Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 39-27: Cancer-Related Hypercalcemia + Key Features Download Section PDF Listen +++ ++ Usually symptomatic and severe (serum calcium ≥ 15 mg/dL [> 3.75 mmol/L)]) The neoplasm is clinically apparent in nearly all cases when hypercalcemia is detected Occurs in 20–30% of patients with cancer Common causes include Myeloma Breast carcinoma Non–small cell lung cancer + Clinical Findings Download Section PDF Listen +++ ++ Symptoms and signs can be subtle More severe symptoms occur with higher levels and with rapid rate of rise of serum calcium Early symptoms typically include Anorexia Nausea Fatigue Constipation Polyuria Later findings may include Muscular weakness and hyporeflexia Confusion Psychosis Tremor Lethargy Hypercalcemia is caused by one of three mechanisms: Systemic effects of tumor-released proteins (eg, parathyroid hormone–related protein [PTHrP]) Direct osteolysis of bone by tumor Vitamin D–mediated osteoabsorption + Diagnosis Download Section PDF Listen +++ ++ Serum calcium increased Initial work-up includes obtaining serum parathyroid hormone (PTH), PTHrP, and calcitriol levels ECG: shortening of the QT interval Be sure to adjust serum calcium level for low albumin or check ionized calcium level + Treatment Download Section PDF Listen +++ ++ Intravenous fluids with 0.9% saline at 100–300 mL/h to ensure rehydration with brisk urinary output in the often volume-depleted patient Bisphosphonate should be given if kidney function is normal or only marginally impaired Pamidronate, 60–90 mg intravenously over 2–4 hours Zoledronic acid, 4 mg intravenously over 15 minutes Once hypercalcemia is controlled, initiate treatment directed at the cancer, if possible Other agents that can be used if hypercalcemia becomes refractory to bisphosphonates Calcitonin, 4–8 international units/kg is given every 12 hours subcutaneously or intramuscularly Can be used in patients with kidney disease Onset of action is within hours but its hypocalcemic effect wanes in 2–3 days Denosumab, 120 mg subcutaneously weekly for 4 weeks, followed by monthly administration for long-term management Corticosteroids (eg, low-dose dexamethasone, 40 mg intravenously weekly, or higher-dose dexamethasone, 40 mg intravenously daily on days 1–4, 9–12, and 17–20 each month) can be useful in patients with myeloma and lymphoma