Association between Pituitary Adenoma Excision and Risk of Cerebrovascular Disease in Cushing's Disease: A Propensity Score Matched Analysis

Introduction: Cushing’s disease (CD) is a hypercortisolemic condition caused by an ACTH-secreting pituitary adenoma (PA). Cerebrovascular disease (CeVD) represents a particularly severe complication of CD, yet its risk has been only sparsely characterized. This study sought to evaluate the risk of CeVD in patients with CD and to examine how surgical treatment influences this risk. Methods: We conducted a retrospective, multicenter study using 20 years of data from 69 healthcare organizations in the TriNetX database. Adult patients in the United States with CD were identified and matched 1:1 to non-CD controls using propensity score matching (PSM) for demographics and tobacco use. Risk ratios were calculated to assess the risk of CeVD in CD versus non-CD patients. Among those with CD, we further identified patients who underwent PA excision after diagnosis. Using 1:1 PSM adjusted for demographics and comorbidities (hypertension, diabetes mellitus, and dyslipidemia), we compared CeVD outcomes between patients who did and did not undergo PA excision. Results: The CD group ( n = 4,265) was 78.4% female with a mean age at CD diagnosis of 51.1 years. After PSM, CD patients had a significantly higher likelihood of any CeVD (RR=1.97, 95%CI: 1.70–2.29), ischemic stroke (RR=2.35, 95%CI: 1.83–3.01), and hemorrhagic stroke (RR=1.75, 95%CI: 1.22–2.49). Stratification by sex identified similar associations among men and women. 1,377 CD patients who underwent PA excision were identified after matching. PA excision after CD diagnosis was associated with lower risk of any CeVD (RR=0.68, 95%CI: 0.55–0.86, NNT=25.6), ischemic stroke (RR=0.50, 95%CI: 0.35–0.72, NNT=33.3), and mortality (RR=0.52, 95%CI: 0.35–0.77, NNT=40.0) compared with those who did not have excision. Conclusion: Patients with CD face a significantly elevated risk of CeVD, including both ischemic and hemorrhagic stroke. Surgical excision of the pituitary adenoma may reduce long-term risk of CeVD and overall mortality, underscoring the potential protective role of timely surgical treatment. Publication History Article published online: 27 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany