What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

The first-line treatment for hypercalcemia is aggressive intravenous fluid resuscitation with normal saline, followed by bisphosphonate therapy (particularly zoledronic acid 4 mg IV over 15 minutes) for moderate to severe cases. 1

Initial Assessment and Classification

• Calculate corrected calcium using formula: Corrected calcium = Total calcium + 0.8 × (4.0 - serum albumin) 1
• Classify severity:
  • Mild: <12 mg/dL
  • Moderate: 12-14 mg/dL
  • Severe: ≥14 mg/dL or symptomatic

Treatment Algorithm

Step 1: Aggressive Hydration

• Begin with IV normal saline to correct hypovolemia and promote calciuresis 1
• Target urine output >2 L/day or >2 mL/kg/hour 1
• Avoid overhydration in patients with cardiac failure 1
• Critical pitfall: Never use diuretics before correcting hypovolemia 1

Step 2: Pharmacological Intervention

• For moderate to severe hypercalcemia:
  • Zoledronic acid 4 mg IV over 15 minutes (first choice) 1, 2
    • Superior efficacy and longer duration of action (30-40 days) compared to pamidronate (17 days) 1
    • Dose adjustment required for renal impairment (see table below) 2
  • Alternative: Pamidronate 90 mg IV over 2 hours 1, 3

Baseline Creatinine Clearance (mL/min)	Zoledronic Acid Recommended Dose (mg)
>60	4
50-60	3.5
40-49	3.3
30-39	3

Step 3: Additional Therapies Based on Specific Scenarios

• For refractory hypercalcemia or severe renal impairment:
  • Denosumab (effective response rate of 64%) 1
• For vitamin D toxicity, granulomatous disorders, or lymphomas:
  • Glucocorticoids 1
• For immediate short-term management of severe symptomatic hypercalcemia:
  • Calcitonin (rapid but short-lived effect) 1
• For enhanced calcium excretion after adequate hydration:
  • Loop diuretics (only after adequate hydration) 1

Special Considerations

Primary Hyperparathyroidism

• Observation with monitoring may be appropriate for patients >50 years with serum calcium <1 mg/dL above upper normal limit without skeletal or kidney disease 1
• Parathyroidectomy is the only curative intervention for primary hyperparathyroidism 4

Malignancy-Related Hypercalcemia

• More aggressive treatment required due to typically higher calcium levels and more severe symptoms 5
• Retreatment with zoledronic acid may be considered if calcium doesn't normalize
• Wait minimum of 7 days before retreatment 1, 2

Renal Impairment

• Reduce bisphosphonate dose in patients with renal impairment 1
• Consider denosumab instead of bisphosphonates in severe renal impairment 1
• Monitor renal function closely before and during treatment 2

Monitoring and Follow-up

• Regular monitoring of serum calcium, phosphate, magnesium, and renal function 1
• Watch for hypocalcemia after treatment, especially with denosumab 1
• Assess for adequate urine output (target >2 L/day) 1

Potential Complications to Monitor

• Hypocalcemia (occurs in up to 50% of treated patients) 1
• Electrolyte imbalances (hypokalemia, hypomagnesemia) 1
• Acute-phase reaction with bisphosphonates (fever, myalgia) within 36 hours of first dose 1
• Osteonecrosis of jaw (higher risk with zoledronic acid 3.7% vs. clodronate 0.5%) 1

Common Pitfalls to Avoid

• Using diuretics before correcting hypovolemia 1
• Inadequate hydration before bisphosphonate administration 1
• Administering bisphosphonates too rapidly 1
• Treating laboratory values without addressing the underlying cause 1
• Delaying treatment of severe hypercalcemia 1
• Failing to monitor for hypocalcemia after treatment 1

Remember that while treating the hypercalcemia is crucial, identifying and addressing the underlying cause is essential for long-term management and improved outcomes.