Heredity and lifestyle in the determination of between-subject variation in thyroid hormone levels in euthyroid men

TLDR: Both genetic and lifestyle-related factors play a role in determining between-subject variation in TH levels in euthyroid young men, although genetic factors seem most important.

Abstract: Objective: Variation in thyroid hormone (TH) concentrations between subjects is greater than in a single subject over a prolonged period of time, suggesting an individual set point for thyroid function. We have previously shown that TH levels within normal range are associated with clinical indices such as bone mass, BMI, and heart rate. The aim of this study on young men was therefore to gain insight into the determinants of variation in TH levels among healthy subjects. Methods: Healthy male siblings (n=941, 25-45 years) were recruited in a cross-sectional, population-based study; a history or treatment of thyroid disease and thyroid auto-immunity were exclusion criteria. A complete assessment of TH status was performed (TSH, free thyroxine (FT4), free triiodothyronine (FT3), thyroperoxidase, and thyroglobulin antibodies, reverse T-3 (rT(3)), thyroid-binding globulin (TBG), and urinary iodine levels). Genotyping was performed by TaqMan and KASP (KBiosciences) genotyping assays. Results: (F)T-4, rT(3), and TBG had heritability estimates between 80 and 90%. Estimates were lower for (F)T-3 (60%) and lowest for TSH (49%). Significant associations were observed between different single-nucleotide polymorphisms (SNPs) in the thyroid pathway and TSH, FT4, ratio FT3:FT4, and rT(3). Nevertheless, these SNPs only explain a limited part of the heredity. As to age and lifestyle-related factors, (F)T-3 was negatively related to age and education level, positively to smoking and BMI (all P<0.0001) but not substantially to urinary iodine concentrations. Smoking was also negatively related to TSH and positively to FT4. Conclusion: Both genetic and lifestyle-related factors play a role in determining between-subject variation in TH levels in euthyroid young men, although genetic factors seem most important.