What are the treatment options for hypercalcemia?

Treatment Options for Hypercalcemia

The treatment of hypercalcemia should begin with aggressive IV fluid resuscitation with normal saline followed by bisphosphonates (zoledronic acid 4 mg IV over at least 15 minutes), with additional therapies based on severity, cause, and response to initial treatment. 1

Classification and Assessment

Hypercalcemia is classified by severity based on corrected serum calcium levels:

• Mild: < 12 mg/dL
• Moderate: 12-13.5 mg/dL
• Severe: > 13.5 mg/dL 1

Calculate corrected calcium using: Corrected calcium = Total calcium + 0.8 × (4.0 - serum albumin) 1

Treatment Algorithm

Step 1: Aggressive Hydration

• Administer IV normal saline to correct hypovolemia and promote calciuresis
• Target: Restore urine output to approximately 2 L/day 1, 2
• Caution: Avoid overhydration in patients with cardiac failure 2

Step 2: Pharmacological Intervention

Based on severity and cause:

For Malignancy-Related Hypercalcemia:

1. Bisphosphonates (First-line)

   • Zoledronic acid 4 mg IV over at least 15 minutes 1, 2
   • Alternative: Pamidronate 90 mg IV over 2 hours 1
   • Expected to normalize calcium in 50% of patients by day 4 1
   • Retreatment may be considered if calcium doesn't normalize (minimum 7 days between treatments) 2

2. Denosumab

   • For hypercalcemia refractory to bisphosphonates
   • For patients with severe renal impairment 1

3. Calcitonin

   • For immediate short-term management of severe symptomatic hypercalcemia
   • Provides rapid but modest effect 1, 3

For Other Causes:

• Glucocorticoids

  • Effective for vitamin D toxicity, granulomatous disorders, or some lymphomas 1, 3, 4

• Loop Diuretics (e.g., Furosemide)

  • Only after adequate hydration to enhance calcium excretion 1
  • Important: Do not use diuretics before correcting hypovolemia 1, 2

Step 3: Specific Treatments for Underlying Causes

• Primary hyperparathyroidism: Consider parathyroidectomy 5
• Vitamin D or calcium supplementation in CKD: Reduce or discontinue supplements 1
• Malignancy: Address underlying cancer with appropriate oncologic therapy 6

Step 4: Monitoring and Follow-up

• Regular monitoring of serum calcium, phosphate, magnesium, and renal function
• Watch for hypocalcemia after treatment, especially with denosumab 1
• Assess need for retreatment with bisphosphonates if calcium doesn't normalize 1, 2

Special Considerations

Renal Impairment

• Assess serum creatinine prior to each zoledronic acid treatment 2
• For patients with CrCl 50-60 mL/min: Reduce zoledronic acid dose to 3.5 mg
• For patients with CrCl 40-49 mL/min: Reduce dose to 3.3 mg
• For patients with CrCl 30-39 mL/min: Reduce dose to 3 mg 2
• Consider denosumab or hemodialysis for severe renal impairment 1, 6

Supplementation

• Administer oral calcium supplement of 500 mg and vitamin D 400 IU daily during treatment 2
• Monitor for hypocalcemia, especially after denosumab treatment 1

Common Pitfalls to Avoid

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

Prognosis

• Malignancy-related hypercalcemia has a poor prognosis (median survival approximately 1 month in lung cancer) 1
• Prognosis for asymptomatic primary hyperparathyroidism is excellent with either medical or surgical management 5