2178 Sustained Post-Operative Nadir Cortisol Outperforms 8-Week Nadir as a Prognostic Biomarker of Recurrence in Pathology-Confirmed Cushing Disease

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INTRODUCTION: Predicting recurrence and long-term remission after transsphenoidal surgery for Cushing's disease remains clinically challenging. METHODS: We performed a retrospective analysis of patients with pathology-confirmed Cushing disease who underwent transsphenoidal surgery between 2007-2019 and achieved post-operative biochemical remission. Sustained nadir was defined as the nadir achieved during three post-operative values within 0.5 μg/dL over an 18-hour period. Sustained nadir and 8-week nadir were compared after adjusting for confounders. Time-to-recurrence was analyzed using adjusted Cox proportional hazards regression. RESULTS: A total of 205 patients, predominantly female (81.5%), with microadenomas (66.3%), and a mean age of 38.8 ± 13.1 years were analyzed. Median follow-up was 5.6 years (IQR 3.0-9.3). Mean sustained nadir and 8-week nadir were 1.93 ± 3.42 μg/dL and 3.79 ± 4.26 μg/dL, respectively. Eleven patients (5.4%) experienced recurrence, with a mean time-to-recurrence of 2.7 ± 2.1 years. Four of 161 patients (2.5%) with nadir <2 μg/dL experienced recurrence, compared to 7 of 44 patients (15.9%) with nadir ≥2 μg/dL. Multivariate Cox regression analysis yielded a hazard ratio (HR) of 0.15 (p = 0.0026) for nadir cortisol <2 μg/dL. Age at surgery was also significant, with older age associated with a lower risk of recurrence (HR = 0.93 per year, p = 0.004). The 8-week nadir <2 μg/dL showed a trend toward lower recurrence rate (HR = 0.38; p = 0.18), with recurrence rates of 3.0% (3/101) and 7.7% (8/104) for levels <2 and ≥2 μg/dL, respectively. Combining nadir <2 and 8-week nadir <2 yielded a slightly stronger hazard ratio (HR = 0.12, p = 0.046), but did not substantially improve risk stratification compared to post-operative nadir alone. CONCLUSIONS: Sustained post-operative nadir cortisol <2 μg/dL outperforms 8-week nadir as a prognostic biomarker for long-term in pathology-confirmed Cushing disease.

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