The clinical expression of thyrotropin receptor mutations

Recent studies have demonstrated that mutations of the thyrotropin receptor (TSHR) are responsible for several specific thyroid diseases. Point mutations at specific sites, most commonly involving the transmembrane domain of TSHR, result in constitutive activation of the receptor and give the cells that harbor them a growth and functional advantage over nonaffected cells. This type of mutation is most commonly found in autonomously functioning ('hot') thyroid nodules and also has been described in familial nonimmune hyperthyroidism. Alternatively, TSH resistance and some cases of congenital hypothyroidism may be secondary to inactivating mutations of TSHR. These examples serve to advance our understanding of the molecular basis of thyroid disease and of the role of hormone receptor activation in endocrine cell growth and function.