1233 A Benchmark for Early Biochemical Success and Long-term Remission After Resection of Corticotroph Adenomas in Cushing Disease

Abstract

INTRODUCTION: In Cushing disease, the definition of success after resection of corticotroph adenomas remains unclear given inconsistent pathology and high recurrence rates despite initial biochemical remission. METHODS: We collected 12 years of in-hospital cortisol data after the removal of pathology-confirmed corticotroph adenomas in patients with Cushing disease. A novel cortisol halving time analysis was performed using exponential decay modeling, results were dichotomized a priori, and then applied to an external cohort of patients. Halving time was compared to first post-operative cortisol and nadir cortisol variables by estimating long-term remission and time-to-recurrence using Cox regression modeling and the Kaplan-Meier method. RESULTS: A total of 320 patients met inclusion/exclusion criteria for the final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 2.1 years, although 62 patients had five years or longer follow-up time. Higher first post-operative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first post-operative cortisol = 50 µd/dL were 4.1 times more likely to recur than those with a first post-operative cortisol < 50 µd/dL (HR 4.1, 1.8-9.2; p = 0.0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, p = 0.18). Patients with a nadir cortisol =2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, p < 0.0001). CONCLUSIONS: Post-operative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first post-operative cortisol and cortisol halving time, a nadir < 2 µg/dL occurring within the first three post-operative days showed the strongest association with long-term remission.