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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 macronodular adrenal hyperplasia (AIMAH) or adrenocortical tumors. We studied a 36-yr-old woman with Cushing's syndrome, AIMAH, and orthostatic hypotension. During upright posture, cortisol and aldosterone were stimulated despite suppression of ACTH and renin. Arginine vasopressin (AVP, 10 U im), under dexamethasone suppression, increased plasma cortisol (3.4-fold), aldosterone (67-fold), and androgens in this patient but not in controls. ACTH 1-24, but not desmopressin acetate, angiotensin II, isoproterenol, or other hormones stimulated steroidogenesis in vivo. Plasma AVP was undetectable initially and increased suboptimally during posture tests after bilateral adrenalectomy. AVP stimulated cortisol production more in dispersed cells from the AIMAH than from a normal adult adrenal (424 vs. 135% at 10 nmol/L). Adrenal V1-AVP receptor presence and mediation of response were shown by RT-PCR and by binding and [Ca+2]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 adrenal and vascular responses of the V1-AVP receptor-effector pathway underlie this new syndrome.

the journal of clinical endocrinology and metabolism/journal of clinical endocrinology and metabolism

Abnormal Adrenal and Vascular Responses to Vasopressin Mediated by a V<sub>1</sub>-Vasopressin Receptor in a Patient with Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia, Cushing’s Syndrome, and Orthostatic Hypotension<sup>1</sup>

Abnormal Adrenal and Vascular Responses to Vasopressin Mediated by a V1-Vasopressin Receptor in a Patient with Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia, Cushing’s Syndrome, and Orthostatic Hypotension1

Abnormal Adrenal and Vascular Responses to Vasopressin Mediated by a V₁-Vasopressin Receptor in a Patient with Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia, Cushing’s Syndrome, and Orthostatic Hypotension¹