Early appearance of thyroid autoimmunity in children followed from birth for type 1 diabetes risk.

PURPOSE: Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) define pre-clinical autoimmune thyroid disease (AITD) which can progress to either clinical hypo- or hyperthyroidism. We determined the age at seroconversion in children genetically at risk for type 1 diabetes. METHODS: TPOAb and TgAb seropositivity were determined in 5066 healthy children with HLA DR3 or DR4 containing haplogenotypes from The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Children seropositive on the cross-sectional initial screen at 8-13 years of age had longitudinally collected samples (from 3.5 months of age) screened retrospectively and prospectively for thyroid autoantibodies to identify the age at seroconversion. First-appearing autoantibody was related to sex, HLA genotype, family history of AITD, and subsequent thyroid dysfunction and disease. RESULTS: The youngest appearance of TPOAb and TgAb was 10 and 15 months of age, respectively. Girls had higher incidence rates of both autoantibodies. Family history of AITD was associated with a higher risk of TPOAb hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.17, 3.08; and TgAb HR 2.55, 95% CI 1.91, 3.41. The risk of progressing to hypo- or hyperthyroidism was not different between TgAb and TPOAb, but children with both autoantibodies appearing at the same visit had a higher risk compared to TPOAb appearing first (HR 6.34, 95% CI 2.72, 14.76). MAIN CONCLUSION: Thyroid autoantibodies may appear during the first years of life, especially in girls, and in children with a family history of AITD. Simultaneous appearance of both autoantibodies increases the risk for hypo- or hyperthyroidism.

Impact of Thyroid Autoimmunity on the Clinical and Biochemical Characteristics of Type 1 Diabetes Mellitus Patients.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is frequently associated with other autoimmune disorders that are characterized by the presence of organ-specific autoantibodies. Autoimmune thyroid disease (AIT) is the most frequent autoimmune disorder associated with T1DM. Thyroid peroxidase antibodies (TPOAb) serve as a marker for diagnosing AIT. Prior research indicates that thyroid dysfunction can negatively impact linear growth and glycemic control in subjects with T1DM. The present study was done to determine the impact of thyroid autoimmunity on the clinical and biochemical characteristics of patients with newly diagnosed T1DM. METHODS: In this single-center, hospital-based, observational cross-sectional study, we enrolled 70 patients with newly diagnosed T1DM ≤18 years of age. Type 1 diabetes mellitus was diagnosed based on the acute onset of osmotic symptoms with or without diabetic ketoacidosis (DKA), severe hyperglycemia (blood glucose >13.9 mmol/l (>250 mg/dl)), and insulin requirement from the onset of diabetes. Secondary diabetes, pancreatic diabetes (Type 3c), and maturity-onset diabetes of the young (MODY) were excluded. Participants were screened for AIT disease using TPOAb testing. Based on the presence or absence of TPOAb, the participants were categorized into two groups: Group A comprised individuals with T1DM who tested positive for TPOAb, while Group B consisted of those who tested negative for TPOAb. RESULTS: Out of 70 patients, 41.4% were girls and 58.6% were boys, with a mean age of 9.8±4.4 years. The prevalence of TPOAb among the cohort was 18.6%. A significant majority of patients (71.4%), presented with DKA. Group A showed significantly lower mean height standard deviation scores (SDS) compared to Group B (-0.3±0.6 vs. -0.8±0.5, p = 0.004), but no differences in weight SDS or BMI SDS. Hemoglobin A1C (HbA1c) levels, C-peptide levels, and frequency of DKA did not differ between groups. Group A had higher mean thyroid-stimulating hormone (TSH) levels (4.8±3.7 µU/ml vs. 2.6±1.5 µU/ml, p = 0.001) and a greater proportion of patients with TSH levels above the upper limit of normal compared to Group B (38.4% vs. 7.1%, p = 0.008). Additionally, Group A exhibited a higher frequency of glutamic acid decarboxylase antibody (GADA) positivity compared to Group B (46.1% vs. 17.5%, p = 0.04). CONCLUSION: Patients positive for TPOAb exhibited significantly lower height SDS compared to TPOAb-negative patients. Additionally, T1DM patients with TPOAb positivity showed an increased frequency of GADA compared to those without TPOAb. However, no significant differences were found in HbA1c levels, C-peptide levels, or hematological parameters between TPOAb-positive and TPOAb-negative patients. These findings emphasize the impact of TPOAb on growth parameters in T1DM and advocate for routine screening of TPOAb in all T1DM patients, starting at the time of diabetes diagnosis.

