What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

The first-line treatment for hypercalcemia is aggressive IV hydration with normal saline followed by bisphosphonate therapy (zoledronic acid or pamidronate) for moderate to severe cases, while addressing the underlying cause. 1, 2

Initial Assessment and Management

• Measure intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, calcium, albumin, magnesium, and phosphorus levels to determine the underlying cause 1, 3
• Evaluate for symptoms such as polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, myalgia, dehydration, and mental status changes 1, 2
• Classify severity:
  • Mild: total calcium <12 mg/dL (<3 mmol/L) 4
  • Moderate to severe: total calcium ≥12 mg/dL (≥3 mmol/L) 4
  • Crisis: total calcium ≥15 mg/dL (≥3.75 mmol/L) 5

Treatment Algorithm

1. Hydration

• Administer IV normal saline to correct hypovolemia and promote calciuresis 1, 2
• Target urine output of approximately 2 L/day throughout treatment 6, 7
• Avoid overhydration, especially in patients with cardiac failure 6, 7

2. Bisphosphonate Therapy

• For moderate to severe hypercalcemia:
  • Zoledronic acid 4 mg IV over at least 15 minutes as a single dose 6
  • OR Pamidronate IV in conjunction with adequate hydration 7
• Retreatment with zoledronic acid may be considered if serum calcium does not normalize, with a minimum of 7 days between treatments 6
• Monitor renal function carefully; assess serum creatinine prior to each treatment 6

3. Additional Therapies

• Loop diuretics (only after adequate hydration is achieved) to enhance calcium excretion 2, 8
• Calcitonin for immediate short-term management of severe symptomatic hypercalcemia 8
• Glucocorticoids for hypercalcemia due to vitamin D-mediated causes (sarcoidosis, lymphomas, vitamin D intoxication) 2, 4
• Dialysis for severe hypercalcemia with renal failure 8

Treatment Based on Underlying Cause

Primary Hyperparathyroidism

• Consider parathyroidectomy based on age, serum calcium level, and kidney or skeletal involvement 4
• For patients >50 years with serum calcium <1 mg/dL above upper normal limit without skeletal or kidney disease, observation may be appropriate 4

Malignancy-Associated Hypercalcemia

• Treat the underlying cancer when possible 1, 2
• Continue bisphosphonate therapy for up to 2 years in patients with multiple myeloma or bone metastases 1

Vitamin D-Mediated Hypercalcemia

• Discontinue vitamin D supplements 1, 2
• Administer glucocorticoids 4, 9

Special Considerations

Renal Impairment

• For patients with reduced renal function receiving zoledronic acid for multiple myeloma or bone metastases, adjust dosing based on creatinine clearance 6:
  • CrCl 50-60 mL/min: 3.5 mg
  • CrCl 40-49 mL/min: 3.3 mg
  • CrCl 30-39 mL/min: 3.0 mg
• For hypercalcemia of malignancy, dose adjustments are not necessary for mild-to-moderate renal impairment 6
• Consider denosumab in patients with kidney failure 4

Asymptomatic Hypercalcemia

• Mild asymptomatic hypercalcemia usually does not need acute intervention 4
• Prevent volume contraction and prolonged bed rest 9
• Avoid sedatives and narcotic analgesics that may reduce activity and oral intake 9

Follow-up and Monitoring

• Monitor serum calcium, renal function, and electrolytes regularly to assess treatment effectiveness 1, 2
• For patients receiving bisphosphonates, monitor serum creatinine before each dose 6
• Administer oral calcium supplements (500 mg) and vitamin D (400 IU) daily for patients on long-term bisphosphonate therapy 6

Common Pitfalls and Caveats

• Do not use diuretic therapy prior to correction of hypovolemia 6, 7
• Avoid vitamin D supplements in patients with hypercalcemia 1, 2
• Do not delay bisphosphonate administration as they have a delayed hypocalcemic action 9
• Be aware that the prognosis for hypercalcemia of malignancy is generally poor, with median survival approximately 1 month after discovery in some cancers 3