Endocrine Abstracts

In the last few years studies have shown that subtle variations in thyroid function, including subclinical thyroid dysfunction, and even variation in thyroid function within the normal range, are associated with morbidity and mortality. It is estimated that 40–65% of the inter-individual variation in serum TSH and FT4 levels is determined by genetic factors. To identify these factors, various linkage and candidate gene studies have been performed in the past, which have identified only a few genes. In the last decade, genome-wide association studies identified >100 genetic variants, while whole exome and whole genome sequencing studies are expected to further clarify the genetic basis of thyroid function in the near future. The identification of these genes has paved the way for various lines of research. Examples of follow-up in vitro characterization studies of these genes include the identification of SLC17A4 as a novel thyroid hormone transporter and AADAT as a novel thyroid hormone metabolizing enzyme. Furthermore, mendelian randomization studies are expected to clarify whether the observed associations between minor variations in thyroid function and clinical endpoints are causal or not, which is key when considering treatment for these mild variations in thyroid function. Finally, these genetic markers have been associated with normal range thyroid function as well as thyroid dysfunction, thereby possibly serving as predictive markers for the individual thyroid setpoint and for thyroid disease.