ECE2008 Poster Presentations Adrenal (61 abstracts)
A case of renin-producing adrenocortical carcinoma with Cushing's syndrome: in vitro effect of serotonin on renin and cortisol secretions
Estelle Louiset 1 , Karen Isvi 2 , Jean-Marie Gasc 3 , Céline Duparc 1 , Bruno Cauliez 4 , Annie Laquerrière 5 , Jean-Marc Kuhn 1 & Hervé Lefebvre 1
1INSERM U413, IFRMP 23, University of Rouen, Mont Saint Aignan, France; 2Department of Endocrinology, Institute for Biomedical Research, University Hospital of Rouen, University of Rouen, Rouen, France; 3INSERM U833, Laboratory of Embryological ad Pathological Angiogenesis, Collège de France, Paris, France; 4Laboratory of Biochemistry, Institute for Biomedical Research, University Hospital of Rouen, University of Rouen, Rouen, France; 5Department of Pathology, Institute for Biomedical Research, University Hospital of Rouen, University of Rouen, Rouen, France.
A 48-year-old woman was referred for ACTH-independent Cushing’s 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.
Volume 16
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Endocrine Abstracts
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