How to manage hypercalcemia?

Management of Hypercalcemia

The management of hypercalcemia should begin with aggressive hydration with intravenous normal saline, followed by bisphosphonate therapy, with zoledronic acid being the preferred agent for moderate to severe cases. 1

Initial Assessment

• Determine the severity of hypercalcemia based on calcium levels: mild (<12 mg/dL), moderate (12-13.5 mg/dL), or severe (>13.5 mg/dL) 2
• Evaluate for symptoms including polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, myalgia, dehydration, and mental status changes 1
• 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

Treatment Algorithm

1. Hydration and Volume Expansion

• Administer intravenous normal saline to correct hypovolemia and promote calciuresis 1
• Maintain a urine output of at least 100 ml/hour (3 ml/kg/hour in children <10 kg) 1
• Loop diuretics (e.g., furosemide) may be necessary in patients with renal or cardiac insufficiency to prevent fluid overload 1

2. Bisphosphonate Therapy

• For moderate to severe hypercalcemia, administer intravenous bisphosphonates 1, 2
• Zoledronic acid is the preferred agent for treatment of hypercalcemia, especially in cases associated with malignancy 3, 1
• Typical dosing is zoledronic acid 4 mg IV or pamidronate 60-90 mg IV 4, 5
• Administer as a 15-minute infusion rather than a 5-minute infusion to reduce risk of renal toxicity 5

3. Additional Therapies Based on Severity and Cause

• For severe, symptomatic hypercalcemia requiring rapid correction, consider calcitonin in addition to bisphosphonates 6
• For hypercalcemia due to malignancy, treat the underlying cancer when possible 1
• For hypercalcemia due to multiple myeloma, consider continuing bisphosphonate therapy for up to 2 years 3, 1
• For hypercalcemia due to granulomatous disorders or vitamin D intoxication, glucocorticoids may be effective 2, 6

Special Considerations

Renal Impairment

• In patients with renal failure, consider denosumab and/or dialysis with calcium-free or low-calcium solution 2, 6
• Monitor renal function when using bisphosphonates, especially in patients with pre-existing kidney disease 7

Hypercalcemia in Multiple Myeloma

• Hydration, furosemide, bisphosphonates, steroids, and/or calcitonin are recommended 3
• Among bisphosphonates, zoledronic acid is preferred for treatment of hypercalcemia in multiple myeloma 3
• Plasmapheresis should be used as adjunctive therapy for symptomatic hyperviscosity 3

Mild Asymptomatic Hypercalcemia

• For mild hypercalcemia due to primary hyperparathyroidism, maintain normal calcium intake (minimum 1g per day) and avoid excessive supplementation 7
• Regular monitoring of serum calcium, renal function, and electrolytes is recommended 7

Follow-up and Monitoring

• Monitor serum calcium, renal function, and electrolytes regularly to assess treatment effectiveness 7
• For patients receiving bisphosphonates, be aware of potential side effects including osteonecrosis of the jaw (3.7% with long-term zoledronic acid use) 3
• In patients with primary hyperparathyroidism, consider parathyroidectomy based on age, serum calcium level, and evidence of kidney or skeletal involvement 2

Common Pitfalls to Avoid

• Avoid using vitamin D supplements in patients with hypercalcemia, particularly in early childhood 3
• Do not delay bisphosphonate therapy in moderate to severe hypercalcemia, as temporary measures like insulin and beta-agonists provide only short-term benefit (1-4 hours) 3
• Avoid NSAIDs and intravenous contrast media in patients with renal impairment to prevent worsening renal function 3
• Do not restrict calcium intake without medical supervision in patients with Williams syndrome and normocalcemia 3