Endocrine Abstracts

Adequate thyroid hormone (TH) levels are essential for normal growth and differentiation, for the regulation of energy metabolism, and for the physiological function of virtually all human tissues. Epidemiological evidence shows that minor variation in TH serum levels, even within the normal range, can have important effects on different TH related clinical endpoints, such as bone mineral density, atrial fibrillation, metabolic syndrome and cardiovascular mortality.

In healthy subjects, serum TSH and TH levels show substantial inter-individual variability leading to wide laboratory reference ranges, whereas the intra-individual variability is within a much more narrow range. This suggests that every person has its own individual thyroid function ‘set-point’. Approximately 45–65% of this inter-individual variation in serum TSH and TH levels is determined by genetic factors, but the causative genes are not yet well established. Recent genome wide association studies have demonstrated associations of polymorphisms located in Phosphodiesterase 8B and the CAPZB locus with serum TSH levels, and well-known TH pathway genes such as the deiodinases, TSH receptor and TH transporters have been associated with TH serum levels in candidate gene analyses.

However, the variation that can be explained by these gene variants so far is only modest. This could be due to the presence of not-analyzed rare variants, or gene-environment and gene-gene interactions. Novel analytic approaches and the availability of whole-genome sequencing of large numbers of individuals will provide important new information on this topic in the upcoming years.

This presentation will focus on the interpretation of different genetic studies in thyroid hormone research and discusses its clinical relevance.