study. CONCLUSION: Authors conclude that VD insufficiency is common in Slovak premenopausal women independently of the presence of AITD. Vitamin D insufficiency is not associated with thyroid autoimmunity in patients with early diagnosis of AITD. [ABSTRACT FROM AUTHOR]

Background: Autoimmune thyroid disease (AITD) manifests with a female predominance, and much attention has been directed towards the integral membrane protein 2 A (ITM2A) gene located on the X chromosome. Methods: In a study of 166 pediatric patients with autoimmune thyroid disease (AITD), the ITM2A rs1751094 single‐nucleotide polymorphism (SNP) was genotyped. The sample comprised 143 females and 23 males, with 67 patients diagnosed with Hashimoto chronic thyroiditis (HD) and 99 with Graves' disease (GD). In the 99 GD patients, 49 (49.5%) exhibited thyroid‐associated ophthalmopathy (TAO). Among the 85 GD patients, 70.6% (60/85) were considered intractable GD. The results were compared to those from 198 healthy Korean individuals, including 97 females and 101 males. Results: The frequency of the rs1751094 C allele and CC/AC genotype were higher in AITD, GD and HD patients compared to controls, while the frequency of the A allele and AA genotype were lower. The results were more pronounced in female AITD and GD patients compared to male patients. The association was also found in intractable GD and TAO patients. Target SNP fits Hardy–Weinberg equilibrium. Conclusions: These findings indicate that the ITM2A gene polymorphism on the X chromosome may contribute to the immunological basis of female‐predominant AITD in Korean children. [ABSTRACT FROM AUTHOR]

Environmental endocrine disrupting chemicals (EDC) are widespread in people’s production and living environment. Due to a wide variety of endocrine disruptors, they not only interfere with human reproductive system, nervous system and immune system, but also exert a non⁃negligible influence on the thyroid, which is the largest endocrine organ in the body. The previous studies mostly focused on thyroid hormone and histopathology, and few reports were available on the associations between autoimmune thyroid diseases (AITD) or thyroid cancer (TC) and EDC. Therefore, the current review elucidates the potential adverse effects of EDC on thyroid, especially in autoimmune thyroid diseases and thyroid cancer, including induction of thyroid autoantibodies and the effect on T cell differentiation, etc., which may provide a basis for the study of the potential environmental exposure risk factors of autoimmune thyroid diseases and thyroid cancer, and has positive significance on prevention and treatment of these diseases. [ABSTRACT FROM AUTHOR]

Background: Little is known about the association between juvenile idiopathic arthritis (JIA) and autoimmune thyroid disease (AITD) and therefore there are no indications for AITD screening in this population, which is possible using standard blood tests. The objective of this study is to determine the prevalence and predictors of symptomatic AITD in JIA patients from the international Pharmachild registry. Methods: Occurrence of AITD was determined from adverse event forms and comorbidity reports. Associated factors and independent predictors for AITD were determined using univariable and multivariable logistic regression analyses. Results: The prevalence of AITD after a median observation period of 5.5 years was 1.1% (96/8965 patients). Patients who developed AITD were more often female (83.3% vs. 68.0%), RF positive (10.0% vs. 4.3%) and ANA positive (55.7% vs. 41.5%) than patients who did not. AITD patients were furthermore older at JIA onset (median 7.8 years vs. 5.3 years) and had more often polyarthritis (40.6% vs. 30.4%) and a family history of AITD (27.5% vs. 4.8%) compared to non-AITD patients. A family history of AITD (OR = 6.8, 95% CI: 4.1 – 11.1), female sex (OR = 2.2, 95% CI: 1.3 – 4.3), ANA positivity (OR = 2.0, 95% CI: 1.3 – 3.2) and older age at JIA onset (OR = 1.1, 95% CI: 1.1 – 1.2) were independent predictors of AITD on multivariable analysis. Based on our data, 16 female ANA positive JIA patients with a family history of AITD would have to be screened during ±5.5 years using standard blood tests to detect one case of AITD. Conclusions: This is the first study to report independent predictor variables for symptomatic AITD in JIA. Female ANA positive JIA patients with positive family history are at increased risk of developing AITD and thus might benefit from yearly serological screening. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid disease (AITD), including Graves' disease (GD) or Hashimoto's thyroiditis (HT), occurs due to genetic susceptibility and environmental factors, among which the role of stressful events remains controversial. This study investigated the relationship between the number and impact of stressful life events in AITD patients with selenium status, and the Th1/Th2/Th17 immune response. The study population included three groups: HT (n = 47), GD (n = 13), and a control group (n = 49). Thyroid function parameters, autoantibody levels, and the plasma levels of cytokines, selenium, selenoprotein P (SeP), and glutathione peroxidase 3 (GPx) activity were measured. Participants filled out the Life Experiences Survey. No significant differences in the number of stressful life events were found among the patients with HT, GD, and the controls. A higher (median (interquartile range)) negative stress level (8 (4–12)) than a positive stress level (3 (1–9)) was found in the HT group. The HT group showed a correlation between SeP and the positive stress level: rs = −0.296, p = 0.048, and the GD group between GPx and the negative stress level (rs = −0.702, p = 0.011). Significant positive correlations between thyroid peroxidase antibody level and the total number of major life events (p = 0.023), the number of major life events in the last 7–12 months, and the number of major life events with no impact and a negative stress level were found. We suggest that the measurements of Th2-related cytokines and selenoproteins could be used as biomarkers for the development of AITD in cases where stress is considered a component cause of the pathogenic mechanism of the disease. [ABSTRACT FROM AUTHOR]

