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

ABSTRACT

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 µg 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 µg/dl) were recorded after stimulation with 1 µg 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.