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Key Features

  • Usually symptomatic and severe (≥ 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

  • Symptoms and signs can be subtle

  • More severe symptoms occur with higher levels of serum calcium and with a rapid rate at which the calcium level rises

  • 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

    • Direct osteolysis of bone by tumor

    • Vitamin D–mediated osteoabsorption

Diagnosis

  • Serum calcium increased

  • ECG: shortening of the QT interval

  • Be sure to adjust serum calcium level for low albumin or check ionized calcium level

Treatment

  • Intravenous fluids with 0.9% saline at 100–300 mL/h to ensure rehydration with brisk urinary output of 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

    • Ibandronate 2–4 mg intravenously over 2 hours

  • 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

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