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  • Usually symptomatic and severe (15 mg/dL [3.75 mmol/L] or more).

  • Most common paraneoplastic endocrine syndrome; accounts for most inpatients with hypercalcemia.

  • The neoplasm is clinically apparent in nearly all cases when hypercalcemia is detected.


Hypercalcemia affects 20–30% of cancer patients at some point during their illness. The most common cancers causing hypercalcemia are myeloma, breast carcinoma, and NSCLC. Hypercalcemia is caused by one of three mechanisms: systemic effects of tumor-released proteins, direct osteolysis of bone by tumor, or vitamin D–mediated osteoabsorption.


A. Symptoms and Signs

Symptoms and signs of hypercalcemia can be subtle; more severe symptoms occur with higher levels of hypercalcemia and with a rapidly rising calcium. Early symptoms typically include anorexia, nausea, fatigue, constipation, and polyuria; later findings may include muscular weakness and hyporeflexia, confusion, psychosis, tremor, and lethargy.

B. Laboratory Findings

Symptoms and signs are caused by free calcium; as calcium is bound by protein in the serum, the measured serum calcium will underestimate the free or ionized calcium in patients with low albumin levels. In the setting of hypoalbuminemia, the corrected serum calcium should be calculated by one of several available formulas (eg, corrected calcium = measured calcium – measured albumin + 4). Free ionized calcium can be measured. When the corrected serum calcium rises above 12 mg/dL (3 mmol/L), especially if the rise occurs rapidly, sudden death due to cardiac arrhythmia or asystole may occur. Initial work-up for hypercalcemia includes obtaining serum PTH, PTHrP, and calcitriol levels. The presence of hypercalcemia does not invariably indicate a dismal prognosis, especially in patients with breast cancer, myeloma, or lymphoma. In the absence of symptoms or signs of hypercalcemia, a laboratory finding of elevated serum calcium should be retested immediately to exclude the possibility of error.


Electrocardiography in hypercalcemia often shows a shortening of the QT interval (eFigure 39–11).

eFigure 39–11.

Hypercalcemia in a patient with carcinoma. The QT interval is only 0.28–0.3 because of virtual absence of the QT segment. (Reproduced, with permission, from Goldschlager N, Goldman MJ. Principles of Clinical Electrocardiography, 13th ed. Originally published by Appleton & Lange. Copyright © 1989 by The McGraw-Hill Companies, Inc.)


Emergency management should begin with the initiation of intravenous fluids with 0.9% saline at 100–300 mL/h to ensure rehydration with brisk urinary output of the often volume-depleted patient. If kidney function is normal or only marginally impaired, a bisphosphonate should be given. Choices include pamidronate, 60–90 mg intravenously over 2–4 hours, or zoledronic acid, 4 mg intravenously over 15 minutes. Zoledronic acid is more potent than pamidronate and has the advantage of a shorter administration time as well as ...

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