Mortality in Cushing’s Syndrome: Declining Over Two Decades but Remaining Higher Than the General Population

Abstract

Objective

Patients with endogenous Cushing’s syndrome (CS) have elevated mortality, particularly during active disease. A recent meta-analysis reported reduced mortality rates after 2000 in adrenal CS and Cushing disease (CD), though many studies lacked population-matched controls.

Methods Nationwide retrospective study (2000–2023) in Israel using the Clalit Health Services database to assess all-cause mortality in patients with endogenous CS matched 1:5 with controls by age, sex, socioeconomic-status, and BMI. Primary outcome was all-cause mortality. Secondary outcomes included cause-specific mortality, impact of hypercortisolism remission, disease source, and mortality risk factors.

Results The cohort included 609 cases with CS (mean age 48.1±17.2 years; 65.0% women) and 3,018 matched controls (47.9±17.2 years; 65.4% women). Over a median follow-up of 16 years, 133 cases (21.8%) and 472 controls (15.6%) died (HR=1.44, 95% CI, 1.19–1.75). Both patients with CD (HR=1.73, 95% CI, 1.27–2.36) and adrenal CS (HR=1.31, 95% CI, 1.00–1.81) had increased mortality risk. Patients without remission within 2 years had a higher mortality risk than those achieving remission (HR=1.44, 95% CI, 1.00–2.17). Mortality was similar for CD and adrenal CS (HR=0.83, 95% CI, 0.56–1.24). Older age, male gender, and prior malignancy were independent risk factors for mortality.

Conclusion This is the largest national cohort study on mortality risk in CS over the past two decades, showing a significantly higher risk compared to matched controls in a homogeneous database. While etiology had no impact, remission significantly affected mortality, highlighting the importance of disease control for long-term survival.

Request the full article at https://www.researchgate.net/publication/390437820_Mortality_in_Cushing’s_Syndrome_Declining_Over_Two_Decades_but_Remaining_Higher_Than_the_General_Population

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