What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

The treatment of hypercalcemia requires aggressive IV fluid resuscitation with normal saline followed by bisphosphonates (e.g., zoledronic acid 4 mg IV over 15 minutes) for severe symptomatic cases. 1

Assessment and Classification

• Hypercalcemia is classified as:

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

• Initial workup should include:

  • Serum calcium (corrected for albumin)
  • Intact parathyroid hormone (iPTH)
  • Parathyroid hormone-related protein (PTHrP)
  • 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D
  • Complete blood count, urinalysis, TSH, liver function tests 1

• Calculate corrected calcium using: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 1

Step-wise Treatment Approach

1. Aggressive IV Fluid Resuscitation

• Normal saline (0.9% NaCl) is the cornerstone of initial management
• Corrects hypercalcemia-associated hypovolemia
• Promotes calciuresis
• Patients should be adequately rehydrated prior to other interventions 1, 2

2. Bisphosphonates

• First-line pharmacological intervention, especially for cancer-related hypercalcemia
• 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% vs 33% of patients by day 4) 1
• Assess renal function before administration 2

3. Additional Pharmacological Options

• Denosumab: For hypercalcemia refractory to bisphosphonates or in patients with severe renal impairment 1
• Calcitonin: For immediate short-term management of severe symptomatic hypercalcemia 1
• Glucocorticoids: For vitamin D toxicity, granulomatous disorders, or some lymphomas 1
• Loop diuretics (e.g., furosemide): To enhance calcium excretion, but only after adequate hydration 1

4. Dose Adjustments for Renal Impairment

• For patients with CrCl 50-60 mL/min: Zoledronic acid 3.5 mg
• For patients with CrCl 40-49 mL/min: Zoledronic acid 3.3 mg
• For patients with CrCl 30-39 mL/min: Zoledronic acid 3.0 mg 2

Special Considerations

Retreatment

• May consider retreatment with zoledronic acid 4 mg if calcium does not normalize
• Allow minimum of 7 days between treatments for full response 2
• For refractory cases, zoledronic acid 8 mg may be considered 1

Supportive Care

• Administer oral calcium supplement of 500 mg and vitamin D 400 IU daily during treatment 2
• Regular monitoring of serum calcium, phosphate, magnesium, renal function, and electrolytes 1
• Mobilize patients when possible to promote normal bone remodeling 3

Common Pitfalls to Avoid

• Using diuretics before correcting hypovolemia (dangerous error) 1
• Failing to correct calcium for albumin (leads to misdiagnosis) 1
• Inadequate hydration before bisphosphonate administration (reduces efficacy) 1, 2
• Administering bisphosphonates too rapidly (increases risk of adverse effects) 1
• Treating laboratory values without addressing the underlying cause 1
• Failing to monitor for hypocalcemia after treatment, especially with denosumab 1
• Overhydration in patients with cardiac failure 2

Prognosis

• Hypercalcemia-induced delirium is often reversible (in 40% of episodes) 1
• Malignancy-associated hypercalcemia has a poor prognosis with median survival of about 1 month in lung cancer patients 1
• Both hypercalcemia and delirium are independent negative prognostic factors for survival in cancer patients 1

The treatment approach should be tailored based on the severity of hypercalcemia, underlying cause, and patient's renal function, with prompt intervention for severe cases to reduce morbidity and mortality.