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Hypercoagulable State in Cushing’s Syndrome: A Systematic Review

Department of Internal Medicine (B.V.Z., E.N., V.E.A.G., D.P.M.B.), Slotervaart Hospital, 1066 EC Amsterdam, The Netherlands; Department of Vascular Medicine (B.V.Z., A.S., M.B.T., V.E.A.G., H.R.B.), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Department of Clinical Medicine (A.S.), University of Insubria, 21100 Varese, Italy; Departments of Clinical Epidemiology (O.M.D.) and Endocrinology and Metabolic Diseases (O.M.D.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; and Department of Endocrinology and Metabolism (E.F.), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: B. Van Zaane, Department of Internal Medicine, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. E-mail: b.vanzaane{at}amc.uva.nl.

Context: It has been debated whether an increased risk of venous thromboembolism (VTE) exists in patients with Cushing’s syndrome.

Objective: We aimed to summarize published literature on the effects of endogenous hypercortisolism on coagulation and fibrinolysis, as well as on the clinical outcome of VTE.

Data Sources: We searched the MEDLINE and EMBASE databases up to July 2008. Review of reference lists further identified candidate studies.

Study Selection: Two investigators independently performed study selection and data extraction. Eligible studies had to include Cushing’s syndrome patients and either evaluate hemostatic parameters in comparison with control persons or posttreatment levels or describe the occurrence of VTE.

Data Extraction: The Newcastle-Ottawa Scale was used to assess study quality. A scoring system divided studies into categories of low, medium and high quality.

Data Synthesis: Of 441 identified publications, 15 reports were included. They contained information on eight cross-sectionals, two intervention, and eight cohort studies. No high-quality studies were identified. Hypercoagulability was suggested by high levels of factor VIII, factor IX, and von Willebrand factor and by evidence of enhanced thrombin generation. A risk of 1.9 and 2.5% was reported for VTE not provoked by surgery, whereas risk of postoperative VTE varied between 0 and 5.6%, with one outlier of 20%. VTE was reported as the cause of death in 0–1.9% of Cushing’s syndrome patients.

Conclusions: Available studies suggest a high risk of venous thrombosis in patients with Cushing’s syndrome. Glucocorticoid-induced hypercoagulability as well as surgery and obesity almost certainly contribute to this thrombotic tendency.