Prognostic Value of Intraoperative Desmopressin Test for Long-Term Remission in Cushing's Disease: A Prospective Cohort Study

BACKGROUND AND OBJECTIVES: The desmopressin stimulation test is a cornerstone for the diagnosis of Cushing's disease (CD). Recent evidence suggests its potential for early recurrence prediction when performed postoperatively. However, its application as a real-time intraoperative prognostic tool has never been explored. This study aimed to investigate, for the first time, the prognostic value of an intraoperative desmopressin test for predicting long-term remission in CD. METHODS: In this prospective cohort study (November 2019-December 2023), 79 CD patients underwent endoscopic transsphenoidal surgery with intraoperative desmopressin test performed immediately after presumed total resection. The adrenocorticotropic hormone (ACTH) response ratio (post-stimulation/baseline × 100%) was calculated at 15 and 30 minutes. Predictive performance was assessed by receiver operating characteristic analysis, and Firth's penalized-likelihood regression estimated relative risks for nonremission/recurrence. Longitudinal ACTH trajectories were compared using linear mixed-effects modeling. RESULTS: At 2-year follow-up, 70 patients (88.6%) sustained remission, whereas9 (11.4%) experienced nonremission/recurrence. The 15-minute ACTH response ratio demonstrated outstanding predictive accuracy (area under the curve = 0.962), with an optimal cutoff value of ≥110%. A 15-minute ratio ≥110% was associated with a relative risks of 188.54 (95% CI, 20.11-25373.13, P < .001). Linear mixed-effects modeling confirmed a significant group-by-time interaction (P < .001), with diverging ACTH trajectories between outcome groups. CONCLUSION: The intraoperative desmopressin test is a powerful real-time predictor of long-term surgical outcome. A 15-minute ACTH response ratio ≥110% provides a critical intraoperative threshold that may guide surgical strategy and postoperative management.