The Hypercoagulable State in Cushing's Disease Is Associated with Increased Levels of Procoagulant Factors and Impaired Fibrinolysis, But Is Not Reversible after Short-Term Biochemical Remission Induced by Medical Therapy

Rob Pas, Christiaan Bruin, Frank Leebeek, Moniek de Maat, Dick Rijken, AM Pereira, JA Romijn, RT Netea-Maier, AR Hermus, PMJ Zelissen, Frank Jong, AJ (Aart-Jan) van der Lely, W.W. de Herder, S.W.J. Lamberts, Leo Hofland, R.A. Feelders

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Context: Cushing's disease (CD) is accompanied by an increased risk of venous thromboembolism. Surgery is the primary treatment of CD. Objective: The aim of the study was to compare hemostatic parameters between patients with CD and controls and to evaluate the effect of medical treatment of CD on hemostasis. Design and Setting: During 80 d, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline, and ketoconazole, which suppresses adrenocortical steroidogenesis, at four university medical centers in The Netherlands. Patients: Seventeen patients with de novo, residual, or recurrent CD were included. Main Outcome Measures: We measured urinary free cortisol and parameters of coagulation and fibrinolysis. Results: Patients with CD had significantly higher body mass index (P < 0.001), shortened activated partial thromboplastin time (P < 0.01), and higher levels of fibrinogen, Factor VIII, and protein S activity (P < 0.05) compared to healthy control subjects. In addition, fibrinolytic capacity was impaired in patients with CD as reflected by prolonged clot lysis time (P < 0.001) and higher levels of plasminogen activator inhibitor type 1, thrombin-activatable fibrinolysis inhibitor, and alpha 2-an Conclusions: The hypercoagulable state in patients with CD, which is explained by both increased production of procoagulant factors and impaired fibrinolysis, is not reversible upon short-term biochemical remission after successful medical therapy. This may have implications for the duration of anticoagulant prophylaxis in patients with (cured) CD. (J Clin Endocrinol Metab 97: 1303-1310, 2012)
Original languageUndefined/Unknown
Pages (from-to)1303-1310
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number4
Publication statusPublished - 2012

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