Suppression of Aldosterone by Cyproheptadine in Idiopathic Aldosteronism

• Published in: The New England journal of medicine Vol. 305; no. 4; pp. 181 - 185
• Main Authors: Gross, Milton D, Grekin, Roger J, Gniadek, Thomas C, Villareal, Jesus Z
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 23.07.1981
• Subjects: Adenoma; Adenoma - complications; Adrenal Gland Neoplasms - complications; Adult; Aldosterone; Aldosterone - blood; Aldosterone - secretion; Cyproheptadine; Cyproheptadine - pharmacology; Depression, Chemical; Dexamethasone; Diet, Sodium-Restricted; Endocrine disorders; Humans; Hyperactivity; Hyperaldosteronism - etiology; Hyperaldosteronism - physiopathology; Hyperplasia; Male; Neuroendocrine tumors; Renin; Renin - blood; Serotonin; Serotonin - physiology; Sodium
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198107233050401

To study the role of serotonin in regulating the release of aldosterone, we gave single, oral doses of cyproheptadine, an antiserotoninergic agent, to five normal volunteers with high aldosterone levels secondary to sodium deprivation and to 14 patients with aldosteronism (six with idiopathic aldosteronism due to bilateral adrenal hyperplasia and eight with adrenal adenoma). A diet containing 150 mmol of sodium was given to the patients with spontaneous aldosteronism, and one containng 10 mmol of sodium was given to the normal subjects, for three days before treatment and throughout the study. All subjects received dexamethasone, 2 mg daily. Serum aldosterone was measured with the subject in the recumbent position before cyproheptadine administration and at 30-minute intervals for two hours afterward. Serum aldosterone fell significantly (P<0.025) from the basal level in the patients with idiopathic aldosteronism due to hyperplasia. No fall was observed in the normal subjects or in the patients with adenoma. No changes were seen in renin activity, cortisol, sodium, or potassium, in any group after cyproheptadine. Suppression of aldosterone with cyproheptadine suggests a serotonin-mediated aldosterone-stimulating system. Hyperactivity of this system may be the cause of idiopathic aldosteronism associated with adrenal hyperplasia. (N Engl J Med. 1981; 305:1815.) IDIOPATHIC aldosteronism is a syndrome characterized by hypertension, hypokalemia, and bilateral adrenal hypersecretion of aldosterone. Plasma renin activity is suppressed, and none of the mechanisms known to control the secretion of aldosterone appear to be responsible for the development of the syndrome. 1 2 3 Several investigators have suggested that idiopathic aldosteronism is associated with overproduction of an unknown aldosterone secretagogue. 4 , 5 A likely source for such a secretagogue is the pituitary gland, since patients with hypopituitarism have an impaired aldosterone response to sodium restriction. 6 7 8 An aldosterone secretagogue originating in the central nervous system or pituitary gland would probably be under the control of . . .