Mild Autonomous Cortisol Secretion and Psychiatric Morbidity in Patients With Adrenal Tumors: A Cohort Study

Mild autonomous cortisol secretion (MACS) in adrenal tumors (ATs) is associated with cardiometabolic disease, but its relationship with psychiatric morbidity is poorly defined.

To investigate psychiatric outcomes in relation to cortisol autonomy in patients with ATs.

Population-based retrospective cohort study of 3195 patients with a first benign AT diagnosis (2005-2018) and an available 1-mg dexamethasone suppression test (DST) result in the Stockholm Region, Sweden, identified via national registers and regional laboratories. Patients were classified as having MACS (DST >50 nmol/L) or non-functional AT (NFAT) (DST ≤50 nmol/L). Prevalent and incident psychiatric diagnoses and dispensed psychotropic medications were analyzed by logistic and Cox regression, adjusted for age, sex, and socioeconomic status.

Of 3195 patients (median age, 64 years; 58.9% women), 1979 had NFAT and 1216 had MACS. Psychiatric disorders were more common with MACS (adjusted odds ratio, 1.35 [95% CI, 1.11-1.64]). Over 4.7 years' median follow-up, MACS was associated with higher incidence of psychiatric disorders (adjusted hazard ratio [aHR], 1.79 [1.43-2.23]), including anxiety, mood, and substance use disorders (aHR range, 1.41-2.50), with the highest point estimate among men younger than 65 years (aHR, 3.11 [1.87-5.18]). However, after correction for multiple comparisons only psychiatric disorders and substance use disorders remained significant. Findings were consistent across categorical and continuous cortisol measures.

Psychiatric disorders were more common among patients with MACS than NFAT. These findings suggest that mild cortisol autonomy may contribute to psychiatric vulnerability and support consideration of psychiatric history and symptoms when assessing patients with ATs.