Unprecedented complexity of six coexisting autoimmune diseases: A case report.

INTRODUCTION: Autoimmune disorders often exhibit interconnectedness, although encountering multiple autoimmune conditions in a single patient is uncommon. Multiple autoimmune syndrome is characterized by the presence of at least three distinct autoimmune diseases in an individual. This report outlines the case of a middle-aged woman diagnosed with autoimmune thyroiditis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, and antisynthetase syndrome. Additionally, it includes a literature review encompassing multiple autoimmune syndromes involving five or more autoimmune diseases. OBSERVATION: A 57-year-old woman, with no previous medical history, presented with fever, extensive muscle weakness, progressive exertional dyspnea, inflammatory polyarthralgia, dysphagia, and dry mouth. Clinical examination revealed muscular deficit in the scapular and pelvic girdles, distal muscular deficit, synovitis in the wrists, and features indicative of "mechanic's hand". Laboratory examinations showed cytolysis, cholestasis, elevated muscle enzymes, hypergammaglobulinemia and elevated thyroid stimulating hormone. Immunoassays showed positive results for antinuclear antibodies, anti-histidyl-t-RNA synthetase, anti-Sjögren's-syndrome-related antigen A, anti-ribonucleic-acid-polymerase-III-RP155, anti-fibrillarin, anti-mitochondrial, anti-liver/kidney microsomal type 1, anti-glycoprotein 210, and anti-thyroid peroxidase antibodies. Further investigations led to the diagnosis of a multiple autoimmune syndrome involving autoimmune thyroiditis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, and antisynthetase syndrome. The patient received treatment with intravenous immunoglobulins, corticosteroids, azathioprine, and ursodeoxycholic acid, which resulted in favorable clinical and biological outcomes. CONCLUSION: This patient presented with six concurrent distinct autoimmune disorders, categorizing this case as a type two multiple autoimmune syndrome. The identification of antisynthetase syndrome notably distinguishes this case.

Prevalence of autoimmune thyroiditis among children with autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is an organ specific autoimmune disease, which can manifest at any age of life. there is a high prevalence of extrahepatic autoimmune diseases in patients with AIH. Autoimmune thyroid diseases (ATDs) are the most frequent extrahepatic autoimmune disorders among patients with AIH. Aim of work is to detect the frequency of ATDs among Egyptian children with AIH. METHODS: This research is a cross-sectional study conducted on 58 children with AIH aged ≤ 18 years. All patients were tested for free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG). Thyroid ultrasound (US) and thyroid scan were performed for patients with abnormal thyroid profile, borderline values, positive anti-TPO or anti-TG. RESULTS: The mean ± standard deviation (SD) for the age of the patients was 11.3 ± 4.5 years. Out of 58 patients of AIH, 28 patients (48.3%) had associated other autoimmune diseases. Autoimmune thyroiditis was the most common associated autoimmune disease being present in 10 patients (17.2%). The thyroid status of AIT patients showed that 6 patients (60%) were euthyroid, 3 patients (30%) had subclinical hypothyroidism and only one patient (10%) was hyperthyroid. CONCLUSION: Autoimmune hepatitis in Egyptian children is commonly associated with other autoimmune diseases. Autoimmune thyroiditis is the most common to be associated with AIH in pediatric patients. As it is not usually clinically manifesting, regular screening for AIT in children with AIH is mandatory.

A Flexible Mouse Model of Autoimmune Thyroiditis Induced by Immunization with an Adenovirus Containing Full-Length Thyroglobulin cDNA.

