From the Guidelines
The initial evaluation of a patient with hypercalcemia should include measuring serum concentrations of intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, calcium, albumin, magnesium, and phosphorus, as well as assessing renal function and screening for malignancy 1. When evaluating a patient with elevated calcium levels, it is crucial to assess the severity of hypercalcemia and identify the underlying cause. The diagnostic workup should include:
- Serum calcium levels
- Ionized calcium
- Phosphorus
- PTH
- Vitamin D levels
- Renal function tests
- Screening for malignancy This comprehensive approach allows for the identification of the underlying cause of hypercalcemia, which is essential for guiding treatment.
In terms of management, aggressive intravenous fluid resuscitation with normal saline at 200-300 mL/hour is recommended to restore intravascular volume and enhance renal calcium excretion, followed by the administration of loop diuretics such as furosemide 20-40 mg IV every 2-4 hours to prevent fluid overload and further promote calcium excretion 1. For severe or symptomatic hypercalcemia, bisphosphonates such as zoledronic acid 4 mg IV over 15-30 minutes or pamidronate 60-90 mg IV over 2-4 hours can rapidly lower calcium levels within 24-48 hours 1. Additionally, calcitonin 4-8 IU/kg subcutaneously every 12 hours can provide rapid but short-term calcium reduction while waiting for bisphosphonates to take effect, and denosumab 120 mg subcutaneously may be used in renal impairment when bisphosphonates are contraindicated 1. Glucocorticoids (prednisone 40-60 mg daily) are particularly effective for hypercalcemia caused by certain malignancies or granulomatous diseases 1.
It is also important to consider the potential risks associated with hypercalcemia, including the development of acute renal failure and mental status changes, and to take a cautious approach to treatment, avoiding inappropriate calcium loading and aggressive phosphate-lowering therapy, especially in patients with chronic kidney disease 1.
From the FDA Drug Label
Patients with hypercalcemia of malignancy must be adequately rehydrated prior to administration of zoledronic acid injection. Standard hypercalcemia-related metabolic parameters, such as serum levels of calcium, phosphate, and magnesium, as well as serum creatinine, should be carefully monitored following initiation of therapy with zoledronic acid injection The maximum recommended dose of zoledronic acid injection in hypercalcemia of malignancy (albumin-corrected serum calcium greater than or equal to 12 mg/dL [3. 0 mmol/L]) is 4 mg.
The initial evaluation and management of a patient with hypercalcemia includes:
- Adequate rehydration prior to administration of zoledronic acid injection
- Monitoring of serum creatinine prior to each treatment
- Measurement of standard hypercalcemia-related metabolic parameters, such as serum levels of calcium, phosphate, and magnesium
- Consideration of the severity and symptoms of tumor-induced hypercalcemia when deciding on treatment with zoledronic acid injection
- Vigorous saline hydration to restore urine output to about 2 L/day throughout treatment 2
- Conservative measures, such as saline hydration with or without loop diuretics, for mild or asymptomatic hypercalcemia 2
From the Research
Initial Evaluation of Hypercalcemia
The initial evaluation of a patient with hypercalcemia involves several laboratory tests to determine the underlying cause of the condition. Some of the key tests include:
- Serum intact parathyroid hormone (PTH) levels to distinguish between PTH-dependent and PTH-independent causes of hypercalcemia 3
- Total calcium levels to assess the severity of hypercalcemia
- Ionized calcium levels to confirm the diagnosis of hypercalcemia
- Electrolyte panel to evaluate for any electrolyte imbalances
- Renal function tests to assess for any kidney damage or disease
Management of Hypercalcemia
The management of hypercalcemia depends on the underlying cause and severity of the condition. Some of the key management strategies include:
- Hydration to help lower calcium levels
- Intravenous bisphosphonates, such as zoledronic acid or pamidronate, to reduce bone resorption and lower calcium levels 3
- Glucocorticoids to reduce intestinal calcium absorption and lower calcium levels
- Denosumab and dialysis may be indicated in patients with kidney failure 3
- Parathyroidectomy may be considered in patients with primary hyperparathyroidism (PHPT) and severe hypercalcemia
Laboratory Approaches for Diagnosis
Laboratory approaches for the diagnosis and assessment of hypercalcemia include:
- Measurement of blood calcium levels to confirm the diagnosis of hypercalcemia
- Measurement of PTH levels to distinguish between PTH-dependent and PTH-independent causes of hypercalcemia
- Measurement of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels to evaluate for any vitamin D abnormalities
- Measurement of electrolyte and renal function tests to evaluate for any electrolyte imbalances or kidney damage 4
Vitamin D Replacement
Vitamin D replacement may be considered in patients with hypercalcemia and vitamin D deficiency. Studies have shown that vitamin D replacement is safe and effective in patients with mild asymptomatic primary hyperparathyroidism and coexistent vitamin D deficiency 5. However, the impact of vitamin D replacement on hypercalcemia is not well understood and requires further study.