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

Patients: Out 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.

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 2 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%, 7 of 33 evaluated) was not different from previously published long term studies, in 3 of 7 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.