Endocrine Abstracts

Background: Cushing’s syndrome (CS) and hypertension (HT) are associated with alterations of coagulation. This is the first study that compares parameters of fibrin clot and fibrinolysis in CS with patients with essential hypertension (EHT) and healthy normotensive controls (HC).

Methods: The patients were recruited at the university hospital of Ludwig-Maximilians-Universität München (Germany) and the Department of Hypertension, Institute of Cardiology, Warsaw (Poland). We analyzed 31 patients (mean age: 42.9±13.2 years, 25 females, 86% HT) with active CS (n=25) and subclinical CS (n=6). They were compared with 31 age, sex and BMI matched patients with EHT (mean age: 44.3±12.7 years, 25 females) and 31 age and sex matched HC (mean age: 43.8±12.8 years, 25 females). The following variables were assessed: plasma fibrin clot permeability (Darcy’s constant, Ks), clot lysis time (CLT) and a kinetics profile of thrombin generation i.a. the endogenous thrombin potential (ETP) with the use of a calibrated automated thrombogram. Immunoenzymatic and chromogenic assays were used to determine plasminogen activator inhibitor-1 (PAI-1) and plasma-activated thrombin-activatable fibrinolysis inhibitor antigen (TAFI).

Results: Fibrin clot structure in patients with CS is less dense in comparison to EHT, but comparable to HC (median Ks in CS 6.98 [5.53–8.91] vs. EHT 4.68 [3.96–6.11] 10⁻⁹ cm², P<0.001; CS 6.98 [5.53–8.91] vs. HC 7.89 [7.19–8.36] 10⁻⁹ cm², P=0.09). Higher density is generally found in patients with higher cardiovascular risk. Fibrin clot structure was most resistant to lysis in EHT (median CLT CS 97.10 [90.0–113.6] vs. EHT 110.5 [95.8–126.3] vs. HC 93.8 [79.2–104.0] min, CS vs. EHT P<0.039). Furthermore, CS patients present with a higher ETP as compared to healthy controls, but in EHT this is even more pronounced (median ETP in CS 1753.3 [1370.2–1881.4] vs. EHT 2087.6 [1946.0–2394.4], nM*min, P<0.001; CS 1753.3 [1370.2–1881.4] vs. HC 1132.6 [1048.1–1256.6] nM*min, P<0.001). Proteins inhibiting fibrinolysis such as PAI-1 and TAFI are significantly higher in CS than in EHT (mean PAI-1: CS 49.22±26.43 vs. EHT 24.44±23.79 ng/ml, P< 0.001; mean TAFI: CS 131.25±13.86 vs. EHT 95.03±26.59 AG %, P<0.001).

Conclusion: Despite an overlap of hypertension in CS and EHT, we observe significant differences in fibrin clot structure and fibrinolysis in both entities. Fibrin clot density, CLT and ETP are more altered in EHT than in CS, whereas proteins inhibiting fibrinolysis are higher in CS.