EFFECTS OF SEROTONIN AND VASOPRESSIN ON CORTISOL PRODUCTION FROM AN ADRENOCORTICAL TUMOR CAUSING SUBCLINICAL CUSHING'S SYNDROME

In dexamethasone-suppressed healthy volunteers, the serotonin4 (5-HT4) receptor agonist cisapride and lysine vasopressin [LVP, an analog of arginine vasopressin (AVP)] have no influence on plasma cortisol levels (PCL). In contrast, cisapride and AVP have been shown to stimulate cortisol secretion in patients with adrenal tumor or bilateral adrenal hyperplasia and Cushing's syndrome. In this report, we describe a case of adrenocortical adenoma causing subclinical Cushing's syndrome. Cisapride and terlipressin, a precursor of LVP, both induced an increase in PCL reaching +88% and +100%, respectively, without any significant variation of plasma ACTH levels. In vitro experiments were conducted to investigate the effects of 5-HT and AVP on cortisol production from cultured tumor cells and normal adrenocortical cells. 5-HT and AVP both induced a dose-dependent increase in cortisol production from cultured tumor cells. Comparison of the data obtained with tumor and normal cells, respectively, showed that 5-HT was more efficient to stimulate steroidogenesis in adenomatous than normal cells. Concurrently, the efficacy and potency of AVP were both higher in tumor than normal cells. Collectively, these results show that the abnormal in vivo responses of the adrenocortical adenoma to cisapride and LVP could be ascribed to an increased sensitivity of the tumor tissue to 5-HT and AVP. The data also suggest that the adrenocortical tumor overexpressed eutopic 5-HT4 and V1 receptors.