The main challenge in the "post-GWAS" era is to determine the functional meaning of genetic variants and their contribution to disease pathogenesis. Development of suitable mouse models is critical because disease susceptibility is triggered by complex interactions between genetic, epigenetic, and environmental factors that cannot be modeled by in vitro models. Thyroglobulin (TG) is a key gene for autoimmune thyroid disease (AITD) and several single nucleotide polymorphisms (SNPs) in the TG coding region have been associated with AITD. The classical model of experimental autoimmune thyroiditis (EAT), based on immunization of genetically susceptible mouse strains with purified TG protein in adjuvant, does not allow testing the impact of TG sequence variants on the development of autoimmune thyroiditis. Here we describe a protocol for the induction of EAT by immunization of mice susceptible to thyroiditis with an adenovirus vector carrying full-length human TG cDNA (Ad-TG EAT). We also provide support protocols for evaluation of autoimmune thyroiditis including serological assessment of TG antibodies, in vitro splenocyte proliferation assay and cytokines secretion, thyroid histology, and evaluation of thyroid lymphocytic infiltration by immunostaining. This protocol for EAT induction allows manipulation of the TG cDNA to introduce variants associated with AITD, enabling the testing of the functional effects of susceptible variants and their haplotypes on the immunogenicity of TG. Furthermore, the Ad-TG EAT mouse model is a valuable model for studying the interactions of the TG variants with non-genetic factors influencing AITD development (e.g., cytokines, iodine exposure) or with variants of other susceptible genes (e.g., HLA-DRß1). © 2024 Wiley Periodicals LLC. Basic Protocol: Development of a mouse model of autoimmune thyroiditis induced by immunization with adenovirus containing full-length thyroglobulin cDNA Support Protocol 1: Splenocytes isolation Support Protocol 2: T cell stimulation and carboxyfluorescein diacetate succinimidyl ester (CFSE) based cell proliferation assay Support Protocol 3: Cytokine assays: measuring levels of interferon gamma (IFNγ) and interleukins IL-2, IL-4, and IL-10 in splenocyte supernatants Support Protocol 4: Evaluating thyroid histology and infiltration with immune cells: hematoxylin-eosin staining of mice thyroid glands Support Protocol 5: Immunohistochemistry of thyroid tissues: Immunofluorescence protocol of paraffin-embedded thyroid sections Support Protocol 6: Anti-thyroglobulin antibody measurement in mice sera by enzyme-linked immunosorbent assay (ELISA).

Gluten-Free Diet Alters the Gut Microbiome in Women with Autoimmune Thyroiditis.

The gut microbiome may contribute to the development of autoimmune diseases, such as autoimmune thyroiditis (AIT). Diet has a critical impact on the gut microbiome, and it has been shown that a gluten-free diet can negatively affect its composition. A gluten-free diet is popular among patients, and therefore the aim of this study was to check whether it affects thyroid function and gut microbiome composition in AIT. Thirty-one women with AIT complied with a gluten-free diet for 8 weeks. After the first 4 weeks, participants were divided into two groups: the first group received gluten in capsules and the other one-rice starch (placebo). Blood and stool samples were examined before diet (T0), after 4 weeks (T1) and after 8 weeks of diet (T2). The only significant difference in blood parameters was observed between T1 and T2 in the placebo group for the thyroid peroxidase antibody level. After the first 4 weeks, a significant increase in Desulfobacterota, Proteobacteria, Prevotella and Parasutterella and a significant decrease in Actinobacteriota, Coriobacteriaceae and Bifidobacterium were observed. The detected microbiome alterations may indicate increasing inflammation; however, further research is required, and for now, a gluten-free diet should be used cautiously in AIT.

Protective effect of thyroid and restores of ovarian function of Buzhong Yiqi granule on experimental autoimmune thyroiditis in female rats.

