SUN-617 IGF-2-Mediated Hypoglycemia in a Patient with Newly Diagnosed Metastatic Sarcoma: A Rare Paraneoplastic Syndrome

Abstract Disclosure: P. Chekka: None. P. Choksi: None. Background: IGF-2 mediated hypoglycemia is an extremely uncommon and unfavorable paraneoplastic complication of certain malignancies. Clinical Case: A 69-year old man with medical history of hypertension presented with one week of intermittent confusion and neuroglycopenic symptoms. On admission, he was noted to have point of care glucose of 26 mg/dL, requiring D50 push, immediately improving mentation. Upon admission, he was placed under a supervised 72-hour fast resulting in hypoglycemia within 3 hours of initiating fast. Laboratory results demonstrated a serum glucose of 37 mg/dL, with insulin (<1 µU/mL; normal: 2-23 µU/mL), C-peptide (<0.1 ng/mL; normal: 0.8-5.2 ng/mL), beta-hydroxybutyrate (0.15 mmol/L; normal: 0.27-1.0 mmol/L), proinsulin intact (≤.2 pmol/L; normal: <7.2), suggesting an insulin-independent mechanism for the hypoglycemia. Further laboratory work revealed IGF-2 (219 ng/mL; 180–580 ng/mL) and IGF-1(21 ng/mL; 29-245 ng/mL), with IGF-2 to IGF-1 ratio greater than 10, confirming diagnosis of IGF-2 mediated hypoglycemia. CT abdomen identified two large retroperitoneal masses, one 12 x11 x13 cm and another 15 x 12 x15 cm as well as extensive metastatic disease in liver and lung. Biopsy confirmed the mass to be a dense fibrous sarcoma. Given the advanced stage of the malignancy, surgical resection was not feasible. Hypoglycemia was managed with dextrose drip, frequent small meals and steroids to help reduce IGF-2 production. Subsequently, chemotherapy with temozolomide and bevacizumab was initiated. Following this treatment, he was gradually weaned off the dextrose infusion and his glycemic control improved. Conclusion: IGF-2 mediated hypoglycemia is a rare paraneoplastic syndrome seen in malignancies such as sarcomas or hepatoblastomas. Hypoglycemia occurs due to overproduction of IGF-2 by the tumor which has insulin like-effects. Unlike insulin-mediated hypoglycemia, IGF-2-induced hypoglycemia occurs in the absence of insulin or C-peptide. An IGF-2: IGF-1 ratio greater than 10 confirms non-islet cell tumor hypoglycemia. Diagnosis is challenging as it is extremely rare with documentation only in few case reports. Treatment includes treating the underlying malignancy with surgical resection or debulking and chemotherapy. Neoadjuvant chemoradiation and arterial embolization has been described in the literature in the context of a non- resectable solitary fibrous tumor. Hypoglycemia is managed with supportive measures via corticosteroids, diazoxide, glucagon infusion pumps, recombinant growth hormone or dextrose fluids. This case underscores the importance of maintaining a high index of suspicion for IGF-2-mediated hypoglycemia in patients with newly diagnosed malignancy. A multidisciplinary approach to treatment is essential in treating these complex patients as IGF-2 producing tumors pose a significant mortality risk. Presentation: Sunday, July 13, 2025