Denosumab for the Treatment of Refractory Hypercalcemia in Metastatic Parathyroid Carcinoma

ABSTRACT Objective: Parathyroid carcinoma is a rare malignant neoplasm. Hypercalcemia due to parathyroid carcinoma is often resistant to medical management in the advanced stage. Here we report the usefulness of denosumab as an option for managing refractory hypercalcemia in the setting of parathyroid carcinoma. Methods: A 39-year-old Japanese female with metastatic parathyroid carcinoma was referred to our hospital due to frequent episodes of hypercalcemia. Upon admission, her respective serum calcium (Ca) and intact parathyroid hormone (PTH) levels were 13.3 mg/dL (reference range, 8.5–10.2 mg/dL) and 1,920 pg/mL (reference range, 10–65 pg/mL). Although her hypercalcemia initially responded to strengthened standard therapy, it became unmanageable as her disease progressed. A single denosumab injection dramatically decreased her hypercalcemia from 15.1 to 10.1 mg/dL within 10 days. Her Ca levels remained in the reference range for more than 1 month. Her hypercalcemia could be controlled by denosumab injected at a frequency lower than that used for the bone metastasis of malignant tumors. Results: Although her serum PTH level increased to 4,130 pg/mL, her condition has remained good for the last 14 months. Conclusions: Denosumab is a humanized monoclonal antibody that inhibits the receptor activator of nuclear factor-κB ligand (RANKL) and is a potentially important palliative treatment for refractory hypercalcemia due to parathyroid carcinoma. Abbreviations: Ca calcium PTH parathyroid hormone RANK receptor activator of nuclear factor-κB RANKL receptor activator of nuclear factor-κB ligand TRACP-5b tartrate-resistant acid phosphatase 5b