What are the steps for managing hypercalcemia?

Hypercalcemia Workup and Management

Hypercalcemia should be treated with aggressive IV fluid resuscitation with normal saline, followed by bisphosphonates, with zoledronic acid 4 mg IV over 15 minutes being the preferred first-line treatment for moderate to severe hypercalcemia. 1

Diagnosis and Initial Evaluation

Laboratory Assessment

• Calculate corrected calcium: 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
• Additional tests:
  • Complete blood count, urinalysis, TSH
  • Liver function tests
  • Serum phosphorus and magnesium
  • Vitamin D metabolites (25-OH and 1,25-OH2)
  • PTH-related protein (PTHrP) if malignancy suspected 1

Treatment Algorithm

1. Immediate Management for Moderate to Severe Hypercalcemia

• Aggressive IV fluid resuscitation with normal saline to restore volume and enhance calcium excretion 1
• Loop diuretics (furosemide) only after adequate hydration to enhance calcium excretion 1
• Bisphosphonates:
  • Zoledronic acid 4 mg IV over 15 minutes (preferred for hypercalcemia) 2, 3
  • Pamidronate 60-90 mg IV over 4 hours as alternative 4
  • Dose adjustment required for renal impairment 3

2. Alternative or Adjunctive Therapies

• Denosumab for hypercalcemia refractory to bisphosphonates or in patients with severe renal impairment 1
• Glucocorticoids for vitamin D toxicity, granulomatous disorders, or some lymphomas 1
• Calcitonin for immediate short-term management of severe symptomatic hypercalcemia 5
• Plasmapheresis for symptomatic hyperviscosity 2
• Dialysis for severe hypercalcemia complicated by renal failure 5

3. Management of Underlying Causes

• Malignancy-related hypercalcemia:
  • Treat the underlying cancer
  • Continue bone-targeting treatment (bisphosphonates or denosumab) for up to 2 years 2
• Medication-induced hypercalcemia:
  • Discontinue offending agents (thiazide diuretics, calcium supplements, vitamin D/A supplements) 1

Special Considerations

Renal Function

• Monitor renal function before and during bisphosphonate therapy 3
• Zoledronic acid should be administered over 15 minutes (not 5 minutes) to reduce renal toxicity 3
• Denosumab is preferred in patients with renal disease 2

Monitoring Response

• Regular monitoring of serum calcium, phosphate, magnesium, renal function, and electrolytes 1
• Watch for hypocalcemia after treatment, especially with denosumab 1

Common Pitfalls to Avoid

• Failing to correct calcium for albumin may lead to inaccurate diagnosis 1
• Inadequate hydration before bisphosphonate administration can worsen renal function 1
• Treating laboratory values without addressing the underlying cause leads to poor outcomes 1
• Administering loop diuretics before adequate volume restoration can worsen dehydration 1
• Not adjusting bisphosphonate dosing for renal function can lead to toxicity 3

Duration of Therapy

• For malignancy-related bone disease, continue bone-targeting treatment for up to 2 years 2
• Continuing beyond 2 years should be based on clinical judgment 2
• Frequency of dosing (monthly vs every 3 months) depends on individual patient criteria and response to therapy 2

By following this algorithmic approach to hypercalcemia management, focusing first on aggressive hydration and then appropriate pharmacologic intervention with bisphosphonates (preferably zoledronic acid), most cases can be effectively managed while addressing the underlying cause.