MON-328 Twenty-Year Follow-Up of a Patient with a Novel MEN1 Gene Mutation

Background: The multiple endocrine neoplasia type 1 (MEN1) syndrome is a rare autosomal dominant inherited tumor syndrome. Mutations in the MEN1 gene are detectable in approximately 70-90% of kindreds with classic MEN1 syndrome (1). We present the case of a patient with a novel MEN1 gene mutation. Clinical Case: A 41 year old Caucasian male with a diagnosis of MEN1 syndrome has been followed up in our clinic for 20 years. At the age of 21, he had two parathyroid glands resection for hypercalcemia which revealed an adenoma of the right superior parathyroid gland. He had one more parathyroid gland resected 6 months later for persistent hypercalcemia. Around that time, he also had appendectomy for suspected appendicitis and the pathology results showed a carcinoid tumor of the appendix. At the age of 33, he underwent total parathyroidectomy, thymectomy, and auto transplantation of half parathyroid gland in the left forearm for recurrent hypercalcemia. At the age of 39, he developed frequent hypoglycemic episodes with symptoms including confusion. Serum glucose levels of 20-30 mg/dL were documented during the episodes. A 72 hours fasting test showed a plasma glucose level of 53 mg/dL, with insulin level of 25.6 mU/L, proinsulin level of 5.2 pmol/L, C-peptide level of 5 ng/mL and low beta- hydroxybutyrate level. In response to 1 mg glucagon intravenous injection, plasma glucose level improved by 83 mg/dL in 30 minutes. He then had selective arterial calcium stimulation test and the results showed the insulin peak rising after stimulation in the splenic artery suggested that the lesion was in the body and tail of the pancreas. He had partial pancreatectomy for insulinoma, however, the pathology results were consistent with vasoactive intestinal polypeptide- producing tumor (VIPoma) rather than insulinoma. The serum tests also supported a diagnosis of VIPoma: the VIP levels were 96.3 pg/mL preoperatively and 65 pg/mL postoperatively. Notably, he had intermittent abdominal pain after food intake and chronic watery diarrhea 5-7 times a day before pancreatectomy, which resolved after the surgery. The patient underwent genetic screening for MEN1 mutations which revealed the presence of a novel germline deletion mutation in exon 8 (1078delC), resulting in frame shifting of its coded menin protein (Arg360fsX13). Conclusion: We describe a novel MEN1 gene mutation (1078delC) in a patient with typical clinical manifestations of MEN1 syndrome including parathyroid adenomas, appendix carcinoid tumor, VIPoma, and insulinoma. The concurrence of pancreatic VIPoma and insulinoma or the existence of a pancreatic neuroendocrine tumor co-producing insulin and VIP in MEN1 patients has not been reported previously. Reference: (1) Agarwal SK. The future: genetics advances in MEN1 therapeutic approaches and management strategies. Endocr Relat Cancer. 2017;24:T119-T134.