A Rare Case of Hypercalcemia Mediated by PTHrP and 1,25-dihyroxyvitamin D in a Patient with Pancreatic Neuroendocrine Tumor

In patients with hypercalcemia of malignancy, the secretion of parathyroid hormone-related protein (PTHrP) is commonly seen. Rarely, neoplasms can cause hypercalcemia from multiple mechanisms, which can affect the treatment options. We present a patient with metastatic pancreatic neuroendocrine tumor who developed hypercalcemia secondary to simultaneous elevations in both PTHrP and 1,25-dihydroxyvitamin D.

Case Description:

A 60-year-old man with history of metastatic pancreatic neuroendocrine tumor presented with intra-abdominal abscesses requiring multiple drain placements. Routine laboratory studies demonstrated a recent gradual rise in his serum calcium level from 10.9 to 12.4 mg/dL with stable serum albumin of approximately 2.5 g/dL. The patient remained asymptomatic. Despite administration of intravenous fluids, hypercalcemia persisted. Laboratory evaluation revealed an elevated PTHrP of 102 pmol/L, a suppressed intact PTH of 5 pg/ml, and a low 25-hydroxyvitamin D at 7 ng/mL. Multiple calcium reducing agents were administered within the next week including two doses of intravenous zoledronic acid 4 mg, four doses of calcitonin, and one dose of subcutaneous denosumab 120 mg. Despite these treatments, the patient’s serum calcium continued to be elevated at 13.3 mg/dL with an albumin level of 3.6 g/dL. To complete the work-up, a serum 1,25-dihydroxyvitamin D was obtained and noted to be markedly elevated at 202 ng/mL. The patient was then started on a 7-day course of prednisone 40 mg daily and also restarted on concurrent chemotherapy. His serum calcium level improved to 10.5 mg/dL with albumin level of 3 g/dL on the day of discharge, three days after the completion of his steroid course.

Discussion:

This is the second report describing dual mechanisms of hypercalcemia with simultaneous elevations in PTHrP and 1,25-dihydroxyvitamin D in a patient with pancreatic neuroendocrine tumor. While PTHrP mediated hypercalcemia typically responds well to the calcium lowering effects of denosumab and bisphosphonate therapy, these agents in this patient had minimal effect, a finding similar to another case described by Van Den Eynden et al. Only the treatment with steroids combined with chemotherapy successfully led to improvement in hypercalcemia. This case highlights that a thorough evaluation of the etiologies of hypercalcemia is crucial for an optimal therapy, especially for patients with underlying malignancy.