SUN-326 Hypoglycemia and Lactic Acidosis: The Deadly Signs of Untreated Non-Hodgkin's Lymphoma

Introduction The presentation of hypoglycemia with lactic acidosis is rare, though well-described. It is most commonly associated with hematologic malignancies and is attributed to the Warburg effect in which cells consume large amounts of glucose through the glycolytic pathway with lactic acid production, even in aerobic conditions. Clinical Case 64yo WM with cirrhosis due to hemochromatosis, atrial fibrillation, type 2 diabetes mellitus managed by diet, initially presented with weakness, malaise and thrombocytopenia. Imaging revealed splenomegaly, bilateral adrenal masses, and diffuse lymphadenopathy. He was admitted, given IV fluid hydration, and discharged to have outpatient lymph node biopsy. Prior to biopsy he developed worsening weakness, fatigue, shortness of breath, and hypoxia. Lactate was 8.1mmol/L, n=0.7-2.1. He was admitted for sepsis secondary to pneumonia. During hospitalization, he was noted to be hypoglycemic (serum glucose 40mg/dL), requiring continuous dextrose infusion and dextrose 50% boluses. Evaluation was consistent with insulin independent hypoglycemia with labs as follows: Insulin <1 microU/mL (2-25), c-peptide 0.65ng/mL (0.78-5.19), proinsulin 4.2pmol/L (3.6-22), beta-hydroxybutyrate 4.07mg/dL (0.2-2.8), glucose 49mg/dL then 44mg/dL 30 minutes after administration of glucagon. ACTH 8.1pg/mL (7.2-63) and cortisol 11mcg/dL then 14.8mcg/dL after cosyntropin stimulation. He was started on stress dose steroids. Lactic acidosis persisted and worsened (>15mmol/L). Repeat CT imaging was obtained to search for potential source of lactic acidosis, though none was found. It was later noted that increasing lactate levels occurred with increased dextrose administration. A perirenal lymph node biopsy was performed. Shortly after the procedure, the patient rapidly decompensated. He was started on continuous renal replacement therapy and given rasburicase for suspected tumor lysis syndrome. Despite these efforts, the patient died. Pathology later returned positive for Non-Hodgkin’s Lymphoma. Discussion In this case, hypoglycemia was initially confounded by a history of cirrhosis and possible adrenal insufficiency. However, no improvement with steroids and worsening of lactic acidosis with increasing dextrose administration demonstrated that hypoglycemia was due to the Warburg effect in the setting of undiagnosed Non-Hodgkin’s Lymphoma. Recognizing this phenomenon is imperative as it coincides with high mortality, and the treatment of underlying disease may be the only effective option. References Georges C. Elhomsy, 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, Volume 97, Issue 12, 1 December 2012, Pages 4311-4316.