Analysis of T follicular and T peripheral helper lymphocytes in autoimmune thyroid disease.

PURPOSE: Peripheral helper T (Tph) cells have an important role in the induction of humoral immune responses and autoantibody production. Accordingly, it is feasible that this lymphocyte subset has a relevant role in the pathogenesis of autoimmune thyroid diseases (AITD). In this study we aim to analyze the levels and function of Tph cells in blood samples from patients with AITD. METHODS: We performed an observational study with cases and controls. Blood samples were obtained from nineteen patients with Hashimoto's thyroiditis (HT), twenty-four with Graves' disease (GD), and fifteen healthy controls. In addition, the levels of follicular T helper (Tfh) cells and Tph cells, the release of interleukin-21 (IL-21) by these lymphocytes and the number of plasmablasts were analyzed by multi-parametric flow cytometry analyses. RESULTS: Increased percentages of Tfh and Tph lymphocytes were detected in patients with HT and GD. Furthermore, an enhanced synthesis of the cytokine IL-21 by these cells was observed. Accordingly, we detected significant higher percentages of plasmablasts in patients with GD, and these values tended to be also higher in HT patients. Moreover, significant positive associations were observed between the levels of Tfh or Tph and the number of plasmablast or anti-TSHR Ab titers in patients with AITD. CONCLUSION: Our data suggest that Tph lymphocytes may have a relevant role in the pathogenesis of AITD.

Exploring Thyroid Function after Kidney Transplantation: The Complex Interplay Unacknowledged in Post-Transplant Care.

Background/Objectives: The interplay between thyroid function and kidney graft function following kidney transplantation remains incompletely understood. Thyroid disorders are more prevalent in kidney transplant recipients than in the general population and are associated with poorer outcomes. Methods: This prospective, single-center study was designed to estimate thyroid function (thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), free thyroxine (FT4), as well as anti-thyroid peroxidase antibody (anti-TPO), anti-thyroglobulin antibody (anti-Tg), and thyroid-stimulating immunoglobulin (TSI)) and its influence on kidney graft function among a cohort of 23 kidney transplant recipients during a follow-up period of 12 months. Results: Significantly increased levels of T4 and T3 were observed 12 months post-transplantation, with FT3 levels increasing significantly after 6 months. The prevalence of immeasurably low anti-Tg antibodies rose during follow-up. Initially, 8% of patients showed positive TSI, which turned negative for all after 6 months. A statistically significant correlation was found between the initial TSH and the estimated glomerular filtration rate (eGFR) value 6 months after transplantation (p = 0.023). The graft function was stable. Proteinuria was statistically significantly lower 12 months after transplantation. Conclusions: Identifying additional risk factors, understanding their impact on kidney graft function, and recognizing cardiovascular comorbidities could enhance patient care. Notably, this study marks the first prospective investigation into thyroid function after kidney transplantation in Croatia, contributing valuable insights to the global understanding of this complex interplay.

Autoimmune thyroid disease and ovarian hypofunction: a review of literature.

Thyroid hormones(THs) are essential for the proper functioning of the ovaries, and multiple studies have shown that thyroid abnormalities, especially during adolescence and reproductive age, can lead to lifelong ovarian dysfunction. Autoimmune thyroid disease (AITD), one of the most common organ specific autoimmune diseases, is mainly mediated by cellular autoimmune reactions, and has strong inflammatory infiltration and immune active cells, including chemokines and cytokines, which are important components of ovarian aging. This suggests that autoimmune and inflammatory molecular processes may play a role in the emergence of ovarian dysfunction. The purpose of this review is to summarize recent in vivo and in vitro evidence of a complex relationship between AITD and ovarian dysfunction. AITD is closely related to the decline of ovarian function from the perspective of antibody, cytokine, oxidative stress, and genetic factors. Finally, some of the currently known treatments for AITD and hypo ovarian disease are summarized.