To explore the role of gut microbiota in Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Seventy fecal samples were collected, including 27 patients with GD, 27 with HT, and 16 samples from healthy volunteers. Chemiluminescence was used to detect thyroid function and autoantibodies (FT3, FT4, TSH, TRAb, TGAb, and TPOAb); thyroid ultrasound and 16S sequencing were used to analyze the bacteria in fecal samples; KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (Clusters of Orthologous Groups) were used to analyze the functional prediction and pathogenesis. The overall structure of gut microbiota in the GD and HT groups was significantly different from the healthy control group. Proteobacteria and Actinobacteria contents were the highest in the HT group. Compared to the control group, the GD and HT groups had a higher abundance of Erysipelotrichia, Cyanobacteria, and Ruminococcus_2 and lower levels of Bacillaceae and Megamonas. Further analysis of KEGG found that the “ABC transporter” metabolic pathway was highly correlated with the occurrence of GD and HT. COG analysis showed that the GD and HT groups were enriched in carbohydrate transport and metabolism compared to the healthy control group but not in amino acid transport and metabolism. Our data suggested that Bacillus, Blautia, and Ornithinimicrobium could be used as potential markers to distinguish GD and HT from the healthy population and that “ABC transporter” metabolic pathway may be involved in the pathogenesis of GD and HT.

Dissection of the cervical arteries is the leading cause of stroke in young adults, yet the aetiology and pathogenesis of this event remain unclear. However, a growing number of data in the literature support the potential implications of immunological mechanisms in the pathogenesis. Several large patient groups and multicentre cohorts have reported significant associations with recent infections and elevated inflammatory markers. There are also several case reports and case series suggesting an association with various autoimmune disorders and viral infections. Some case reports have also detailed cervical artery dissections linked to the use of biological therapies for other pathologies. In the present case, a 38-year-old female patient with triple spontaneous cervical artery dissection presented multiple potential trigger factors as recent infection, autoimmune thyroid disease, primary thrombophilia and hyperhomocysteinemia. This report sought first presents this case, and then reviews the existing relevant literature data regarding the potential immunological mechanisms implicated in the pathogenesis of cervical artery dissection.

Abstract Background Relapsing polychondritis (RP) is a rare inflammatory disease characterized by recurrent inflammation and destruction of cartilaginous tissues. RP has characteristics of autoimmune disease and some reports have noted co-occurrence with autoimmune thyroid disease (AITD), consisting of Graves’ disease (GD) and Hashimoto thyroiditis (HT). However, there have been no detailed studies on the co-occurrence of RP and AITD. In this study, we aimed to determine whether patients with RP tend to be complicated with AITD. We also analyzed the clinical and genetic profiles of patients in whom these diseases co-occur. Methods We recruited 117 patients with RP and reviewed their medical records. Furthermore, we genotyped Human Leucocyte Antigen (HLA)-A, B Cw, DRB1, DQB1, and DPB1 alleles for 93 of the 117 patients. The prevalence of AITD among the patients with RP was compared with that among the general Japanese population. We also analyzed the clinical and genetic features of the patients with both RP and AITD. Results The prevalence of GD among the patients with RP was 4.3% (5 among 117 patients), significantly higher than that among Japanese (0.11%) (p = 2.44 × 10–7, binomial test). RP patients with GD tended to have nasal involvement (p = 0.023) (odds ratio (OR) 2.58) and HLA-DPB1*02:02 (p = 0.035, OR 10.41). We did not find significant enrichment of HT in patients with RP. Conclusions Patients with RP appear to be at elevated risk of GD. Nasal involvement and HLA-DPB1*02:02 characterize the subset of RP patients with GD, which may guide attempts to characterize a distinct subtype of RP for precision medicine.

• Heterogeneity of integrin expressed on B cells in thyroid and circulation in AITD. • Circulating α4β7+ and α4β1+ B cells correlate with thyroid function and TSI in GD. • Intrathyroidal α4β1+ B cells exhibit positive association with TSH levels in HT. • Intrathyroidal α4β7+ B cells and α4β1+ B cells correlate with elevated zonulin in HT. Integrins are upregulated on endothelial cells and T-lymphocytes in autoimmune thyroid disease (AITD), potentially contributing to immune response localization. The role of integrins on B-cells in AITD remains unclear. Peripheral blood samples were collected from healthy controls (n = 56), patients with Graves' disease (GD) (n = 37) and Hashimoto's thyroiditis (HT) (n = 52). Ultrasound-guided fine-needle aspiration (FNA) of the thyroid was performed in patients with non-autoimmune thyroid disease (nAITD) (n = 19), GD (n = 11), and HT (n = 40). Integrins α4β7, α4β1, and αEβ7 in B cells were measured by flow cytometry. Serum zonulin levels were quantified via ELISA. Associations of integrins on B cells with thyroid hormones, thyroid autoantibodies, AITD duration, and zonulin were analyzed. HT patients exhibited lower α4β7 and higher α4β1 expression on B cells compared to healthy controls and GD patients. While α4β7 was predominant on circulating B cells, the dominant integrin expressed on intrathyroidal B cells varied with specific thyroid diseases. In GD patients, α4β7 and α4β1 expression on circulating B cells correlated positively and negatively with thyroid function and thyroid stimulating immunoglobulins (TSI) levels, respectively. Intrathyroidal α4β1+ B cells positively correlated with TSH levels in HT patients. Additionally, serum zonulin was elevated in HT patients, and intrathyroidal α4β7+ B cells and α4β1+ B cells correlated negatively and positively with zonulin levels, respectively. Integrin αEβ7 on B cells showed no significant association with AITD. Integrins expressed on B cells potentially play a role in the pathogenesis of AITD and might serve as immune biomarkers for the disease. [ABSTRACT FROM AUTHOR]

