Abstract
Background
Pathophysiology
Local osteolytic hypercalcemia due to direct effect of bone metastases.
Humoral hypercalcemia of malignancy—secretion of parathyroid hormone related protein (PTHrP) by malignant tumors.
1,25(OH)2D (vitamin D)-secreting lymphomas.
Ectopic secretion of authentic PTH (very rare).
Symptoms/Signs
Symptoms roughly correlate with the degree of hypercalcemia (corrected) and the rapidity of increase: mild (10.5–11.9 mg/dL); moderate (12–13.9 mg/dL); severe (>14 mg/dL).
Cognitive: sedation, delirium, coma. Gastrointestinal: anorexia, nausea, vomiting. Renal: dehydration, polyuria, thirst/polydipsia.
Diagnostics
Total serum calcium, corrected for albumin (Formula: [(4 − albumin) × 0.8] + Ca++]).
Ionized calcium.
Renal function, phosphate, magnesium and potassium—monitor during treatment.
Antitumor Therapy
Treatment of the underlying malignancy with systemic therapy (e.g., chemotherapy) is essential for long-term management. In cases in which further antineoplastic therapy is not feasible, the decision to treat or not treat hypercalcemia should be made by careful exploration of the patient's goals of care. In advanced untreatable cancer, the decision to not treat hypercalcemia may be very appropriate.
Supportive Measures
Saline hydration and loop diuretics: Normal saline 200–500 mL/hr increases glomerular filtration rate (GFR), increases filtered load of calcium, and is calciuretic. Loop diuretics (e.g., furosemide) blocks calcium resorption in the loop of Henle. Note: only use diuretics once dehydration has been corrected.
Discontinue medications that can increase serum calcium (e.g., lithium, vitamin D, supplements containing calcitriol, thiazides, calcium antacids); removal of calcium from total parenteral nutrition (TPN).
Increase mobility if possible.
Bisphosphonates are the drug class of choice for most patients. They work via blocking osteoclastic bone resorption. Pamidronate and zoledronic acid are used in the United States with full efficacy noted 2–4 days after administration; responses last 1–3 weeks. May lead to hypocalcemia or azotemia; use with caution in renal dysfunction. Pamidronate = 60–90 mg. Repeat only after 7 days have elapsed after first dose. Repeat infusions every 2–3 weeks or longer according to the degree and of severity of hypercalcemia. Zoledronic acid = 4 mg (maximum). Wait at least 7 days before considering retreatment.
Other agents: glucocorticoids are useful in lymphoid malignancies that secrete 1,25(OH)2 vitamin D. Calcitonin may lead to acute reductions in serum calcium (12–24 hours) but reductions are small and transient. Calcitonin is administered intramuscularly or subcutaneously; initially 4 U/kg every 12 hours; may increase up to 8 U/kg every 12 hours to a maximum of every 6 hours. Mithramycin was the standard agent prior to bisphosphonates; now it is used only rarely due to a higher side effect profile. Gallium nitrate is usually impractical due to the need for a 5-day intravenous infusion. Renal dialysis can be used in cases of acute/chronic renal failure.
Summary
Hypercalcemia is a common oncologic complication that often portends a very short prognosis. The decision to attempt reversal should be made after first exploring the goals of care and assessing the feasibility of future systemic anticancer treatments. Vigorous hydration and bisphosphonates are the cornerstones of short-term hypercalcemia therapy.
Footnotes
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Fast Facts are edited by Drew A. Rosielle, M.D., Palliative Care Center, Medical College of Wisconsin. For comments/questions write to: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: 
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Disclaimer: Fast Facts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.
This Fast Fact was originally edited by David E. Weissman, M.D. and published in February 2006. Current version recopy edited in April 2009.