Vitamin D: An Essential Nutrient in the Dual Relationship between Autoimmune Thyroid Diseases and Celiac Disease-A Comprehensive Review.

Autoimmune thyroid diseases (AITD) are among the most frequent autoimmune disorders, with a multifactorial etiology in which both genetic and environmental determinants are probably involved. Celiac disease (CeD) also represents a public concern, given its increasing prevalence due to the recent improvement of screening programs, leading to the detection of silent subtypes. The two conditions may be closely associated due to common risk factors, including genetic setting, changes in the composition and diversity of the gut microbiota, and deficiency of nutrients like vitamin D. This comprehensive review discussed the current evidence on the pivotal role of vitamin D in modulating both gut microbiota dysbiosis and immune system dysfunction, shedding light on the possible relevance of an adequate intake of this nutrient in the primary prevention of AITD and CeD. While future technology-based strategies for proper vitamin D supplementation could be attractive in the context of personalized medicine, several issues remain to be defined, including standardized assays for vitamin D determination, timely recommendations on vitamin D intake for immune system functioning, and longitudinal studies and randomized controlled trials to definitely establish a causal relationship between serum vitamin D levels and the onset of AITD and CeD.

Increased frequency of microalbuminuria in patients with type 3 autoimmune polyglandular syndrome (APS) compared to isolated autoimmune type 1 diabetes mellitus: A real-life study.

AIM OF THE STUDY: The primary aim of the study was to evaluate the differences in metabolic control and chronic microvascular complications in patients with type 3 autoimmune polyglandular syndrome (APS3), compared to type 1 diabetes mellitus (T1DM) alone. Secondary aims were to evaluate the age of autoimmune thyroid disease (AIT) onset and the effects of levothyroxine treatment on metabolic control in patients with APS3. MATERIAL AND METHODS: We retrospectively reviewed 276 patients with T1DM alone and 214 patients with APS3 and evaluated clinical and metabolic parameters and microvascular complications. RESULTS: Patients with T1DM showed a longer duration of diabetes (p = 0.001) and lower age of diabetes onset (p = 0.020) compared to patients with APS3. Female gender (p = 0.001) and microalbuminuria (p = 0.006) were significantly more frequent in patients with APS3 compared to T1DM. In addition, patients with APS3 showed higher AIT onset frequency in the 16-30 quartile age-range. Furthermore, APS3 patients treated with levothyroxine showed significantly better HbA1c values than non-treated patients (p = 0.001). CONCLUSIONS: We found that patients with APS3 showed positive microalbuminuria, earlier than T1DM. Patients with APS3 showed higher frequency of AIT age of onset in the 16-30 age-range and those treated with levothyroxine had better metabolic control, than untreated ones.

[Expression of miR-142 and its relationship with Th17/Treg imbalance in children with autoimmune thyroid disease]. / miR-142åœ¨å„¿ç«¥è‡ªèº«å ç–«æ€§ç”²çŠ¶è ºç–¾ç— ä¸­è¡¨è¾¾åŠä¸ŽTh17/Tregå¤±è¡¡å ³ç³»çš„ç ”ç©¶.

OBJECTIVES: To investigate the expression of microRNA-142 (miR-142) in children with autoimmune thyroid disease (AITD) and its relationship with the imbalance of helper T cell 17 (Th17) and regulatory T cell (Treg). METHODS: A total of 89 children hospitalized for AITD from January 2019 to December 2022 were prospectively selected as the study subjects, including 48 children with Graves' disease (GD group) and 41 children with Hashimoto's thyroiditis (HT group). Additionally, 55 healthy children undergoing physical examinations during the same period were selected as the control group. The differences in serum miR-142, antithyroglobulin antibody (TGAb), antithyroperoxidase antibody (TPOAb), Th17/Treg, and interleukin-17 (IL-17) expression were compared among the groups. RESULTS: The expression of miR-142, TPOAb, TGAb, Th17, Th17/Treg, and IL-17 in the GD group and HT group was higher than that in the control group, while Treg was lower than that in the control group (P<0.05). Pearson correlation analysis revealed that in the GD group, miR-142 was positively correlated with TPOAb, TGAb, Th17, Th17/Treg, and IL-17 (r=0.711, 0.728, 0.785, 0.716, 0.709, respectively; P<0.001) and negatively correlated with Treg (r=-0.725, P<0.001); in the HT group, miR-142 was positively correlated with TPOAb and TGAb (r=0.752, 0.717, respectively; P<0.001). CONCLUSIONS: miR-142 is highly expressed in children with AITD, and its expression may be related to the Th17/Treg imbalance in children with GD.

