Endocrine Abstracts

The circulating levels of serum TSH and thyroid hormones represent biochemical phenotypes reflecting thyroid homeostasis. Studying the regulation of biochemical measures related to the thyroid in healthy individuals could prove essential in understanding the pathways that eventually lead to thyroid disease. It is the combined effect of genetic and environmental factors that give rise to these endophenotypes. It has been established that the measures reflecting thyroid homeostasis have a substantial heritable component. Thyroid hormone levels are partly genetically correlated – although most of the genetic variance for these measures is trait specific. Genetic as well as environmental risk factors (such as iodine intake and smoking) with significant influence on the thyroid related phenotypes have been identified. Several specific polymorphisms within obvious candidate genes are associated with serum TSH and thyroid hormone levels, respectively; however these specific polymorphisms account for <2% of the total phenotypic variance. Using simple interaction models it has not been possible to detect any modifying effect of iodine intake (measured as iodine excretion) or cigarette smoking on the effect of a specific polymorphism in the TSHR gene.

Conclusion: Genetic as well as environmental determinants with significant influence on various thyroid related phenotypes in healthy twins has been identified, but neither of these factors have a strong impact on the various thyroid related phenotypes. Many unmeasured genetic variants as well as environmental exposures with influence on thyroid homeostasis remain to be uncovered.