Outcomes and management of patients with Cushing's disease without pathological confirmation of tumor resection after transsphenoidal surgery

Context: Despite the success of transsphenoidal surgery ( TSS) for the treatment of Cushing's disease, in a number of cases, an ACTH-staining pituitary adenoma is not identified histologically. The clinical significance of lack of histological confirmation remains unclear. Setting: This was a retrospective review of patients treated at the University of Virginia Medical Center. Patients: Of 490 TSS procedures for Cushing's disease between 1993 and 2004, we identified 111 cases without histological adenoma confirmation. Main Outcome Measure: Remission and recurrence of Cushing's disease were measured. Results: Overall, 50% of these patients achieved remission, a figure lower than for our entire series ( 79%) and for patients with histological confirmation of an ACTH-staining adenoma ( 88%) ( P < 0.001).Patients with a history of two prior TSS achieved remission less often than patients with a history of fewer TSS ( P < 0.026). No other factors influenced remission rates. Although the overall recurrence rate ( 21%, seven of 33 evaluated) was not different from previously published long-term studies, in three of seven cases of recurrence, early recurrences were noted between 2 and 4 months after remission. In patients who did not achieve remission, the most common and effective treatment options were repeat TSS, gamma-knife radiosurgery, and bilateral adrenalectomy. Conclusion: The lower remission rate in patients without histological evidence of an adenoma is most likely a result of a decreased rate of adenoma extirpation. The incidence of early recurrence may be a unique feature of this patient population; patients without histological confirmation of tumor resection therefore require close and consistent monitoring postoperatively.