Case Presentation:

A 65–year–old Hispanic male presented to the hospital for recurrent episodes of dizziness and diaphoresis over 2 month duration. In the ER, the patient’s blood glucose was 30 mg/dl and his symptoms resolved after 50% dextrose administration. Patient had no significant PMH. Review of systems, physical examination and vitals was normal. The patient developed several episodes of hypoglycemia during the hospitalization. Lab work revealed serum insulin level of less than 2 (N 5–29 uIU/ml), low pro–insulin level, C–peptide level 0.08 (N 0.8–3.9 ng/ml), IGF I of less than 25 (which is very low), IGF Bp3 level 1 (N 3–6mg/dl), and a negative sulfonylurea screen. LFT revealed AST of 256, ALT of 64, Alk. phos of 160 and INR 1.5. As the patient had elevated liver enzymes, a CT/MRI abdomen with contrast was ordered which showed a large mass in the right lobe of the cirrhotic liver, measuring 17.5 cm, and right portal vein thrombosis. His Alfa –Feto protein was more than 3000 and CT guided needle biopsy of liver mass confirmed the diagnosis of Hepatocellular Carcinoma (HCC). The patient had chemo–embolization of the right hepatic tumor using LC beads loaded with adriamycin and was started on sorafenib, which significantly improved his hypoglycemic episodes.

Discussion:

In 1929, Nadler and Wolfer first described the development of hypoglycemia in a patient with HCC. Hypoglycemia is extremely uncommon as the first presentation of HCC, and it occurs predominantly as a paraneoplastic manifestation. Hypoglycemia associated with HCC has been described in two distinct types. Type A hypoglycemia usually occurs during the terminal stage of the disease and is related to a progressive increase in demand for glucose by the tumor, coupled with a reduction in hepatic glucose output due to hepatic failure and poor nutrition. Type B is seen in a smaller proportion (5%) of patients, develops earlier in the course of the disease and has been associated with the production of IGF II by the tumor. Growth hormone and IGF – I concentration are reduced due to negative feedback mediated by IGF – II. In our case, the IGF–II levels were not obtained due to non–availability of the test and the patient’s financial constraints. In addition, plasma insulin, C–peptide and pro–insulin levels are low during hypoglycemia associated with HCC, which distinguishes it from an insulinoma.

Conclusions:

This is only the second case of HCC presenting as hypoglycemia reported in literature. Our patient had no significant past medical history and presented with recurrent episodes of hypoglycemia at the age of 65 years. If the patient was not worked up extensively, his diagnosis of HCC would have been missed and the patient would have presented with advanced stage HCC later. Thus, although rare, it is important to remember HCC as a differential diagnosis of hypoglycemia, given the clinical implications of early diagnosis for the patient.

Figure 1MRI with contrast showing 17.5 × 9.6 × 13.4 cm mass in the right lobe of the cirrhotic liver.

Figure 2CT and MRI of abdomen showing the liver mass.