Abstract
A 35-year-old gentleman presented with epigastric pain and bilious emesis. He also endorsed urinary frequency, non-bloody diarrhea and diffuse bone pain. On physical examination he had epigastric tenderness and multiple hyperpigmented skin lesions.
An abdominal computed tomography (CT) scan revealed multiple diverticula with peri-colonic fat stranding in the descending and sigmoid colon, concerning for diverticulitis. He was started on a course of metronidazole and ciprofloxacin. A 3.1 cm mass was incidentally noted in the uncinate process of the pancreas. Bilateral adrenal nodules were also appreciated.
An endoscopic ultrasound (EUS) guided trans-gastric fine needle aspiration biopsy was performed, revealing a well differentiated pancreatic neuroendocrine tumor (pNET - pT3N1Mx, intermediate risk). Chromogranin A was elevated to 108 ng/ml (reference range <93 ng/ml). Serum and urine metanephrine, V-peptide, gastrin, glucagon and parathyroid hormone related peptide were all normal; indicating a nonfunctioning neuroendocrine tumor. He underwent a pancreaticoduodenectomy. Octreotide scan was unrevealing for residual uptake. Adrenal biopsy revealed adrenal adenomas.
Three years later, he presented with severe abdominal pain and a new pancreatic mass was noted on CT. Chromogranin A was elevated to 227 ng/mL. EUS revealed a 0.35 cm mass in the bed of the pancreatic head, encasing the superior mesenteric artery. Pathology was positive for recurrence of the neuroendocrine tumor.
He was hypercalcemic to 11.4 mg/dL and parathyroid hormone was elevated to 319 pg/mL. CT neck revealed a 0.1 cm nodule concerning for parathyroid adenoma. He underwent a subtotal parathyroidectomy.
Genetic testing confirmed Multiple Endocrine Neoplasia Type 1 (MEN1) with a heterozygous mutation of the menin1 gene.
MEN1 is a rare genetic syndrome with affected individuals at increased risk of developing pancreatic, pituitary, parathyroid gland and cutaneous tumors. With a kaleidoscope of presentations, clinicians must maintain a high index of suspicion for MEN1, particularly for cases with nonfunctioning pNETs which present insidiously and are the foremost cause of mortality in MEN1 patients.1
Further clarity is needed on MEN1 associated pNET prognostic risk stratification, surveillance and targeted immunochemotherapy.2 Timely and algorithmic screening for MEN 1 syndrome in patients with pancreatic incidentalomas is essential to improving patient outcomes.
1.
Kamilaris CDC, Stratakis CA. Multiple Endocrine Neoplasia Type 1 (MEN1): An Update and the Significance of Early Genetic and Clinical Diagnosis. Front Endocrinol. 2019;10:339. doi:10.3389/fendo.2019.00339
2.
Yates CJ, Newey PJ, Thakker RV. Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1. Lancet Diabetes Endocrinol. 2015;3(11):895-905. doi:10.1016/S2213-8587(15)00043-1
Patients with Multiple Endocrine Neoplasia Type 1 with Gastrinomas Have an Increased Risk of Severe Esophageal Disease Including Stricture and the Premalignant Condition, Barrett’s Esophagus