Endocrine Abstracts

Background: Interindividual variation in thyroid hormone concentrations is greater than intraindividual variation, suggesting that individuals have different set-points for pituitary–thyroid axis function. Variation in thyroid hormone levels within the normal range has clinical effects and is associated with a number of clinical parameters such as bone mass, BMI, metabolic parameters, and heart rate. The aim of this study was therefore to gain a better insight into the determinants of this between-subject variation in thyroid hormone levels in healthy young men.

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. In these subjects, a complete assessment of thyroid hormone status was performed (TSH, F(T₄), F(T₃), TPO and TG Ab, reverse T₃ (rT₃), TBG and urinary iodine levels). Genotyping was performed by TaqMan SNP Genotyping assays and by KBiosciences.

Results: Total and free T₄, rT₃ and TBG had heritability estimates between 80 and 90%. Calculated estimates for (F)T₃ were considerably lower (60%), while TSH had the lowest estimate (49%). Significant associations were observed between SNPs in the thyroid pathway (rs4704397 in PDE8B, rs10149689 and rs12050077 in TSHR, rs11206244 and rs2235544 in DIO1 and rs13063628 in THRB) and TSH, FT₄, ratio FT₃/FT₄ and rT₃. Nevertheless, these SNPs only explain a limited part of the between-subject variability in thyroid hormones. As to age and life-style related factors, (F)T₃ was negatively related to age and positively to smoking and BMI (all P<0.0001) but not to urinary iodine concentrations. Smoking was negatively related to TSH (P=0.003) and positively to FT₄ (P=0.0009).

Conclusion: Both genetic and life-style related factors play a role in determining between-subject variation in thyroid hormones in euthyroid young men, although genetic factors are most important.