SUN-677 The Warburg Effect: A Case of Persistent Hypoglycemia and Lactic Acidosis

Abstract

Background: It is well established that malignant cells are able to metabolize glucose to lactate in the presence of oxygen, known as the Warburg effect (WE) - a rare metabolic complication of malignancies, presenting with lactic acidosis & hypoglycemia. It signifies a poor prognosis with high mortality rates. We present the case of a woman with malignancy who presented with persistent hypoglycemia requiring a dextrose drip and type B lactic acidosis. Clinical case: A 63-year-old female was referred to our institution for persistent hypoglycemia and lactic acidosis after being admitted to another hospital for a urinary tract infection. Her history was notable for generalized fatigue & weight loss. She had lactic acidosis (18-25mEq/L; Normal: 0.5–2.2mEq/L) despite stable hemodynamics that did not improve with resuscitation & antibiotics. Her hospital course was complicated by worsening mental status & non- hypoxic respiratory distress due to profound acidosis, requiring intubation. She required a dextrose infusion of up to 40g/hour to maintain normoglycemia and with the infusion, an increase in lactate level was noted. Workup to rule out insulin-dependent hypoglycemia, adrenal insufficiency, GH deficiency, MELAS, mesenteric ischemia & drug-related lactic acidosis was unremarkable. EEG was not suggestive of seizure activity. Initial labs were notable for elevated levels of CA-19-9 408U/mL (normal: 0–34), & CA 125 430U/mL (normal: 0–34) which were attributed to her newly diagnosed cirrhosis. However, the degree of her liver dysfunction was felt to be not severe enough to cause hypoglycemia. Imaging studies looking for tumors were unrevealing. A bone marrow biopsy done to rule out occult malignancy showed metastatic carcinoma with neuroendocrine features. Further treatment was not pursued by her family. Based on the diagnosis of metastatic cancer, it was felt that her persistent hypoglycemia was due to the Warburg effect. Conclusion: The Warburg effect (WE) is observed in cancers when the malignant cells utilize glycolysis over oxidative phosphorylation, regardless of oxygen content, for energy production. This involves aerobic glycolysis & lactic acid is its by-product. Cancer cells use more glucose via the glycolysis pathway to meet their demands leading to hypoglycemia & concurrent lactic acidosis despite normal oxygen levels. WE is a rare but severe complication of malignancies that signifies a poor prognosis. Patients with this complication need to be monitored closely until definitive treatment can be implemented. This case highlights the importance of maintaining a high clinical index of suspicion for diagnosing WE. Reference Elhomsy G. C., Eranki V., Albert S. G., et al. “Hyper-warburgism,” a cause of asymptomatic hypoglycemia with lactic acidosis in a patient with non-Hodgkin’s lymphoma. The Journal of Clinical Endocrinology & Metabolism. 2012;97(12):4311–4316.