S5763 Hypoglycemia as the Initial Presentation of Advanced Hepatocellular Carcinoma

Introduction: Hepatocellular carcinoma (HCC) can cause non-islet cell hypoglycemia (NICTH), a paraneoplastic syndrome that is widely regarded to be a terminal stage sequela of HCC. Here, we present a case of NICTH as the initial presentation of HCC. Case Description/Methods: A 55-year-old man with alcohol-associated cirrhosis was brought to the emergency department after experiencing acute dizziness with a blood glucose of 34 mg/dL, which improved to 154 mg/dL after receiving intravenous (IV) dextrose. He was not diabetic and did not take insulin, but he reported abdominal bloating, distension, and a 30-lb weight loss over the past 3 months. He had not been screened for HCC in the past 4 years. Physical examination was unremarkable. Laboratory testing revealed elevated aspartate aminotransferase, alanine aminotransferase, bilirubin, and international normalized ratio. Serum insulin and C-peptide levels were low. Ratio of serum insulin-like growth factors 2 to 1 (IGF-2 to IGF-1) was 6.6 (79 ng/mL over 12 ng/mL). Thyroid and adrenal gland testing was unremarkable. Serum alpha-fetoprotein (AFP) level was greater than 60,500 ng/mL. Computed tomography of the abdomen revealed large infiltrative liver masses with central necrosis. Similar findings were seen on magnetic resonance imaging. The hypoglycemia remained refractory to dietary interventions, IV dextrose, and steroids. Long-term nutritional support was provided by total parenteral nutrition, as the patient was a poor candidate for gastrostomy tube. He was offered immunotherapy and trans-arterial chemoembolization, but he chose comfort care and home hospice services. He was deceased 23 days after presentation. Discussion: Hypoglycemia in HCC can be due to replacement of liver parenchyma with tumor tissue and subsequent failure of the liver to satisfy the glucose demands of the growing tumor and other tissues. This commonly occurs in advanced disease with large tumor burden. Another mechanism is the defective processing of pro-IGF-2, which interacts with IGF-1, IGF-2, and insulin receptors. NICTH is characterized by low serum levels of insulin, C-peptide, and IGF-1. IGF-2 may be increased, decreased, or normal. NICTH is initially managed with the correction of hypoglycemia, which may require IV dextrose, steroids, and nutritional support. Definitive treatment is by addressing the primary malignancy. Our case demonstrates a rare initial presentation of HCC as NICTH, highlighting the importance of considering it as part of the differential diagnosis of unexplained hypoglycemia.