Gs alpha mutations in hyperfunctioning thyroid adenomas

Hyperfunctioning thyroid adenomas are benign tumors characterized by their autonomous growth and functional activity,which frequently cause clinical h yperthyroidism rind show a predominant radioactive iodine uptake in the nod ule. Activating mutations in the gene encoding the alpha subunit of the sti mulatory G protein(Gs alpha), as well as activating mutations in the gene e ncoding thyrotropin receptor in hyperfunctioning thyroid adenomas, have bee n reported. The mutations in Gs alpha involved the replacement of either ar ginine 201 with cysteine or histidine, or glutamine 227 with arginine or le ucine. These residues are involved in GDP/GTP binding of Gs alpha and these mutations inhibit intrinsic GTPase activity that results in constitutive a ctivation of adenylyl cyclase. The pathophysiological roles of these mutati ons in the formation of hyperfunctioning thyroid adenoma have been suggeste d. (C) 2000 IMSS. Published by Elsevier Science Inc.