Context: Few studies have systematic analyzed the long-term recurrence rates of Cushing's disease after initial successful transsphenoidal surgery.

Setting: Retrospective review of patients treated at the University of Virginia Medical Center.

Patients: 215 subjects with Cushing's disease who underwent initial transsphenoidal surgery for resection of a presumed pituitary microadenoma from 1992-2006 were included.

Main Outcome Measures: Remission and recurrence rates of Cushing's disease. Recurrence was defined as an elevated 24-hour UFC with clinical symptoms consistent with Cushing's disease.

Results: Of the 215 patients who underwent transsphenoidal surgery for Cushing's disease, surgical remission was achieved in 184 (85.6%). The mean length of follow-up was 45 months. Actuarial recurrence rates of Cushing's disease after initially successful transsphenoidal surgery at 1 year, 2 years, 3 years and 5 years were 0.5%, 6.7%, 10.8% and 25.5% respectively. Among the 184 patients who achieved remission, 32 (17.4%) patients followed for greater than 6 months ultimately had a recurrence of Cushing's disease. The median time to recurrence was 39 months. Immediate postoperative hypocortisolemia (serum cortisol 2 µg/dl within 72 hours of surgery) was achieved in 97 (45.1%) patients. Patients who had postoperative serum cortisol of > 2 µg/dl were 2.5 times more likely to have a recurrence than patients who had serum cortisol 2 µg/dl (OR = 2.5, 95%CI = 1.12-5.52, P = 0.022).

Conclusions: A quarter of the patients with Cushing's disease who achieve surgical remission following transsphenoidal surgery, recur with long-term follow-up. This finding emphasizes the need for continued biochemical and clinical follow-up to ensure remission following surgery.