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

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 (nZ941, 25-45 years) were recruited in a cross-sectional, populationbased 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 (FT 4 ), free triiodothyronine (FT 3 ), thyroperoxidase, and thyroglobulin antibodies, reverse T 3 (rT 3 ), thyroidbinding 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, FT 4 , ratio FT 3 :FT 4 , 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 FT 4 . 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.

Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling

“…The limited number of included patients, a consequence of strict inclusion and exclusion criteria, may result in low statistical power. Calculated parameters like SPINA-GD or the FT 3 /rT 3 ratio may provide valuable physiological insights, as they did in previous trials on NTIS [30,31,32,49,50], but they are also faced with limitations, since hormone concentrations also depend on tissue distribution and elimination. Therefore, future interventional trials with enhanced methodology and a larger number of included patients are necessary to provide more details on these associations or cause-effect relationships involved in NTIS and POAF.…”

“…Secondary outcome measures were concentrations of other hormones involved in thyroid homeostasis (total and free T 4 , TSH), total T 3 and nonclassical TH [3,5-diiodothyronine (3,5-T 2 ), 3,3′,5′-triiodothyronine (reverse, rT 3 ) and 3-iodothyronamine (3-T 1 AM)]. In order to get exploratory information on pathophysiological processes, derived parameters of thyroid homeostasis were calculated, including thyroid's secretory capacity (SPINA-GT), total deiodinase activity (SPINA-GD), FT 3 /rT 3 , 3,5-T 2 /FT 3 and 3,5-T 2 /rT 3 ratios [3,28,29,30,31,32] (see online suppl. methods for a detailed description; see www.karger.com/doi/10.1159/000381543 for all online suppl.…”

New EU criteria for endocrine disrupters

“…The variation in serum markers for thyroid function measured in repeated measures from the same subject is however relatively small compared to the inter-individual variability. A Belgian study of male siblings with normal thyroid function (euthyroid; n=941, 25-45 years) showed that serum levels of free T4, total T4, reverse T3 and thyroglobulin had the highest genetic or familial component of 80-90% [15]. Serum levels of free and total T3 had a moderate genetic influence of 60% and TSH had the lowest, 49%.…”

“…The Organisation for Economic Cooperation and Development (OECD) presented guidelines for testing of chemicals with putative endocrine disrupting properties in 2012. 15 These tests are focussed on the HPG-and the HPT-axes, and are based on classical acute and long-term toxicity studies. Here, the ambition was to identify adverse effects on endocrine systems from an endocrine point of view.…”

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation

“…Genome-wide association studies (GWAS) performed so far have revealed genetic variants in about 30 loci robustly associated with thyroid function [11][12][13] . However, these variants explain only <9% of the heritability of TSH and FT4 variation 14 , while in total, it has been estimated at 65 and 39-80% for TSH and FT4, respectively 15,16 , suggesting that many loci still await discovery.…”