IGF-Mediated Hypoglycemia as the First Manifestation of Huge Hepatocellular Carcinoma (HCC) in a Chronic Hepatitis B Infected Patient

Abstract

Paraneoplastic hypoglycemia is a rare presentation of HCC1. Treatment for such episode has not been standardized2. Most patients do not respond to intravenous glucose infusion.A 54-year-old male presented with alteration of consciousness. He had anorexia and 20-kilograms weight lost within 4 months, recurrent dizziness and palpitations which improved with food intake for 2 weeks. Physical examination revealed enlarged liver. No sign of chronic liver stigmata was noted. Others were unremarkable. Hypoglycemia was diagnosed by plasma glucose of 21 mg/dL. Serum insulin and C-peptide level was <2 μIU/mL (8.9-28.4) and 0.3 ng/mL (0.9-7.1), respectively, suggestive of insulin-like growth factor (IGF)-mediated hypoglycemia. CT scan showed 16 cm-arterial enhancing and delayed wash-out mass with central necrosis, occupying almost entire right lobe on non-cirrhotic liver (pic 1). The mass abutted right portal vein, no metastatic foci was seen. Alpha-fetoprotein was 52,300 IU/mL. Diagnosis of HCC was made. The etiology of HCC was chronic hepatitis B infection. HBV DNA was 319 IU/mL. Initially, continuous intravenous glucose infusion of 8 gm/h was given, but hypoglycemia persisted. Continuous glucose infusion of 10 gm/hr with frequent meals was required to maintain blood glucose level above 80 mg/dL. On admission day 3, TACE was done to reduce tumor burden. The need for glucose infusion was rapidly decreased and can be stopped within 3 days after TACE procedure (pic 2). Hepatectomy was successfully performed 1 month after diagnosis. Pathologic examination showed bizarre multinucleated giant tumor cell compatible with moderately differentiated HCC grade III-IV (pic 3).2449_A Figure 1. Picture1.CT abdomen revealed 16 cm hypo-density mass occupying right hepatic lobe with arterial enhancing, delayed wash-out rim and central necrosis.2449_B Figure 2. Level of capillary glucose and amount of glucose infusion during hospitalization2449_C Figure 3. Picture 3. Bizarre multinucleated giant tumor cell compatible with moderately differentiated hepatocellular carcinoma grade III-IVHypoglycemia presenting as the first manifestation of HCC, particularly in non-cirrhotic patients is very rare1. It is caused by production of HCC peptides with insulin-like structure and bioactivity, e.g. IGF-II. IGF-II binds to the IGF-I, IGF-II, and insulin receptors, resulting in dramatic increasing glucose uptake.2 The mainstay of HCC treatment is to reduce tumor burden. Our patient had dramatic response to TACE, followed by surgical resection. After resection for 4 months, the patient was doing well without signs of HCC recurrence.