Recent studies have confirmed that B cell-related genes CD20 and FCRL5 may be involved in the pathogenesis of autoimmune thyroid diseases (AITDs). However, there is a lack of comprehensive genetic susceptibility studies on this subject. The purpose of this study was to investigate the relationship of CD20 and FCRL5 gene polymorphisms with AITD susceptibility. A total of 1740 subjects were recruited from the Chinese Han population. They consisted of 1007 patients with AITD and 633 healthy controls. Multiplex polymerase chain reaction (PCR) combined with high-throughput sequencing was used to genotype four screened single nucleotide polymorphisms (SNPs). The four SNPs were rs7126354 of CD20 and rs6667109, rs6692977 and rs3811035 of FCRL5. The minor allele frequency of rs7126354 was significantly lower in patients with AITD and Hashimoto's thyroiditis (HT) than in healthy controls (P = 0.031; P = 0.017). The minor allele frequency of rs6667109 was significantly higher in the Graves' disease (GD) subgroup than in the healthy control group (P = 0.029). In the Log-additive model, rs6667109 in the GD group also showed an increased risk of onset disease. This study presents robust evidence of a genetic association of CD20 and FCRL5 with AITDs. The C allele of CD20 rs7126354 is a protective factor for HT susceptibility. The A allele of FCRL5 rs6667109 is a risk factor for the susceptibility to GD. [ABSTRACT FROM AUTHOR]

The association between thyroid function and viral pneumonia has undergone extensive examination, yet the presence of a causal link remains uncertain. The objective of this paper was to employ Two-Sample Mendelian Randomization (MR) analysis to investigate the connections between three thyroid diseases and thyroid hormone indicators with viral pneumonia and COVID-19. We obtained summary statistics datasets from seven genome-wide association studies (GWASs). The primary method used for estimating relationships was inverse-variance weighting (IVW). In addition, we employed weighted median, weighted mode, MR-Egger, and MR-PRESSO as supplementary analytical tools. Sensitivity analyses encompassed Cochran’s Q test, MR-Egger intercept test, and MR-PRESSO. Our study revealed significant causal relationships between having a genetic predisposition to autoimmune thyroid disease (AITD) and an increased susceptibility to viral pneumonia (odds ratio [OR]: 1.096; 95% confidence interval [CI]: 1.022–1.176). Moreover, it demonstrated a heightened susceptibility and severity of COVID-19 (OR for COVID-19 susceptibility, COVID-19 hospitalization, and COVID-19 critical illness, with 95% CIs of 1.016, 1.001–1.032; 1.058, 1.003–1.116; 1.045, 1.010–1.081). However, no statistically significant associations were found between TSH, FT4, subclinical hypo- or hyperthyroidism, and the risk of viral pneumonia incidence, or the susceptibility and severity of COVID-19 (all p > 0.05). This study establishes a cause-and-effect relationship between AITD and the development of viral pneumonia, as well as the susceptibility and severity of COVID-19.

Hashimoto’s thyroiditis (HT) is an autoimmune disruption manifested by immune cell infiltration in thyroid tissue and the production of antibodies against thyroid-specific antigens, such as the thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb). TPOAb and TGAb are commonly used in clinical tests; however, handy indicators of the diagnosis and progression of HT are still scarce. Extracellular proteins are glycosylated and are likely to enter body fluids and become readily available and detectable biomarkers. Our research aimed to discover extracellular biomarkers and potential treatment targets associated with HT through integrated bioinformatics analysis and clinical sample validations. A total of 19 extracellular protein-differentially expressed genes (EP-DEGs) were screened by the GSE138198 dataset from the Gene Expression Omnibus (GEO) database and protein annotation databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE, and Cytohubba were used to construct a protein–protein interaction (PPI) network and screen key EP-DEGs. Six key EP-DEGs (CCL5, GZMK, CXCL9, CXCL10, CXCL11, and CXCL13) were further validated in the GSE29315 dataset and the diagnostic curves were evaluated, which all showed high diagnostic accuracy (AUC > 0.95) for HT. Immune profiling revealed the correlation of the six key EP-DEGs and the pivotal immune cells in HT, such as CD8+ T cells, dendritic cells, and Th2 cells. Further, we also confirmed the key EP-DEGs in clinical thyroid samples. Our study may provide bioinformatics and clinical evidence for revealing the pathogenesis of HT and improving the potential diagnosis biomarkers and therapeutic strategies for HT.

