Pathology of the TSH receptor

Gain of function and loss of function mutations of the TSH receptor have be en implicated in the pathogenesis of various thyroid diseases. Gain of func tion mutations, when somatic, are the first cause of autonomous nodules; wh en germline, they are responsible for hereditary non-autoimmune toxic thyro id hyperplasia and for some cases of sporadic congenital hyperthyroidism. A subset of mutations modifying the receptor selectivity have recently been found to be involved in the pathogenesis of familia! gestational hyperthyro idism. These mutations are of great interest for understanding the mechanis m of receptor activation. Loss of function mutations of the TSH receptor ar e responsible for different phenotypes ranging from asymptomatic resistance to TSH to overt congenital hypothyroidism.