What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

The treatment of hypercalcemia requires aggressive IV fluid resuscitation with normal saline followed by bisphosphonates (such as zoledronic acid 4 mg IV over 15 minutes) as the first-line pharmacological intervention, especially for severe symptomatic hypercalcemia. 1

Severity Assessment and Initial Management

Hypercalcemia is classified based on severity:

• Mild: Total calcium <12 mg/dL
• Severe: Total calcium ≥14 mg/dL 1

Step 1: Rehydration

• Aggressive IV fluid resuscitation with normal saline is the initial treatment for all patients with symptomatic hypercalcemia
• This corrects hypercalcemia-associated hypovolemia and promotes calciuresis
• Patients should be adequately rehydrated prior to administration of other treatments 1, 2

Important caveat: Diuretic therapy should not be employed prior to correction of hypovolemia, as this is a common pitfall in management 1, 2

Step 2: Pharmacological Interventions

After adequate hydration, the following medications should be considered:

1. Bisphosphonates:

   • Zoledronic acid 4 mg IV over no less than 15 minutes is the preferred agent 1, 2
   • More effective than pamidronate (normalizes calcium in 50% of patients by day 4, compared to 33% with pamidronate) 1
   • For relapsed or refractory cases, zoledronic acid 8 mg dose may be considered 1
   • Dose adjustments needed for patients with renal impairment 2

2. Denosumab:

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

3. Calcitonin:

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

4. Glucocorticoids:

   • Effective for hypercalcemia due to vitamin D toxicity, granulomatous disorders, or some lymphomas 1, 4

5. Loop diuretics:

   • Should only be used after adequate hydration
   • Enhances calcium excretion 1, 3

Treatment Based on Underlying Cause

Primary Hyperparathyroidism

• Parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement
• In patients older than 50 years with serum calcium levels less than 1 mg/dL above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate 4

Malignancy-Associated Hypercalcemia

• Requires aggressive treatment with IV fluids and bisphosphonates
• Poor prognosis with median survival of about 1 month in lung cancer patients 1

Other Causes

• Granulomatous diseases (sarcoidosis): Glucocorticoids are effective 1, 4
• Vitamin D toxicity: Glucocorticoids 1, 4
• Medication-induced: Discontinue causative medications 4

Monitoring and Follow-up

Regular monitoring should include:

• Serum calcium, phosphate, magnesium
• Renal function and electrolytes
• Assessment for retreatment 1, 2

For retreatment with zoledronic acid:

• Allow minimum of 7 days between treatments for full response
• Reassess serum creatinine prior to retreatment
• Consider retreatment if serum calcium does not normalize 2

Common Pitfalls to Avoid

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

Hypercalcemia management requires prompt recognition and treatment, with particular attention to the underlying cause for long-term management and prevention of recurrence.