Ye Hu,1 Jia Zheng,2 Xiao Ye,1 Yingxiang Song,1 Xiaohong Wu1 1Department of Health Management Center, Endocrinology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Xiaohong Wu, Tel/Fax +86-579-85893937, Email drxhwu@163.comObjective: Obesity and autoimmune thyroid disease (AITD) are both common disorders in the general population, which are major drivers for adverse medical conditions. While an interaction between thyroid function and visceral obesity is thought to exist, but very few studies have examined the relationship between AITD and visceral obesity, especially in the patients with type 2 diabetes mellitus (T2DM). In the present study, we investigated the association between elevated thyroid peroxidase antibody (TPOAb) titer and visceral fat area in T2DM patients.Methods: A total of 390 T2DM patients who met the criteria for admission and joined the National Metabolic Management Center (MMC) in the Zhejiang Provincial People’s Hospital from April 2020 to December 2020 were enrolled in this study. The participants were divided into two groups based on visceral obesity. Thyroid function, thyroid associated antibody and other metabolic indicators were measured by blood tests. The visceral fat area (VFA) and the subcutaneous fat area (SFA) were measured by bioelectrical impedance analysis.Results: There were 185 participants (47.4%) had visceral obesity. The positive rate of TPOAb was significantly higher in T2DM patients with visceral obesity (12.97% vs 5.37%, p < 0.01). Free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) were both significantly higher in T2DM patients with visceral obesity (p < 0.05). The increased TPOAb titer was significantly positively correlated with visceral fat area (r = 0.175, p < 0.01). Binary logistic analysis showed that the positive rate of TPOAb was associated with an increased risk of visceral obesity [(OR) 4.258, 95% confidence interval (CI) 1.594, 11.375, p = 0.004].Conclusion: TPOAb-positive is more common in T2DM patients with visceral obesity, which has some effects on visceral obesity independent of thyroid function. This suggests that elevated TPOAb titer is a predictor of visceral obesity in T2DM patients.Keywords: type 2 diabetes mellitus, visceral obesity, autoimmune thyroid disease, thyroid peroxidase antibody

Abstract Background Autoimmune thyroid disease (AITD) manifests with a female predominance, and much attention has been directed towards the integral membrane protein 2 A (ITM2A) gene located on the X chromosome. Methods In a study of 166 pediatric patients with autoimmune thyroid disease (AITD), the ITM2A rs1751094 single‐nucleotide polymorphism (SNP) was genotyped. The sample comprised 143 females and 23 males, with 67 patients diagnosed with Hashimoto chronic thyroiditis (HD) and 99 with Graves' disease (GD). In the 99 GD patients, 49 (49.5%) exhibited thyroid‐associated ophthalmopathy (TAO). Among the 85 GD patients, 70.6% (60/85) were considered intractable GD. The results were compared to those from 198 healthy Korean individuals, including 97 females and 101 males. Results The frequency of the rs1751094 C allele and CC/AC genotype were higher in AITD, GD and HD patients compared to controls, while the frequency of the A allele and AA genotype were lower. The results were more pronounced in female AITD and GD patients compared to male patients. The association was also found in intractable GD and TAO patients. Target SNP fits Hardy–Weinberg equilibrium. Conclusions These findings indicate that the ITM2A gene polymorphism on the X chromosome may contribute to the immunological basis of female‐predominant AITD in Korean children.

Background and aimsNumerous studies have found an association between vitamin deficiency and thyroid disorders (TD). The presence of anti-parietal cell antibodies is indicative of reduced ability to absorb vitamin B12. Thus, this study reviewed the existing studies with the objective of assessing differences in the serum levels of vitamin B12 among patients with and without TD, the frequency of vitamin B12 deficiency in patients with TD, and the presence of anti-parietal cell antibodies in patients with TD.MethodsA meta-analysis of random-effects model was conducted to calculate pooled frequencies, mean differences (MD), and their respective 95% confidence intervals (CI). We identified 64 studies that met our inclusion criteria (n = 28597).ResultsWe found that patients with hypothyroidism had lower vitamin B12 levels than healthy participants (MD: −60.67 pg/mL; 95% CI: −107.31 to −14.03 pg/mL; p = 0.01). No significant differences in vitamin B12 levels were observed between healthy participants and patients with hyperthyroidism (p = 0.78), autoimmune thyroid disease (AITD) (p = 0.22), or subclinical hypothyroidism (SH) (p = 0.79). The frequencies of vitamin B12 deficiency among patients with hypothyroidism, hyperthyroidism, SH, and AITD were 27%, 6%, 27%, and 18%, respectively.ConclusionsPatients with hypothyroidism had lower levels of vitamin B12 than healthy participants. No significant differences were observed between vitamin B12 levels and hyperthyroidism, AITD, or SH.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324422, identifier (CRD42022324422).

