D-dimer as a significant marker of deep vein thrombosis in patients with subclinical or overt Cushing’s syndrome

Abstract

Venous thromboembolism (VTE) is frequently associated with hypercortisolemia. This retrospective singlecenter study aimed to clarify the significance of plasma D-dimer levels for VTE screening in patients with subclinical or overt Cushing’s syndrome (soCS). A total of 72 consecutive treatment-naïve patients with soCS diagnosed at Kobe University Hospital between 2002 and 2014 were enrolled. Patients with both lower extremity ultrasound and D-dimer measurement data (n = 19) were recruited in study 1 and divided into 2 groups, a deep vein thrombosis (DVT) (-) group (n = 12) and DVT (+) group (n = 7) for a comparison of the associated factors. The age and D-dimer levels were higher in the DVT (+) group than in the DVT (-) group (p = 0.04 and 0.02, respectively). A receiver operating characteristic analysis found that D-dimer level ≥2.6 μg/mL correlated with the presence of DVT (sensitivity, 100%; specificity, 91.7%). Next, patients with D-dimer measurement data (n = 36) were recruited in study 2 and divided into 2 groups according to D-dimer level: D-dimer (-), <1 μg/mL group (n = 23) and D-dimer (+), ≥1 μg/mL group (n = 13); the groups were compared with respect to various VTE-related risk factors. A logistic regression analysis revealed that elevated cortisol level after lowdose dexamethasone suppression was a significant risk factor for D-dimer elevation (OR = 1.21, p = 0.02). In conclusion, these data demonstrate that a D-dimer level ≥2.6 μg/mL is an indicator of DVT in treatment naïve patients with soCS and suggests that relatively high autonomous cortisol secretion may be associated with thrombus formation.