Negative feedback effects on ACTH secretion by cortisol in Cushing's disease

Bioassayable plasma ACTH and corticosteroid levels were measured during constant infusions of low doses of cortisol (3-15 mg/h) into normal subjects and into two patients with Cushing's disease. Plasma ACTH levels decreased significantly in all subjects within 60 min from the start of the infusion. The rate of rise of plasma corticosteroid levels concomitant with this feedback suppression were considerably higher in the patients with Cushing's disease (greater than 13 nmol/l/min) than in normal subjects (3-6 nmol/l/min). In one of the Cushing's patients, ACTH secretion resumed in spite of the corticosteroid levels rising at a rate of greater than 20 nmol/l/min. It is concluded that cortisol-induced suppression of ACTH secretion may be operational in Cushing's disease but that the mechanism is less sensitive than in normal subjects.