Endoscopic endonasal approach for adrenocorticotropic hormone-producing pituitary neuroendocrine tumor causing Cushing's disease: multicenter retrospective study on 162 patients with early postoperative cortisol assessment.

OBJECTIVE: Cushing's disease (CD) is a severe endocrine disorder that remains difficult to treat. The first-line treatment for confirmed CD is selective pituitary adenoma resection. Postoperative hormonal remission may not be achieved, though, despite surgical intervention. Effective postoperative monitoring of the hormonal response in CD remains challenging. METHODS: A multicenter observational retrospective cohort study was conducted including 162 patients with CD who underwent endoscopic endonasal resection from January 2007 to September 2021. Three institutions from the United States and Europe participated: University of Southern California, University of Naples Federico II, and Medical University of Vienna. Clinical information including age, sex, preoperative serum and urinary free cortisol levels, imaging findings, histopathological examination including immunohistochemical results, postoperative endocrinological results, and time to follow-up were reported. RESULTS: Data were reviewed for 162 patients with biochemically confirmed CD undergoing surgery via an endoscopic endonasal approach. Morning cortisol < 2 µg/dL or < 5 µg/dL during the first 3 postoperative days (PODs) was associated with lower odds of recurrence (for < 2 µg/dL: OR 0.08, 95% CI 0.004-0.38 [p = 0.01]; for < 5 µg/dL: OR 0.25, 95% CI 0.09-0.61 [p = 0.003]). However, when comparing the two cutoff values (< 2 µg/dL and < 5 µg/dL), a trend toward increased risk was observed in patients with higher cortisol levels, although the difference was not statistically significant (OR 2.1, 95% CI 0.59-7.81; p = 0.25). CONCLUSIONS: Early postoperative hypocortisolemia with cortisol levels < 5 µg/dL within the first 3 days after surgery is a strong predictor of long-term remission. A cortisol level < 2 µg/dL on POD 1 was also significantly associated with a lower risk of recurrence, corresponding to a 91.8% recurrence-free survival rate with a mean follow-up of 29.8 ± 28.7 months.