ABNORMAL ADRENAL AND VASCULAR-RESPONSES TO VASOPRESSIN MEDIATED BY A V-1-VASOPRESSIN RECEPTOR IN A PATIENT WITH ADRENOCORTICOTROPIN-INDEPENDENT MACRONODULAR ADRENAL-HYPERPLASIA, CUSHINGS-SYNDROME, AND ORTHOSTATIC HYPOTENSION

The elucidation of gastric inhibitory polypeptide-dependent Cushing's syndrome suggested that ectopic expression or increased responsiveness of other adrenal hormone receptors may underlie ACTH-independent macr onodular adrenal hyperplasia (AIMAH) or adrenocortical tumors. We stud ied a 36-yr-old woman with Gushing's syndrome, AIMAH, and orthostatic hypotension. During upright post;re. cortisol and aldosterone were sti mulated despite suppression of ACTH and renin. Arginine vasopressin (A VP, 10 U im), under dexamethasone suppression, increased plasma cortis ol (3.4-fold), aldosterone (67-fold), and androgens in this patient bu t not in controls. ACTH 1-24, but not desmopressin acetate, angiotensi n II, isoproterenol, or other hormones stimulated steroidogenesis in v ivo. Plasma AVP was undetectable initially and increased suboptimally during posture tests after bilateral adrenalectomy. AVP stimulated cor tisol production more in dispersed cells from the AIMAH than from a no rmal adult adrenal (424 vs. 135% at 10 nmol/L). Adrenal V-1-AVP recept or presence and mediation of response were shown by RT-PCR and by bind ing and [Ca++](i) studies. Post adrenalectomy, orthostatic hypotension persisted: a prolonged vasoconstrictive response to AVP was found in vitro in the patient's sc small arteries. We propose that altered adre nal and vascular responses of the V-1-AVP receptor-effector pathway un derlie this new syndrome.