Delayed Remission After Transsphenoidal Surgery in Patients with Cushing's Disease

Background: Transsphenoidal surgery (TSS) is the treatment of choice for Cushing's disease (CD). Postoperative hypercortisolemia mandates further therapy.

Objective: The aim of the study was to characterize patients without immediate postoperative remission who have a delayed decrease to normal or low cortisol levels without further therapy.

Design And Setting: A retrospective case series was conducted at three tertiary care centers.

Patients And Intervention: We reviewed the records of 620 patients (512 females, 108 males; mean age, 38 +/- 13 yr) who underwent transsphenoidal pituitary surgery for CD between 1982 and 2007.

Results: Outcomes were classified into the following three groups based upon the postoperative pattern of cortisol testing: group IC (immediate control) included 437 of the 620 patients (70.5%) with hypocortisolism and/or cortisol normalization throughout the postoperative follow-up; group NC (no control) included 148 of 620 patients (23.9%) with persistent hypercortisolism; and group DC (delayed control) included 35 of 620 patients (5.6%) who had early elevated or normal UFC levels and developed a delayed and persistent cortisol decrease after an average of 38 +/- 50 postoperative days. The total rate of recurrence was 13% at a median follow-up time of 66 months after TSS; the cumulative rate of recurrence at 4.5 yr was significantly higher in group DC vs. group IC (43 vs. 14%; P = 0.02).

Conclusions: Hormonal assessment in the immediate postoperative period after TSS for CD may be misleading because delayed remission can occur in a subset of patients. Expectant management and retesting may spare some patients from unnecessary further treatment. Optimal timing to determine the need for further therapy after TSS remains to be determined.