OBJECTIVE: To observe the effects of Buzhong Yiqi granule on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis (EAT). METHODS: EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine. Rats were randomly divided into normal control (NC) group, EAT model (EAT) group, selenium yeast (PC) group, low dose Buzhong Yiqi (BZYQ-L) group, medium dose Buzhong Yiqi (BZYQ-M) group and high dose Buzhong Yiqi (BZYQ-H) group. After two months of drug intervention according to dosage, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) in peripheral blood of rats. The pathological changes of rat thyroid tissues were observed under light microscope with HE staining; ELISA was used to determine estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-müllerian hormone (AMH), and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining. RESULTS: Compared with the NC group, BZYQ granule improved the thyroid and ovarian tissue morphology, and the levels of TPOAb, TGAb and TSH in the model group rats significantly increased (P < 0.05), the thyroid tissue was severely destroyed, the levels of E2, FSH, LH, T, AMH significantly increased (P < 0.05), and the ovary exhibited polycystic changes; Compared with the model group, TSH level in the BZYQ-L group rats decreased (P < 0.05), FSH, T, AMH levels decreased (P < 0.05), in the BZYQ-M group TPOAb, TSH levels decreased (P < 0.05), FSH, LH, T, AMH levels significantly decreased (P < 0.05), BZYQ-H group TPOAb, TGAb, TSH levels significantly decreased (P < 0.05), FSH, LH, T, AMH levels significantly decreased (P < 0.05), with the greatest improvement and significantly better than selenium yeast group (P < 0.05). CONCLUSIONS: BZYQ granule could regulate the thyroid function of EAT rats, reduce thyroid antibody titers, then act on the ovarian function, regulate hormone disorders, and alleviate the pathological damage of rat's ovarian tissues. The effect of high dose Buzhong Yiqi granule is the best.

Alteration in kynurenine pathway metabolites in young women with autoimmune thyroiditis.

The kynurenine pathway (KP) of tryptophan degradation includes several compounds that reveal immunomodulatory properties. The present study aimed to investigate the alteration in KP metabolites in young women with autoimmune thyroiditis (AIT) and their associations with thyroid function. The thyroid function tests, antithyroid antibodies measurement and ultrasonography of the thyroid gland have been performed in 57 young women with AIT and 38 age-matched healthy controls. The serum levels of tryptophan, kynurenine (KYN) and its metabolites were determined, and the activity of KP enzymes was calculated indirectly as product-to-substrate ratios. KP was activated and dysregulated in AIT, along with significantly elevated levels of KYN and anthranilic acid (AA), at the expense of the reduction of kynurenic acid (KYNA), which was reflected by the increase in the AA/KYNA ratio (p < 0.001). In univariate and multiple regression analyses, peripheral deiodinase (SPINA-GD) activity in AIT was positively associated with KYNA, AA, and quinolinic acid (QA). The merger of AA, AA/KYNA ratio, QA and SPINA-GD exhibited the highest sensitivity and specificity to predict AIT (p < 0.001) in receiver operating characteristic (ROC) analysis. In conclusion, the serum KYN metabolite profile is dysregulated in young women with AIT and could serve as a new predictor of AIT risk.

The impact of gut microbiota on autoimmune thyroiditis and relationship with pregnancy outcomes: a review.

Autoimmune thyroiditis (AITD) is a T-cell-mediated, organ- specific autoimmune disease caused by interactions between genetic and environmental factors. Patients with AITD show thyroid lymphocyte infiltration and an increase in the titer of thyroid autoimmune antibodies, thereby altering the integrity of thyroid follicle epithelial cells and dysregulating their metabolism and immune function, leading to a decrease in multi-tissue metabolic activity. Research has shown that patients with AITD have a significantly higher risk of adverse pregnancy outcomes, such as infertility and miscarriage. Levothyroxine(LT4) treatment can improve the pregnancy outcomes of normal pregnant women with thyroid peroxidase antibodies(TPOAb) positivity, but it is not effective for invitro fertilization embryo transfer (IVF-ET) in women with normal thyroid function and positive TPOAb. Other factors may also influence pregnancy outcomes of patients with AITD. Recent studies have revealed that the gut microbiota participates in the occurrence and development of AITD by influencing the gut-thyroid axis. The bacterial abundance and diversity of patients with Hashimoto thyroiditis (HT) were significantly reduced, and the relative abundances of Bacteroides, fecal Bacillus, Prevotella, and Lactobacillus also decreased. The confirmation of whether adjusting the composition of the gut microbiota can improve pregnancy outcomes in patients with AITD is still pending. This article reviews the characteristics of the gut microbiota in patients with AITD and the current research on its impact in pregnancy.

