FRI667 Profound And Persistent Hypoglycemia With Hepatocellular Carcinoma- A Non-islet Cell Tumor

• Published in: Journal of the Endocrine Society Vol. 7; no. Supplement_1
• Main Authors: Muneeb, Ahmad, Shahid, Maham, Waleed Raza, Muhammad, Zahoor, Hovra, Sultan, Senan
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 05-10-2023
• Subjects: Diabetes And Glucose Metabolism
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/jendso/bvad114.885

Abstract
Disclosure: A. Muneeb: None. M. Shahid: None. M. Raza: None. H. Zahoor: None. S. Sultan: None.
Introduction: Tumor related hypoglycemia is rare and can be caused by islet cell tumors or non-islet cell tumors (NICT). Proposed mechanisms for non-islet cell tumor hypoglycemia (NICTH) include: increased big-IGF production (precursor of IGF2 which acts similar to insulin); increased insulin production; infiltration of liver/adrenals; and autoantibodies to insulin receptors. Clinical Case: A 78-year-old female with pertinent medical history of recently diagnosed locally advanced hepatocellular carcinoma (HCC) was found unresponsive at home. On arrival of EMS, the blood glucose (BG) level was in 30s. Dextrose water was administered that resulted in improvement of her mentation. She was alert and awake when brought to the hospital but was persistently hypoglycemic despite frequent feeding. She was started on dextrose infusion and was admitted for workup of persistent hypoglycemia. She denied history of diabetes, insulin or sulfonylurea use. She reported an admission to another facility for hypoglycemia 4 days ago where adrenal insufficiency was ruled out with normal morning cortisol levels. During this hospitalization, CBC and CMP were unremarkable except low BG. A CT scan of the abdomen/pelvis was consistent with locally advanced HCC. Fasting protocol was started and BG monitoring was performed every 30 minutes. When BG fell below 55 mg/dL; C-peptide, insulin and proinsulin levels were drawn which came back severely suppressed at 0.13 ng/mL, <1 mU/L, and 2.7 pmol/L respectively. IGF2 was low-normal at 339 ng/mL. Given aforementioned workup and exclusion of other causes including medications, insulinoma and adrenal insufficiency, hypoglycemia was attributed to big-IGF mediated NICTH. Dextrose infusion was re-initiated but the patient continued to have BG in 30s, which was verified by both finger-stick and serum chemistry. Dexamethasone was initiated and dextrose infusion was continued. Oncology deemed her a poor surgical candidate. She declined other therapies for HCC. BG stabilized after institution of steroids, dextrose infusion was weaned successfully, and patient was discharged. Conclusion: A high index of suspicion should be held for NICTH in patients with profound hypoglycemia refractory to dextrose infusions in the setting of NICT. The diagnosis of NICTH can be made with suppressed insulin and C-peptide, elevated big-IGF, and normal-reduced IGF2 levels. Management of NICTH related to HCC is tumor resection. However, local anti-tumor therapies can be considered in non-surgical candidates. Since NICTH can be refractory to dextrose infusion, steroids with or without GH are an effective option. In refractory cases, continuous glucagon infusion and parenteral nutrition can be considered. Further research is needed to help develop better treatment options. We hope to contribute to the current literature regarding NICTH and bring awareness to the medical community.
Presentation: Friday, June 16, 2023