UTILITY OF ADRENOCORTICOTROPIC HORMONE IN ASSESSING THE RESPONSE TO TRANSSPHENOIDAL SURGERY FOR CUSHING'S DISEASE

Objectives: To compare adrenocorticotrophic hormone (ACTH) and cortisol dynamics in subjects with Cushing's disease (CD) following transsphenoidal surgery (TSS) and to determine the value of early postoperative ACTH levels in predicting subsequent hypocortisolemia. Methods: Following TSS for CD, serum cortisol and plasma ACTH were measured every 6 hours in the absence of empiric glucocorticoid coverage. Results: A total of 26 subjects (25 female) underwent 28 operations. Hypocortisolemia was achieved in 21 (81%) subjects after the initial TSS. Repeat TSS was performed in 2 subjects, resulting in hypocortisolemia in 1. Subjects who achieved hypocortisolemia had significantly lower ACTH levels by 19 hours postoperatively (P = .007). Plasma ACTH fell to <30 pg/mL in 86% and <20 pg/mL in 82% of subjects who subsequently achieved hypocortisolemia. Plasma ACTH declined to <30 pg/mL by a mean of 10 hours and to <20 pg/mL by 13 hours prior to hypocortisolemia. Follow-up data were available on 25 patients for a median of 23 months. Three subjects who achieved initial surgical remission had disease recurrence at 19, 24, and 36 months; all of these subjects had a postoperative nadir serum cortisol levels <3 mu g/dL and plasma ACTH <20 pg/mL. Conclusion: Following TSS for CD, plasma ACTH declined prior to achievement of hypocortisolemia in most subjects. In the majority, the ACTH level reached a nadir of <20 pg/mL. Low early postoperative ACTH levels predict early hypocortisolemia but may not accurately predict long-term remission.