Persistent hypoglycemia as an early, atypical presentation of hepatocellular carcinoma: A case report and systematic review of the literature

Abstract

The current study presents a case of persistent hypoglycemia as the initial manifestation of advanced hepatocellular carcinoma (HCC), as well as a systematic review of the management of hypoglycemia associated with HCC. A 42-year-old female presented with loss of consciousness and a blood glucose level of 30 mg/dl (normal range, 80–140 mg/dl). Abdominal ultrasound and computed tomography were performed to investigate tenderness in the right upper quadrant, and the results revealed a hepatic mass of 15 cm in diameter, with metastasis. A diagnosis of insulinoma was ruled out by examining the insulin level. Prednisolone treatment was ineffective for relieving the persistent hypoglycemia, however, a single dose of palliative radiotherapy reduced the hypoglycemic episodes to once monthly. Due to the advanced disease, the patient refused further treatment, with the exception of a palliative therapy with glucose fluid. The patient succumbed to pneumonia with sepsis. A systematic review of the literature indicated that steroids were the most commonly used drug for hypoglycemia associated with HCC, however, in the majority of cases no effect was noted as observed in this study. Cytoreduction by surgery or systemic chemotherapy has been the most effective treatment. Although rare, hypoglycemia may be the initial symptom of HCC. Cytoreduction is the most effective method of treating hypoglycemia associated with HCC.

Increase of α-dicarbonyls in liver and receptor for advanced glycation end products on immune cells are linked to nonalcoholic fatty liver disease and liver cancer

“… 45–47 The decreased level of glucose that we observed in HCC is further consistent with previous reports. 48 , 49 …”

Paraneoplastic Phenomena in Patients with Hepatocellular Carcinoma

“…There are no differences in the other clinical characteristics between patients with HCC with or without hypoglycemia at the time of diagnosis. However, patients with this paraneoplastic syndrome have a significantly worse prognosis than those without this complication [21,22]. The patients are also younger and have higher rates of portal vein thrombosis, bilobar tumor involvement and tumor size greater than 10 cm in diameter than do patients without the syndrome [2,13].…”

“…Hypoglycemia is usually present in the terminal stages of the illness, with survival times from the occurrence of this syndrome to the time of death being as short as 36 days [2,13,17,18,22,23]. In some populations or patients, however, hypoglycemia occurs early in the course of the tumor and these patients have a longer survival time [5][6][7].…”

“…In Type A hypoglycemia, which occurs more commonly and is poorly differentiated, the hypoglycaemia is mild or moderate in severity and is a late event which is not too difficult to control. By contrast, in Type B hypoglycemia, in which the tumor is less common, well-differentiated and slower growing, the hypoglycaemia occurs early and is difficult to control [22,24].…”

Dysregulated transmethylation leading to hepatocellular carcinoma compromises redox homeostasis and glucose formation

“…For example, glucose production in response to gluconeogenic stimuli such as glucagon is diminished in patients with HCC [12]. Also, hypoglycemia has been reported as an early characteristic in a subset of individuals with HCC [13], [14].…”