IN-VIVO AND IN-VITRO EFFECTS OF AVP AND V-1A RECEPTOR ANTAGONIST ON CUSHINGS-SYNDROME DUE TO ACTH-INDEPENDENT BILATERAL MACRONODULAR ADRENOCORTICAL HYPERPLASIA

We examined the possibility that AVP and V-1a receptors were involved in regulating cortisol production in a 49 year old man with ACTH-indep endent bilateral macronodular adrenocortical hyperplasia (AIMAH), and investigated the effects of a V-1a receptor antagonist. An iv injectio n of a small dose (0.1 or 0.3 U) of AVP, insulin-induced hypoglycaemia , upright posture tests, and oral administration of a V-1a receptor an tagonist (OPC-21268; 300 mg), and its repeated administration at a dos e of 600mg/day for 8 days were performed. An in vitro study of dispers ed cells obtained from resected AIMAH tissue was also conducted. Plasm a ACTH, AVP and cortisol levels and 24-h urinary free cortisol excreti on were measured in the in vivo studies and cortisol concentrations in incubation media in the in vitro study. Injection of small doses of A VP stimulated cortisol secretion without any elevation of plasma ACTH, Insulin-induced hypoglycaemia caused a rise in plasma AVP followed by an increase in plasma cortisol, Although plasma cortisol levels were not affected by single or repeated administrations of OPC-21268, 24-h urinary free cortisol excretion was significantly decreased by the rep eated treatment. In the in vitro study, more cortisol was stimulated b y AVP from adrenal cells of the AIMAH tissue than from those of a norm al adrenal gland, and this secretion was completely suppressed by OPC- 21268, These results suggested that hypersensitivity to AVP may have c ontributed to overproduction of cortisol in this case of ACTH-independ ent bilateral macronodular adrenocortical hyperplasia, and may have co ntributed to its pathogenesis.