What is the initial workup and management for a patient with hypercalcemia?

Initial Workup and Management of Hypercalcemia

The initial workup for hypercalcemia should include intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, complete blood count, urinalysis, thyroid-stimulating hormone (TSH), liver function tests, and serum concentrations of calcium, albumin, magnesium, and phosphorus, followed by aggressive IV fluid resuscitation with normal saline as first-line treatment. 1

Diagnosis and Assessment

Essential Laboratory Tests

• Intact parathyroid hormone (iPTH)
• Parathyroid hormone-related protein (PTHrP)
• 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D
• Complete blood count
• Urinalysis
• Thyroid-stimulating hormone (TSH)
• Liver function tests
• Serum calcium (total and ionized)
• Albumin (for calcium correction)
• Magnesium and phosphorus levels
• Renal function tests

Severity Classification

• Mild: Total calcium <12 mg/dL (<3 mmol/L)
• Moderate: Total calcium 12.0-13.5 mg/dL (3.0-3.4 mmol/L)
• Severe: Total calcium ≥14 mg/dL (≥3.5 mmol/L) or ≥12 mg/dL with symptoms 1, 2

Treatment Algorithm

Step 1: Aggressive IV Fluid Resuscitation

• Normal saline (0.9% NaCl) is the first-line treatment for hypercalcemia
• Initial rate: 200-300 mL/hour, adjusted based on cardiovascular status
• Goal: Correct hypovolemia and enhance renal calcium excretion 1

Step 2: Pharmacological Intervention Based on Severity

For Severe Hypercalcemia (>14 mg/dL or symptomatic)

1. Bisphosphonates:

   • Zoledronic acid 4 mg IV over 15 minutes is the preferred agent
   • Response rate: 50% by day 4
   • Contraindicated in severe renal impairment (creatinine >4.5 mg/dL) 1, 3

2. Calcitonin for immediate short-term management:

   • Dosing: 4 USP Units/kg body weight every 12 hours subcutaneously or intramuscularly
   • May increase to 8 USP Units/kg every 12 hours if response is unsatisfactory
   • Maximum dose: 8 USP Units/kg every 6 hours
   • Provides rapid but short-lived calcium reduction 1, 4

3. Denosumab for patients with renal impairment or refractory cases:

   • 120 mg subcutaneously every 4 weeks
   • Additional doses on days 8 and 15 of the first month 1

4. Loop diuretics (e.g., furosemide):

   • Use only after adequate hydration
   • Enhances calcium excretion
   • Caution: Do not use before correcting hypovolemia 1, 5

For Moderate Hypercalcemia (12.0-13.5 mg/dL)

• IV fluids with normal saline
• Consider bisphosphonates if symptomatic or if calcium is trending upward
• Monitor renal function and electrolytes

For Mild Hypercalcemia (<12 mg/dL)

• Usually doesn't require acute intervention
• Treat underlying cause
• Ensure adequate hydration
• Avoid medications that can worsen hypercalcemia (e.g., thiazide diuretics) 2

Step 3: Specific Treatments Based on Etiology

• Primary hyperparathyroidism:

  • Parathyroidectomy for symptomatic patients or those meeting surgical criteria
  • For non-surgical candidates: consider calcimimetics 2, 6

• Malignancy-associated hypercalcemia:

  • Bisphosphonates as first-line therapy
  • Denosumab for refractory cases 1, 6

• Vitamin D toxicity or granulomatous disorders:

  • Glucocorticoids are effective
  • Limit calcium and vitamin D intake 1, 2

Monitoring and Follow-up

• Regular calcium monitoring every 1-2 weeks initially, then monthly after stabilization
• Monitor renal function before each bisphosphonate treatment
• Watch for hypocalcemia, especially with denosumab treatment
• Monitor serum phosphate, magnesium, and electrolytes 1

Common Pitfalls to Avoid

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

Special Considerations

• Renal impairment: Zoledronic acid should be used with caution; consider denosumab or dose adjustment 3
• Pregnancy: Calcitonin may be safer than bisphosphonates 4
• Cardiac or renal failure: Consider calcium-free dialysis if fluid administration is contraindicated 5

Remember that severe hypercalcemia (>3.5 mmol/L) is a life-threatening emergency requiring immediate intervention to reduce mortality and improve quality of life 1, 5.