Is There a Link between Thyroid Peroxidase Gene Promoter Polymorphisms and Autoimmune Thyroiditis in the Polish Population?

(1) Autoimmune thyroiditis (AIT) is the most common cause of primary hypothyroidism and one of the most frequent organ-specific autoimmune diseases. Its pathogenesis is polygenic and still requires further research. The aim of the study was to assess, for the first time in the Caucasian population, the role of selected TPO gene promoter polymorphisms (rs2071399 G/A, rs2071400C/T, rs2071402 A/G, and rs2071403 A/G) in the development of AIT. A total of 237 patients diagnosed with AIT and 130 healthy controls were genotyped for four TPO gene polymorphisms, and the results were statistically analyzed to check for the role of these polymorphisms. There were no significant differences in the genotype and allele frequencies of the studied TPO gene promoter polymorphisms between patients and controls (p > 0.05). The haplotype distribution (rs2071400-rs2071402-rs2071403) between the two studied groups was similar for the most common variants (CGA, CAG, TGG). Only a rare haplotype (CGG) occurred more frequently among patients compared to controls (p = 0.04). The studied TPO gene promoter polymorphisms did not show an association with susceptibility to AIT in the Caucasian Polish population, contrary to the results in Japanese patients.

Aversion of surgical exploration in patients with complex ovarian cysts secondary to overt hypothyroidism: A series of three cases.

Long-standing, overt hypothyroidism-induced bilateral multiloculated ovarian cysts represent an infrequent occurrence. Our first case, presented with bilateral complex ovarian masses, exhibited overt hypothyroidism symptoms, including lethargy, weight gain and subfertility, prompting consideration for surgical intervention. Similarly, in the second case, a girl aged 11 years with stunting, delayed bone age and academic challenges was referred for surgical exploration due to bilateral complex ovarian masses. Both cases revealed elevated thyroid-stimulating hormone levels during preoperative workup. Commencing levothyroxine replacement therapy resulted in complete regression of ovarian cysts and substantial symptom improvement within an 8-week timeframe. The third case, a previously diagnosed patient with Hashimoto's thyroiditis, benefited from the lessons gleaned in managing the initial cases, responding well to levothyroxine therapy, thereby averting the necessity for surgery in all three instances. These cases underscore the significance of considering thyroid function in the evaluation of ovarian masses and highlight the efficacy of levothyroxine replacement therapy in resolving both hypothyroidism and associated ovarian cysts, thereby obviating the need for surgical intervention.

Negative causal exploration of systemic sclerosis: a Mendelian randomization analysis.

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-related connective tissue disease with a complex and unknown pathophysiological mechanism with genes association. Several articles have reported a high prevalence of thyroid disease in SSc patients, while one study suggested a potential contribution of appendicitis to the development of SSc. To investigate this causal association, we conducted Mendelian randomization (MR) analysis using instrumental variables (IVs) to assess exposure and outcome. In the MR study involving two cohorts, all analyses were conducted using the TwoSampleMR package in R (version 4.3.0). Single nucleotide polymorphisms (SNPs) meeting a statistically significant threshold of 5E-08 were included in the analysis. Multiple complementary approaches including MR-IVW, MR-Egger, weighted median, simple mode, and weighted mode were employed to estimated the relationship between the exposure and outcome. Leave-one-out analysis and scatter plots were utilized for further investigation. Based on the locus-wide significance level, all of the MR analysis consequences manifested no causal association between the risk of appendicitis with SSc (IVW OR 0.319, 95% CI 0.063-14.055, P = 0.966). Negative causal effects of autoimmune thyroiditis (AT) on SSc (IVW OR 0.131, 95% CI 0.816-1.362, P = 0.686), Graves' disease (GD) on SSc (IVW OR 0.097, 95% CI 0.837-1.222, P = 0.908), and hypothyroidism on SSc (IVW OR 1.136, 95% CI 0.977-1.321, P = 0.096) were derived. The reverse MR revealed no significant causal effect of SSc on thyroid disease. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates. The consequences indicated no significant association between AT, GD, and hypothyroidism with SSc. Similarly, there was no observed relationship with appendicitis.

