How do you treat hypercalcemia?

Management of Hypercalcemia

The treatment of 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 Treatment

Severity Assessment

• Mild hypercalcemia: Total calcium <12 mg/dL
• Moderate hypercalcemia: Total calcium 12.0-13.5 mg/dL
• Severe hypercalcemia: Total calcium >13.5 mg/dL or >14 mg/dL 2

Step 1: Hydration

• Vigorous saline hydration should be initiated promptly
• Target urine output: approximately 2 L/day throughout treatment 3
• IV normal saline is the fluid of choice
• Patients should be adequately hydrated, but overhydration must be avoided, especially in those with cardiac failure 3

Step 2: Bisphosphonate Therapy

• For moderate to severe hypercalcemia (albumin-corrected serum calcium ≥12 mg/dL):
  • Zoledronic acid 4 mg IV over no less than 15 minutes is the preferred agent 1, 3
  • Alternative: Pamidronate 90 mg IV 4
• Assess renal function before administration
• Dose adjustments are not necessary for mild-to-moderate renal impairment (serum creatinine <4.5 mg/dL) 3

Special Considerations

Renal Impairment

• For patients with severe renal impairment:
  • Denosumab is preferred over bisphosphonates 1
  • Consider dialysis with calcium-free or low-calcium solution for patients with renal failure 5

Diuretic Therapy

• Loop diuretics (furosemide) should only be used after adequate hydration 1
• Diuretic therapy should not be employed prior to correction of hypovolemia 3

Additional Therapies

• For immediate short-term management of severe symptomatic hypercalcemia: Calcitonin 1, 5
• For hypercalcemia due to vitamin D toxicity, granulomatous disorders, or lymphomas: Glucocorticoids 1, 5
• Discontinue medications that may contribute to hypercalcemia (thiazide diuretics, calcium supplements, vitamin D supplements) 1

Monitoring and Follow-up

• Regular monitoring of:
  • Serum calcium, phosphate, magnesium
  • Renal function and electrolytes 1
• Calculate corrected calcium using the formula: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 1
• Retreatment with zoledronic acid 4 mg may be considered if serum calcium does not normalize after initial treatment
• Allow minimum of 7 days before retreatment to allow for full response to initial dose 3

Treatment Based on Underlying Cause

Malignancy-Related Hypercalcemia

• Treat the underlying cancer
• Continue bone-targeting treatment (bisphosphonates or denosumab) for up to 2 years 1
• Zoledronic acid has been proven more effective than pamidronate with higher complete response rate, longer response duration, and longer time to relapse 6

Primary Hyperparathyroidism

• Parathyroidectomy may be considered depending on age, serum calcium level, and evidence of kidney or skeletal involvement 2
• For patients >50 years with serum calcium <1 mg above upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate 2

Common Pitfalls to Avoid

• Failing to correct calcium for albumin, leading to inaccurate diagnosis 1
• Inadequate hydration before bisphosphonate administration, which can worsen renal function 1
• Using diuretics before correcting hypovolemia 3
• Not monitoring for hypocalcemia after treatment, especially with denosumab 1
• Treating the laboratory value without addressing the underlying cause 1
• Overlooking renal function when dosing bisphosphonates, which can lead to toxicity 1

By following this algorithmic approach to hypercalcemia management, clinicians can effectively reduce serum calcium levels, improve symptoms, and address the underlying cause of the condition.