The Mechanism of the Suppressive Action of Bromocriptine on Adrenocorticotropin Secretion in Patients with Cushing′s Disease and Nelson′s Syndrome*

Abstract

The oral administration of 2.5 mg bromocriptine elicited a significant suppression of plasma ACTH and cortisol in 6 of 13 patients with untreated Cushing′s disease. In the responding patients, mean plasma ACTH levels were higher and pituitary tumor size was larger than in the nonresponders. In two patients with Nelson′s syndrome, plasma ACTH was diminished by 70% and 30%, respectively, from 4-6 h after 2.5 mg bromocriptine. In one patient with ectopic ACTH secretion from a bronchial carcinoid, plasma ACTH was suppressed by 32% from 3-5 h after 2.5 mg bromocriptine. The effects of bromocriptine and cyproheptadine on the secretion of ACTH from trypsin-dispersed tumor cells prepared from the ACTH-secreting rat pituitary tumor 7315a were investigated in vitro. Bromocriptine (1 µM) inhibited ACTH secretion by 40% (P < 0.01), while 1 JUM cyproheptadine inhibited ACTH secretion by 25% (P < 0.01). On the basis of 1) the direct effects of bromocriptine and cyproheptadine on ACTH secretion by rat pituitary tumor cells, 2) the suppressive effect of bromocriptine in a patient with ectopic ACTH secretion, and 3) the increasing sensitivity of ACTH secretion to bromocriptine with increasing pituitary tumor size, we suggest that one mechanism of action of bromocriptine is a direct effect on the ACTH-secreting pituitary microadenoma n patients with Cushing′s disease and Nelson′s syndrome.