The association between endothelial function and autoimmune thyroiditis induced by iodine excess.

BACKGROUND: Iodine excess (IE) intake leads to lymphocyte dysfunction and contributes to autoimmune thyroiditis (AIT). Abnormal thyroid function is associated with adverse cardiovascular events, endothelial dysfunction is often an early pathophysiological feature in most cardiovascular disease. However, the relationship between iodine and the cardiovascular system is currently unclear. Therefore, the aim of this study was to investigate the effects of IE on endothelial function in mouse model. METHODS: A total of 24 NOD.H-2h4 mice were randomly divided into different groups. A sodium iodide (NaI) group supplied with 0.05% NaI water for 8 weeks. Serum levels of tumor necrosis factors α (TNFα), interleukin-6 (IL-6) and C-reactive Protein (CRP), as well as endothelin-1 (ET-1), von Willebrand factor (VWF) and thrombomodulin (THBD) were detected by Elisa. In addition, the mRNA and protein expression of these genes were measured by RT-PCR and Western blotting. RESULTS: Here, we found the urinary iodine concentration (UIC) was higher in the NaI group compared to the control group. Serum levels of ET-1, VWF, and THBD were also significantly lower in the NaI group, however, CRP serum levels are significantly increased. In aorta, the mRNA and protein expression of ET-1, VWF, THBD were downregulated, however, the expression of IL-6, CRP and TNFα mRNA and protein were upregulated in the NaI group. A correlation analysis showed negative correlation between UIC with ET-1, VWF, and THBD, similarly, negative correlation between CRP with THBD was observed. In addition, positive correlations between UIC with CRP. CONCLUSION: Collectively, in the NOD.H-2h4 mice, IE supplementation had a suppressive effect on endothelial function, and this inhibition maybe due to the increase expression of inflammatory cytokines.

Autoimmune thyroid disease and myasthenia gravis: a study bidirectional Mendelian randomization.

Background: Previous studies have suggested a potential association between AITD and MG, but the evidence is limited and controversial, and the exact causal relationship remains uncertain. Objective: Therefore, we employed a Mendelian randomization (MR) analysis to investigate the causal relationship between AITD and MG. Methods: To explore the interplay between AITD and MG, We conducted MR studies utilizing GWAS-based summary statistics in the European ancestry. Several techniques were used to ensure the stability of the causal effect, such as random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was evaluated by calculating Cochran's Q value. Moreover, the presence of horizontal pleiotropy was investigated through MR-Egger regression and MR-PRESSO. Results: The IVW method indicates a causal relationship between both GD(OR 1.31,95%CI 1.08 to 1.60,P=0.005) and autoimmune hypothyroidism (OR: 1.26, 95% CI: 1.08 to 1.47, P =0.002) with MG. However, there is no association found between FT4(OR 0.88,95%CI 0.65 to 1.18,P=0.406), TPOAb(OR: 1.34, 95% CI: 0.86 to 2.07, P =0.186), TSH(OR: 0.97, 95% CI: 0.77 to 1.23, P =0.846), and MG. The reverse MR analysis reveals a causal relationship between MG and GD(OR: 1.50, 95% CI: 1.14 to 1.98, P =3.57e-3), with stable results. On the other hand, there is a significant association with autoimmune hypothyroidism(OR: 1.29, 95% CI: 1.04 to 1.59, P =0.019), but it is considered unstable due to the influence of horizontal pleiotropy (MR PRESSO Distortion Test P < 0.001). MG has a higher prevalence of TPOAb(OR: 1.84, 95% CI: 1.39 to 2.42, P =1.47e-5) positivity and may be linked to elevated TSH levels(Beta:0.08,95% CI:0.01 to 0.14,P =0.011), while there is no correlation between MG and FT4(Beta:-9.03e-3,95% CI:-0.07 to 0.05,P =0.796). Conclusion: AITD patients are more susceptible to developing MG, and MG patients also have a higher incidence of GD.

