VASOPRESSIN-RESPONSIVE ADRENOCORTICAL TUMOR IN A MILD CUSHINGS-SYNDROME - IN-VIVO AND IN-VITRO STUDIES

We report a case of a Gushing's syndrome caused by an autonomously sec reting unilateral adrenocortical tumor, characterized by a clinically and biologically mild hypercortisolemic state and an unusual response pattern to vasopressin. Laboratory tests showed normal early morning p lasma cortisol and 24-h urinary cortisol excretion, but lack of nycthe meral variations and suppressed plasma ACTH. Urinary cortisol excretio n was not suppressed by either the low dose or the high dose dexametha sone test. Injection of lysine vasopressin (10 IU, im) induced a marke d increase in plasma cortisol, without an elevation of plasma ACTH. Co mputed tomography scan revealed an adrenocortical mass of the left gla nd with a contralateral atrophic gland. Removal of the tumor led to co mplete remission of Gushing's symptoms. In vitro studies were then per formed to investigate the effect of arginine vasopressin (AVP) on calc ium mobilization in cultured tumor cells using a microfluorimetric tec hnique. Application of AVP in the vicinity of the cells induced a rapi d and marked increase in the intracellular calcium concentration. Prei ncubation of the cells with the V-1 vasopressin receptor antagonist [d (CH2)(5),Tyr(OMe)(2)]AVP totally suppressed the AVP-induced stimulatio n of intracellular calcium concentration. Reverse transcription follow ed by polymerase chain reaction of tumor ribonucleic acid with specifi c oligonucleotides amplified high levels of V-1 receptor signal compar ed with normal adrenocortical ribonucleic acid. Specific oligonucleoti des for the V-2 or V-3 receptors amplified only a faint signal. This i s the first report describing a mild case of Gushing's syndrome caused by an AVP-sensitive cortisol-producing adenoma. The direct effect of AVP on cultured tumor cells was mediated through the V, type of vasopr essin receptor, similar to that previously characterized in normal hum an fasciculata cells, suggesting that the tumor expressed an eutopic V -1 AVP receptor and exhibited overresponsiveness to AVP.