Background: This study aimed to develop an autoimmune thyroid disease (AITD) risk prediction model for patients with vitiligo based on readily available characteristics. Methods: A retrospective analysis was conducted on the clinical characteristics, demographics, skin lesions, and laboratory test results of patients with vitiligo. To develop a model to predict the risk of AITD, the Least Absolute Shrinkage and Selection Operator (LASSO) method was used to optimize feature selection, and logistic regression analysis was used to select further features. The C-index, Hosmer-Lemeshow test, and decision curve analysis were used to evaluate the calibration, discrimination ability and clinical utility of the model. Internally, the model was verified using bootstrapping; externally, two independent cohorts were used to confirm model accuracy. Results: Sex, vitiligo type, family history of AITD, family history of other autoimmune disease, thyroid nodules or tumors, negative emotions, skin involvement exceeding 5% of body surface area, and positive immune serology (IgA, IgG, IgM, C3, and C4) were predictors of AITD in the prediction nomogram. The model showed good calibration and discrimination (C-index: 0.746; 95% confidence interval: 0.701-0.792). The accuracy of this predictive model was 74.6%.In both internal validation (a C-index of 1000 times) and external validation, the C-index outperformed (0.732, 0.869, and 0.777). The decision curve showed that the AITD nomogram had a good guiding role in clinical practice. Conclusion: The novel AITD nomogram effectively evaluated the risk of AITD in patients with vitiligo. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune thyroid disease (AITD) is the most common associated autoimmune disorder in type 1 diabetes (T1D). Early detection of AITD is crucial to optimize glycemic control, growth, and intellectual development. In this prospective cohort study, we sought to characterize the prevalence, incident ages and risk factors of AITD in children and adolescents with T1D. Materials and methods: Patients with T1D diagnosed at ≤ 18 years at MacKay Children's Hospital, Taipei, from 1990 to 2019 underwent annual screening for AITD. Institutional Review Board-approved data on age, sex, and disease profile are collected. Statistical analysis was performed by using independent sample t test for continuous variables, chi-squared test for categorical variables, and Kaplan-Meier estimates of cumulative incidence of AITD were calculated. A p value of <0.05 was considered statistically significant. Results: We prospectively followed up 808 patients with T1D, 761 patients were included in the study. Of these patients, 197 (25.9%) of them had thyroid autoimmunity, meaning positivity of thyroid autoantibodies. Females had a higher prevalence of thyroid autoimmunity than males (59.9%, p = 0.012). Altogether, 5.5% patients developed AITD (4.1% had Graves disease; 1.4% had Hashimoto disease), at a mean age of 17.8 ± 8.5 years. The cumulative incidence of AITD at 30 years of disease duration was 0.29 in the total group and was significantly higher in females (0.39, n = 397) than in males (0.15, n = 364, p<0.001). Discussion: In Taiwan, the prevalence of AITD in pediatric population with T1D increases with age, a longer disease duration and female sex. For early detection of autoimmune thyroid disease in Taiwanese children and adolescents with T1D, an annual AITD screening program should be implemented. [ABSTRACT FROM AUTHOR]

Genetic susceptibility is an essential pathogenetic mechanism in autoimmune thyroid disease (AITD). MBL2 gene polymorphisms have been shown to play a vital role in the pathogenesis of multiple autoimmune disorders, but its contribution to AITD is unclear. The aim of this study was to assess the linkage between MBL2 gene polymorphisms and AITD susceptibility in a Chinese Han population. One thousand seven hundred sixty seven subjects consisting of 965 AITD patients and 802 controls from a Chinese Han population were enrolled in the case–control study. Four common single-nucleotide polymorphisms (SNPs) in the MBL2 gene were tested using high-throughput sequencing technology for sequence-based SNP genotyping. The allele and genotype distribution results showed that the minor alleles of rs198266, rs10824793, and rs4935046 were significantly lower in Hashimoto's thyroiditis (HT) patients than in healthy controls. In further genetic model analysis, the dominant models of rs1982266, rs10824793, and rs4935046 for MBL2 in the AITD group exhibited a lower risk of morbidity. Finally, we discovered that haplotype AAGC was associated with Graves' disease (GD), while AGC was associated with HT. Our study provides strong evidence for a genetic correlation between MBL2 and AITD, and the polymorphism of the MBL2 gene may be a protective factor for AITD, especially for HT. These findings can advance our understanding of the etiology of AITD, as well as provide guidance for prevention and intervention toward AITD. [ABSTRACT FROM AUTHOR]

Background: The gut is a target organ of thyroid hormone (TH) that exerts its action via the nuclear thyroid hormone receptor α1 (TRα1) expressed in intestinal epithelial cells. THs are partially metabolized via hepatic sulfation and glucuronidation, resulting in the production of conjugated iodothyronines. Gut microbiota play an important role in peripheral TH metabolism as they produce and secrete enzymes with deconjugation activity (β-glucuronidase and sulfatase), via which TH can re-enter the enterohepatic circulation. Summary: Intestinal epithelium homeostasis (the finely tuned balance between cell proliferation and differentiation) is controlled by the crosstalk between triiodothyronine and TRα1 and the presence of specific TH transporters and TH-activating and -inactivating enzymes. Patients and experimental murine models with a dominant-negative mutation in the TRα exhibit gross abnormalities in the morphology of the intestinal epithelium and suffer from severe symptoms of a dysfunctional gastrointestinal tract. Over the past decade, gut microbiota has been identified as an essential factor in health and disease, depending on its compositional and functional profile. This has led to a renewed interest in the so-called gut-thyroid axis. Disruption of gut microbial homeostasis (dysbiosis) is associated with autoimmune thyroid disease (AITD), including Hashimoto's thyroiditis, Graves' disease, and Graves' orbitopathy. These studies reviewed here provide new insights into the gut microbiota roles in thyroid disease pathogenesis and may be an initial step toward microbiota-based therapies in AITD. However, it should be noted that cause-effect mechanisms remain to be proven, for which prospective cohort studies, randomized clinical trials, and experimental studies are needed. Conclusion: This review aims at providing a comprehensive insight into the interplay between TH metabolism and gut homeostasis. [ABSTRACT FROM AUTHOR]

