Treatment of Hypercalcemia
The treatment of hypercalcemia should begin with IV hydration using normal saline followed by bisphosphonates, with zoledronic acid being the preferred agent for moderate to severe cases. 1
Assessment and Classification
Hypercalcemia severity determines the treatment approach:
- Mild: Corrected serum calcium <12 mg/dL
- Moderate: Corrected serum calcium 12.0-13.5 mg/dL
- Severe: Corrected serum calcium >13.5 mg/dL or >14.0 mg/dL
Symptoms vary by severity:
- Mild: Often asymptomatic or with fatigue, constipation
- Moderate: Polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, myalgia
- Severe: Mental status changes, bradycardia, hypotension, dehydration, acute renal failure 1
Treatment Algorithm
1. Hydration
- First-line for all cases: Rehydration with IV crystalloid fluids (0.9% sodium chloride) 1
- For mild hypercalcemia: Oral hydration may be effective 1
- Goal: Correct intravascular volume depletion and promote calciuresis
2. Bisphosphonates
- First-line pharmacologic therapy for moderate to severe hypercalcemia 1
- Options:
- For refractory cases: Consider increasing zoledronic acid to 8 mg 1
- Calcium levels normalize in 50% of patients with zoledronic acid by day 4 (vs. 33% with pamidronate) 1
3. Loop Diuretics
- Use after correction of intravascular volume (not as initial therapy) 1
- Furosemide: Promotes calcium excretion
- Caution: Only use after adequate hydration to avoid worsening dehydration
4. Calcitonin
- For rapid but short-term reduction in severe symptomatic hypercalcemia 2
- Starting dose: 4 USP Units/kg body weight every 12 hours SC or IM
- Can increase to 8 USP Units/kg every 12 hours if response unsatisfactory
- Maximum dose: 8 USP Units/kg every 6 hours
- Limitation: Tachyphylaxis develops within 48-72 hours 3
5. Additional Options for Refractory Cases
- Denosumab: For hypercalcemia refractory to bisphosphonates 1
- Effective in 64% of patients with refractory hypercalcemia within 10 days
- FDA-approved for malignancy-related hypercalcemia refractory to bisphosphonates
- Glucocorticoids: For hypercalcemia due to vitamin D excess, granulomatous disorders, or some lymphomas 1, 4
- Dialysis: For patients with severe renal failure or when other measures fail 4
Special Considerations
Malignancy-Related Hypercalcemia
- Accounts for approximately 45% of all hypercalcemia cases 4
- Often more severe and rapid in onset than other causes
- Treat the underlying malignancy when possible 3
- Bisphosphonates are particularly effective for this etiology 1
Monitoring
- Monitor serum calcium, creatinine, and albumin during treatment 1
- For patients on bisphosphonates:
- Monitor for renal dysfunction
- Discontinue if unexplained albuminuria >500 mg/24 hours or serum creatinine increases by >0.5 mg/dL 1
- After denosumab: Monitor for hypocalcemia and provide calcium/vitamin D supplements if needed 1
Common Pitfalls
- Inadequate hydration: Many clinicians underestimate the degree of dehydration
- Premature use of loop diuretics: Should only be used after volume repletion
- Delayed initiation of bisphosphonates: Should be started early due to delayed onset of action
- Overreliance on calcitonin alone: Effective short-term but develops tachyphylaxis
- Failure to identify and treat the underlying cause: Essential for long-term management
By following this systematic approach based on severity and underlying cause, hypercalcemia can be effectively managed to reduce morbidity and mortality associated with this potentially life-threatening condition.