Aberrant membrane hormone receptors in incidentally discovered bilateral macronodular adrenal hyperplasia with subclinical Cushing's syndrome

Cortisol secretion in adrenal Cushing's syndrome can be regulated by the ab errant adrenal expression of receptors for gastric inhibitory polypeptide, vasopressin, catecholamines, LH/human CG (LH/hCG), or serotonin. Four patients with incidentally discovered bilateral macronodular adrenal h yperplasia without clinical Cushing's syndrome were evaluated for the possi ble presence of aberrant adrenocortical hormone receptors. Urinary free cor tisol levels were within normal limits, but plasma cortisol levels were sli ghtly elevated at nighttime and suppressed incompletely after dexamethasone administration. Plasma ACTH was partially suppressed basally but increased after administration of ovine CRH. A 51-yr-old woman had ACTH-independent increases of plasma cortisol after 1 0 IU AVP im (292%), 100 mug GnRH iv (184%), or 10 mg cisapride orally (310% ); cortisol also increased after administration of NaCl (3%), hCG, human LH , and metoclopramide. In a 61-yr-old man, cortisol was increased by AVP (34 9%), GnRH (155%), hCG (252%), and metoclopramide (191%). Another 53-yr-old male increased plasma cortisol after AVP (171%) and cisapride (142%). Corti sol secretion was also stimulated by vasopressin in a 54-yr-old female. This study demonstrates that subclinical secretion of cortisol can be regul ated via the aberrant function of at least VI-vasopressin, LH/hCG, or 5-HT4 receptors in incidentally identified bilateral macronodular adrenal hyperp lasia.