Primary Endoscopic Transnasal Transsphenoidal Surgery for Magnetic Resonance Image–Positive Cushing Disease: Outcomes of a Series over 14 Years

Background

There are scant data of endoscopic transsphenoidal surgery (ETS) with adjuvant therapies of Cushing disease (CD).

Objective

To report the remission rate, secondary management, and outcomes of a series of CD patients.

Methods

Patients with CD with magnetic resonance imaging (MRI)-positive adenoma who underwent ETS as the first and primary treatment were included. The diagnostic criteria were a combination of 24-hour urine-free cortisol, elevated serum cortisol levels, or other tests (e.g., inferior petrosal sinus sampling). All clinical and laboratory evaluations and radiological examinations were reviewed.

Results

Forty consecutive CD patients, with an average age of 41.0 years, were analyzed with a mean follow-up of 40.2 ± 29.6 months. These included 22 patients with microadenoma and 18 with macroadenoma, including 9 cavernous invasions. The overall remission rate of CD after ETS was 72.5% throughout the entire follow-up. Patients with microadenoma or noninvasive macroadenoma had a higher remission rate than those who had macroadenoma with cavernous sinus invasion (81.8% or 77.8% vs. 44.4%, P = 0.02). After ETS, the patients who had adrenocorticotropic hormone–positive adenoma had a higher remission rate than those who had not (76.5% vs. 50%, P = 0.03). In the 11 patients who had persistent/recurrent CD after the first ETS, 1 underwent secondary ETS, 8 received gamma-knife radiosurgery (GKRS), and 2 underwent both. At the study end point, two (5%) of these CD patients had persistent CD and were under the medication of ketoconazole.

Conclusion

For MRI-positive CD patients, primary (i.e., the first) ETS yielded an overall remission rate of 72.5%. Adjuvant therapies, including secondary ETS, GKRS, or both, yielded an ultimate remission rate of 95%.

Introduction

Patients with Cushing disease (CD) are exposed to excessive glucocorticoids, which could cause various medical conditions and increase the risk of mortality 5, 17. Treatment is therefore warranted once the diagnosis of CD is established. Transsphenoidal surgery (TS) has long been the standard of care for patients with CD 3, 19, 20, 32, 33, 35, 36. Different reports have demonstrated variable remission rates after microscopic TS ranging from 50% to over 90% 2, 3, 4, 10, 14, 15, 29, 31. Multiple reasons could be attributed to the great variety of rates reported, such as diagnostic criteria, tumor size, assessment of remission, follow-up duration, adjuvant management, and even the nature of CD itself 25, 26.

In recent decades, application of endoscopes has gained great popularity in the approach to TS. Many reports have demonstrated that endoscopic transsphenoidal surgery (ETS) is a viable and effective approach for pituitary adenoma 6, 14, 39. It is generally accepted that ETS provides a more panoramic view than microscopic TS, allowing an increased surgical field and a close-up visual examination of the anatomic structures around the sella. However, there are scant data on the actual outcomes of ETS for CD. Whether the rates of remission, recurrence, and complications of ETS are comparable with microscopic TS remains elusive.

This study aimed to report a series of CD patients with magnetic resonance imaging (MRI)-proven microadenoma and macroadenoma managed by ETS. Not only the remission rates but also the management of relapses/nonremissions of CD are reported in detail. This is, to date, the first series to specifically examine MRI-positive CD patients managed primarily with ETS.