Late Recurrences of Cushing’s Disease after Initial Successful Transsphenoidal Surgery

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Abstract
Context: Few studies have systematically analyzed the long-term recurrence rates of Cushing’s disease after initial successful transsphenoidal surgery. Setting: This was a retrospective review of patients treated at the University of Virginia Medical Center. Patients: A total of 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 were examined. Recurrence was defined as an elevated 24-h urine free cortisol 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, 2, 3, and 5 yr were 0.5, 6.7, 10.8, and 25.5%, respectively. Among the 184 patients who achieved remission, 32 (17.4%) patients followed for more 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-h surgery) was achieved in 97 (45.1%) patients. Patients who had postoperative serum cortisol of more than 2 μg/dl were 2.5 times more likely to have a recurrence than patients who had serum cortisol less than or equal to 2 μg/dl (odds ratio = 2.5; 95% confidence interval 1.12–5.52; P = 0.022). Conclusions: A quarter of the patients with Cushing’s disease who achieve surgical remission after transsphenoidal surgery, recur with long-term follow-up. This finding emphasizes the need for continued biochemical and clinical follow-up to ensure remission after surgery.

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