Exploring the link between obesity and hypothyroidism in autoimmune thyroid diseases: a metabolic perspective.

Background: The management of primary hypothyroidism demands a comprehensive approach that encompasses both the implications of autoimmune thyroid disease and the distinct effects posed by obesity and metabolic irregularities. Despite its clinical importance, the interplay between obesity and hypothyroidism, especially in the context of metabolic perspectives, is insufficiently explored in existing research. This study endeavors to classify hypothyroidism by considering the presence of autoimmune thyroid disease and to examine its correlation with various metabolic obesity phenotypes. Method: This research was conducted by analyzing data from 1,170 individuals enrolled in the Thyroid Disease Database of Shandong Provincial Hospital. We assessed four distinct metabolic health statuses among the participants: Metabolically Healthy No Obese Metabolically Healthy Obese Metabolically Unhealthy No Obese and Metabolically Unhealthy Obese Utilizing logistic regression, we investigated the association between various metabolic obesity phenotypes and hypothyroidism. Results: The study revealed a significant correlation between the Metabolically Unhealthy Obese (MUO) phenotype and hypothyroidism, particularly among women who do not have thyroid autoimmunity. Notably, the Metabolically Unhealthy No Obese (MUNO) phenotype showed a significant association with hypothyroidism in individuals with thyroid autoimmunity, with a pronounced prevalence in women. Furthermore, elevated levels of triglycerides and blood glucose were found to be significantly associated with hypothyroidism in men with thyroid autoimmunity and in women without thyroid autoimmunity. Conclusion: Effective treatment of hypothyroidism requires a thorough understanding of the process of thyroid autoimmune development. In patients without concurrent thyroid autoimmunity, there is a notable correlation between obesity and metabolic issues with reduced thyroid function. Conversely, for patients with thyroid autoimmunity, a focused approach on managing metabolic abnormalities, especially triglyceride levels, is crucial.

Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease.

BACKGROUND: In recent years, the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes (T1D). While it has been established that 20%-30% of T1D patients suffer from autoimmune thyroid disease (AITD), there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients. Among commercially available anti-islet autoantibodies, glutamic acid decarboxylase 65 autoantibodies (GADAs) are often the first marker measured in general clinical practice. AIM: To investigate the frequency of anti-islet autoantibodies in AITD patients. METHODS: Our study involved four hundred ninety-five AITD patients, categorized into three distinct groups: AITD with T1D (n = 18), AITD with phenotypic type 2 diabetes (T2D) (n = 81), and AITD without diabetes (n = 396), and the enzyme-linked immunosorbent assay (ELISA) was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody (3 Screen ICA), GADA, insulinoma-associated antigen-2 autoantibodies (IA-2As), and zinc transporter 8 autoantibodies (ZnT8As) within these groups. RESULTS: The frequency of 3 Screen ICA in AITD patients with T1D, T2D, and those without diabetes were 88.9%, 6.2%, and 5.1%, respectively, with no significant difference seen between the latter two groups. Notably, the frequency of 3 Screen ICA was 11.1% higher in AITD patients with T1D, 1.3% higher in AITD patients with T2D, and 1.1% higher in AITD patients without diabetes compared to GADA, respectively. Furthermore, 12.5%, 20.0%, and 20.0% of the 3 Screen ICA-positive patients were negative for GADA. Additionally, 1.3% of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies. Among the 3 Screen ICA-positive patients, there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes (37.5% vs 5.0%, P < 0.05). However, this proportion was similar to that in AITD patients with T2D (20.0%). Nevertheless, there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes (436.8 ± 66.4 vs 308.1 ± 66.4 index). Additionally, no significant difference in 3 Screen ICA titers was observed between Graves' disease and Hashimoto's thyroiditis in any of the groups. CONCLUSION: Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D. Thus, 3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.

