What is the initial workup for a patient with severe hypercalcemia?

Initial Workup for Severe Hypercalcemia (Calcium > 14 mg/dL)

For severe hypercalcemia with calcium greater than 14 mg/dL, the initial workup should include aggressive IV fluid resuscitation with normal saline (200-300 mL/hour initially), essential laboratory tests including intact parathyroid hormone (iPTH), and preparation for bisphosphonate therapy with zoledronic acid 4 mg IV. 1

Immediate Management Steps

1. Aggressive IV fluid resuscitation:

   • Start normal saline at 200-300 mL/hour
   • Target urine output > 3 L/day
   • Monitor for fluid overload in patients with cardiac or renal disease

2. Essential laboratory tests (obtain before or concurrent with treatment):

   • Intact parathyroid hormone (iPTH) - most important initial test
   • Albumin (for corrected calcium calculation)
   • Parathyroid hormone-related protein (PTHrP)
   • 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D
   • Complete blood count
   • Renal function tests (BUN, creatinine)
   • Serum phosphorus and magnesium
   • Urinalysis
   • Thyroid-stimulating hormone (TSH)
   • Liver function tests

3. Calculate albumin-corrected calcium:

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

Pharmacologic Intervention

After initiating fluid resuscitation, prepare for:

1. Bisphosphonate therapy:

   • Zoledronic acid 4 mg IV over no less than 15 minutes is the preferred first-line treatment 1, 2
   • Adjust dose for renal impairment
   • Do not administer through lines containing calcium or divalent cation solutions 2

2. Alternative or adjunctive treatments:

   • Calcitonin for immediate short-term management of severe symptomatic hypercalcemia 1, 3
   • Loop diuretics (only after adequate hydration) to enhance calcium excretion 1
   • Denosumab for patients with severe renal impairment or hypercalcemia refractory to bisphosphonates 1
   • Glucocorticoids for vitamin D toxicity, granulomatous disorders, or some lymphomas 1

Diagnostic Algorithm Based on PTH Results

• Elevated/normal PTH: Suggests primary hyperparathyroidism 4
• Suppressed PTH (<20 pg/mL): Indicates non-PTH dependent causes such as:
  • Malignancy (check PTHrP)
  • Vitamin D toxicity
  • Granulomatous disorders
  • Medication-induced (review thiazides, supplements, etc.) 4, 5

Monitoring During Initial Management

• Frequent serum calcium measurements (every 6-12 hours initially)
• Continuous cardiac monitoring for arrhythmias
• Fluid status and urine output
• Electrolytes, especially potassium and magnesium
• Renal function
• Mental status changes

Common Pitfalls to Avoid

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

Special Considerations

• For patients with cardiac or renal disease, more cautious fluid administration may be necessary 3
• If rapid correction is needed and there are contraindications to increased fluid administration, calcium-free dialysis may be required 3
• Hypercalcemic crisis (calcium >14 mg/dL with severe symptoms) is a medical emergency requiring immediate intervention 3

Remember that while addressing the acute hypercalcemia is critical, identifying and treating the underlying cause is essential for long-term management.