A nomogram for predicting adverse pathologic features in low-risk papillary thyroid microcarcinoma.

BACKGROUND: Identifying risk factors for adverse pathologic features in low-risk papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of surgical or non-surgical treatment. This study aims to develop a nomogram for predicting the probability of adverse pathologic features in low-risk PTMC patients. METHODS: A total of 662 patients with low-risk PTMC who underwent thyroid surgery were retrospectively analyzed in Qilu Hospital of Shandong University from May 2019 to December 2021. Logistic regression analysis was used to determine the risk factors for adverse pathologic features, and a nomogram was constructed based on these factors. RESULTS: Most PTMC patients with these adverse pathologic features had tumor diameters greater than 0.6 cm (p < 0.05). Other factors (age, gender, family history of thyroid cancer, history of autoimmune thyroiditis, and BRAFV600E mutation) had no significant correlation with adverse pathologic features (p > 0.05 each). The nomogram was drawn to provide a quantitative and convenient tool for predicting the risk of adverse pathologic features based on age, gender, family history of thyroid cancer, autoimmune thyroiditis, tumor size, and BRAFV600E mutation in low-risk PTMC patients. The areas under curves (AUC) were 0.645 (95% CI 0.580-0.702). Additionally, decision curve analysis (DCA) and calibration curves were used to evaluate the clinical benefits of this nomogram, presenting a high net benefit. CONCLUSION: Tumor size > 0.60 cm was identified as an independent risk factor for adverse pathologic features in low-risk PTMC patients. The nomogram had a high predictive value and consistency based on these factors.

Research progress in the construction of animal models of autoimmune thyroiditis.

Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT), is an autoimmune disease that is characterised by elevated thyroid-specific antibody titres. The incidence of AIT is increasing year over year, making it urgent to establish a suitable animal model for this condition, in order to better explore its pathogenesis and potential pharmaceutical mechanisms for treatment. Owing to a lack of basic research on this disease, problems such as disparate modelling methods with unclear and varying success rates make it difficult for researchers to obtain effective information on AIT in the short term. This report summarises and analyzes the current literature on AIT and combines actual operability to explain the selection and specific implementation processes behind the uses of different modelling approaches, to provide a better overall understanding of autoimmune thyroid diseases.

Effect of disulfidptosis-related genes SLC3A2, SLC7A11 and FLNB polymorphisms on risk of autoimmune thyroiditis in a Chinese population.

PURPOSE: This study aimed to evaluate the associations between disulfidptosis related genes-SLC3A2, SLC7A11 and FLNB polymorphisms and risk of autoimmune thyroiditis (AIT). METHODS: Six SNPs in the SLC3A2, SLC7A11 and FLNB were genotyped in 650 AIT cases and 650 controls using a MassARRAY platform. RESULTS: Minor alleles of SLC3A2-rs12794763, rs1059292 and FLNB-rs839240 might lead to a higher risk of AIT (p < 0.001), while SLC7A11-rs969319-C allele tends to decrease the risk of the disease (p = 0.006). Genetic model analysis showed that SLC3A2-rs12794763, SLC3A2-rs1059292 and FLNB-rs839240 polymorphisms were risk factors for AIT (p < 0.001); while SLC7A11-rs969319 showed a protective role for the disease in all genetic models (p < 0.005). Stratification analysis showed that SLC3A2-rs1059292 and rs12794763 were correlated with higher risk of AIT regardless of sex (p < 0.05). Moreover, FLNB-rs839240 exhibited higher risk of disease only in females (p < 0.05). By contrast, SLC7A11-rs969319 showed a protective role only in females (p < 0.05). CONCLUSION: Our results shed new light on the association between disulfidptosis-related genes and AIT risk.

