Molecular insights into inherited ACTH resistance syndromes

The ACTH resistance syndromes-familial glucocorticoid deficiency (FGD) and the triple-A syndrome-have long been postulated to result from genetic defects of the ACTH receptor. We have demonstrated a point mutation that reduced function of this receptor in FGD, and subsequently we, and others, have identified other mutations of this gene in other families with this condition. Gene linkage studies, however, show that the ACTH receptor is not associated with either a subgroup o f FGD in which mutations in the ACTH receptor gene cannot be found or with the triple-A syndrome. The study of these diseases may reveal new aspects of adrenal development and function, and provide insights into the molecular mechanisms of ACTH receptor action.