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

Initial Workup and Treatment for Hypercalcemia

The initial workup for hypercalcemia should include measurement of corrected calcium, intact parathyroid hormone (iPTH), complete blood count, urinalysis, thyroid-stimulating hormone, liver function tests, parathyroid hormone-related protein, vitamin D metabolites, albumin, magnesium, and phosphorus, followed by aggressive intravenous fluid rehydration as first-line treatment. 1

Diagnostic Approach

Step 1: Laboratory Evaluation

• Calculate corrected calcium using the formula: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 1
• Measure intact PTH level to differentiate causes:
  • Elevated/normal PTH: PTH-dependent causes (primary hyperparathyroidism)
  • Suppressed PTH (<20 pg/mL): PTH-independent causes (malignancy, granulomatous disease) 1
• Obtain vitamin D levels (25-OH and 1,25-OH2) to identify granulomatous disease or lymphoma 1
• Complete blood count may reveal anemia in malignancy-associated hypercalcemia 2

Step 2: Severity Assessment

• Mild hypercalcemia: Corrected calcium <12 mg/dL (<3 mmol/L)
• Moderate hypercalcemia: Corrected calcium 12-13.5 mg/dL
• Severe hypercalcemia: Corrected calcium >13.5 mg/dL or >14 mg/dL 1, 3, 4

Treatment Algorithm

1. Immediate Management for Symptomatic or Severe Hypercalcemia

• Vigorous saline hydration (cornerstone of initial treatment):
  • Target urine output of approximately 2 L/day
  • Avoid overhydration in patients with cardiac failure 1, 3
• Loop diuretics (only after adequate volume repletion):
  • Furosemide to enhance calcium excretion
  • Do not use diuretics prior to correction of hypovolemia 1, 3

2. Pharmacologic Intervention Based on Severity

• For moderate hypercalcemia (12-13.5 mg/dL):

  • Pamidronate 60-90 mg IV as a single dose over 2-24 hours 3
  • Longer infusions (>2 hours) recommended for patients with renal insufficiency 3

• For severe hypercalcemia (>13.5 mg/dL):

  • Pamidronate 90 mg IV as a single dose over 2-24 hours 3
  • Zoledronic acid 4 mg IV over 15 minutes is preferred for malignancy-associated hypercalcemia 1
  • Consider calcitonin combined with bisphosphonates for severe hypercalcemia to hasten normalization 5

3. Treatment Based on Underlying Cause

• PTH-dependent hypercalcemia (primary hyperparathyroidism):

  • Surgical consultation for parathyroidectomy if indicated
  • Medical management for those not surgical candidates 1, 4

• Malignancy-associated hypercalcemia:

  • Bisphosphonates (zoledronic acid or pamidronate) 1, 2
  • Denosumab for cases refractory to bisphosphonates or with severe renal impairment 1

• Medication-induced hypercalcemia:

  • Discontinue offending agents (thiazide diuretics, calcium supplements, vitamin D/A supplements) 1

• Vitamin D toxicity or granulomatous disorders:

  • Glucocorticoids 1, 2

Monitoring and Follow-up

• Regular monitoring of serum calcium, phosphate, magnesium, renal function, and electrolytes 1
• Monitor for hypocalcemia after treatment, especially with denosumab 1
• Retreatment with bisphosphonates may be considered if calcium levels don't normalize
• Allow minimum of 7 days between bisphosphonate treatments 1, 3

Common Pitfalls to Avoid

• Failing to correct calcium for albumin, leading to inaccurate diagnosis 1
• Administering loop diuretics before adequate hydration 1, 3
• Overlooking renal function when dosing bisphosphonates 1
• Treating the laboratory value without addressing the underlying cause 1
• Delaying treatment of severe hypercalcemia while awaiting complete diagnostic workup 1
• Failing to monitor for hypocalcemia after treatment 1

Remember that while immediate management focuses on lowering calcium levels, identifying and treating the underlying cause is essential for long-term management and prevention of recurrence.