The causal relationship between autoimmune thyroid disorders and telomere length: A Mendelian randomization and colocalization study.

This study aimed to evaluate whether there is a causal relationship between autoimmune thyroid disorders (AITDs) and telomere length (TL) in the European population and whether there is reverse causality. In this study, Mendelian randomization (MR) and colocalization analysis were conducted to assess the potential causal relationship between AITDs and TL using summary statistics from large-scale genome-wide association studies, followed by analysis of the relationship between TL and thyroid stimulating hormone and free thyroxine (FT4) to help interpret the findings. The inverse variance weighted (IVW) method was used to estimate the causal estimates. The weighted median, MR-Egger and leave-one-out methods were used as sensitivity analyses. The IVW method results showed a significant causal relationship between autoimmune hyperthyroidism and TL (ß = -1.93 × 10-2 ; p = 4.54 × 10-5 ). There was no causal relationship between autoimmune hypothyroidism and TL (ß = -3.99 × 10-3 ; p = 0.324). The results of the reverse MR analysis showed that genetically TL had a significant causal relationship on autoimmune hyperthyroidism (IVW: odds ratio (OR) = 0.49; p = 2.83 × 10-4 ) and autoimmune hypothyroidism (IVW: OR = 0.86; p = 7.46 × 10-3 ). Both horizontal pleiotropy and heterogeneity tests indicated the validity of our bidirectional MR study. Finally, colocalization analysis suggested that there were shared causal variants between autoimmune hyperthyroidism and TL, further highlighting the robustness of the results. In conclusion, autoimmune hyperthyroidism may accelerate telomere attrition, and telomere attrition is a causal factor for AITDs.

Effects of altitude on thyroid disorders according to Chinese three-rung, ladder-like topography: national cross-sectional study.

BACKGROUND: Chinese topography appears a three-rung ladder-like distribution of decreasing elevation from northwest to southeast, which is divided by two sloping edges. Previous studies have reported that prevalence of thyroid diseases differed by altitude, and geographical factors were associated with thyroid disorders. To explore the association between three-rung ladder-like regions and thyroid disorders according to unique Chinese topographic features, we conducted an epidemiological cross-sectional study from 2015-2017 that covered all 31 mainland Chinese provinces. METHODS: A total of 78,470 participants aged ≥ 18 years from a nationally representative cross-sectional study were included. Serum thyroid peroxidase antibody, thyroglobulin antibody, and thyroid-stimulating hormone levels; urine iodine concentration; and thyroid volume were measured. The three-rung ladder-like distribution of decreasing elevation from northwest to southeast in China was categorized into three topographic groups according to elevation: first ladder, > 3000 m above sea level; second ladder, descending from 3000-500 m; and third ladder, descending from 500 m to sea level. The third ladder was further divided into groups A (500-100 m) and B (< 100 m). Associations between geographic factors and thyroid disorders were assessed using linear and binary logistic regression analyses. RESULTS: Participants in the first ladder group were associated with lower thyroid peroxidase (ß = -4.69; P = 0.00), thyroglobulin antibody levels (ß = -11.08; P = 0.01), and the largest thyroid volume (ß = 1.74; P = 0.00), compared with the other groups. The second ladder group was associated with autoimmune thyroiditis (odds ratio = 1.30, 95% confidence interval [1.18-1.43]) and subclinical hypothyroidism (odds ratio = 0.61, 95%confidence interval [0.57-0.66]) (P < 0.05) compared with the first ladder group. Group A (third ladder) (500-100 m) was associated with thyroid nodules and subclinical hypothyroidism (P < 0.05). Furthermore, group B (< 100 m) was positively associated with autoimmune thyroiditis, thyroid peroxidase and thyroglobulin antibody positivity, and negatively associated with overt hypothyroidism, subclinical hypothyroidism, and goiter compared with the first ladder group(P < 0.05). CONCLUSION: We are the first to investigate the association between different ladder regions and thyroid disorders according to unique Chinese topographic features. The prevalence of thyroid disorders varied among the three-rung ladder-like topography groups in China, with the exception of overt hyperthyroidism.

