Do we treat hypercalcemia?

Management of Hypercalcemia

Yes, hypercalcemia should be treated, especially when symptomatic or severe (calcium >12 mg/dL), as it can lead to significant morbidity and mortality if left untreated. 1, 2, 3

Evaluation of Hypercalcemia

Before initiating treatment, determine:

• Severity of hypercalcemia:
  • Mild: <12 mg/dL (<3 mmol/L)
  • Severe: ≥12 mg/dL (≥3 mmol/L) or ≥14 mg/dL (≥3.5 mmol/L)
• Presence of symptoms (nausea, vomiting, confusion, dehydration)
• Underlying cause (primary hyperparathyroidism vs. malignancy vs. other causes)
• Corrected calcium level using formula:
  • Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 [4.0 - patient albumin (g/dL)] 2

Treatment Algorithm Based on Severity

For Severe Hypercalcemia (≥12 mg/dL or Symptomatic)

1. Aggressive hydration:

   • IV normal saline to restore euvolemia and promote calciuresis 1, 3
   • Target urine output >2 L/day 1
   • Caution with overhydration in patients with cardiac failure 2

2. Bisphosphonates:

   • First-line pharmacologic therapy for hypercalcemia of malignancy 1, 2
   • Zoledronic acid 4 mg IV over 15 minutes (preferred) 2
   • Alternative: Pamidronate 90 mg IV over 2 hours 1
   • Adjust dose for renal impairment 2
   • Monitor renal function before each treatment 2

3. For refractory cases:

   • Consider retreatment with zoledronic acid after minimum 7 days 2
   • Higher dose (8 mg) may be considered for relapsed/refractory cases 1
   • Denosumab for patients with renal failure 3

4. For specific causes:

   • Glucocorticoids for hypercalcemia due to lymphoma, granulomatous diseases, or vitamin D intoxication 3, 4
   • Calcitonin for immediate short-term management of severe symptomatic hypercalcemia 4
   • Dialysis for severe cases with renal failure 4

For Mild Hypercalcemia (<12 mg/dL, Asymptomatic)

• Primary hyperparathyroidism:

  • Consider parathyroidectomy based on age, calcium level, and organ involvement 3
  • Observation may be appropriate for patients >50 years with calcium <1 mg/dL above upper limit and no evidence of skeletal or kidney disease 3

• Malignancy-related:

  • Treat underlying malignancy 4
  • Consider bisphosphonates for prevention of skeletal complications 5

Special Considerations

• Chronic Kidney Disease (CKD):

  • Discontinue or reduce active vitamin D therapy 6
  • Consider switching from calcium-based to non-calcium-based phosphate binders 6
  • Monitor PTH levels according to CKD stage 6

• Multiple Myeloma:

  • Bisphosphonates (pamidronate or zoledronic acid) every 3-4 weeks 1
  • Monitor renal function and adjust dosing accordingly 1

Potential Pitfalls and Caveats

• Avoid overhydration in patients with cardiac failure 2
• Do not use diuretics before correcting hypovolemia 2
• Monitor renal function closely with bisphosphonates 1, 2
• Discontinue bisphosphonates if unexplained albuminuria (>500 mg/24 hours) or increase in serum creatinine (>0.5 mg/dL) occurs 1
• Consider vitamin D status, as deficiency can affect treatment response 6
• Avoid aggressive calcium-lowering therapy in patients with adynamic bone disease 6

Follow-up

• Monitor serum calcium, phosphorus, and renal function regularly
• Frequency depends on severity of hypercalcemia and underlying condition
• For CKD patients, follow monitoring schedule based on stage 6
• Consider retreatment with bisphosphonates if calcium levels rise again 2

Remember that while treating the acute hypercalcemia is important, identifying and addressing the underlying cause is essential for long-term management and improved outcomes.