Daily Endocrinology Research Analysis

OBJECTIVE: The risk of autoimmune disease could be increased in transgender (TG) persons and could be affected by TG care. We assessed the risk of autoimmune diseases in TG compared with controls before and after TG care. METHODS: A national register-based Danish cohort study in individuals diagnosed with gender dysphoria year 2000-2021. For each case, five age-matched cisgender controls of same birth sex and five age-matched controls of the opposite birth sex were included. Any autoimmune disease, type 1 diabetes and/or thyroid disease were study outcomes (International Classification of Diseases (ICD)-10 diagnosis and/or medical treatment for type 1 diabetes or thyroid disease). RESULTS: The cohort included 3812 TG and 38 120 controls. Before TG diagnosis, the incidence rate (IR) of type 1 diabetes was significantly higher in transmasculine persons (TM, n = 1993) compared with controls of same birth sex: incidence rate ratio (IRR) = 1.98 (1.16; 3.36). In transfeminine persons (TF, n = 1819) versus controls of same birth sex, the IRR for type 1 diabetes was 1.66 (1.05; 2.61) and for any autoimmune disease 1.35 (1.04; 1.77). Higher incidence of any autoimmune disease in TG was associated with higher age, medical morbidity, and psychiatric disease.After TG diagnosis, the IRR for thyroid disease was 1.98 (1.09; 3.61) in TF versus controls of same birth sex, whereas the IRR for remaining autoimmune outcomes were comparable between TG and controls of same birth sex. TM using GAHT had higher incidence of autoimmune disease 2.50 (1.10; 5.67) compared with nonusers. CONCLUSION: Higher incidence of type 1 diabetes in TG compared with cisgender controls could be attenuated by TG care.

BACKGROUND AND AIM: Arrhythmia is a common manifestation of hyperthyroidism, and blood metabolites may play a regulatory role in cardiovascular health and thyroid function. However, the mediating role of blood metabolites between arrhythmia and hyperthyroidism, particularly in East Asian populations, remains unclear. METHODS AND RESULTS: We used large-scale GWAS data from East Asian populations for a two-step Mendelian randomization (MR) analysis. First, we assessed the causal link between arrhythmia and hyperthyroidism, then evaluated the mediating role of blood metabolites. GWAS data on arrhythmia, hyperthyroidism, and metabolites were used. Mediation effects were calculated, and sensitivity analyses ensured robustness. The inverse-variance weighted (IVW) method was the primary tool, while colocalization analysis assessed shared genetic loci, confirming if the genetic signals for these traits arise from the same variants. The analysis revealed a significant association between arrhythmia and increased hyperthyroidism risk (OR = 1.272, p = 0.003), and reverse MR confirmed a positive association (OR = 1.039, p = 0.036), indicating a bidirectional link. Sensitivity analyses using weighted median, simple mode, and weighted mode provided consistent results. Blood urea nitrogen was identified as a key mediator, explaining 9.7 % of the causal relationship between arrhythmia and hyperthyroidism. These findings were unaffected by heterogeneity or pleiotropy. CONCLUSIONS: Blood urea nitrogen is a novel mediator in the arrhythmia-hyperthyroidism relationship, highlighting its potential role in cardiovascular and thyroid health.

The global increase in childhood overweight and obesity presents significant public health concerns due to its long-term health implications. Emerging evidence suggests that exposure to endocrine disrupting chemicals, such as per- and polyfluoroalkylated substances (PFAS), may be obesogenic and contribute to adiposity. This study aimed to investigate the association between prenatal PFAS exposure and markers of adiposity in 7-year-old children, focusing on potential sex-specific differences. Data was analyzed from 881 mother-child pairs in the Odense Child Cohort, Denmark. Maternal serum concentrations of perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in early pregnancy. At age 7, body composition, including body mass index (BMI), lean mass and fat distribution (total, gynoid, and android), was assessed using dual-energy X-ray absorptiometry (DXA). The median (25th;75th percentile) concentrations of PFHxS, PFOS, PFOA, PFNA, and PFDA were 0.4 (0.2;0.5), 7.6 (5.6;10.4), 1.7 (1.1;2.3), 0.6 (0.5;0.8), and 0.3 (0.2;0.4) ng/mL, respectively. Multiple linear regressions were used to assess sex specific associations between maternal PFAS concentrations and markers of adiposity. In girls, 1 ng/mL increase in maternal PFOA was associated with 2.0 % (95 % confidence interval: 0.3; 3.7) increase in total fat, 1.3 % (-0.3; 2.9) increase in gynoid fat, and 3.8 % (0.6; 7.0) increase in android fat. Associations for PFNA and PFDA followed similar trends, whereas higher maternal PFOS concentrations were associated with lower BMI among both girls and boys. These findings suggest that prenatal exposure to certain PFAS may influence the accumulation of excess fat in girls. Our findings highlight the importance of studying sex specific differences and using accurate measures of body composition as BMI may not adequately reflect body fat in children during growth.