A Cyproheptadine-Reversible Defect in ACTH Control Persisting after Removal of the Pituitary Tumor in Cushing's Disease

Abstract

We studied two phases of cortisol feedback suppression of ACTH in nine patients who had had adrenalectomy for Cushing's disease. Four had been treated by adrenalectomy alone and presumably had ACTH-secreting pituitary tumors. Five others were studied two or more years after transsphenoidal removal of an ACTH-secreting microadenoma. In both groups, cortisol-ACTH feedback during the first 30 minutes of cortisol infusion was abnormal; plasma ACTH fell only 2.7±2.6 per cent (mean ±S.E.), as compared with 28.0±10.1 per cent in five hypoadrenal controls (P<0.01). The fall in ACTH during the second phase of cortisol infusion was similar in the patients and the controls. Cyproheptadine corrected the feedback abnormality occurring during the first phase in both groups of patients with Cushing's disease; ACTH fell by 24.4±4.8 per cent (P<0.005). Persistence of a cortisol-ACTH feedback abnormality after removal of the pituitary tumor in Cushing's disease, as well as the correction by cyproheptadine, suggests that higher centers have a role in the pathophysiology of Cushing's disease. (N Engl J Med. 1981; 305:1244–8.)