Failure of Cyproheptadine to Inhibit Vasopressin-Stimulated Cortisol Release in a Patient with Cushing’s Disease

Abstract

A case of a 21-year-old woman with Cushing’s disease due to a pituitary tumor is described. The patient was treated with cyproheptadine for 4 weeks immediately following pituitary α-particle irradiation. A standard vasopressin test to measure ACTH-mediated cortisol release was performed four times: prior to pituitary irradiation, after irradiation, after 4 weeks of cyproheptadine therapy, and off cyproheptadine for 2 weeks. Cyproheptadine failed to modify vasopressin-stimulated cortisol release in the patient described. This study suggests that cyproheptadine, which has previously been shown to decrease ACTH secretion, probably acts principally at the hypothalamic, rather than at the pituitary level.

Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness

“…The cortisol response to hypoglycaemia has been inhibited by the 5-HT antagonists methysergide, cyproheptidine (Plonk et al 1974) and metergoline (Cavagnini et al 1976), and the ACTH response to metyrapone has been inhibited by metergoline (Cavagnini et al 1975). Only the responses to vasopressin resist suppression by metergoline (Cavagnini et al 1976) and cyproheptidine (George et al 1976), possibly because vasopressin acts directly upon pituitary. If 5-HT antagonists inhibit ACTH responses more readily than 5-HT agonists release ACTH, then 5-HT may function in these neuroendocrine systems by facilitating the influence of other monoamine systems.…”

Effect of cyproheptadine on episodic ACTH and cortisol secretion

“…Contradictory to these findings, some authors [14,15], but not others [18], have found a decrease in ACTH and -endorphin secretion from pituitary adenomas treated with cyproheptadine in vitro, indicating a direct pituitary effect of 5-HT. It was suggested that this phenomenon may occur only if the adenoma originates from the intermediate lobe [14].…”

“…Cyproheptadine, a non-specific 5-HT antagonist, decreases ACTH and cortisol secretion without disturbing the circadian rhythm [5][6][7][8][9][10]. This inhibitory effect may occur at the pituitary [11][12][13][14][15][16] or hypothalamic level [7,8,[17][18][19][20][21]. It is not known whether in the latter case the effect is brought about by a decrease in frequency or amplitude of ACTH and cortisol secretory episodes.…”

Management of acute hypercortisolism

“…Cyproheptadine, a serotonin antagonist, has been used with mixed results [26][27][28]. Its mechanism of action is believed to be the inhibition of CRF at the hypothalmic level, as this hormone's release is mediated by serotonin.…”

“…The purpose in using these drugs is an attempt to suppress secretion of ACTH by the pituitary gland. Theoretically, these drugs should be most effective in patients with a disorder of the CRF/ACTH regulatory mechanism and in patients with Cushing's disease due to microadenomas [26][27][28][29][30][31][32].…”