Introduction: Refractory hypoglycemia is a rare paraneoplastic manifestation of hepatocellular carcinoma (HCC) with poor prognosis. We present a patient with hypoglycemia as initial presentation of HCC.
Case Description/Methods: A 68-year-old male with decompensated Child-Pugh class B hepatitis C cirrhosis with sustained virologic response initially presented to an outside facility for syncope. He was diagnosed with 22 centimeter multifocal metastatic HCC to bone and lung (Figure 1). He suffered hypoglycemia-induced seizures requiring debulking therapy with transarterial bland embolization (TAE) and dexamethasone. Two months later he was hospitalized at our facility for altered mental status and found to have blood glucose (BG) 12 milligrams per deciliter. He received 50 grams intravenous dextrose and intramuscular glucagon with improvement but continued to have recurrent hypoglycemia despite oral intake. Laboratory testing was consistent with HCC-related hypoglycemia (Table 1). Endocrinology recommended dextrose 10% infusion, corticosteroids, and frequent meals. His BG remained labile with frequent morning hypoglycemia. Previous TAE limited further options for locoregional therapy (LRT). Sorafenib was considered for palliation, but the patient opted for comfort-directed care and died one month after admission.
Discussion: Two types of hypoglycemia are seen in HCC patients. Type A hypoglycemia is mild, occurs in rapidly-growing tumors, and mortality may occur within weeks. It is caused by the inability of a tumor-ridden liver to meet the body’s glucose demand. Type B hypoglycemia is severe, occurs with slowly-growing tumors, and mortality may occur within a year. It is caused by defective processing of the insulin-like growth factor (IGF)-2 precursor by tumor cells, resulting in increased glucose uptake. Our patient’s persistent and profound hypoglycemia made type B most likely, and his low insulin, c-peptide, IGF-1, normal IGF-2 and high IGF-2/IGF-1 ratio confirmed non-islet cell tumor hypoglycemia. Current literature suggests the most effective management of HCC-induced hypoglycemia is cytoreduction by surgery, chemotherapy and LRT. There is little data on effective pharmaceutical treatments. Steroids, frequent feeding, dextrose infusion, and growth hormone have been attempted with mixed results. Patients with cirrhosis and refractory hypoglycemia should be screened for HCC as this may be a presenting symptom as in our case. Tumor reduction appears the most durable method for hypoglycemia management.
