Pituitary-adrenocortical response to metoclopramide in patients with acromegaly and prolactinoma: a clinical evaluation of catecholamine-mediated adrenocorticotropin secretion.
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.
D000172:Acromegaly / Q000503:physiopathology; D000302:Adrenal Cortex / Q000187:drug effects / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002395:Catecholamines / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006966:Hyperprolactinemia / Q000503:physiopathology; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology; D007328:Insulin; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects / Q000503:physiopathology*; D010911:Pituitary Neoplasms / Q000503:physiopathology; D011388:Prolactin / Q000378:metabolism
D002395:Catecholamines; D007328:Insulin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D003346:Corticotropin-Releasing Hormone; D008787:Metoclopramide; D006854:Hydrocortisone