We have demonstrated that metoclopramide stimulates cortisol secretion at least in part by a stress-mediated effect in normal men. To examine further the effect of the drug on the hypothalamo-pituitary adrenal system, we studied the cortisol response to 20 mg metoclopramide in patients with acromegaly, prolactinomas, and functional hyperprolactinemia and compared the results with the responses to insulin-induced hypoglycemia. In some patients, the effects of metoclopramide on CRH-induced ACTH and cortisol increase were studied to determine whether a change in dopaminergic (catecholaminergic) activity altered CRH stimulation of pituitary-adrenal function. No cortisol response to 20 mg metoclopramide occurred in 13 tests on 8 of 9 patients with prolactinoma or acromegaly with hyperprolactinemia, whereas both acromegalic patients without hyperprolactinemia had a response. All of the patients had a normal cortisol response to insulin-induced hypoglycemia. Pretreatment with metoclopramide enhanced the CRH-induced cortisol increase from 30–120 min after CRH in normal men, but only at 15 and 30 min in 5 agromegalic patients. The results suggest that metoclopramide acts in the hypothalamus to release ACTH through a dopamine antagonist-mediated (catecholaminergic) mechanism, and that metoclopramide may act additively with CRH to stimulate ACTH secretion in normal men. The absence of a metoclopramide-induced cortisol response in patients with acromegaly or prolactinomas and the absence of a normal cortisol response to metoclopramide-CRH in acromegalic patients could be due to endogenous catecholamine deficiency in these patients.
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