Is VTE Prophylaxis Necessary on Discharge for Patients Undergoing Adrenalectomy for Cushing Syndrome?

Bruna Babic; Amory De Roulet; Anita Volpe; Naris Nilubol


J Endo Soc. 2019;3(2):304-313. 

In This Article

Abstract and Introduction


Background: Patients with Cushing syndrome (CS) have an increased risk for venous thromboembolism (VTE). However, it is unclear whether patients undergoing adrenalectomy for CS are at increased risk for postoperative VTE. The aim of this study was to determine the rate of postoperative VTE in patients undergoing adrenalectomy for CS.

Methods: A retrospective analysis of patients in the American College of Surgeons National Surgical Quality Improvement Program database who underwent adrenalectomy from 2005 to 2016 was performed. We compared the clinical characteristics and 30-day postoperative VTE occurrence in patients with and without CS.

Results: A total of 4217 patients were analyzed; 2607 (61.8%) were female and 310 (7.4%) had CS. The overall prevalence of postoperative VTE was 1.0% (n = 45). The rates of VTE were higher in patients with CS (2.6% vs 0.9%; P = 0.007). In the two groups, CS was associated with younger age, increased body mass index, and diabetes mellitus (P < 0.001). CS was also associated with longer length of operation and longer hospital length of stay (P < 0.001). In the subgroup of patients who had diagnosed VTE, CS was associated with longer length of operation (P < 0.001). Rates of laparoscopic vs open surgery were equivalent between patients with and without CS, and VTE events did not differ. The median time to VTE event was 14.5 days (range, 1 to 23 days) in the CS group and 4 days (range, 2 to 25 days) in the group without CS.

Conclusions: The prevalence of postoperative VTE was increased in patients undergoing adrenalectomy for CS. In patients with CS undergoing adrenalectomy, VTE prophylaxis for 28 days should be considered upon discharge.


Endogenous Cushing syndrome (CS) results in chronic glucocorticoid excess. The etiology includes ACTH-dependent and -independent causes. The former is most commonly from a pituitary adenoma [Cushing disease (CD)], whereby excess ACTH from the anterior pituitary results in hypercortisolism, in addition to ectopic sources of excess ACTH production from a nonpituitary tumor. ACTH-independent CS results from excess glucocorticoid production directly from the adrenal glands, and the pathology is associated with unilateral or bilateral disease, as well as benign and malignant disease. Excess cortisol production is associated with increased metabolic complications (obesity, hypertension, diabetes), in addition to increased incidence of cardiovascular and venous thromboembolism (VTE) complications.[1,2]

The pathogenesis of VTE events includes hypercoagulability from increased levels of multiple coagulation factors and von Willebrand factor, as well as decreased fibrinolysis activity via increased plasminogen activator inhibitor-1 (inhibits urokinase plasminogen activator, which is required for cleavage of plasminogen).[2–6] It has been reported that patients with CD tend to be more hypercoagulable than those with ACTH-independent CS pathology secondary to their coagulation profiles.[7] However, the latter also have increased incidence of VTE events,[8] as do those undergoing surgery, although the rates have varied from 0% to 20%.[4,8–11] The higher rate of VTE has predominantly been shown in individuals with CD undergoing transsphenoidal surgery, whereas individuals with ACTH-independent CS undergoing adrenalectomy have lower rates and no evidence of VTE.[8,10] A recent analysis of American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data of all patients undergoing adrenalectomy found a low incidence of VTE, at ≤1.4% overall.[12] This is similar to the general postoperative risk for VTE.

Most of the aforementioned studies have a small population and are predominantly composed of individuals with CD undergoing transsphenoidal surgery. In light of the inherent hypercoagulability of those with CS, the question remains as to whether the subgroup of patients with CS undergoing adrenalectomy have an increased risk for VTE and whether they should receive thromboprophylaxis upon discharge. The aim of this retrospective analysis was to evaluate the incidence and characteristics of VTE events in patients from the ACS-NSQIP database who underwent adrenalectomy and for whom the indication was CS.