Refractory Hypoglycemia Secondary to the Warburg Effect in Diffuse Large B-Cell Lymphoma

Spontaneous and refractory hypoglycemia in malignancy poses diagnostic challenges, since its exact underlying mechanisms remain unclear. A 62-year-old female patient with a 10-year type 2 diabetes mellitus history presented with abdominal pain and spontaneous hypoglycemia despite discontinuation of her diabetic treatments. An initial computed tomography (CT) scan revealed a large perinephric tumor, and a second CT, performed a week later, demonstrated significant tumor growth. On admission, she had no neuroglycopenic symptoms despite a serum glucose level of 25 mg/dL (1.39 mmol/L). She showed suppressed insulin and insulin-like growth factor (IGF)-1 levels, elevated lactate levels, a pH of 7.434 with an anion gap of 24.1, and a negative test for anti-insulin antibody. A percutaneous CT-guided tumor biopsy revealed diffuse large B-cell lymphoma. She received continuous dextrose supplementation and prednisolone to alleviate the severe hypoglycemia, but she died from the tumor burden on the sixth day of hospitalization. Postmortem serum immunoblotting revealed the absence of partially processed IGF-2 precursors. The patient's refractory hypoglycemia and hyperlactatemia were consistent with tumor-associated aerobic glycolytic lactate production, known as the Warburg effect. This case illustrates the importance of increased awareness of this underrecognized oncologic emergency in the differential diagnosis of profound spontaneous hypoglycemia in malignancy.