Up to 30% of patients with cancer develop hypercalcemia. Approximately 50% of these patients will die within 30 days of a hypercalcemia diagnosis. The most common cancers leading to hypercalcemia are squamous cell cancers of lung; head, neck, and esophagus; breast cancer; renal cell carcinoma; lymphomas and multiple myeloma.
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 rise:
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
• Ionized calcium
• Renal function, phosphate, magnesium and potassium — monitor during treatment
Management
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.
• Saline hydration and loop diuretics.
• Discontinue medications that can increase serum calcium (lithium, Vitamin D, supplements containing calcitriol, thiazides, calcium antacids); remove calcium from 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 U.S. with full efficacy noted 2-4 days after administration; responses last 1-3 weeks.
• 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.
• Mithramycin was the standard agent prior to bisphosphonates; now used rarely due to a higher side effect profile.
• Renal dialysis can be used in cases of acute/chronic renal failure.
Adapted from Siddiqui F and Weissman DE. Palliative Care Network of Wisconsin. Fast facts and concepts #151. Hypercalcemia of malignancy. Internet. Accessed on June 21, 2016.