SUN-277 An Unexpected Manifestation of NonIslet Cell Tumor Hypoglycemia in Pancreatic Ductal Adenocarcinoma

Abstract Disclosure: J. Kaur: None. T. Alomar: None. M.H. Horani: None. Famously known for its aggressive nature and high mortality rate, pancreatic ductal adenocarcinoma (PDAC) accounts for >90% of pancreatic cancer cases. However, PDAC is not known for its association with nonislet cell tumor hypoglycemia (NICTH) - a paraneoplastic condition well-documented in other malignancies. An 81-year-old male with stage IV PDAC presented to the ED with fatigue and blood glucose of 32 in the absence of diabetes or offending medications. Despite D50W (dextrose 50% in water) infusions, his hypoglycemia persisted. Suppressed fasting insulin (<1 ulU/mL) and C-peptide (0.1 ng/mL) ruled out an insulinoma, negative insulin autoantibody decreased suspicion for autoimmune hypoglycemia, and a cortisol stimulation test ruled out adrenal insufficiency. The IGF 2/IGF-I ratio of 457 (ng/mL) / 7 (ng/mL) was diagnostic for IGF-2 induced hypoglycemia - consistent with NICTH in the setting of PDAC. The remainder of the course was unfortunately short for the patient. His glucose stabilized after starting TPN, but he died shortly after the hospital course secondary to cancer related complications. NICTH is typically mediated by IGF-2 which, along with IGF-1, has essential roles in growth and cellular regulation. Dysregulation of the IGF system has been implicated in several tumors overproducing IGF-2 to sustain autocrine and paracrine signaling, enhancing growth and invasiveness. This overproduction may cause hypoglycemia by mimicking insulin highlighting the tumor-derived dysregulation of the IGF system as a significant factor in cancer-associated metabolic disturbances. Of note, confirmed cases of IGF-2-mediated NICTH in the setting of primary PDAC are not readily available in current literature. Van Doorn et al. (2007) reviewed 233 cases of NICTH, identifying fibrous tumors and HCC as the most frequently associated malignancies. Bodnar et al. (2013) reviewed 288 cases of NICTH with mentions of more rare cases including associations with thyroid cancer and adrenal cortical carcinoma. There was no mention of PDAC in any of these reviews. However in 2023, there was a report by Zamparas et al. of the presence of Lambert-Eaton myasthenic syndrome, another paraneoplastic syndrome, in the setting of PDAC. This underscores the need for further investigation regarding the association of NICTH as its occurrence in PDAC remains an outlier in the medical literature to understand this particular carcinoma’s potential for paraneoplastic manifestations. Presentation: Sunday, July 13, 2025