What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

Aggressive IV normal saline hydration followed by bisphosphonate therapy is the cornerstone of hypercalcemia management, with zoledronic acid 4 mg IV over 15 minutes being the first-line treatment for moderate to severe hypercalcemia. 1, 2

Initial Assessment and Treatment Algorithm

Step 1: Determine Severity and Begin Hydration

• Mild hypercalcemia (total calcium <12 mg/dL): May be asymptomatic, can often be managed with oral hydration and treating underlying cause 3
• Moderate hypercalcemia (total calcium 12.0-13.5 mg/dL): Requires IV hydration and likely bisphosphonate therapy
• Severe hypercalcemia (total calcium >13.5 mg/dL or ionized calcium ≥2.5 mmol/L): Requires immediate aggressive treatment

Step 2: Initiate Hydration

• Begin with IV normal saline to restore extracellular volume and promote calciuresis
• Target urine output of at least 100 mL/hour (3 mL/kg/hour in children <10 kg) 1
• Loop diuretics may be required to maintain urine output, but only after adequate volume repletion 4
• Avoid overhydration in patients with cardiac failure 5

Step 3: Administer Antiresorptive Therapy

• First-line: Zoledronic acid 4 mg IV over 15 minutes 1, 2
  • For patients with renal impairment, adjust dose according to creatinine clearance 2
  • CrCl 50-60 mL/min: 3.5 mg
  • CrCl 40-49 mL/min: 3.3 mg
  • CrCl 30-39 mL/min: 3.0 mg
• Alternative: Pamidronate 90 mg IV over 2 hours 1, 5
• For refractory cases: Consider denosumab (subcutaneous), particularly in patients with severe renal impairment 1

Treatment Based on Underlying Cause

Primary Hyperparathyroidism (90% of cases with PTH-mediated hypercalcemia)

• Parathyroidectomy for symptomatic cases or those meeting surgical criteria 3
• For patients who cannot undergo surgery, consider calcimimetic agents 6

Malignancy-Associated Hypercalcemia

• Treat underlying malignancy when possible 7
• More aggressive hydration and bisphosphonate therapy typically required 3
• Zoledronic acid is superior to pamidronate for malignancy-associated hypercalcemia 6

Other Causes

• Vitamin D toxicity or granulomatous disorders: Consider glucocorticoids 3, 7
• Medication-induced: Discontinue offending agents (thiazide diuretics, calcium supplements, vitamin D or A supplements) 3

Management of Associated Electrolyte Abnormalities

• Hyperphosphatemia: Mild cases (<1.62 mmol/L) may not require treatment or can be managed with aluminum hydroxide 50-100 mg/kg/day divided in 4 doses 4
• Hypocalcemia: Asymptomatic cases don't require treatment; for symptomatic cases (tetany, seizures), administer calcium gluconate 50-100 mg/kg 4
• Hyperkalemia: Mild cases (<6 mmol/L) can be managed with hydration, loop diuretics, and sodium polystyrene; severe cases require insulin, glucose, calcium carbonate, and sodium bicarbonate 4

Monitoring and Follow-up

• Monitor serum calcium, phosphate, magnesium, renal function, and electrolytes regularly 1
• Assess for treatment response and adjust therapy accordingly
• For bisphosphonate therapy, retreatment may be considered if calcium doesn't normalize, with minimum 7 days between treatments 2
• Monitor for hypocalcemia after treatment, especially with denosumab 1

Special Considerations

• Renal failure: Consider denosumab or dialysis with calcium-free or low-calcium solution 7, 8
• Cardiac disease: Optimize heart failure management before invasive procedures 1
• Severe symptomatic hypercalcemia: Consider adding calcitonin for rapid but short-term effect 7

Common Pitfalls to Avoid

• Failing to adequately hydrate before administering bisphosphonates
• Overlooking renal function when dosing bisphosphonates
• Not monitoring for hypocalcemia after treatment
• Delaying treatment of severe hypercalcemia while awaiting complete diagnostic workup
• Treating the laboratory value without addressing the underlying cause 1