ACUTE EFFECTS OF BROMOCRIPTINE, CYPROHEPTADINE, AND VALPROIC ACID ON PLASMA ADRENOCORTICOTROPIN SECRETION IN NELSONS SYNDROME

Previous studies have found that bromocriptine, cyproheptadine, and va lproic acid can reduce ACTH secretion in Nelson's syndrome, but none o f these agents has achieved widespread use due to their failure to nor malize ACTH in most patients. The current study was undertaken to dete rmine whether these three agents, which act through different mechanis ms, decrease plasma ACTH synergistically when administered together. S ix adult female patients (mean age, 41 yr) with Nelson's syndrome were studied. ACTH was measured every 20 min for 8 h, 2 h before and 6 h a fter each of the following six treatments: placebo, bromocriptine (2.5 mg), cyproheptadine (8 mg), valproic acid (1 g), cyproheptadine plus valproic acid, and the combination of all three drugs. The sequence of treatments was determined randomly, and there was an interval of at l east 2 days between each treatment. The hourly ACTH values were averag ed, and the percent maximal suppression of plasma ACTH, relative to th e baseline values before drug administration, was compared among the s ix treatments. Basal plasma ACTH levels in the six patients ranged fro m 40-3324 pmol/L (normal range, 1-8). The percent maximal suppression of ACTH after administration of placebo (6+/-11%), cyproheptadine (17/-15%), valproic acid (37+/-10%), or the combination of cyproheptadine and valproic acid (19+/-14%) did not achieve statistical significance . Bromocriptine, bn the other hand, caused a significant decrease in p lasma ACTH (52+/-8%; P <0.05), as did the combination of bromocriptine , cyproheptadine, and valproic acid (58+/-1245; P <0.05). However, the combined effect of the three drugs did not significantly exceed the e ffect of bromocriptine alone. We conclude that at the doses studied, b romocriptine had the greatest acute effect in suppressing ACTH secreti on in Nelson's syndrome, and that combined administration with valproi c acid and cyproheptadine did not further increase this acute ACTH-sup pressive effect.