Depression and anxiety in patients with endogenous Cushing syndrome: a nationwide matched-cohort study using...

Cushing syndrome (CS) is associated with depression and anxiety. This study compared treated mood and anxiety disorders between patients with CS and controls, assessing differences by etiology and remission status.

A retrospective matched-cohort study of patients with endogenous CS (2000-2024) from the Clalit Health Services database. Each patient was matched with 5 controls by age, sex, socioeconomic status, and BMI. Mood and anxiety disorders were identified through affective drug dispensations (ADD). Drug discontinuation was defined as ≥1 month without dispensations.

The cohort included 540 patients with CS (mean age 47.79 ± 17.01 years; 64.44% women) and 2517 controls, with a median follow-up of 13.20 years (IQR 8.41-18.42). At baseline, patients with CS had nearly twice the odds of receiving ADD than controls (OR = 1.93, 95% CI,1.39-2.66), with a significant excess in women (12.93% vs. 6.93%, OR = 1.99, 95% CI, 1.38-2.87). During the entire follow-up, drug discontinuation rates did not differ (HR = 0.72, 95% CI, 0.50-1.04), whereas the risk of new-onset ADD was 2-fold higher in CS (HR = 2.23, 95% CI, 1.89-2.62). This increased risk was observed in both Cushing disease (HR = 2.44, 95% CI, 1.90-3.13) and adrenal CS (HR = 2.17, 95% CI, 1.64-2.88). Using a 2-year landmark analysis initiated 2 years after diagnosis, the increased risk persisted in patients who achieved remission (HR = 2.10, 95% CI, 1.59-2.78) and in those who did not (HR = 2.38, 95% CI, 1.60-3.55).

Endogenous CS is associated with a persistently increased risk of treated affective disorders at diagnosis and throughout long-term follow-up, underscoring the need for ongoing psychological care.