Pituitary Adenoma Excision Is Associated with Reduced Risk of Cerebrovascular Disease and Mortality in Cushing’s Disease: A Propensity Score Matched Analysis

Introduction: Cushing’s disease (CD) is a hypercortisolemic state resulting from an ACTH-secreting pituitary adenoma (PA). CD is associated with serious comorbidities including dyslipidemia, hypertension, and abnormal glucose metabolism. Cerebrovascular disease (CeVD) is a particularly dangerous sequelae of CD, yet few studies have characterized its risk in CD. This multicenter study aimed to report the subsequent risk of CeVD in patients with and without surgical treatment of CD.

Methods: This multicenter cohort study from the TriNetX database included 20 years of data from 66 healthcare organizations. TriNetX was searched for medical records for U.S. adults with CD. We used 1:1 propensity score matching (PSM) for demographic characteristics and tobacco use to identify a matched non-CD cohort. Odds ratios were calculated to explore the risk of CeVD (includes the subsets of stroke, subarachnoid/intracranial/intracerebral hemorrhage, stenosis of precerebral/cerebral arteries, non-ruptured intracranial aneurysm) after PSM. Among patients with CD, we identified those who underwent PA excision during the same time period 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 cohort.

Results: The CD cohort (n=5,111) was 70.2% female with a mean age at CD diagnosis of 51.1 years. After PSM, CD patients had a significantly increased likelihood of any CeVD (OR=3.60, 95%CI: 3.11-4.17), stroke (OR=3.98, 95%CI: 2.50-6.34), and mortality (OR=1.98, 95%CI: 1.79-2.19). Stratification by sex identified similar associations among women and men. 1,333 patients in TriNetX underwent PA excision. PA excision after CD diagnosis was associated with reductions in risk of any CeVD (OR=0.61, 95%CI: 0.50-0.80), stroke (OR=0.43 , 95%CI: 0.28-0.67), and mortality (OR=0.20, 95%CI: 0.14-0.29).

Conclusion : This study demonstrates that patients with CD are at an increased risk for mortality and any CeVD, including stroke. PA excision for patients with CD reduces lifetime CeVD risk and mortality.