What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

The first-line treatment for hypercalcemia is aggressive rehydration with intravenous normal saline, followed by bisphosphonates such as zoledronic acid for moderate to severe cases. 1

Diagnosis and Assessment

Before initiating treatment, proper evaluation is essential:

• Measure serum calcium (corrected for albumin), intact parathyroid hormone (iPTH), PTH-related protein (PTHrP), vitamin D metabolites, albumin, magnesium, and phosphorus 1
• Calculate corrected calcium using: Corrected calcium = Total calcium + 0.8 × (4.0 - serum albumin) 1
• Determine if hypercalcemia is PTH-dependent or PTH-independent by measuring intact PTH 1
• Assess severity based on calcium levels:
  • Mild: < 12 mg/dL
  • Moderate: 12-14 mg/dL
  • Severe: > 14 mg/dL 2

Treatment Algorithm

Step 1: Rehydration

• Administer aggressive IV fluid resuscitation with normal saline (avoid calcium-containing solutions) 3, 1
• This corrects dehydration, promotes calciuresis, and is the cornerstone of initial management 1
• For mild hypercalcemia, oral hydration may be effective 3

Step 2: Pharmacological Intervention

Based on severity:

For Moderate to Severe Hypercalcemia:

• Bisphosphonates: First-line pharmacological treatment 1

  • Zoledronic acid 4 mg IV over 15 minutes (preferred agent with 50% response by day 4) 1
  • Pamidronate is an alternative option 1, 4

• For immediate short-term management of severe symptomatic hypercalcemia:

  • Calcitonin can be added for rapid effect (within hours) while waiting for bisphosphonates to work 5, 4
  • FDA-approved for early treatment of hypercalcemic emergencies 5
  • Starting dose: 4 International Units/kg body weight every 12 hours subcutaneously or intramuscularly 5
  • Can increase to 8 International Units/kg every 12 hours if response is unsatisfactory 5
  • Maximum dose: 8 International Units/kg every 6 hours 5

For Refractory Cases:

• Denosumab: For hypercalcemia refractory to bisphosphonates or in patients with severe renal impairment 1
  • Dose: 120 mg subcutaneously every 4 weeks, with additional doses on days 8 and 15 of the first month 1

For Specific Causes:

• Glucocorticoids: For vitamin D toxicity, granulomatous disorders, or some lymphomas 1, 6
• Loop diuretics (e.g., furosemide): Only after adequate hydration to enhance calcium excretion 3, 1

Step 3: Monitoring and Follow-up

• Regular monitoring of serum calcium, phosphate, magnesium, and renal function 1
• Verify renal function before each dose of bisphosphonates 1
• Monitor for hypocalcemia, especially in patients receiving denosumab 1

Special Considerations

Malignancy-Associated Hypercalcemia

• Occurs in 10-25% of patients with lung cancer, most commonly in squamous cell carcinoma 3
• Median survival after discovery is approximately 1 month 3
• Aggressive treatment is warranted due to poor prognosis 3

Renal Impairment

• Use denosumab instead of bisphosphonates in patients with severe renal insufficiency 1
• Consider dialysis for severe cases with renal failure 6

Common Pitfalls to Avoid

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

Underlying Cause Management

• Primary hyperparathyroidism: Consider parathyroidectomy based on age, calcium levels, and organ involvement 2
• Malignancy: Treat the underlying cancer when possible 4
• Vitamin D intoxication or granulomatous disorders: Glucocorticoids may be effective 4

By following this evidence-based approach, hypercalcemia can be effectively managed to reduce morbidity and mortality while addressing the underlying cause.