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 bisphosphonates such as zoledronic acid 4 mg IV over 15 minutes for moderate to severe cases. 1

Diagnosis and Assessment

Before initiating treatment, it's important to:

• Calculate corrected calcium using the formula: Corrected calcium = Total calcium + 0.8 × (4.0 - serum albumin) 1, 2
• Determine severity:
  • Mild: < 12 mg/dL (usually asymptomatic)
  • Moderate: 12-14 mg/dL (polyuria, polydipsia, nausea, vomiting)
  • Severe: > 14 mg/dL (mental status changes, bradycardia, hypotension) 1, 3
• Identify underlying cause through laboratory tests:
  • Intact parathyroid hormone (iPTH)
  • Phosphorus, magnesium, renal function tests
  • 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels 1

Treatment Algorithm

Step 1: Aggressive IV Fluid Resuscitation

• Administer normal saline to correct hypovolemia and promote calciuresis
• Target urine output > 2 L/day
• Avoid overhydration in patients with cardiac failure 1, 2, 4

Step 2: Pharmacological Interventions

For moderate to severe hypercalcemia:

1. Bisphosphonates:

   • Zoledronic acid 4 mg IV over 15 minutes (first choice due to superior efficacy and longer duration of action) 1, 2
   • Alternative: Pamidronate for patients with renal impairment 4
   • Dose adjustment for renal impairment:

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

2. Denosumab: For hypercalcemia refractory to bisphosphonates or in patients with severe renal impairment 1

3. Calcitonin: For immediate short-term management of severe symptomatic hypercalcemia 1, 5

4. Glucocorticoids: For hypercalcemia due to vitamin D toxicity, granulomatous disorders, or lymphomas 1, 5

5. Loop diuretics: Only after adequate hydration to enhance calcium excretion 1

Step 3: Monitoring and Follow-up

• Monitor serum calcium, phosphate, magnesium, and renal function regularly
• Watch for hypocalcemia after treatment, especially with denosumab
• Retreatment with zoledronic acid may be considered if serum calcium does not normalize
• Allow minimum of 7 days before retreatment to allow for full response 1, 2

Special Considerations

• Primary hyperparathyroidism: For patients older than 50 years with serum calcium < 1 mg/dL above upper normal limit and no evidence of skeletal or kidney disease, observation with monitoring may be appropriate 1, 3

• Malignancy-related hypercalcemia: Poor prognosis with median survival of approximately 1 month in lung cancer 1

• Chronic kidney disease: Patients have altered vitamin D metabolism, making them susceptible to vitamin D-related hypercalcemia 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

• Avoid medications that can worsen hypercalcemia:

  • NSAIDs (especially in renal impairment)
  • Thiazide diuretics
  • Excessive vitamin D or calcium supplements 1