Association Between Pituitary Adenoma Excision and Risk of Cerebrovascular Disease and Mortality in Patients With Cushing's Disease: A Propensity Score–Matched Analysis

BACKGROUND AND OBJECTIVES: Cushing's disease (CD) is a hypercortisolemic state resulting from an adrenocorticotropic hormone-secreting pituitary adenoma (PA). Cerebrovascular disease (CeVD) is a dangerous sequela of CD, yet few studies have characterized its risk in CD. This study aimed to report the risk of CeVD in CD patients with and without surgical treatment. METHODS: This retrospective multicenter study from the TriNetX database included 20 years of data from 69 healthcare organizations. TriNetX was searched to identify adults in the United States with CD. We used 1:1 propensity score matching (PSM) for demographic characteristics and tobacco use to identify a matched non-CD group. Risk ratios were calculated to identify the risk of CeVD. Among patients with CD, we identified those who underwent PA excision after diagnosis and determined associations with CeVD. We used 1:1 PSM matching for demographic characteristics and comorbidities (hypertension, diabetes mellitus, dyslipidemia) to identify a matched non-PA excision CD group. RESULTS: The CD group (n = 4265) was 78.4% female with a mean age at CD diagnosis of 45.7 years. After PSM, patients with CD had a significantly higher risk of any CeVD (risk ratio [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. One thousand three hundred seventy-seven patients with CD who underwent PA excision were identified after matching. PA excision was associated with lower risk of any CeVD (RR = 0.68, 95% CI: 0.55-0.86, number needed to treat [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. Sensitivity analyses using medication-based proxies for biochemical remission showed similar trends between curative and noncurative resection but were not statistically significant. CONCLUSION: This study demonstrated that patients with CD are at an increased risk of CeVD, including ischemic and hemorrhagic stroke. PA excision for patients with CD may reduce lifetime CeVD risk and mortality.