Unraveling susceptibility genes: A contemporary overview of autoimmune thyroid diseases.

Autoimmune thyroid diseases (AITDs), including Graves' disease and Hashimoto's thyroiditis, are organ-specific autoimmune disorders characterized by conditions including goiter, autoimmune thyroiditis, hyperthyroidism, and hypothyroidism, which represent the most severe clinical manifestations of AITDs. The prevalence of autoimmune thyroid disorders is on the rise, influenced by increased environmental factors and changes in modern lifestyles. Understanding the pathophysiology of AITDs is crucial for identifying key factors that affect the disease's onset, progression, and recurrence, thereby laying a solid foundation for precise diagnosis and treatment. The development of AITDs involves a complex interplay of environmental influences, immune dysfunctions, and genetic predispositions. Genetic predispositions, in particular, are significant, with numerous genes identified as being linked to AITDs. This article focuses on examining the genes vulnerable to AITDs to deepen our understanding of the relevant genetic contributors, ultimately facilitating the development of effective prevention and treatment methods.

Characteristics of Human Leukocyte Antigen Class II Genes in Japanese Patients with Type 1 Diabetes and Autoimmune Thyroid Disease.

Genetic factors, particularly human leukocyte antigen (HLA) class II genes, are known to significantly influence the onset of type 1 diabetes (T1D). Additionally, patients with T1D often develop autoimmune thyroid diseases (AITD). Despite this association, comprehensive research on individuals with both AITD and T1D in Japan, especially regarding the influence of specific HLA alleles, remains insufficient. In this retrospective study, we analyzed 44 inpatients diagnosed with T1D. These patients were predominantly female, with an average onset age of 35 years, poor blood sugar control, and approximately 43.2% had concurrent AITD. We observed significant associations of HLA-DRB1*04:05, HLA-DRB1*09:01 and HLA-DRB1*15:02 alleles with T1D regardless of AITD presence, which had been previously established for T1D in Japanese. In this context, comparing Japanese patients with AITD alone, we noted AITD comorbidity with T1D results in alterations in the frequencies of HLA-DRB1*09:01, HLA-DRB1*04:03, and HLA-DRB1*15:02. Furthermore, HLA-DRB1*04:05, HLA-DRB1*09:01, HLA-DRB1*13:02, and HLA-DRB1*15:01 alleles may be alleles whose susceptibility varies for both conditions. These findings underscore the importance of understanding the relationship between T1D, AITD, and HLA genetics, which may inform personalized treatment strategies and facilitate the development of targeted therapies. Future research endeavors should aim to elucidate underlying mechanisms and validate these findings in larger cohorts.

Home capillary sampling and screening for type 1 diabetes, celiac disease, and autoimmune thyroid disease in a Swedish general pediatric population: the TRIAD study.

Objective: To screen a general pediatric population for type 1 diabetes (T1D), celiac disease (CD), and autoimmune thyroid disease (AITD) after home capillary sampling. Methods: Swedish schoolchildren between 6-9 years and 13-16 years of age were invited to screening by taking a capillary sample at home. Samples were returned by mail and assessed for autoantibodies associated with T1D, CD, and AITD. Persistently autoantibody-positive children were referred for clinical follow-up. Results: Of 19,593 invited, 3,527 (18.0%) consented to participate and 2,315/3,527 (65.6%) returned a blood sample of sufficient volume. Hemolysis occurred in 830/2,301 (36.1%) samples. After exclusion of 42 children with previously known T1D, CD, or AITD, and two autoantibody-positive children who declined a confirmatory sample, 2,271/19,593 (11.6%) were included. 211/2,271 (9.3%) had persistent autoantibodies: 60/2,271 (2.6%) with T1D autoantibodies, 61/2,271 (2.7%) with CD autoantibodies, and 99/2,271 (4.4%) with AITD autoantibodies; 9/2,271 (0.4%) were autoantibody positive for ≥1 disease. After clinical follow-up, 3/2,271 (0.1%) were diagnosed with T1D, 26/2,271 (1.1%) with CD, and 6/2,271 (0.3%) with AITD. Children with a first-degree relative (FDR) with T1D, CD, and/or AITD, had higher occurrence of autoantibodies compared to children without an FDR (63/344, 18.3%, vs. 148/1,810, 8.2%) (p < 0.0001, OR 2.52, 95% CI 1.83-3.47), and higher occurrence of screening-detected diagnosis (14/344, 4.1%, vs. 21/1,810, 1.2%) (p < 0.0001, OR 3.61, 95% CI 1.82-7.18). Half of these children screened positive for another disease than the FDR. Conclusion: Screening for T1D, CD, and AITD by home capillary sampling in a Swedish general pediatric population detected autoimmunity in 9.3% and undiagnosed disease in 1.5%.

Clinical Outcomes of MOK Pharmacopuncture in an Elderly Male Patient with Hypothyroidism-A Case Report and Literature Review.

Hypothyroidism is more common in women and individuals between 30 and 50 years old. This case report depicts the clinical outcomes of MOK pharmacopuncture, a type of Korean medicine treatment, for an elderly male patient with hypothyroidism who was on long-term L-thyroxine (LT4) therapy but still felt chronically lethargic and tired and was generally in poor health. A 72-year-old Korean man has been on LT4 since being diagnosed with hypothyroidism 16 years ago and has tried to discontinue hormone supplements in the past. The patient was treated with MOK pharmacopuncture, mainly at the ST10 acupoint, twice a week for four months. Following the treatment, the T3, free-T4, and TPO Ab levels and thyroiditis status on ultrasound showed improvement. Additionally, there were a normalization of ESR levels, an enhancement in the quality of life, a reduction in depression scores, an improvement in the antioxidant status, and an alleviation of major symptoms when compared to pre-treatment conditions. This case report demonstrates the potential of MOK pharmacopuncture as a complementary treatment for an elderly man with hypothyroidism who had a poor quality of life due to fatigue and lethargy despite LT4 treatment.

Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management.

As a common hyperglycemic disease, type 1 diabetes mellitus (T1DM) is a complicated disorder that requires a lifelong insulin supply due to the immune-mediated destruction of pancreatic ß cells. Although it is an organ-specific autoimmune disorder, T1DM is often associated with multiple other autoimmune disorders. The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease (AITD), which mainly exhibits two extremes of phenotypes: hyperthyroidism [Graves' disease (GD)] and hypo-thyroidism [Hashimoto's thyroiditis, (HT)]. However, the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications. Thus, routine screening of thyroid function has been recommended when T1DM is diagnosed. Here, first, we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases. Subsequently, an updated review of the association between T1DM and AITD is offered. Finally, we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD, suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.

Risk of Thyroid Cancer in People With Type 1 Diabetes by Autoimmune Thyroid Diseases and Tumor Histology.

Context: Thyroid cancer is the most common endocrine cancer, but little is known about it in type 1 diabetes (T1D) and its potential association with autoimmune diseases. Objective: This study aims to assess the risk of thyroid cancer in adults with long-term T1D compared to individuals without diabetes and the proposed association of thyroid autoimmune diseases with thyroid cancer. Methods: The study included 4758 individuals with T1D participating in the Finnish Diabetic Nephropathy Study and 12 710 controls. Thyroid cancers were obtained from the Finnish Care Registers for Health Care. Results: 27 (0.57%) individuals with T1D had thyroid cancer compared to 27 (0.21%) in the controls (standardized incidence ratio 2.43; 95% confidence interval 1.59-3.56). The absolute increase in incidence was modest, with a 0.36%-unit rise. This translates to 17 additional cases among 4710 individuals with T1D. Cancer type was papillary in 81.5% of individuals with T1D and 88.9% of the controls; the rest were follicular. In T1D the distribution of hypothyreosis was similar between those with (n = 5, 18.5%) and without (18.1%) cancer, but hyperthyreosis was diagnosed more often with thyroid cancer (n = 3, 11.1%) than without (2.3%, P = .003). None of the thyroid cancers were invasive or had metastatic characteristics. Conclusion: Although there is an excess risk of thyroid cancer, it is only marginally increased (0.36%-unit) in individuals with T1D compared to control individuals and was not associated with increased morbidity or mortality. An overdiagnosis effect due to regular health care contacts is the most likely explanation for the higher risk.

