Hyperfunctioning thyroid adenoma and activating mutations in the TSH receptor gene

Thyrotropin (TSH) positively controls the function, differentiation, and gr owth of thyrocytes. TSH interacts with thyrocytes through the TSH receptor and its action is mediated by cyclic AMP-dependent mechanisms. From data ga thered on adrenergic receptors, it was hypothesized that TSH receptor mutat ions that lead to constitutive activation of the TSH receptor would also re sult in autonomous thyroid growth and function. Indeed, such mutations were shown to be the main molecular mechanisms leading to toxic thyroid adenoma s. The same mechanism was shown to be operating in "hot" thyroid nodules fr om multinodular goiter. A low iodine supply seems to increase the clinical expression of such somatic mutations responsible for thyroid autonomy. More over, the presence of such mutations has helped to define a working model f or TSH receptor physiology. The unliganded TSH receptor maintains a negativ e constraint on the signal transduced, whereas the presence of specific mut ations activates the receptor. (C) 2000 IMSS. Published by Elsevier Science Inc.