Patients with endogenous Cushing syndrome (CS), including those with Cushing disease (CD), have a mortality rate that is 3 times higher than the general population.1, 2, 3, 4, 5 This increased mortality is primarily attributed to cardiovascular conditions (acute myocardial infarction, stroke, congestive heart failure, and venous thromboembolic [VTE] events), hyperglycemia, and infections.4

It is well-established that endogenous CS is intrinsically associated with VTE events,6, 7, 8, 9, 10, 11 independent of surgical procedures and metabolic disturbances. Previous studies have reported significant rates of VTE events in patients with CS, ranging from 2.6% to 18.2% (predominantly deep vein thrombosis [DVT] and pulmonary embolism [PE]),6, 7, 8, 9, 10, 11, 12 which is approximately 10 times higher than general population (DVT 0.53 to 1.62 per 1000 person-years and PE 0.39 to 1.15 per 1000 person-years).13

The pathophysiological mechanism underlying hypercortisolism as a thrombogenic condition is not fully understood. However, it is primarily attributed to the genomic action of cortisol, which leads to the upregulation of mRNA transcription for hemostatic factors, resulting in the activation of the coagulation cascade and impaired fibrinolytic capacity.6,14 Altered hemostatic parameters are observed even when compared to high-risk groups, such as those with metabolic syndrome.15, 16, 17 The studies reported increased levels of factor VIII, factor IX, von Willebrand factor, and fibrinogen; a shortened activated partial thromboplastin time (APTT); and elevated levels of factors that reduce fibrinolysis, such as plasminogen activator inhibitor-1, thrombin-activatable fibrinolysis inhibitor, and alpha-2-antiplasmin. Some studies also describe an increase in anticoagulant factors, such as protein C, protein S, and antithrombin III, likely through a compensatory mechanism.18

VTE prevalence in CD varies widely across studies, likely due to differences in populations, CS etiologies, inclusion of other events (eg, stroke), and timing (preoperative vs postoperative).6, 7, 8, 9, 10, 11, 12

These factors, along with variability in evaluated hemostatic parameters and use of thromboprophylaxis, hinder consensus on prophylaxis.18, 19, 20

The present study aimed to identify the prevalence and risk profile of VTE events in a large cohort of patients with CD.