SUN-124 Are Venous Thromboembolic Events Increased in MEN1 Patients?

Abstract

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder in which patients develop multiple simultaneous hormone-secreting tumors. Most common tumors include: anterior pituitary adenomas (50%), multi-gland parathyroid adenomas (95%), and gastroenteropancreatic neuroendocrine tumors (40-80%). Only rare MEN1 associated glucagonomas (<1%), and ACTH-producing neuroendocrine tumors (<5%) are known to increase risk of hypercoagulability. It is unknown if patients with MEN1 syndrome have increased risk of venous thrombolytic events (VTE), defined as a deep-vein thrombosis and/or pulmonary embolism. Methods: We queried a prospective natural history study of MEN1 patients who tested positive for germline MEN1 mutations (n=287) between 1991-2019 (54 patients on our current protocol were followed before 1991; the earliest was 1971). All lifetime events of VTE were included. Search terms included: DVT, thromb, embol, PE, pulmonary embolism, clot, hematology consult, anticoagulant, coumadin, lovenox, xarelto, warfarin, aspirin, rivaroxaban and apixaban. After initial screening, 10 patients were removed due to insufficient clinical data. Kaplan-Meier analysis was performed to compare age of death between the two cohorts. Results were expressed as mean ± standard deviation. Results: Thirty-four subjects (mean 57.5 years-old, 17 women) were identified with any VTE, yielding a prevalence rate of 13.4%. The incidence of VTE corresponded to 264 events per 100,000 patient-years, which was ~2-fold higher than the estimated annual incidence rate in the general population (104-183/100,000 patient years).1 Kaplan-Meier analysis revealed no significant difference in survival between the two groups (non-VTE cohort mean 81.1 years ± 2.23; VTE cohort mean 77.4 years ± 3.45; p = 0.96). Thirty-two events occurred during the surveillance period at our institution; 9 individuals had more than one VTE. At the time of VTE, 80% had hyperparathyroidism (mean PTH ± SD; 97.56 pg/mL ± 90.76), 21% had hyperprolactinemia (prolactin 25.7μg/L ± 43.41), 62.5% had hypergastrinemia (mean gastrin 1100.9 pg/mL ± 3127.8), and 84.6% had non-functional pancreatic neuroendocrine tumors. One patient was identified to have a Factor V Leiden mutation, 3 patients had lupus anti-coagulant. Eleven patients experienced events within a post-surgical period of 3 months. Conclusions: Hypercoagulability in MEN1 has been previously unidentified. Our cohort data suggests a two-fold increase in the incidence of VTE as compared to the general population, with a high risk occurring within the perioperative period. Further mechanistic investigation and validation from other cohorts are needed to confirm the increased prevalence of VTE in this population. 1Heit, John A., et al. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015 Aug;12(8): 464-474.