Methylation levels of the IL10 gene in peripheral blood are related to the intractability of Graves' disease.

The prognosis of autoimmune thyroid diseases (AITDs), including Hashimoto's disease (HD) and Graves' disease (GD), is difficult to predict. DNA methylation regulates gene expression of immune mediating factors. Interleukin (IL)-10 is a Th2 cytokine that downregulates inflammatory cytokines produced by Th1 cells. To clarify the role of methylation of the IL10 gene in the prognosis of AITD, we evaluated the methylation levels of two CpG sites in the IL10 promoter using pyrosequencing. The methylation levels of the -185 CpG site of the IL10 gene were related to age and GD intractability in GD patients. Furthermore, the C carrier of the IL10-592 A/C polymorphism was related to low methylation levels of the -185 CpG site. The methylation levels of the IL10-185 CpG site of the IL10 gene were related to the intractability of GD and were lower in individuals with the C allele of the IL10-592 A/C polymorphism.

Causal relationship between inflammatory cytokines and autoimmune thyroid disease: a bidirectional two-sample Mendelian randomization analysis.

Background: Autoimmune thyroid disease (AITD) ranks among the most prevalent thyroid diseases, with inflammatory cytokines playing a decisive role in its pathophysiological process. However, the causal relationship between the inflammatory cytokines and AITD remains elusive. Methods: A two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal connection between AITD and 41 inflammatory cytokines. Genetic variations associated with inflammatory cytokines were sourced from the FinnGen biobank, whereas a comprehensive meta-analysis of genome-wide association studies (GWASs) yielded data on Graves' disease (GD) and Hashimoto thyroiditis. Regarding the MR analysis, the inverse variance-weighted, MR-Egger, and weighted median methods were utilized. Additionally, sensitivity analysis was conducted using MR-Egger regression, MR-pleiotropy residual sum, and outliers. Results: Seven causal associations were identified between inflammatory cytokines and AITD. High levels of tumor necrosis factor-ß and low levels of stem cell growth factor-ß were indicative of a higher risk of GD. In contrast, high levels of interleukin-12p70 (IL-12p70), IL-13, and interferon-γ and low levels of monocyte chemotactic protein-1 (MCP-1) and TNF-α suggested a higher risk of HD. Moreover, 14 causal associations were detected between AITD and inflammatory cytokines. GD increases the levels of macrophage inflammatory protein-1ß, MCP-1, monokine induced by interferon-γ (MIG), interferon γ-induced protein 10 (IP-10), stromal cell-derived factor-1α, platelet-derived growth factor BB, ß-nerve growth factor, IL-2ra, IL-4, and IL-17 in blood, whereas HD increases the levels of MIG, IL-2ra, IP-10, and IL-16 levels. Conclusion: Our bidirectional MR analysis revealed a causal relationship between inflammatory cytokines and AITD. These findings offer valuable insights into the pathophysiological mechanisms underlying AITD.

Pulmonary Hypertension and Hypothyroidism-Still an Important Clinical Coincidence in Paediatric Population, an Endocrinologist's Point of View.

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.

Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases: A case report.

BACKGROUND: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are two common clinical autoimmune liver diseases, and some patients have both diseases; this feature is called AIH-PBC overlap syndrome. Autoimmune thyroid disease (AITD) is the most frequently overlapping extrahepatic autoimmune disease. Immunoglobulin (IgG) 4-related disease is an autoimmune disease recognized in recent years, characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues. CASE SUMMARY: A 68-year-old female patient was admitted with a history of right upper quadrant pain, anorexia, and jaundice on physical examination. Laboratory examination revealed elevated liver enzymes, multiple positive autoantibodies associated with liver and thyroid disease, and imaging and biopsy suggestive of pancreatitis, hepatitis, and PBC. A diagnosis was made of a rare and complex overlap syndrome of AIH, PBC, AITD, and IgG4-related disease. Laboratory features improved on treatment with ursodeoxycholic acid, methylprednisolone, and azathioprine. CONCLUSION: This case highlights the importance of screening patients with autoimmune diseases for related conditions.