Hypercalcemia, Malignant

Key Features

• 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

• Symptoms and signs can be subtle

• More severe symptoms occur with higher levels of serum calcium and with a rapidly rising calcium level

• 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 serum albumin or to check ionized serum calcium level

• Initial work-up for hypercalcemia includes obtaining

  • Serum parathyroid hormone level

  • Serum parathyroid hormone-related peptide level

  • Calcitriol (1,25-dihydroxycholecalciferol) level

Treatment

• Intravenous fluids with 0.9% saline administered 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

    • More potent than pamidronate, it has a shorter administration time, and a longer duration of effect

• 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 subcutaneously or intramuscularly every 12 hours

    • 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 can be useful in patients with hypercalcemia due to plasma cell myeloma and lymphoma