Recurrent Hypercalcemia in a Patient with Hodgkin Lymphoma with Concurrent Elevated Parathyroid Hormone-Related Peptide (PTHrP) and Vitamin D

Introduction: Hypercalcemia occurs in approximately 30 percent of patients with malignancy. Malignancy-associated hypercalcemia has been attributed to several distinct mechanisms: osteolytic metastases, humoral production of parathyroid hormone-related peptide (PTHrP), excess 1-alpha hydroxylase associated production of 1,25 dihydroxyvitamin D (1,25(OH)2D), and rarely ectopic parathyroid hormone (PTH) secretion. We report a case of hypercalcemia associated with elevated levels of both 1,25(OH)2D and PTHrP in a patient with newly diagnosed Hodgkin lymphoma. Case Description: A 68 year old man with a history of hypertension initially presented for inguinal hernia repair and was found to have a mediastinal mass on cross sectional imaging. A biopsy revealed Hodgkin's lymphoma. He was scheduled to start chemotherapy as an outpatient, but was found to have severe hypercalcemia with a serum calcium level of 14.7 mg/dL and impaired kidney function with serum creatinine of 2.85 mg/dL. He was hospitalized and received intravenous normal saline, calcitonin 8 units/kg twice daily for 48 hours, and intravenous pamidronate. A workup revealed a suppressed PTH level of 1.4 pmol/L, elevated PTHrP of 3.6 pmol/L, and elevated 1,25(OH)2 D of 220.8 pg/mL. His calcium improved to 9.6 mg/dL and the creatinine improved to 2.0 mg/dL prior to discharge. The following week, his calcium was elevated to 11.4 mg/dL, and he was prescribed prednisone 100 mg for five days. The calcium continued to rise to 13.9 mg/dL and he was again hospitalized and received intravenous fluids, calcitonin, and bisphosphonate therapy. Discussion: Hypercalcemia of malignancy can be due to a single or a combination of disparate mechanisms. Solid organ tumors are typically associated with PTHrP production while hematologic malignancies are typically associated with increased activity of 1-alpha hydroxylase. We report a case of a patient with Hodgkin lymphoma associated hypercalcemia with elevated levels of both PTHrP and 1,25(OH)2D. His hypercalcemia was not responsive to oral corticosteroids despite the elevated 1,25(OH)2D, suggesting that the hypercalcemia was at least partially attributable to the PTHrP. There have been a few cases of co-secretion of PTHrP and 1,25(OH)2D in Non-Hodgkin’s lymphoma; this appears to be the first reported case in a patient with Hodgkin lymphoma.