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

Department of Neurosurgery (C.G.P., S.P.L., L.K., E.R.L.), Stanford University School of Medicine, Stanford, California 94305; Department of Neurological Surgery (D.M.P.), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213; and Department of Internal Medicine-Endocrinology (M.L.V., M.O.T.), University of Virginia Health System, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Chirag G. Patil, M.D., Stanford Hospital, Department of Neurosurgery, 300 Pasteur Drive, Room R281 MC5327, Stanford, California 94305. E-mail: chiragpatil{at}gmail.com.

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.