title: Multisystem morbidity and mortality in Cushing's syndrome: a cohort study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Population-based cohort study.
  
  
  METHODS
  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.
  
  
  METHODS
  Benign CS of adrenal or pituitary origin and a matched population comparison cohort were included.
  
  
  METHODS
  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.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden 2300RC, The Netherlands. o.m.dekkers@lumc.nl
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Horváth-Puhó
authors.forename: Jens Otto L
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Cannegieter
authors.forename: Vera
authors.initials: V
authors.lastname: Ehrenstein
authors.forename: Jan P
authors.initials: JP
authors.lastname: Vandenbroucke
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
authors.forename: Henrik Toft
authors.initials: HT
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003480:Cushing Syndrome / Q000150:complications / Q000401:mortality* / Q000601:surgery; D005260:Female; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D009203:Myocardial Infarction / Q000209:etiology; D016016:Proportional Hazards Models; D020521:Stroke / Q000209:etiology; D054556:Venous Thromboembolism / Q000209:etiology