Background: This study was aimed at determining the frequency of thyroid autoimmunity and subclinical hypothyroidism in patients with hyperprolactinemia due to prolactinoma compared to well-matched healthy controls. Methods: This was a cross-sectional study wherein 78 treatment naïve prolactinoma patients and ninety-two healthy control subjects were recruited. Serum prolactin (PRL), thyroid-stimulating hormone (TSH), total thyroxine (T4), circulating anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-Tg) antibody levels were measured in all study subjects. Progression of the antibody-positive population to subclinical hypothyroidism was determined. Results: The median PRL level among patients was 166 ng/ml (IQR 85-467) compared to 11.4 ng/ml (IQR 8.5-15.9) in controls (P < 0.001). There was no significant difference in levels of T4 (P = 0.83) and TSH (P = 0.82) between the cases and controls. Overall, 25% of patients had the presence of anti-thyroid antibodies as compared to 20% of controls (P = 0.56). SCH was more common in antibody-positive hyperprolactinemia subjects compared with antibody-positive controls. Conclusion: We did not find an increased prevalence of thyroid autoimmunity among untreated prolactinoma patients compared to healthy controls. At the same time, subclinical hypothyroidism was more common in thyroid antibody-positive patients with hyperprolactinemia than positive controls. [ABSTRACT FROM AUTHOR]

Background: Some degree of platelet index abnormality has been found clinically in the autoimmune thyroid disease (AITD), but the findings are not uniform. Methods: The PubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published up to August 16th, 2022, with no restrictions on the language of the articles. Reference lists of eligible articles were also searched. A random effect model was used to pool the standardized mean difference (SMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), and platelet distribution width (PDW) between AITD patients and healthy controls, and subgroup analyses were performed. Results: A total of 19 articles with 6173 people (3824 AITD patients and 2349 healthy people) were included in the meta-analysis. The results showed that PLT and MPV values were significantly increased in AITD patients when compared with healthy people (SMD: 0.164, 95% CI: 0.044 to 0.285; SMD: 0.256, 95% CI: 0.013 to 0.500), while no significant difference was found in PDW between the AITD group and the control group (SMD: 0.060, 95% CI: -0.164 to 0.284). Subgroup analysis according to disease type and thyroid function revealed that for PLT, this difference was only found in the Hashimoto's thyroiditis (HT) and hypothyroid groups, but not in the Graves' disease (GD) and hyperthyroid groups. For MPV, the results were the opposite of those for PLT: MPV was significantly higher in the GD, hyperthyroid, and euthyroid groups than in the control group, but not in the HT and hypothyroid groups. Sensitivity analysis showed that the stability of the pooled MPV was not good. No publication bias was found. Conclusions: PLT and MPV are significantly elevated in patients with AITD, with PLT being more significantly elevated in HT and hypothyroidism, and MPV being more significantly increased in GD and hyperthyroidism. Appropriate clinical attention can be paid to the thyroid function of patients when abnormal platelet indices are found, and conversely, the consequences of abnormal platelet parameters such as elevated MPV lead to an increased occurrence of cardiovascular events, which should also be addressed in the AITD population. [ABSTRACT FROM AUTHOR]

Background: Autoimmune thyroiditis (AIT) is the most common thyroid pathology in pediatric patients among which Hashimoto’s thyroiditis has the highest prevalence. Along with size, measuring mechano-acoustic tissue elasticity is evolving as an important parameter in the evaluation of diffuse thyroid pathology. This study aims to investigate the role of shear wave elastography (SWE) in the diagnosis of autoimmune thyroid disease (AITD) in the pediatric population and also compare the elasticity between them and healthy individuals. Results: This case–control analytical study was carried out on 64 pediatric subjects ranging in age from 7 to 17 years. All the cases were diagnosed as AIT by anti-thyroid antibodies, and their thyroid function was evaluated by thyroid hormones. We performed thyroid Ultrasonography and Shear wave elastography. Patients with AIT had significantly higher elasticity values (35.6 kPa, IQR 8.43–103.7 kPa) than the control group (9.35 kPa, IQR 5.73–13.21 kPa). There was no correlation of elasticity values of thyroid gland in patients with AIT with autoantibodies and thyroid function test, respectively. The cutoff value for elasticity was 12.317 kPa with sensitivity and specificity of 96.9% and 100%, respectively. Conclusions: SWE is a highly sensitive imaging method integrating routine ultrasonography in the diagnosis of AITD which estimates the extent of fibrosis in numerical value. [ABSTRACT FROM AUTHOR]

