Impact of Female Sex and Mild Cortisol Secretion on Coagulation Profile in Adrenal Incidentalomas

Context: Studies describing the coagulation profile in adrenal adenomas still need to be added. Objective: We explored how sex and mild autonomous cortisol secretion (MACS) affect coagulation parameters in patients with adrenal adenomas. Design: Cross-sectional study. Methods: From January 2019 until April 2023, participants in the Impact of Adrenal IncidenTalomas and Possible Autonomous Cortisol Secretion on Cardiovascular and Metabolic Alterations trial (NCT04127552) diagnosed with adrenal adenoma were categorised according to the 1 mg overnight dexamethasone-suppression test (1 mg-DST). Coagulation parameters were evaluated, and two-way ANOVA was used to elucidate the cortisol-by-sex interaction. Results: Of 153 patients screened, 90 were enrolled (62.2% female, mean age 62 ± 10 years): 41 with non-functioning adrenal tumour (1 mg-DST ≤ 1.8 µg/dL), and 49 with a MACS (1 mg-DST > 1.8 µg/dL). Platelet counts were higher in the MACS group (P = .01). Regression analysis identified female sex (B = 36.603, P = .011), 1mg-DST (B = 0.238, P = .042), and younger age (B = −1.452, P = .038) as independent predictors for elevated platelet count. In patients with MACS, women exhibited higher levels of procoagulant factors fibrinogen (P = .004) and factor VIII (P < .001), and coagulation inhibitors protein C (P = .003) and antithrombin III (P = .005) than males. No differences were observed in the non-functioning adrenal tumour group, providing a cortisol-by-sex interaction regarding fibrinogen (P = .047), factor VIII (P = .046), and protein C (P = .028). Conclusion: Our findings revealed a worse coagulation profile in women with MACS, underscoring the need for a sex-specific approach in clinical practice to manage thrombotic risks effectively. Dedicated prospective studies are needed to validate and integrate these findings into clinical strategies for thromboprophylaxis.