Glucagonoma: “A Diagnostic Challenge”

Abstract

\n Introduction: Glucagonoma is a rare pancreatic α-islet cell tumor accounting for nearly 1% of all the neuroendocrine tumors (NET), with an incidence of 1 in 20 million people. We present here a patient with glucagonoma with uncontrolled diabetes mellitus (DM) for over ten years and necrolytic migratory erythema (NME) for two years. Clinical Case: A 50-year-old Caucasian male was referred to the endocrinology team for uncontrolled DM type 2. The DM was diagnosed over 10 years prior with initial HbA1c of 10.2% and remained uncontrolled with HbA1c >9%, despite compliance with lifestyle modifications and treatment with multiple agents including metformin, glipizide, empagliflozin, and pioglitazone. Given poor glycemic control, the treatment was escalated to glargine and lixisenatide. Over the years, the patient presented with unintentional weight loss of 105 pounds, fatigue, normocytic normochromic anemia, and diffuse erythematous rash with plaques and scaling on the trunk, flexor surfaces of lower and upper extremities, soles of hands and feet. Punch biopsy of the lesions revealed neutrophilic infiltration. He denied diarrhea, deep venous thrombosis, pulmonary embolism, psychiatric symptoms, or family history of neuroendocrine tumor (NET) or MEN 1 syndrome. A CT chest abdomen and pelvis revealed a 5 cm mass on the pancreatic tail along with liver metastasis. The biopsy confirmed a well-differentiated NET. Serum glucagon and chromogranin-A levels were elevated at 2967 pg/mL (N: 50-150 pg/mL) and 263.8 ng/mL (N: 0-101.8 ng/mL) respectively, consistent with pancreatic glucagonoma. Octreoscan revealed diffuse uptake in the liver, omentum, and spleen. He was started on Octreotide injections monthly, followed by distal pancreatectomy, splenectomy, hepatic wedge resection, and excision of the omental implant with the plan to treat the residual liver metastasis with radioembolization. Pathology analysis showed local invasion and metastasis to local lymph nodes with immunostaining positive for AE1/3, synaptophysin, chromogranin, and Ki67 index <2% consistent with Grade I well-differentiated NET. Post-surgery, serum glucagon and chromogranin-A levels dropped to 400 pg/mL and 68.8 ng/mL respectively. Insulin requirements markedly dropped with an improvement in glycemic control and resolution of the rash. Conclusions: Glucagonoma is an uncommon, slow-growing pancreatic neoplasm resulting in excessive glucagon secretion and it is characterized by diabetes mellitus, NME, chronic diarrhea, and deep vein thrombosis. Nearly 50% of glucagonomas are metastatic at the time of diagnosis. Patients without metastasis have a 10-year survival rate of almost 100%, compared with 51.6% of patients with metastasis, emphasizing the importance of early diagnosis and multidisciplinary treatment approach to achieve a better therapeutic outcome.