Associations Between Transsphenoidal Surgery and Neuropsychiatric Disorders for Patients With Cushing's Disease

Cushing's disease (CD) is a hypercortisolemic state caused by an adrenocorticotropic hormone-secreting pituitary tumor and is associated with significant neuropsychiatric comorbidities. The prevalence of associated neuropsychiatric disorders (NPD) after surgical resection is not well-characterized. The goal of this study was to report the comparative lifetime risk of NPD in CD patients and evaluate how transsphenoidal tumor resection may be protective against these comorbidities.

Using the TriNetX database, we conducted retrospective analyses of International Classification of Diseases-10 coded data from 144 healthcare organizations to determine the relative risk of NPD among CD patients (N = 4390) compared with patients without CD (N = 6 445 925) and patients with nonfunctional pituitary adenomas (NFPA) (N = 111 878). Among those with CD, we compared NPD prevalence in patients with or without surgical PA resection (N = 1261). We performed 1:1 propensity score matching based on demographic characteristics for all comparisons and adjusted for comorbidities (hypertension, diabetes mellitus, dyslipidemia) in the comparative resection analysis.

Compared with non-CD patients, CD patients exhibited significantly increased risks of anxiety disorders (risk ratio [RR] = 1.31, CI: 1.19-1.44, P < .001), major depressive disorder (RR = 1.39, CI: 1.23-1.57, P < .001), depressive episodes (RR = 1.43, CI: 1.274-1.600, P < .001), persistent mood disorders (RR = 2.30, CI: 1.57-3.36, P < .001), and sleep disorders (RR = 1.90, CI: 1.71-2.12, P < .001). These significantly increased NPD risks in CD patients persisted when compared with NFPA patients. Surgical resection was significantly associated with decreased risk of anxiety disorders (RR = 0.78, CI: 0.64-0.95, P = .012), generalized anxiety disorder (RR = 0.60, CI: 0.40-0.89, P = .011), major depressive disorder (RR = 0.58, CI: 0.45-0.75, P < .001), depressive episodes (RR = 0.68, CI: 0.54-0.87, P = .0017), sleep disorders (RR = 0.69, CI: 0.56-0.86, P < .001), and substance use disorders (RR = 0.69, CI: 0.50-0.96, P < .027).

This study shows that CD patients are at greater risk of mental health and mood disorders compared with the general population and NFPA patients. Our data suggest that surgical resection of PAs causing CD is associated with decreased lifetime risk of NPD.