Treatment of Hypercalcemia
Intravenous hydration with normal saline followed by bisphosphonates (preferably zoledronic acid) is the first-line treatment for moderate to severe hypercalcemia, especially in malignancy-associated cases. 1, 2
Initial Assessment and Management
- Evaluate for symptoms such as polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, and dehydration to determine severity 1, 3
- Measure intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), vitamin D metabolites, calcium, albumin, magnesium, and phosphorus to determine the underlying cause 1, 3
Treatment Algorithm
1. Hydration
- Administer IV normal saline to correct hypovolemia and promote calciuresis as the first step in management 1, 4
- Maintain urine output of at least 100 ml/hour (3 ml/kg/hour in children <10 kg) 1
- Consider loop diuretics (furosemide) only in patients with renal or cardiac insufficiency to prevent fluid overload 1, 5
2. Bisphosphonate Therapy
- For moderate to severe hypercalcemia, especially malignancy-associated, administer IV bisphosphonates after initial hydration 1, 2
- Zoledronic acid is preferred over other bisphosphonates for treatment of hypercalcemia 6, 1
- Pamidronate is an alternative option, particularly when zoledronic acid is unavailable 2, 5
3. Calcitonin
- Consider calcitonin (100 IU subcutaneously or intramuscularly) for rapid but short-term reduction of calcium levels while waiting for bisphosphonates to take effect 1, 7
- Calcitonin's effect is modest but rapid, making it useful as a bridge therapy 7, 8
4. Additional Therapies
- Glucocorticoids are effective for vitamin D-mediated hypercalcemia (sarcoidosis, lymphomas, vitamin D intoxication) 1, 5
- Consider plasmapheresis as adjunctive therapy for symptomatic hyperviscosity, particularly in multiple myeloma 6, 1
- Hemodialysis may be necessary for severe hypercalcemia complicated by renal insufficiency 1, 5
Special Considerations
Malignancy-Associated Hypercalcemia
- For hypercalcemia due to multiple myeloma, use hydration, furosemide, bisphosphonates, steroids, and/or calcitonin 6
- Treat the underlying cancer when possible 1, 4
- Continue bisphosphonate therapy for up to 2 years in patients with multiple myeloma or bone metastases 1
Primary Hyperparathyroidism
- Consider parathyroidectomy for patients with primary hyperparathyroidism 1, 4
- In patients older than 50 years with mild hypercalcemia and no evidence of skeletal or kidney disease, observation may be appropriate 4
Medication Considerations
- Avoid NSAIDs and intravenous contrast media in patients with renal impairment 6, 1
- Avoid vitamin D supplements in patients with hypercalcemia 1, 3
- Monitor renal function when using bisphosphonates, especially in patients with pre-existing kidney disease 8
Monitoring and Follow-up
- Regularly monitor serum calcium, renal function, and electrolytes to assess treatment effectiveness 1, 3
- Anticipate potential side effects of bisphosphonates including transient fever, lymphocytopenia, and rarely renal dysfunction 8
By following this algorithm, clinicians can effectively manage hypercalcemia while addressing the underlying cause to improve patient outcomes and quality of life.