Exploring the Metabolic and Endocrine Preconditioning Associated with Thyroid Disorders: Risk Assessment and Association with Acne Severity.

Metabolic preconditioning, characterized by conditions like obesity and insulin resistance syndrome, disrupts hormonal balance. Elevated androgen levels stimulate excessive sebum production and follicular cell proliferation, leading to acne lesions. Similarly, thyroid hormone imbalances affect sebaceous gland activity, epidermal lipid composition, and skin cell turnover, impacting acne occurrence and severity. This study aimed to assess the potential contribution of metabolic and endocrine preconditions to acne development. A total of 389 patients diagnosed with acne were included and divided into three groups: the metabolic precondition group (MPG, N = 163, 41.9%), the endocrine precondition group (EPG, N = 162, 41.65%), and the control group (CG, N = 89, 22.88%). Data related to the degree of acne severity and comorbidities of interest were collected from the patients' medical records. In the groups with concomitant diseases, moderate and severe acne were significantly more prevalent (56.44% and 41.10% in MPG, and 35.80% and 61.11% in EPG) compared to the control group (5.61% and 4.89%). The most prevalent preconditions observed were insulin resistance syndrome in MPG (63.8%) and autoimmune thyroiditis in EPG (95.06%). Significant age-related differences in acne severity were found across all study groups (p < 0.05). In MPG, the age variable was significantly higher in the presence of mild acne, while in EPG, the age variable was significantly lower for the mild acne group. A positive association was observed between the severity of acne and insulin resistance syndrome, obesity, autoimmune thyroiditis, and hypothyroidism (p < 0.05). Risk analysis indicated a significantly higher risk (RR > 1, 95% CI RR > 1, p < 0.001) of developing moderate and severe acne in the presence of these preconditions. The presence of both metabolic and endocrine preconditions significantly increased the likelihood of developing severe acne, leading to the hypothesis that both conditions may be contributing factors to the development of acne.

Impact of metformin on hypothalamic-pituitary-thyroid axis activity in women with autoimmune and non-autoimmune subclinical hypothyroidism: a pilot study.

BACKGROUND: Metformin reduces plasma TSH levels if these levels are elevated. No study has investigated whether the hormonal effects of metformin are impacted by thyroid autoimmunity. The current study aimed to compare the effect of metformin on hypothalamic-pituitary-thyroid axis activity between subjects with mild hypothyroidism of different origins. METHODS: The study population consisted of two groups of women with prediabetes and mildly elevated TSH levels, matched by age, insulin sensitivity, TSH, and thyroid hormone levels. Group A included 26 women with autoimmune thyroiditis, while group B enrolled 26 individuals with hypothyroidism of non-autoimmune origin. Both groups were treated with metformin (2.55-3 g daily). Circulating levels of TSH, total and free thyroid hormones, glucose, insulin, prolactin, high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D, concentrations of thyroid antibodies, and structure parameters of thyroid homeostasis were assessed at baseline and 6 months later. RESULTS: All patients completed the study. At baseline, both groups differed in concentrations of thyroid peroxidase antibodies, thyroglobulin antibodies, hsCRP, and 25-hydroxyvitamin D. The drug reduced TSH and Jostel's index, with no difference between the study groups. The improvement in insulin sensitivity, observed in both groups, was more pronounced in group B than in group A. In women with autoimmune hypothyroidism, the drug increased SPINA-GT and decreased hsCRP levels. The remaining markers did not change throughout the study. CONCLUSIONS: The obtained results suggest that, despite differences in thyroid output, the impact of metformin on TSH levels is similar in hypothyroid women with and without thyroid autoimmunity.