What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

The first-line treatment for hypercalcemia is aggressive IV fluid resuscitation with normal saline, followed by bisphosphonates (preferably zoledronic acid 4 mg IV over 15 minutes) for moderate to severe cases. 1

Assessment and Diagnosis

• Calculate corrected calcium using the formula: Corrected calcium = Total calcium + 0.8 × (4.0 - serum albumin) 1, 2
• Severity classification:
  • Mild: Total calcium <12 mg/dL (<3 mmol/L)
  • Severe: Total calcium ≥14 mg/dL (≥3.5 mmol/L) 3
• Initial laboratory workup:
  • Intact parathyroid hormone (iPTH)
  • Phosphorus, magnesium
  • Renal function tests
  • 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels
  • Urinary calcium/creatinine ratio 1

Treatment Algorithm

Step 1: Aggressive IV Fluid Resuscitation

• Administer normal saline to:
  • Correct hypercalcemia-associated hypovolemia
  • Promote calciuresis
  • Target urine output >2 L/day 1
• Caution: Avoid overhydration in patients with cardiac failure 2
• Pitfall: Do not use diuretics before correcting hypovolemia 1, 2

Step 2: Bisphosphonate Therapy

• For moderate to severe hypercalcemia (especially malignancy-related):
  • Zoledronic acid 4 mg IV over 15 minutes (preferred) OR
  • Pamidronate 90 mg IV over 2 hours 1, 2
• Dose adjustments for renal impairment:

  Baseline CrCl (mL/min)	Zoledronic Acid Dose (mg)
  >60	4
  50-60	3.5
  40-49	3.3
  30-39	3

Step 3: Additional Therapies Based on Cause and Severity

• For refractory cases or severe renal impairment:

  • Denosumab (dose not specified in evidence) 1

• For vitamin D toxicity, granulomatous disorders, or some lymphomas:

  • Glucocorticoids 1, 3, 4

• For immediate short-term management of severe symptomatic hypercalcemia:

  • Calcitonin (can be combined with bisphosphonates for faster effect) 1, 5, 4

• For severe cases with renal failure:

  • Consider hemodialysis with low calcium dialysate 1, 6

Special Considerations

Primary Hyperparathyroidism

• For mild asymptomatic hypercalcemia due to primary hyperparathyroidism:
  • Observation with monitoring may be appropriate for patients >50 years with serum calcium <1 mg/dL above upper normal limit and no evidence of skeletal or kidney disease 1, 3
  • Definitive treatment is parathyroidectomy for symptomatic cases 3

Chronic Kidney Disease

• Avoid calcium-based phosphate binders in hypercalcemic patients with CKD 1
• Monitor for hypercalcemia in CKD patients due to altered vitamin D metabolism 1
• For CKD patients with biochemical abnormalities and low bone mineral density or fragility fractures, treatment choices should consider the magnitude and reversibility of biochemical abnormalities 7

Malignancy-Related Hypercalcemia

• Carries poor prognosis (median survival ~1 month in lung cancer) 1
• Requires prompt treatment of underlying malignancy in addition to hypercalcemia management 6

Monitoring and Follow-up

• Monitor serum calcium, phosphate, magnesium, and renal function regularly 1
• Watch for hypocalcemia after treatment, especially with denosumab 1
• Retreatment with zoledronic acid may be considered if calcium doesn't normalize
  • Allow minimum 7 days between treatments for full response 2
• Assess renal function before each dose of zoledronic acid 2

Common Pitfalls to Avoid

• Using diuretics before correcting hypovolemia
• Inadequate hydration before bisphosphonate administration
• Administering bisphosphonates too rapidly
• Treating laboratory values without addressing the underlying cause
• Delaying treatment of severe hypercalcemia
• Failing to monitor for hypocalcemia after treatment 1