What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

The treatment for hypercalcemia should begin 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

Initial Assessment and Classification

• Calculate corrected calcium using the formula: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 1
• Classify hypercalcemia severity:
  • Mild: Corrected calcium < 12 mg/dL
  • Moderate to severe: Corrected calcium ≥ 12 mg/dL

Treatment Algorithm

Step 1: Hydration

• Initiate vigorous saline hydration with normal saline (0.9% NaCl)
• Target urine output of approximately 2 L/day 2
• Avoid overhydration, especially in patients with cardiac failure 2

Step 2: Pharmacologic Therapy

For moderate to severe hypercalcemia (≥ 12 mg/dL):

1. First-line: Zoledronic acid 4 mg IV over no less than 15 minutes 1, 2

   • Higher complete response rate, longer response duration, and longer time to relapse compared to pamidronate 1
   • No dose adjustment needed for mild-to-moderate renal impairment (serum creatinine < 4.5 mg/dL) 2

2. Alternative: Pamidronate 90 mg IV if zoledronic acid unavailable 1, 3

3. For refractory cases or severe renal impairment: Denosumab 1

4. For immediate short-term management: Calcitonin (rapid but short-acting) 1

5. For specific causes:

   • Vitamin D toxicity, granulomatous disorders, or lymphomas: Glucocorticoids 1
   • Medication-induced: Discontinue offending agents (thiazide diuretics, calcium supplements, vitamin D/A supplements) 1

Step 3: Loop Diuretics

• Use only after adequate hydration to enhance calcium excretion 1
• Never use diuretics before correcting hypovolemia 2

Step 4: Monitoring and Retreatment

• Monitor serum calcium, phosphate, magnesium, renal function, and electrolytes regularly 1
• Consider retreatment with zoledronic acid 4 mg if serum calcium doesn't normalize
• Allow minimum 7 days before retreatment 2

Special Considerations

Renal Impairment

• For severe renal impairment: Denosumab preferred over bisphosphonates 1
• Consider dialysis with calcium-free or low-calcium solution for patients with renal failure 1, 4
• Dose adjustments for bisphosphonates based on creatinine clearance 1

Diagnostic Workup

• Measure intact PTH level to differentiate causes:
  • Elevated/normal PTH: PTH-dependent causes (primary hyperparathyroidism)
  • Suppressed PTH (<20 pg/mL): PTH-independent causes (malignancy) 1, 4
• Check vitamin D levels (25-OH and 1,25-OH2) to identify granulomatous disease or lymphoma 1

Common Pitfalls to Avoid

1. Failing to correct calcium for albumin, leading to inaccurate diagnosis 1
2. Inadequate hydration before bisphosphonate administration 1
3. Using diuretics before correcting hypovolemia 1, 2
4. Not monitoring for hypocalcemia after treatment, especially with denosumab 1
5. Treating the laboratory value without addressing the underlying cause 1
6. Delaying treatment of severe hypercalcemia, which can lead to serious complications 1

Underlying Cause Treatment

• Treatment of the underlying cause (especially malignancy) is crucial for long-term management 1, 5
• For primary hyperparathyroidism, consider parathyroidectomy based on age, serum calcium level, and evidence of kidney or skeletal involvement 1, 5