Acute and Life-threatening Complications in Cushing Syndrome: Prevalence, Predictors, and Mortality

J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2035-e2046. doi: 10.1210/clinem/dgab058.


Context: Cushing syndrome (CS) results in significant morbidity and mortality.

Objective: To study acute and life-threatening complications in patients with active CS.

Methods: We performed a retrospective cohort study using inpatient and outpatient records of patients with CS in a tertiary center. A total of 242 patients with CS were included, including 213 with benign CS (pituitary n = 101, adrenal n = 99, ectopic n = 13), and 29 with malignant disease. We collected acute complications necessitating hospitalization, from appearance of first symptoms of hypercortisolism until 1 year after biochemical remission. Mortality data were obtained from the national registry. Baseline factors relating to and predicting acute complications were tested using uni- and multivariate analysis.

Results: The prevalence of acute complications was 62% in patients with benign pituitary CS, 40% in patients with benign adrenal CS, and 100% in patients with ectopic CS. Complications observed in patients with benign CS included infections (25%), thromboembolic events (17%), hypokalemia (13%), hypertensive crises (9%), cardiac arrhythmias (5%), and acute coronary events (3%). Among these patients, 23% had already been hospitalized for acute complications before CS was suspected, and half of complications occurred after the first surgery. Glycated hemoglobin (HbA1c) and 24-hour urinary free cortisol positively correlated with the number of acute complications per patient. Patients with malignant disease had significantly higher rates of acute complications. Mortality during the observation period was 2.8% and 59% in benign and malignant CS, respectively.

Conclusions: This analysis highlights the whole spectrum of acute and life-threatening complications in CS, and their high prevalence even before disease diagnosis and after successful surgery.

Keywords: Cushing syndrome; comorbidities; hospitalization; infection; malignancy; thromboembolism.

MeSH terms

  • Adult
  • Austria / epidemiology
  • Cushing Syndrome / complications*
  • Female
  • Follow-Up Studies
  • Humans
  • Hypokalemia / epidemiology
  • Hypokalemia / etiology
  • Hypokalemia / mortality*
  • Hypokalemia / pathology
  • Infections / epidemiology
  • Infections / etiology
  • Infections / mortality*
  • Infections / pathology
  • Male
  • Middle Aged
  • Neoplasms / epidemiology
  • Neoplasms / etiology
  • Neoplasms / mortality*
  • Neoplasms / pathology
  • Prevalence
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Thromboembolism / epidemiology
  • Thromboembolism / etiology
  • Thromboembolism / mortality*
  • Thromboembolism / pathology