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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
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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
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
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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
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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
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