FRI663 A Rare Case Of Igf-2 Induced Hypoglycemia Associated With Metastatic Colon Cancer

Abstract

Abstract Disclosure: A. Alshaakh Mohd Mari: None. A. Varshney: None. A. Sidhu: None. M. Matos: None. M. Kinaan: None. Introduction: The diagnosis of hypoglycemia in patients without diabetes is uncommon and nonislet cell tumor hypoglycemia (NICTH) represent a minority of these cases. The most common mechanism is related to IGF-2 production from tumor cells. Case description: A 66-year-old man with a history of stage IV colon cancer presented to the hospital due to breathlessness while receiving chemotherapy (Bevacizumab plus FOLFOX4). He had partial colectomy and chemotherapy 3 years earlier but was recently found to have metastatic disease to the liver. A CT abdomen during hospitalization showed a 15 cm hepatic mass occupying the entire right hepatic lobe. Endocrinology was consulted due to persistent postprandial and fasting hypoglycemia despite dextrose infusion. He had no history of diabetes and denied taking any diabetes medications. Plasma blood glucose (BG) was noted to be 74 mg/dl (74-106) while on dextrose. An 8AM cortisol was checked to exclude adrenal insufficiency and was 8.08 mcg/dL (4.30-22.40). A 72 hour fast was done but discontinued at 8 hours when plasma BG dropped to 48 and patient became symptomatic. At the time C-peptide and Insulin levels were low <0.05 ng/mL (0.48-5.05) and <1.0 mU/L (3.0-25) respectively, with normal Beta-hydroxybutyrate (BHB) 1.1 mg/dL (0.2-2.8). At the end of the fast 1 mg of glucagon was administered and his BG increased to 112 mg/dl in 2 hrs. IGF-1 levels were undetectable <15 ng/mL and IGF-2 levels were found to be 175 ng/mL. The IGF2:IG1 ratio was at 11 confirming IGF-2 mediated NICTH. Dexamethasone 10 mg daily was started, and BG were maintained > 70mg/dl without dextrose infusion. Discussion: In approximately 50% of NICTH, the tumor is identified prior to the onset of hypoglycemia, but up to 50% of these patients may be asymptomatic despite hypoglycemia. Our patient had a known hepatic lesion and was minimally symptomatic despite very low BG. The mechanism for NICTH can include insulin secretion from the tumor, replacement of hepatic tissue and increased glucose utilization by the tumor, or most commonly, IGF-2 secretion. In the case of IGF-2 mediated hypoglycemia insulin, proinsulin, C-peptide, and β-hydroxybutyrate levels are low. An elevated IGF-2:IGF-1 ratio (>10) confirms the diagnosis. The primary treatment is through surgical removal or debulking of the tumor. Neoadjuvant therapies such as radiation and chemotherapy may reduce occurrences of hypoglycemia, but only temporarily. Glucocorticoids may be used when the underlying malignancy cannot be treated. Presentation: Friday, June 16, 2023