An Unusual Case of Latent Autoimmune Diabetes in Adult and Pancreatic Neuroendocrine Tumor in a Patient Presenting With Diabetes

Abstract

Introduction: Latent autoimmune diabetes in adults (LADA) and pancreatic neuroendocrine tumors (PNETs) are rare causes of adult-onset diabetes mellitus (DM). The existence of both LADA and a PNET in a single patient has not been previously reported.Clinical Case: A 65-year-old female with history of type 2 DM diagnosed 15 months ago, on metformin 500mg twice a day presented with fatigue, dry mouth, polyuria, and blurry vision for one week and weight loss of 12 pounds over 3 months. Plasma glucose was 599 (nl 65–144 mg/dL) with an elevated anion gap (17; nl 5–15 mmol/L), low bicarbonate (19; nl 21–32 mmol/L) and elevated beta hydroxybutyrate (4.79; nl 0.02–0.27 mmol/L). Diabetic ketoacidosis was diagnosed, and intravenous fluids and insulin were administered. Work up revealed HbA1C of 14% (nl 4.2%-5.6%) which had increased from 7% noted three months ago. glutamic acid decarboxylase antibodies (GAD65 Ab) was >250 (0.0–0.5 IU/mL) and C peptide was 0.42 (0.81–3.85 ng/mL). A computed tomogram of the abdomen performed to evaluate the acute worsening of her HbA1C revealed a 1.4 x 1.3 cm poorly defined hypoenhancing pancreatic head lesion, which on magnetic resonance imaging was 1.6 x 1.2 cm. Further evaluation showed normal levels of glucagon (127; nl <=208 ng/L), somatostatin (26; nl <=30ppg/mL) and vasoactive intestinal peptide (<13; nl 0–60 pg/mL), and an elevated chromogranin A (155; nl 0-95ng/mL). An endoscopic ultrasound guided fine needle aspiration of pancreatic head mass revealed a well differentiated NET with Ki-67 proliferation index of <1%. She underwent pylorus preserving pancreaticoduodenectomy and histopathology showed a 2 cm grade one NET on pancreatic head with no involvement of the 23 tested lymph nodes. Immunohistochemistry was positive for chromogranin and synaptophysin and negative for insulin, somatostatin and gastrin, confirming diagnosis of well-differentiated pancreatic NET Stage Ib (T2N0M0). Whole body PET CT scan done 2 months following surgery did not reveal any focal radiotracer uptake to suggest metastasis. Given the presence of GAD65 Ab, age of onset of DM, and an initial non-requirement of insulin, the patient was diagnosed with LADA and insulin therapy was initiated.Conclusion: We report a unique case of a patient with LADA who was incidentally found to have a non-functioning pancreatic NET. Although functional PNETs such as glucagonoma and somatostatinoma cause hyperglycemia, DM associated with non-functioning NETs is rare, but has been reported with gastrointestinal NETs (1). Our patient likely developed uncontrolled hyperglycemia from LADA but was incidentally found to have a PNET which may have contributed to the worsening of hyperglycemia. This highlights the importance of thorough evaluation for the causes for acute worsening of hyperglycemia.