Department of Internal Medicine, AdventHealth Orlando Orlando, FL
Tareq Alsaleh, MD1, Amir Harb, DO1, Azhar Hussain, MD2, Ernesto Robalino. Gonzaga, MD3, Johnathan Ragheb, MD4 1Department of Internal Medicine, AdventHealth Orlando, Orlando, FL; 2University Hospital Galway, Ireland, Galway, Galway, Ireland; 3Department of Gastroenterology and Hepatology, AdventHealth Orlando, Orlando, FL; 4Department of Gastroenterology and Hepatology, AdventHealth Altamonte, Orlando, FL 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 male 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 four years. Physical examination was unremarkable.
Laboratory testing revealed elevated AST, ALT, bilirubin, and INR. 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 (Table 1). Computed tomography of the abdomen revealed large infiltrative liver masses with central necrosis. Similar findings were seen on magnetic resonance imaging (Figure 1).
The hypoglycemia remained refractory to dietary interventions, intravenous (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.
Figure: Table 1. Laboratory values on presentation
Figure: Figure 1A. Large infiltrative masses with associated central necrosis measuring approximately 14.1 x 18.0 x 14.8 cm arising from segments 2 and 3 and 14.5 x 13.9 x 12.2 cm centered at the hepatic dome. Figure 1B. Large partially protruding mass consistent with HCC that almost completely occupied the left hepatic lobe measuring over 17 x 14 cm in size with contiguous extension into the caudate. There was a contiguous tumor thrombus throughout the left portal system extending into the right portal vein and distal main portal vein. There was an additional right hepatic mass measuring 13.2 x 11.9 cm
Disclosures: Tareq Alsaleh indicated no relevant financial relationships. Amir Harb indicated no relevant financial relationships. Azhar Hussain indicated no relevant financial relationships. Ernesto Gonzaga indicated no relevant financial relationships. Johnathan Ragheb indicated no relevant financial relationships.
Tareq Alsaleh, MD1, Amir Harb, DO1, Azhar Hussain, MD2, Ernesto Robalino. Gonzaga, MD3, Johnathan Ragheb, MD4. P4010 - Hypoglycemia as the Initial Presentation of Advanced Hepatocellular Carcinoma, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
