Coagulation parameters in asymptomatic patients with adrenal incidentaloma: is mild autonomous cortisol secretion correlated with thromboembolic risk?

Background: Overt hypercortisolism is highly associated with venous thromboembolism. Patients with Cushing’s syndrome (CS) typically show an alteration of the intrinsic coagulation pathway, especially an increase in factor VIII (f-VIII), and increased levels of coagulation inhibitors (i.e., antithrombin III) as a compensatory response. Mild autonomous cortisol secretion (MACS) has been variably associated with higher risk of cardiovascular events and mortality compared to patients with non-functioning adrenal adenomas (NFAA). However, dedicated studies describing coagulation status in these patients are lacking. Aim: To describe coagulation parameters in patients with MACS compared with patients with NFAA enrolled in the ITACA study (NCT04127552) Method: 56 asymptomatic patients with adrenal incidentaloma without the classic signs or symptoms of overt hypercortisolism were prospectively enrolled. According to post-dexamethasone suppression cortisol values (post-DST), three groups were defined: NFAA (<50 nmol/l), possible MACS [MACS-1] (50 to 138 nmol/l) and MACS [MACS-2] (>138 nmol/l). Coagulation markers (fVIII, fVII, fV, fibrinogen, PT, aPTT, platelets) and coagulation inhibitors (Antitrombin III, Protein C, Protein S) were studied. Patients with an history of thrombosis were excluded. Results: A total of 24 NFA, 22 MACS-1 and 10 MACS-2 were included in the analysis. No differences in coagulation markers and inhibitors were observed between MACS-1 and NFAA. Mean factor VIII levels were significantly increased in the MACS-2 group (167%±54) compared to the NFA group (129%±30; P=0.021) and MACS-1 (122%±32; P=0.012), respectively. Overall, a positive correlation was found between post-DST, platelets (r=0.214; P=0.038) and antithrombin III (r=0.354: P=0.021). Conclusions: asymptomatic patients with elevated post-DST (>138 nmol/l) may show early thrombotic alterations, similar to those in patients with symptomatic CS. Coagulation parameters may help to identify patients with adrenal incidentalomas at high risk of thromboembolic events, who could benefit from anticoagulant prophylaxis prior to adrenal surgery.