How do you manage a case of hypercalcemia?

Management of Hypercalcemia

The management of hypercalcemia should begin with aggressive IV hydration and bisphosphonate therapy, with zoledronic acid being the preferred agent for moderate to severe cases. 1, 2

Initial Assessment and Classification

• Measure intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, calcium, albumin, magnesium, and phosphorus levels to determine the underlying cause 1
• Evaluate for symptoms such as polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, myalgia, dehydration, and mental status changes 1, 3
• Calculate corrected calcium using the formula: cCa in mg/dL = Ca in mg/dL + 0.8 (4.0 g/dL - patient albumin [g/dL]) 2

Treatment Algorithm

1. Hydration

• Administer intravenous normal saline to correct hypovolemia and promote calciuresis 1, 4
• Maintain urine output of at least 100 mL/hour (3 mL/kg/hour in children <10 kg) 1, 5
• Loop diuretics may be required in patients with renal or cardiac insufficiency to prevent fluid overload, but evidence shows they may not provide significant additional calcium-lowering effect compared to hydration alone 1, 4

2. Bisphosphonate Therapy

• For moderate to severe hypercalcemia (albumin-corrected calcium ≥12 mg/dL or 3.0 mmol/L), administer zoledronic acid 4 mg IV over no less than 15 minutes 2, 1
• Zoledronic acid is preferred over other bisphosphonates for hypercalcemia of malignancy 1, 6
• Assess renal function before administering zoledronic acid; dose adjustments are necessary for patients with reduced renal function 2
• Retreatment with zoledronic acid may be considered if serum calcium does not normalize, with a minimum of 7 days between treatments 2

3. Additional Therapies

• For symptomatic hypocalcemia (tetany, seizures), administer calcium gluconate 50-100 mg/kg as a single dose, cautiously repeated if necessary 5
• In cases of hypercalcemia due to vitamin D intoxication, granulomatous disorders, or certain lymphomas, glucocorticoids may be effective 3, 7
• Calcitonin can be used for immediate short-term management of severe symptomatic hypercalcemia, with effects beginning within 1-3 minutes but lasting only 30-60 minutes 1, 8

Special Considerations

Hypercalcemia of Malignancy

• Hydration and rasburicase should be administered to patients with clinical tumor lysis syndrome (TLS) 5
• For patients with multiple myeloma and bone metastases, the recommended zoledronic acid dose is 4 mg IV every 3-4 weeks 2
• Administer oral calcium supplements (500 mg) and vitamin D (400 IU) daily for patients receiving ongoing bisphosphonate therapy 2

Renal Considerations

• For patients with creatinine clearance 50-60 mL/min, reduce zoledronic acid dose to 3.5 mg 2
• For patients with creatinine clearance 40-49 mL/min, reduce zoledronic acid dose to 3.3 mg 2
• For patients with creatinine clearance 30-39 mL/min, reduce zoledronic acid dose to 3.0 mg 2
• Consider hemodialysis for severe hypercalcemia complicated by renal insufficiency 1, 8
• Hemodialysis effectively removes uric acid (clearance 70-100 mL/min) and phosphate 5

Monitoring and Follow-up

• Monitor serum calcium, renal function, and electrolytes regularly to assess treatment effectiveness 1
• For patients receiving zoledronic acid, measure serum creatinine before each dose 2
• Withhold treatment for renal deterioration (increase of 0.5 mg/dL for normal baseline creatinine or 1.0 mg/dL for abnormal baseline) 2

Common Pitfalls and Caveats

• Avoid vitamin D supplements in patients with hypercalcemia 1
• Do not delay bisphosphonate therapy in moderate to severe hypercalcemia 1
• Avoid NSAIDs and intravenous contrast media in patients with renal impairment 1
• Total serum calcium levels may not reflect the severity of hypercalcemia due to concomitant hypoalbuminemia; use corrected calcium values or ionized calcium when available 2
• Administering zoledronic acid over less than 15 minutes increases the risk of renal toxicity 2