SAT159 A Unique Case Of IGF-2 Induced Hypoglycemia As First Manifestation Of Hepatocellular Carcinoma
Authors: Ali Israa , Alnaher Mohammed , Arida Abdul Karim 
Published: October 2023

Abstract
Disclosure: I. Ali: None. M. Alnaher: None. A. Arida: None.
Introduction: Hypoglycemia is one of the manifestations of non-islet cell tumor-induced hypoglycemia (NICTH). In hepatocellular carcinoma (HCC), it has been reported in 4-27% of patients, and it is associated with poor prognosis. Case: Patient is a 70-years-old Female with past medical history of prediabetes and untreated Hepatitis C infection who presented with sever weakness and was found to have blood glucose of 37. She was started on Dextrose 10% with improvement of her symptoms. During hospital course she had recurrent episodes of symptomatic hypoglycemia. Patient denied any family history of diabetes with no access to diabetes medication. Blood work showed elevated AST, ALT with low albumin, low prealbumin and AM cortisol 13, Sulfonylureas screen is Negative. Result of 72 hours hypoglycemia protocol while blood glucose level was 48 mg/dl as follow: Proinsulin, Intact 1.6 mmol/L (Ref: less than 8.0), insulin like growth factor -1 (IGF-1): 10 ng/ml (26-226), IGF-2: 69 ng/ml (180-580) so IGF-2/IGF-1 ratio of 6.9Insulin: 0.2 uIU/ml (1.9-23), C-Peptide 0.1 ng/ml (0.5-3.3) and Beta hydroxybutyrate: 0.1 mmol/L. CT abdomen: 7.0 x 7.2 x 10.5 cm right hepatic lobe mass with extension to right portal vein that is most consistent with hepatocellular carcinoma with background liver cirrhosis with portal hypertension without ascites. Right hepatic artery tumor biopsy showed moderately differentiated HCC. Patient was started on steroid therapy then octreotide. Multidisciplinary meeting discussed in details treatment options and prognosis including treatment of her cancer with surgery vs chemoradiation therapy, but patient and her family opted for DNR/DNI, and patient passed away during that admission. Discussion: Even though HCC-related hypoglycemia is a known phenomenon, knowledge about prevention and treatment is lacking. The suggested mechanism of hypoglycemia in NICTH include increased consumption of glucose by tumor in malnourished patients with low glycogen deposits and defective gluconeogenesis or may be caused by IGF-2 overproduction that crosses capillary membranes and stimulates insulin receptor. Hypoglycemia work up reveals low levels of insulin, pro-insulin, C-peptide, and β-hydroxybutyrate. Levels of GH and IGF-1 will also be low due to the suppressive effect of IGF-2. Total IGF-2 may be elevated or normal but the ratio of IGF-2/IGF-1 is usually elevated 3:1.
Management of an IGF-2 producing tumor with surgical resection, radiation, and/or chemotherapy can potentially resolve hypoglycemia. Medical therapy with glucocorticoids has been utilized by promoting hepatic gluconeogenesis and lipolysis and reducing peripheral glucose uptake. Glucocorticoids also help to decrease the levels of IGF-2 either by decreased tumor production or increased clearance. Case reports have documented the use of glucagon, growth hormone, and octreotide, however, effects are limited.
Presentation: Saturday, June 17, 2023