Endocrine Abstracts

Background: Patients with Cushing’s Syndrome (CS) have a high risk of venous thromboembolism (VTE) related to a hypercoagulable state. Previous studies showed increased levels of procoagulant factors but also an elevation of some of the anticoagulants factors and fibrinolytic enzymes. Once patients achieve disease remission, there is a significant decrease of some procoagulant factors but if these alterations are completely reversible is still unclear. Compared to traditional tests, thrombin generation assay (TGA) provides a global representation of haemostasis. Previous studies with TGA demonstrated that patients with endogenous hypercortisolism present a hypercoagulable profile compared to healthy controls.

Aim: To assess the short- and long-term modification of TGA in patients with CS after disease remission.

Patients and Methods: 19 patients with CS (16 pituitary adenomas, 2 adrenal adenomas, and 1 ectopic CS, female/male: 12/7, mean age 44.8 ± 11,4 years) that achieved surgical remission and 19 controls matched for age and gender. Clinical characteristics, cortisol secretion profile and TGA parameters before surgical intervention, after 6 months and 5 years of persistent remission were assessed. Endogenous thrombin potential (ETP) ratio (ETP with/ETP without thrombomodulin) represents the resistance to the anticoagulant activity of the thrombomodulin and may be considered the best parameter through which in vivosubtle procoagulant imbalance can be detected.

Results: – Cortisol secretion profile: morning serum cortisol levels: 20.3 (median, IQR: 17–29) µg/dl, serum cortisol after 1 mg DXM: 12.7 (IQR: 4.2–17) µg/dl, urinary free cortisol: 1.65 × ULN (IQR: 0.9–2.6)

– TGA: Patients with CS showed an ETP ratio significantly increased compared to controls (0.62 ± 0.09 vs 0.56 ± 0.09; P = 0.034). No significant correlation between ETP ratio and cortisol secretion was found.

6 months after remission

– TGA: CS patients presented an ETP ratio significantly increased compared to controls (0.64 ± 0.09 vs 0.56 ± 0.09, P = 0.01) and similar to baseline (0.64 ± 0.09 vs 0.62 ± 0.09, P = 0.87).

5 years after remission

– TGA: ETP ratio of CS patients showed a significant decrease (0.55 ± 0.14 vs 0.62 ± 0.09, P = 0.02) and was similar to the controls (0.55 ± 0.14 vs 0.56 ± 0.09, P = 0.7).

Before surgery: Conclusions Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term and seems to be reversible after long-term remission of disease. Our observation is in line with other studies that demonstrated an increased VTE risk in post-operative period and suggests that in CS patients, especially in the presence of other risk factors for VTE, a long-term antithrombotic prophylaxis should be considered.