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Coagulation Profile in Patients with Different Etiologies for Cushing Syndrome: A Prospective Observational Study
Amit Tirosh1, Maya Lodish1, Charalampos Lyssikatos1
1Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Insights
Patients with Cushing disease (CD) exhibit distinct coagulation profiles compared to adrenal Cushing syndrome (CS). Higher cortisol levels in CD may contribute to increased risk of venous thromboembolism (VTE).
Area of Science:
- Endocrinology
- Hematology
- Internal Medicine
Background:
- Cushing disease (CD) is associated with a higher incidence of venous-thromboembolic events (VTE) than ACTH-independent Cushing syndrome (CS) from adrenal sources.
- Understanding the coagulation profile differences across CS etiologies is crucial for risk stratification and management.
Purpose of the Study:
- To prospectively evaluate and compare the coagulation profiles of patients with Cushing disease (CD) versus adrenal Cushing syndrome (CS).
- To identify specific hemostatic markers that differ between CD and adrenal CS.
Main Methods:
- A prospective observational study included 85 adult patients with suspected CS, categorized into CD (n=22), adrenal CS (n=21), and rule-out CS (n=42).
- Coagulation profiles (fibrinogen, Factor VIII, vWF:Ag, PAI-1, ATIII, PC, PS, α2AP, aPTT) were measured before and after surgery.
- Statistical analyses controlled for body mass index (BMI) and 24-h urinary free cortisol.
Main Results:
- Patients with CD presented with higher baseline mean cortisol levels, antithrombin III (ATIII) activity, and von Willebrand factor antigen (vWF:Ag) compared to adrenal CS.
- These differences in ATIII activity and vWF:Ag persisted after controlling for BMI.
- ATIII differences remained significant even after adjusting for 24-h urinary free cortisol levels.
Conclusions:
- This study demonstrates, for the first time, distinct coagulation profiles between different etiologies of Cushing syndrome.
- Elevated cortisol burden in CD patients is hypothesized to underlie the observed differences in coagulation and the increased VTE risk compared to primary adrenal CS.
Abstract:
Previous studies reported a higher prevalence of venous-thromboembolic events among patients with Cushing disease (CD) compared to those with ACTH-independent Cushing syndrome (CS) from adrenal sources. The objective of the current study was to evaluate the coagulation profile of patients with CS from different etiologies. A prospective observational study was conducted at a clinical research center. The study included adult patients admitted for evaluation of suspected CS (n=85), that were divided into 3 groups: CD (n=22), ACTH-independent CS from an adrenal tumor/hyperplasia (adrenal CS, n=21), and a control group consisting of subjects with negative screening for CS (rule-out CS, n=42). Coagulation profiles were drawn before and 8.5±4.3 months after surgery (trans-sphenoidal or adrenalectomy, n=18), and included fibrinogen, Factor VIII (FVIII), von Willebrand factor antigen (vWF:Ag), plasminogen activator inhibitor-1 (PAI-1), antithrombin III (ATIII), Protein C (PC), Protein S (PS), α2-antiplasmin (α2AP), and aPTT measurements. Patients with CD had higher baseline mean cortisol levels, ATIII activity and vWF:Ag levels compared with adrenal CS. Differences in ATIII activity and vWF:Ag levels remained even after controlling for BMI, and ATIII after also controlling for 24-h urinary free cortisol collections. Our study showed for the first time the differences in coagulation profiles between various etiologies of CS. We assume that the higher cortisol burden among CD patients may explain the differences found in the coagulation profile as well as the higher risk for VTE compared with primary adrenal CS patients.
