The use of postoperative ACTH levels as a marker for successful transsphenoidal microsurgery in Cushing's disease

Objectives: The declines of ACTH and other POMC metabolites immediately after tumor extirpation do not predict the complete tumor removal of an ACTH-secreting pituitary adenoma in Cushing's disease. However, the pituitary surgeon should be in a position to evaluate the surgical result as soon as possible for the eventual planning of early repeat surgery. So far, subnormal serum cortisol levels after surgery are widely accepted as the criterion for cure. We investigated whether the early postoperative ACTH concentration is a reliable marker for the initial surgical outcome as well as the long-term remission. Methods: In a prospective study, 147 patients undergoing primary transsphenoidal microsurgery for Cushing's disease between 1990 and 1996 were investigated. The early postoperative ACTH courses were reviewed and compared with the long-term outcome. ACTH measurements were performed immediately after tumor excision, 1, 2, 4, 8, and 12 hours later, and the following morning. Further ACTH levels were determined on various days of the hospital stay. Glucocorticoids were not given until hypocortisolism was proven. Results: Ninety-five patients (65%) presented with subnormal ACTH levels (<10 ng/l) during their postoperative stay, of whom two patients (2%) experienced recurrence of disease after 66 and 100 months. Of 29 procedures with early postoperative ACTH levels ranging from 10-20 ng/l (20%), one patient received further treatment for persistent (3.5%) and one patient for recurrent Cushing's disease (3.5%). Of 12 patients (8%) with early postoperative ACTH levels in between 20 to 30 ng/l, one patient received further treatment for persistent (8%) and four patients for recurrent disease (33%). ACTH levels of more than 30ng/l, found in 11 patients (7%), were accompanied by persistent (8 patients, 73%) or recurrent (2 patients, 18%) Cushing's disease. Conclusion: Subnormal (<10 ng/l) or low normal (<20 ng/l) postoperative ACTH levels within the first 7 days after surgery can be regarded as early markers for complete removal of an ACTH adenoma as well as indicators for long-term outcome in Cushing's disease. The risk of persistence or recurrence of Cushing's disease rise with the level of early postoperative ACTH values. Normal ACTH levels should result into further evaluation of the ACTH-cortisol secretion, for example by stimulation- or suppression tests.