Rapid decrease in adrenal responsiveness to ACTH stimulation after successful pituitary surgery in patients with Cushing's disease

Objective The aim of this study was to investigate the effects of transsphenoidal surgery (TS) on the adrenal sensitivity to ACTH (adrenocorticotropin) stimulation in patients with Cushing's disease (CD). Methods We measured the cortisol response to 1 mu g synthetic ACTH (1-24) 6 days after pituitary surgery in 45 patients with CD. Mean follow-up period was 56.5 months (SE 4.7). Results In 24 of 28 patients in sustained remission after pituitary surgery, peak cortisol concentrations below 774 nm (28.0 mu g/dl) were recorded after stimulation with 1 mu g synthetic ACTH (86%). Two patients with recurrent disease after initial remission (late relapse) also showed ACTH-stimulated peak cortisol levels below 774 nm. Fourteen of 15 patients with persistent CD after surgery (early failure) showed absolute peak cortisol levels > 774 nm in response to ACTH stimulation. Conclusion Patients in remission after pituitary surgery for CD showed a rapid decrease of adrenal responsiveness to exogenous ACTH stimulation. This phenomenon may be explained by ACTH-receptor down-regulation in the adrenal cortex after complete removal of the pituitary corticotroph adenoma. In our study, the postoperative low-dose ACTH stimulation test had a sensitivity of 93% and a specificity of 87% in predicting immediate remission of CD after pituitary surgery.