[Illicit hormone receptors in adrenal Cushing's syndrome]

Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. GIP-dependent Cushing's syndrome has been described in patients with either unilateral adenomas or bilateral macronodular adrenal hyperplasia; this syndrome results from the adrenal overexpression of the GIP receptor, which was found to be without an activating mutation. An increased stimulation of cortisol secretion following administration of vasopressin was also reported by several investigators in patients with adrenal Cushing's syndrome; this was linked to an increased expression or abnormal response of the V1-vasopressin receptor. We have conducted a prospective in vivo evaluation of 20 patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In 6 cases of macronodular adrenal hyperplasia, we have identified, in addition to 2 cases of GIP-dependent Cushing's syndrome, 4 other patients in whom cortisol production was regulated abnormally either by vasopressin, B-adrenergic receptor agonists, hCG/LH, or serotonin 5-HT-4 receptor agonists. In 13 patients with unilateral adrenal adenoma, an abnormal response to a mixed meal or to vasopressin was found in 3 cases, suggesting that the presence of ectopic or abnormal hormone receptors is less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists of the abnormal receptors.