Risk Factors for Central Diabetes Insipidus After Pituitary Surgery: Insights from a Multi-Institutional Analysis of 9,290 Patients

Background: Central diabetes insipidus (DI) is a frequent complication of transsphenoidal hypophysectomy for pituitary adenomas, yet risk prediction remains incomplete. Prior studies have focused on traditional risk factors for postoperative DI, such as tumor size, craniopharyngioma histology, and extent of resection. However, the role of patient-specific comorbidities and lifestyle factors has not been fully explored. Therefore, we leveraged a large, multi-institutional database to identify predictors of postoperative DI. Methods: Using the TriNetX Research Network, we identified 9,290 patients with pituitary adenoma (ICD-10 D35.2) who underwent endoscopic transsphenoidal hypophysectomy (ICD-10-PCS 0GB04ZZ). Cohort 1 ( n = 1,514) developed postoperative DI (ICD-10 E23.2); Cohort 2 ( n = 7,776) did not. A Cox proportional hazards model assessed the association of demographic, endocrine, comorbidity, and medication covariates with DI. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. Results: Demographics: Male sex was protective against DI (HR 0.83, 95% CI 0.73–0.94, p = 0.003). Increasing age was also associated with reduced risk (HR 0.99 per year, 95% CI 0.98–0.99, p < 0.001). Endocrine and Tumor Characteristics: Patients with acromegaly or pituitary gigantism demonstrated significantly lower hazard of DI (HR 0.65, 95% CI 0.49–0.85, p = 0.002). Preoperative desmopressin use was a powerful independent predictor, associated with a 62% increased hazard of DI (HR 1.62, 95% CI 1.38–1.90, p < 0.001). Comorbidities and Lifestyle: Cigarette nicotine dependence was strongly associated with increased DI risk (HR 2.23, 95% CI 1.39–3.58, p = 0.001). Chronic kidney disease (HR 1.45, 95% CI 1.09–2.04, p = 0.013) and frailty/age-related physical debility (HR 3.44, 95% CI 1.09–11.1, p = 0.036) were also significant predictors. Obesity (HR 1.18, 95% CI 0.99–1.40, p = 0.067) showed borderline associations. Conclusion: Beyond traditional demographic and endocrine factors, we identify smoking, CKD, and frailty as novel risk factors for postoperative DI in pituitary adenoma patients. The strong association with preoperative desmopressin use highlights a high-risk subgroup that may warrant enhanced perioperative surveillance. These findings can inform preoperative counseling, patient optimization, and risk-stratified follow-up strategies after transsphenoidal surgery. Publication History Article published online: 27 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany