A Rare Presentation of Multiple Endocrine Neoplasia Type 1

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal dominant inherited syndrome caused by mutations in the MEN1 tumor suppressor gene with a reported incidence of 2 in 100,000. Clinical Case: A 26-year-old Caucasian female was seen for surveillance screening given positive familial mutation in the MEN1 gene. She had a significant family history of pathogenic MEN1 in her son, brother, father and paternal aunt. On presentation, she denied any history of headache, nipple discharge, kidney stones, fractures, heart burn, abdominal pain, diarrhea, hypoglycemia, flushing, lightheadedness. She was on hormonal IUD for contraception and had not had menstrual cycles for the last 6 months. Vital signs and physical examination were unremarkable. Her initial evaluation included a normal calcium of 9.8mg/dL (RR:8.6-10.6mg/dL), PTH of 70pg/ml (RR:12-88pg/ml), 25OH-vitamin-D of 11ng/ml (RR:20-80ng/ml). She had normal gastrin, chromogranin A, glucagon, and vasoactive intestinal peptide levels. Prolactin was 17.6ng/ml (RR:3.3-26.7 ng/ml). MRI pituitary showed a 6mm lesion representing a Rathke’s cleft cyst, not compressing surrounding structures. Two months following the initial encounter, she presented with abdominal pain, nausea, vomiting. She was found to have an obstructing renal stone requiring stent placement. Calcium was 10.1mg/dl. She was also noted to have an incidental pancreatic tail mass of 4.2cm on CT abdomen. She underwent laparoscopic robotic distal spleno-pancreatectomy. Surgical pathology showed a well differentiated 3.5cm neuroendocrine tumor with negative margins, which stained positively for insulin. She had not reported symptoms of weight gain or any episodes suspicious for sympathoadrenal activation or neuroglycopenia, and was again confirmed after surgery. Patient was re-admitted to the hospital for right-sided flank pain and was found to have a new 6mm obstructing calculus with moderate hydronephrosis of the right kidney. Corrected calcium level was found to be mildly elevated at 11.1mg/dL. Repeat PTH was stable at 81pg/ml, and urinary calcium was elevated at 447.3mg/24h (RR:50-250mg/24h). Subsequently, she underwent 3.5 gland parathyroidectomy and thymectomy. On POD20, PTH was 29pg/ml and calcium was 8.6mg/dl. Conclusion: This case highlights a rare presentation of MEN1 with an asymptomatic insulinoma and nephrolithiasis, despite having normal calcium and PTH levels initially. Primary hyperparathyroidism is the most common presentation of MEN1, seen in up to 90% of patients. The second most common finding in MEN1 patients, reported in 70% of the cases, are entero-pancreatic tumors, the most common being gastrinoma. Insulinoma, which is less common and is seen in only 10-30% patients, needs documentation of Whipple’s triad. Interestingly, our patient never had any history of hypoglycemia.