Copyright of Osmangazi Journal of Medicine / Osmangazi Tip Dergisi is the property of Eskisehir Osmangazi University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Autoimmune thyroid disease (AITD) is the leading cause of thyroid dysfunction globally, characterized primarily by two distinct clinical manifestations: Hashimoto's thyroiditis (HT) and Graves' disease (GD). The prevalence of AITD is approximately twice as high in women compared to men, with a particularly pronounced risk during the reproductive years. Pregnancy exerts profound effects on thyroid physiology and immune regulation due to hormonal fluctuations and immune adaptations aimed at fostering maternal-fetal tolerance, potentially triggering or exacerbating AITD. The impact of AITD on pregnancy outcomes is multifaceted. Both HT and GD have been associated with adverse obstetric and neonatal outcomes, including miscarriage, preterm delivery, preeclampsia and fetal growth restriction. Inadequately managed AITD can also affect fetal neurodevelopment due to disrupted maternal thyroid hormone availability during critical periods of brain maturation. This review explores the complex interplay between the genetic, epigenetic and environmental factors that drive AITD during pregnancy, highlighting their roles in disease development and impacts on pregnancy outcomes. Gaining a deeper understanding of these mechanisms is crucial for improving diagnostic tools, treatment options and preventive measures to enhance the health and well-being of both the mother and the newborn.

Objective: The oral mucosa mirrors a range of latent systemic disorders, with potential clinical associations noted between autoimmune thyroid disease (AITD) and oral lichen planus (OLP). This study aims to explore the genetic relationship and underlying mechanisms mediating these conditions., Methods: A 2-step Mendelian randomization (MR) analysis was conducted to elucidate the genetic relationship and mediating factors between AITD and OLP. Linkage disequilibrium score regression was employed to assess heritability and genetic correlations among phenotypes, followed by genetic colocalization analysis to discern shared genetic variants. A transcriptome-wide association study (TWAS) was also performed to pinpoint gene expression profiles., Results: Genetically predicted AITD is associated with an increased risk of OLP (OR[95% CI]: 1.44[1.19,1.74], P=1.61 × 10 -4 ), potentially mediated by hypothyroidism. There is strong evidence of colocalization between AITD and OLP, with a shared PTPN22 gene variant driving this association. TWAS further identified RNASET2 and FGFR1OP within the HLA region as high-confidence shared genes for both conditions., Conclusion: Our study provides novel evidence of a possible genetic association between AITD and OLP. These findings highlight the critical role of endocrine alterations in maintaining oral immune homeostasis, though further research is warranted to validate our findings., Competing Interests: Conflict of interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Resistance to thyroid hormone beta (RTHβ) is a rare disorder characterized by a fairly heterogeneous clinical presentation due to varying degrees of tissue response to thyroid hormone. The study aimed to evaluate the clinical, laboratory features and genotype-phenotype relationship of Turkish patients with RTHβ., Methods: Patients who underwent a THRB gene analysis between September 2019 and September 2023 were retrospectively reviewed., Results: 50 patients with the clinical features of RTHβ syndrome or a family history of an index case were included. A total of 8 different heterozygous pathogenic/likely pathogenic missense variants (3 novel) were detected in the THRB gene in 30 patients from 8 unrelated families. Although most patients with RTHβ were asymptomatic, 7 patients had various symptoms. Seven patients had received various treatments before diagnosis. Thyroid autoantibody was positive in 23% of all cases with a variant, and goitre was detected in 56% of children with a variant. While thyroid nodules were detected in 7 adult patients, two adult patients were being followed with papillary thyroid cancer. One child patient had attention-deficit disorder, learning disability, and type 1 diabetes mellitus. Of the 20 patients without a variant, TSHoma was detected in one., Conclusion: The present study, provides an overview of clinical and genetic characteristics of patients with genetically confirmed RTHβ and expanded the THRB gene variant database with 3 novel variants. Although most patients with RTHβ are asymptomatic, molecular genetics analysis of the THRB gene and regular follow-up for potential concurrent autoimmune diseases and thyroid cancer is warranted.

Objectives: Coronavirus infection (COVID-19) has caused a worldwide pandemic and affected many systems. Hashimoto's Thyroiditis is one of the most common diseases in the community and is the prototype of autoimmune thyroid diseases. It is unknown how thyroid autoimmunity and thyroid dysfunction will affect the course of COVID-19. The aim of this study is to show the course of this infection in patients with Hashimoto's Thyroiditis. Materials and Methods: A descriptive study was conducted in which adult patients with Hashimoto's Thyroiditis who received COVID-19 infection from April to October 2020 in our center were recruited retrospectivelly. Those with severe comorbid conditions that may affect the course of the disease,and using immunomodulatory and immunosuppressive drugs, and pregnant women were not included in the study. Results: A total of 232 patients included. Median (IQR=interquartile) age value was 43 (34-54), and the male/female ratio was 21/211 (9.1%/90.9%). In our study, mortality due to COVID-19 in our patients was found to be consistent with the normal population in their age group (1,7%, n:4), and 7 patients were treated in the intensive care unit. A significant negative correlation was found between Anti-Tyroglobuline Antibody (Anti-Tg) and White Blood Cell (WBC) (r=-0.189, p=0.041), Neutrophil (r=-0.191, p=0.040), Neutrophil to Lymphocyte Ratio (NLR) (r=-0.244, p=0.008), Ferritin (r=-0.259, p=0.042). Conclusion: The rate of patients with supressed Thyroid Stimulating Hormone (TSH) in intensive care unit was slightly higher, but since the number of events was low, this finding could not gain significance. Most patients with Hashimoto's Thyroiditis have had a mild infection. Thyroid autoimmunity does not appear to affect the COVID-19 infection’s course.

