SUN-327 Hypercalcemia and Hypoglycemia Due To EBV-Associated Lymphoma

Abstract

Background: Hypercalcemia is uncommon in HIV infection but can occur in the setting of lymphoma. We describe a patient with HIV with hypercalcemia and hypoglycemia due to an initially undetected EBV-associated lymphoma. Clinical Case: A 32-year old Caucasian male with recent diagnosis of HIV was admitted for HIV arthropathy and sepsis, and found to have hypercalcemia (Ca 10.7mg/dL, n 8.9-10.2mg/dL; ionized Ca 6.1mg/dL, n 4.6-5.7mg/dL). PTH was suppressed (<10pg/mL, n 12-72pg/mL). PTH-independent causes of hypercalcemia were unremarkable for humoral hypercalcemia of malignancy (PTHrP 0.2pmol/L, n <2.0pmol/L), vitamin D toxicity (24-hydroxyvitamin D 41ng/mL, n 30-80ng/mL), granulomatous disorders (1,25-dihydroxyvitamin D 24.8pg/mL, n 19.9-79.3pg/mL; quantiferon negative), hyperthyroidism, and adrenal insufficiency. Renal function was normal and there was no thiazide, lithium, calcium, or vitamin A use. Serum protein electrophoresis (PEP) showed hypogammaglobinemia consistent with immunodeficiency. Urine PEP was negative for immunoglobulin light chains. Hypercalcemia was initially attributed to HIV with immobilization and calcium level was expected to normalize with antiretroviral therapy. Workup for infectious etiology was negative, his arthralgia and overall clinical status improved, and he was discharged. Three days later, he was readmitted for altered mental status and anemia. He was hypoglycemic, which was new on readmission, and required dextrose-containing IV fluids in addition to tube feeds to keep his serum glucose within normal range. Work up was negative for insulinoma (C peptide 0.48ng/mL, n 0.81-5.3ng/mL; glucose 31mg/dL) but IGF-2 to IGF-1 ratio was elevated at 4.57 which was suggestive of IGF-2-mediated tumor-associated hypoglycemia. Persistent leukocytosis and type B lactic acidosis also suggested an underlying malignancy. Bronchoscopy, bone marrow biopsy, and CSF cytology were negative for malignancy. CSF was positive for EBV (77,100 copies/mL). CT imaging showed liver lesions and biopsy led to the diagnosis of high-grade B-cell lymphoma. He was started on chemotherapy. Hypoglycemia resolved 10 days later, as did the lactic acidosis. Hypercalcemia was treated with pamidronate with return to normal levels. Conclusion: Hypercalcemia in an HIV patient warrants diligent workup. Hypercalcemia in lymphomas are often attributed to elevated 1,25-dihydroxyvitamin D. A possible explanation for normal 1,25-dihydroxyvitamin D observed in our patient is the effect of antiretroviral therapy on accelerated catabolism of vitamin D. Hypoglycemia may be due to IGF-2 production by tumor and malignancy-related glucose consumption via glycolytic pathway with lactic acid production. Literature on concurrent hypercalcemia and hypoglycemia with B-cell lymphoma is sparse and, to our knowledge, occurrence in the setting of HIV has not been reported.