What is the management for hypercalcemia?

Management of Hypercalcemia

Immediately initiate IV normal saline hydration targeting urine output ≥100 mL/hour (or 3 mL/kg/hour in children <10 kg), followed by IV bisphosphonates—with zoledronic acid 4 mg infused over at least 15 minutes preferred over pamidronate—for moderate to severe hypercalcemia. 1, 2, 3

Initial Assessment and Severity Classification

Before initiating treatment, measure serum calcium, albumin, intact PTH, PTHrP, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, phosphorus, magnesium, creatinine, and BUN to determine the underlying cause 1, 3. Calculate corrected calcium using: Corrected calcium (mg/dL) = Total calcium (mg/dL) - 0.8 × [Albumin (g/dL) - 4], or preferably measure ionized calcium directly to avoid pseudohypercalcemia from hemolysis or improper sampling 1, 3.

Classify severity as:

• Mild: 10-11 mg/dL (2.5-2.75 mmol/L) - typically asymptomatic 1, 4
• Moderate: 11-12 mg/dL (2.75-3.0 mmol/L) - polyuria, polydipsia, nausea, confusion, vomiting 1, 3
• Severe: >14 mg/dL (>3.5 mmol/L) - mental status changes, dehydration, acute renal failure, bradycardia, hypotension 1, 4

Treatment Algorithm by Severity

Mild Hypercalcemia (<12 mg/dL)

For asymptomatic mild hypercalcemia, treatment depends on the underlying cause 4. If due to primary hyperparathyroidism in patients >50 years with calcium <1 mg/dL above upper normal limit and no skeletal or kidney disease, observation with monitoring is appropriate 4. Otherwise, oral hydration, salt restriction, and ambulation may suffice 5.

Moderate to Severe Hypercalcemia (≥12 mg/dL)

Step 1: Aggressive IV Hydration

• Administer IV normal saline immediately to correct hypovolemia and promote calciuresis 1, 2, 3
• Target urine output ≥100 mL/hour (3 mL/kg/hour in children <10 kg) 1, 2
• Monitor fluid status carefully to avoid hypervolemia, especially in patients with renal or cardiac insufficiency 2, 3
• Add loop diuretics (furosemide) only after volume repletion in patients at risk of fluid overload—not routinely 1, 3, 5

Step 2: IV Bisphosphonates (First-Line Definitive Treatment)

• Zoledronic acid 4 mg IV infused over ≥15 minutes is superior to pamidronate and is the preferred agent 1, 2, 3, 6
• Pamidronate 60-90 mg IV over 4 hours is an alternative if zoledronic acid is unavailable 2, 7
• Onset of action: 2-4 days, with peak effect at 7 days 7, 5
• Adjust dose for creatinine clearance <60 mL/min; withhold if renal deterioration occurs 2
• Monitor serum creatinine before each dose 2

Step 3: Calcitonin for Immediate Short-Term Control

• Add calcitonin-salmon 100 IU subcutaneously or intramuscularly every 12 hours for severe symptomatic hypercalcemia while waiting for bisphosphonates to take effect 1, 2, 8
• Onset of action: 1-3 hours, but tachyphylaxis develops within 48 hours, limiting its use 5, 8
• Provides rapid but modest calcium reduction (1-2 mg/dL) 8

Etiology-Specific Treatment

Primary Hyperparathyroidism

• Parathyroidectomy is indicated for symptomatic disease, osteoporosis, impaired kidney function, kidney stones, hypercalciuria, age <50 years, or calcium >0.25 mmol/L above upper normal limit 3
• For patients not meeting surgical criteria, observation with monitoring is appropriate if asymptomatic 4

Malignancy-Associated Hypercalcemia

• Treat the underlying malignancy when possible—this is essential for long-term control 2, 3, 5
• Hydration plus bisphosphonates (zoledronic acid preferred) form the cornerstone of treatment 2, 3
• For refractory cases, consider denosumab 120 mg subcutaneously, especially in patients with renal impairment where bisphosphonates are contraindicated 1, 3
• Prognosis is poor, with median survival approximately 1 month 2

Vitamin D-Mediated Hypercalcemia

• Glucocorticoids are the primary treatment for hypercalcemia due to excessive intestinal calcium absorption (sarcoidosis, granulomatous diseases, lymphomas, vitamin D intoxication) 1, 2, 3, 4
• Prednisone 1 mg/kg/day orally or methylprednisolone IV equivalent 2
• Taper over 2-4 months depending on response 2

Severe Hypercalcemia with Renal Failure

• Hemodialysis with calcium-free or low-calcium dialysate (1.25-1.50 mmol/L) is reserved for severe hypercalcemia complicated by renal insufficiency or oliguria 1, 2, 3, 5

Monitoring and Follow-Up

Monitor serum calcium, renal function, and electrolytes regularly to assess treatment effectiveness 1, 2, 3. Watch for bisphosphonate complications including renal toxicity and osteonecrosis of the jaw with chronic use 1, 3. Correct hypocalcemia before initiating bisphosphonates and monitor closely, especially with denosumab which carries higher risk of hypocalcemia 2.

Critical Pitfalls to Avoid

• Do not use loop diuretics before adequate volume repletion—this worsens dehydration and hypercalcemia 1, 3
• Avoid NSAIDs and IV contrast media in patients with renal impairment to prevent further kidney damage 1, 2
• Do not restrict calcium intake excessively without medical supervision, as this can worsen bone disease 2
• Avoid vitamin D supplements in patients with hypercalcemia, particularly in early childhood 1, 2, 3
• Do not rely on corrected calcium alone—measure ionized calcium when possible to avoid pseudohypercalcemia from hemolysis or improper sampling 3
• Remember that hyperalbuminemia can mask true calcium status; always calculate corrected calcium or measure ionized calcium 1