EFFECTS OF RESERPINE TREATMENT ON PITUITARY-ADRENOCORTICAL AXIS IN PATIENTS WITH CUSHINGS-DISEASE

Effects of reserpine treatment, not associated with pituitary irradiat ion, on the pituitary-adrenocortical axis in a total of 37 untreated p atients with Cushing's disease were evaluated. With short-term treatme nt (2 mg daily for 2 weeks, n=36), basal excretion of urinary 17-OHCS significantly decreased from 11.2+/-5.2 mg/day/m(2) (body surface area ) (mean +/- SD) to 9.6+/-4.4 mg/day/m(2) (P<0.01), and metyrapone-indu ced incremental responses of urinary 17-OHCS decreased from 58.4+/-41. 4 mg/3 days/m(2) to 45.9+/-29.8 mg/3 days/m(2) (P<0.05). Long-term tre atment (1.7+/-0.3 mg/day for a mean of 15.8+/-19.9 weeks) induced a ma rked reduction in plasma cortisol, and 24-h urinary 17-OHCS and/or fre e cortisol in 4 of 8 patients examined. Long-term reserpine administra tion caused normal suppression of plasma cortisol (or 11-OHCS) in 3 of 9 patients with 1 mg, and in all of 5 patients with an 8 mg over-nigh t dexamethasone suppression test. Plasma ACTH response to CRH was evid ently decreased in one patient evaluated one month after the initiatio n of reserpine. The circadian rhythm of plasma cortisol was normal in one patient when the basal glucocorticoid level became normal with res erpine treatment. The present findings suggest that reserpine itself c ontributes in a causal fashion to the effectiveness of our regimen, re serpine and pituitary irradiation, for some Cushing's disease patients in whom it is effective.