Daily Endocrinology Research Analysis
Three studies advance endocrinology across epidemiology and causal inference: a Danish nationwide cohort quantifies autoimmune disease risks in transgender individuals before and after gender-affirming care; a two-step Mendelian randomization in East Asians reveals a bidirectional link between arrhythmia and hyperthyroidism with blood urea nitrogen as a mediator; and a prospective birth cohort connects prenatal PFAS exposure to sex-specific adiposity at age 7 using DXA.
Summary
Three studies advance endocrinology across epidemiology and causal inference: a Danish nationwide cohort quantifies autoimmune disease risks in transgender individuals before and after gender-affirming care; a two-step Mendelian randomization in East Asians reveals a bidirectional link between arrhythmia and hyperthyroidism with blood urea nitrogen as a mediator; and a prospective birth cohort connects prenatal PFAS exposure to sex-specific adiposity at age 7 using DXA.
Research Themes
- Endocrine-immune interactions in gender-affirming care
- Causal pathways linking cardiovascular rhythm and thyroid function
- Developmental origins of metabolic risk via endocrine-disrupting chemicals
Selected Articles
1. Autoimmune diseases in 3812 Danish transgender persons and 38 120 cisgender controls before and after transgender care: a register-based cohort study.
Nationwide Danish registry data show elevated pre-diagnosis incidence of type 1 diabetes in transmasculine and transfeminine individuals and higher overall autoimmune disease in transfeminine persons. After transgender care, thyroid disease incidence increased in transfeminine individuals, while other autoimmune risks were similar to controls; GAHT use in transmasculine individuals was associated with higher autoimmune incidence.
Impact: Provides large-scale, real-world estimates of autoimmune disease patterns in transgender populations before and after care, informing screening and risk mitigation strategies.
Clinical Implications: Consider targeted screening for type 1 diabetes and thyroid disease in transgender patients, particularly around care initiation; incorporate comorbidities and mental health in risk assessment; monitor GAHT users for autoimmune events.
Key Findings
- Pre-diagnosis type 1 diabetes incidence was higher in transmasculine (IRR 1.98 [1.16–3.36]) and transfeminine (IRR 1.66 [1.05–2.61]) individuals versus same-birth-sex controls.
- Transfeminine persons had increased incidence of any autoimmune disease pre-diagnosis (IRR 1.35 [1.04–1.77]).
- Post-diagnosis, thyroid disease incidence increased in transfeminine persons (IRR 1.98 [1.09–3.61]); other autoimmune outcomes were comparable to controls.
- Among transmasculine individuals, GAHT use was associated with higher autoimmune disease incidence (IRR 2.50 [1.10–5.67]) versus nonusers.
Methodological Strengths
- Nationwide register-based cohort with large sample and matched cisgender controls by birth sex and age
- Pre- and post-care comparisons enable temporal risk pattern assessment
Limitations
- Observational design with potential residual confounding and misclassification from registry-based diagnoses
- Generalizability may be limited outside Denmark; details of hormone regimens and adherence not fully captured
Future Directions: Prospective studies integrating detailed GAHT exposure, immunologic biomarkers, and mechanistic pathways are needed to clarify causality and guide screening intervals.
2. Mediating role of blood metabolites in the relationship between arrhythmia and hyperthyroidism in East Asian populations.
Two-step Mendelian randomization using East Asian GWAS data supports a bidirectional causal relationship between arrhythmia and hyperthyroidism. Blood urea nitrogen mediated 9.7% of this relationship, with colocalization and sensitivity analyses confirming robustness and minimal pleiotropy.
Impact: Introduces a metabolite mediator (blood urea nitrogen) in the arrhythmia–hyperthyroidism axis, offering mechanistic insight and potential biomarker utility for risk stratification.
Clinical Implications: Clinicians should be aware of bidirectional risk between arrhythmia and hyperthyroidism; monitoring renal-metabolic status (e.g., BUN) may refine risk assessment and guide integrated cardio-thyroid management.
Key Findings
- Mendelian randomization showed arrhythmia increases hyperthyroidism risk (OR 1.272, p=0.003), with reverse MR also positive (OR 1.039, p=0.036).
- Blood urea nitrogen mediated 9.7% of the causal effect between arrhythmia and hyperthyroidism.
- Colocalization and multiple sensitivity analyses supported robustness with minimal pleiotropy or heterogeneity.
Methodological Strengths
- Two-step Mendelian randomization with IVW primary analysis and multiple sensitivity methods (weighted median, mode-based)
- Colocalization analysis to confirm shared causal variants across traits
Limitations
- Summary-level GWAS data limit individual-level adjustment and clinical covariates
- BUN mediation proportion is modest; clinical translation requires prospective validation
Future Directions: Prospective cohorts integrating serial thyroid, rhythm, and renal-metabolic biomarkers should validate BUN’s mediating role and assess intervention targets.
3. Prenatal PFAS exposure associates with DXA assessed markers of adiposity in 7-year-old children from the Odense Child Cohort.
In 881 mother–child pairs, higher maternal PFOA levels in early pregnancy were associated with greater total and android fat at age 7 in girls, with similar trends for PFNA and PFDA, while PFOS was linked to lower BMI in both sexes. Findings underscore sex-specific effects and the value of DXA over BMI in pediatric adiposity assessment.
Impact: Links prenatal exposure to endocrine-disrupting PFAS with DXA-defined adiposity in children using a well-characterized cohort, advancing developmental origins of health and disease research.
Clinical Implications: Public health strategies should consider reducing prenatal PFAS exposure; pediatric risk assessments may benefit from sex-specific thresholds and DXA-based body composition when feasible.
Key Findings
- Maternal PFOA was associated with higher total fat (+2.0%) and android fat (+3.8%) at age 7 in girls per 1 ng/mL increase.
- PFNA and PFDA showed similar positive trends with adiposity in girls, while higher PFOS correlated with lower BMI in both sexes.
- DXA-based measures revealed associations not fully captured by BMI, highlighting measurement sensitivity.
Methodological Strengths
- Prospective birth cohort with early pregnancy PFAS quantification and DXA body composition at age 7
- Sex-stratified multiple linear regression analyses with confidence intervals
Limitations
- Observational design cannot prove causality; residual confounding (diet, socioeconomic factors) possible
- Single time-point PFAS measures may not capture exposure dynamics; generalizability beyond Denmark uncertain
Future Directions: Longitudinal replication with repeated PFAS measurements, endocrine biomarker panels, and puberty outcomes; mechanistic studies on sex-specific adipogenesis.