Multisystem Morbidity and Mortality in Cushing's Syndrome: A Cohort Study

Context: Cushing's syndrome (CS) is associated with hypercoagulability, insulin resistance, hypertension, bone loss, and immunosuppression. To date, no adequately large cohort study has been performed to assess the multisystem effects of CS. Objective: We aimed to examine the risks for mortality, cardiovascular disease, fractures, peptic ulcers, and infections in CS patients before and after treatment. Design: Population-based cohort study. Setting: Source population was the entire population of Denmark (1980 to 2010). Data were obtained from the Danish National Registry of Patients and the Danish Civil Registration System. Patients: Benign CS of adrenal or pituitary origin and a matched population comparison cohort were included. Outcome measures: We used Cox regression, and computed hazard ratios (HR) with 95% confidence intervals (95% CI). Morbidity was investigated in the 3 years before diagnosis; morbidity and mortality were assessed during complete follow-up after diagnosis and treatment. Results: Included were 343 CS patients and 34 300 controls. Mortality was twice as high in CS patients (HR 2.3, 95% CI 1.8-2.9) compared with controls. Patients with CS were at increased risk for venous thromboembolism (HR 2.6, 95% CI 1.5-4.7), myocardial infarction (HR 3.7, 95% CI 2.4-5.5), stroke (HR 2.0, 95% CI 1.3-3.2), peptic ulcers (HR 2.0, 95% CI 1.1-3.6), fractures (HR 1.4, 95% CI 1.0-1.9), and infections (HR 4.9, 95% CI 3.7-6.4). This increased multimorbidity risk was present before diagnosis. Mortality and risk of myocardial infarction remained elevated during long-term follow-up. Mortality and risks for acute myocardial infarction, venous thromboembolism, stroke, and infections were similarly increased in adrenal and pituitary CS. Conclusions: Despite the apparently benign character of the disease, CS is associated with clearly increased mortality and multisystem morbidity, even before diagnosis and treatment.