ABSTRACT Objective: Although some previous data have suggested a high iodine intake in Brazil, the prevalence of antithyroperoxidase antibodies (TPOAb) in the country is compatible with rates from countries with adequate iodine intake. This observation emphasizes the importance of knowing the incidence of TPOAb in Brazil. Materials and methods: This prospective analysis included euthyroid participants with negative TPOAb at baseline and a thyroid function assessment at a 4-year follow-up. TPOAb was measured by electrochemiluminescence and considered positive when titers were ≥34 IU/mL. TSH and free T4 (FT4) levels were determined by a third-generation immunoenzymatic assay. The incidence of TPOAb is expressed in percentage per year or as a cumulative incidence within the 4-year follow-up period. Results: Of 8,922 euthyroid participants (mean age 51.1 years; 50.9% women) with a negative TPOAb test at baseline, 130 presented incident TPOAb at the 4-year follow-up, yielding an annual incidence of TPOAb of 0.38%/year (95% confidence interval [95% CI], 0.37-0.39%/year) and a cumulative incidence over 4 years of 1.46% (95% CI, 1.21-1.71%). In men, the annual incidence was 0.32% (95% CI, 0.31-0.33%), and the cumulative incidence over 4 years was 1.23% (95% CI, 0.90-1.56%). In women, the annual incidence was 0.43%/year (95% CI, 0.42-0.44%/year) and the cumulative incidence over 4 years was 1.67% (95% CI, 1.30-2.04%). The only factor associated with incident TPOAb was the occurrence of thyroid diseases at follow-up. No differences in TPOAb incidence were detected across ELSA-Brasil research centers. Conclusion: Based on the results of this study, the incidence of TPOAb per year and at a 4-year follow-up period are compatible with those of a country with adequate iodine intake.

Background and Objectives: Thyroid disease has been associated with autoimmune disorders. As systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations spanning across all organ systems, the relationship of SLE with thyroid disorders needs investigation. In particular, the relationship of SLE with autoimmune thyroid disease has attracted the interest of the research community. The aim was to evaluate the relationship of SLE with autoimmune thyroid disease. Materials and Methods: A cohort of 45 consecutive patients with a mean age of 47.97 years (range 21–79 years) and 45 age- and sex-matched controls were prospectively studied over a period of 12 months for the presence of thyroid disease and the prevalence of antithyroid antibodies. Results: Four patients (8.9%) were found to suffer from primary hypothyroidism, five (11.11%) from subclinical hypothyroidism and one (2.22%) from hyperthyroidism, whereas one (2.22%) of the controls had primary hypothyroidism and one (2.22%) had hyperthyroidism. Five patients (11.11%) had a thyroid hormone profile that was compatible with the presence of euthyroid sick syndrome. Thyroid peroxidase (TPOab) and thyroglobulin (Tgab) antibodies were detected in 20/45 and 15/45 of the SLE population and in 7/45 and 5/45 of the controls, respectively (p < 0.05, chi-square test). Conclusions: In conclusion, the incidence of clinical thyroid disease is greater amongst SLE patients than in a control population, and in a significant number of these patients, antithyroid antibodies are detectable. Thus, a subset of lupus patients appears to be predisposed to the development of thyroid disease, and this should be considered when evaluating patients with SLE.

Autoimmune thyroid disease (AITD), the most common autoimmune disease, includes Graves' disease (GD) and Hashimoto's thyroiditis (HT). Currently, the pathogenesis of AITD is not fully understood. Our study aimed to examine the presence of macrophage polarization imbalance in AITD patients, to investigate whether high iodine can cause macrophage polarization imbalance, and to investigate the role of key genes of metabolic reprogramming in macrophage polarization imbalance caused by high iodine. We synergistically used various research strategies such as systems biology, clinical studies, cell culture and mouse disease models. Gene set enrichment analysis (GSEA) revealed that M1 macrophage hyperpolarization was involved in the pathogenesis of AITD. In vitro and in vivo experiments showed that high iodine can affect the polarization of M1 or M2 macrophages and their related cytokines. Robust rank aggregation (RRA) method revealed that hexokinase 3 (HK3) was the most aberrantly expressed metabolic gene in autoimmune diseases. In vitro and in vivo studies revealed HK3 could mediate macrophage polarization induced by high iodine. In summary, hyperpolarization of M1-type macrophages is closely related to the pathogenesis of AITD. High iodine can increase HK3 expression in macrophages and promote macrophage polarization towards M1. Targeting HK3 can inhibit M1 polarization induced by high iodine. [ABSTRACT FROM AUTHOR]