A 48-year-old woman was referred for ACTH-independent Cushings syndrome associated with a left adrenal tumor. Contrasting with hypercortisolism-related hypertension and hypokalemia, renin and aldosterone levels were paradoxically increased. The tumor was surgically removed and pathological examination of the tissue established the diagnosis of corticosurrenaloma. Fragments of the tumor were obtained for in situ hybridization, immunohistochemical and cell incubation studies. The presence of prorenin mRNA and renin immunoreactivity was detected in the tumor tissue. Renin and cortisol were detectable in tumor cells culture supernatants whereas aldosterone was not. ACTH and angiotensin II had no action on renin and cortisol secretion. In contrast, 5-HT inhibited renin production and stimulated cortisol release in a dose-dependent manner. Interestingly, 5-HT-induced cortisol secretion was inhibited by the 5-HT7 receptor antagonist SB269970 but not by GR113808, an antagonist at the eutopic 5-HT4 adrenocortical receptor. One month after surgery, UFC and plasma levels of renin normalized. Six months post-operatively, hypercortisolism and hyperreninism recurred concomitantly with hepatic and pulmonary metastatic diffusion of the disease leading rapidly to the death of the patient. Collectively, in vivo and in vitro data show that the adrenal carcinoma cosynthesized and secreted renin and cortisol. Our results also demonstrate an ectopic expression of 5-HT7 receptors in the tumor tissue mediating a stimulatory effect of 5-HT on cortisol secretion. In contrast, 5-HT inhibited renin secretion by tumor cells through an unknown receptor type.
03 - 07 May 2008
European Society of Endocrinology