An Unexpected Manifestation of Non-islet Cell Tumor Hypoglycemia in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy accounting for more than 90% of pancreatic cancer cases and is rarely associated with paraneoplastic syndromes. Non-islet cell tumor hypoglycemia (NICTH), typically mediated by insulin-like growth factor 2 (IGF-2), is well-described in mesenchymal tumors and hepatocellular carcinoma but has not been documented in PDAC. We report an 81-year-old man with stage IV PDAC who presented with profound hypoglycemia (glucose 32 mg/dL) in the absence of diabetes or hypoglycemic agents. Despite repeated dextrose infusions, his hypoglycemia persisted, necessitating intensive care unit (ICU) admission. Workup excluded insulinoma, autoimmune hypoglycemia, and adrenal insufficiency. An elevated IGF-2/IGF-1 ratio (457/7) was diagnostic for IGF-2-mediated hypoglycemia. The patient's glucose stabilized with total parenteral nutrition, but he succumbed shortly thereafter to cancer-related complications. This is the first documented case of IGF-2-mediated NICTH in PDAC, underscoring the need to consider paraneoplastic hypoglycemia in atypical presentations of pancreatic cancer.