"Hyper-Warburgism," a Cause of Asymptomatic Hypoglycemia with Lactic Acidosis in a Patient with Non-Hodgkin's Lymphoma

Context: In cancer cells, the Warburg effect is defined as the avid consumption of glucose through the glycolytic pathway with concomitant lactate production, even under aerobic conditions. Case: We report a 64-yr-old woman who was referred to our institution for pancytopenia and hypoglycemia. Physical examination demonstrated hepatosplenomegaly and petechiae. She had no clinical manifestation of neuroglycopenia, despite serum glucose of 26 mg/dl (1.4 mmol/liter) and serum lactate of 28.5 mmol/liter (normal range, 0.5-3.4 mmol/liter). Bone marrow biopsy demonstrated diffuse large B-cell lymphoma. Staging F-18-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography showed increased FDG avidity in an enlarged spleen and absent FDG uptake in the brain. Despite dextrose infusions up to 30 g/h, there was no increase in serum glucose, but there was a paradoxical increase in serum lactate. Immunochemotherapy improved the hematological and metabolic abnormalities. Follow-up FDG-positron emission tomography/computed tomography showed a decrease in splenic avidity and an increase in brain FDG avidity. The patient refused further chemotherapy and died 1 wk after discharge. Methods: Literature review of cases of lymphoma with lactic acidosis, with and without hypoglycemia, demonstrated that these combinations occurred in multiple categories of B-and T-cell lymphoma. There was no difference in the mortality rate in those with (75%) or without (74%) concomitant hypoglycemia. Conclusion: This case represents an exaggerated Warburg effect, or "hyper-Warburgism," characterized by excessive lactate production and overwhelming glucose consumption. We speculate that the decreased brain FDG uptake, despite the lack of neuroglycopenic symptoms, supports the hypothesis that lactate served as a fuel for the brain, thus protecting against hypoglycemia. (J Clin Endocrinol Metab 97: 4311-4316, 2012)