Hypercoagulability in Cushing Syndrome, Prevalence of Thrombotic Events: A Large, Single-Center, Retrospective Study

Maria Gabriela Suarez; Madeleine Stack; Jose Miguel Hinojosa-Amaya; Michael D Mitchell; Elena V Varlamov; Chris G Yedinak; Justin S Cetas; Brett Sheppard; Maria Fleseriu

doi:10.1210/jendso/bvz033

Hypercoagulability in Cushing Syndrome, Prevalence of Thrombotic Events: A Large, Single-Center, Retrospective Study

J Endocr Soc. 2019 Dec 15;4(2):bvz033. doi: 10.1210/jendso/bvz033. eCollection 2020 Feb 1.

Authors

Maria Gabriela Suarez^{1

2}, Madeleine Stack², Jose Miguel Hinojosa-Amaya^{2

3

4}, Michael D Mitchell⁵, Elena V Varlamov^{1

2

3}, Chris G Yedinak^{2

3}, Justin S Cetas^{2

3

6}, Brett Sheppard⁷, Maria Fleseriu^{1

2

3}

Affiliations

¹ Department of Medicine (Endocrinology), Oregon Health & Science University, Portland, Oregon, USA.
² Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA.
³ Northwest Pituitary Center, Oregon Health & Science University, Portland, Oregon, USA.
⁴ Endocrinology Division, Department of Medicine, Hospital Universitario "Dr. Jose E. Gonzalez", Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon, Mexico.
⁵ University of Iowa, Iowa City, Iowa.
⁶ Operative Care Division, Portland Veterans Administration Hospital, Portland, Oregon, USA.
⁷ Department of General Surgery, Oregon Health & Science University, Portland, Oregon, USA.

Abstract

Background: The risk of Cushing syndrome (CS) patients experiencing a thrombotic event (TE) is significantly higher (odds ratio; OR 18%) than that of the general population. However, there are currently no anticoagulation guidelines.

Methods: A retrospective, single-center, longitudinal study of patients undergoing all types of treatment-surgical (pituitary, unilateral, and bilateral adrenalectomy) and medical treatment-was undertaken. TEs were recorded at any point up until last patient follow-up; myocardial infarction (MI), deep venous thrombosis (DVT), and pulmonary embolism (PE) or stroke. Patients' doses and complications of anticoagulation were recorded.

Results: Included were 208 patients; a total of 165 (79.3%) were women, and mean age at presentation was 44 ± 14.7 years. Thirty-nine (18.2%) patients had a TE; extremity DVT (38%), cerebrovascular accident (27%), MI (21%), and PE (14%). Of 56 TEs, 27 (48%) were arterial and 29 (52%) were venous. Patients who underwent bilateral adrenalectomy (BLA) had an odds ratio of 3.74 (95% CI 1.69-8.27) of developing a TE. Of patients with TEs, 40.5% experienced the event within the first 60 days after surgery. Baseline 24-hour urinary free cortisol levels did not differ in patients with or without TE after BLA. Of 197 patients who underwent surgery, 50 (25.38%) received anticoagulation after surgery, with 2% having bleeding complications.

Conclusions: The risk of TEs in patients with CS was approximately 20%. Many patients had more than 1 event, with higher risk 30 to 60 days postoperatively. The optimal prophylactic anticoagulation duration is unknown, but most likely needs to continue up to 60 days postoperatively, particularly after BLA.

Keywords: Cushing disease; Cushing syndrome; anticoagulation; bilateral adrenalectomy; hypercoagulability; thrombotic events; transsphenoidal surgery.