From the FDA Drug Label
Total serum calcium levels in patients who have hypercalcemia of malignancy may not reflect the severity of hypercalcemia, since concomitant hypoalbuminemia is commonly present. Ideally, ionized calcium levels should be used to diagnose and follow hypercalcemic conditions; however, these are not commonly or rapidly available in many clinical situations Therefore, adjustment of the total serum calcium value for differences in albumin levels (corrected serum calcium, CSC) is often used in place of measurement of ionized calcium; several nomograms are in use for this type of calculation [see Dosage and Administration (2.1)].
The workup for a serum calcium level of 17.3 would likely involve:
- Correcting the total serum calcium value for differences in albumin levels to get a more accurate picture of the severity of hypercalcemia
- Measuring ionized calcium levels if possible, as this is the ideal method for diagnosing and following hypercalcemic conditions
- Evaluating for underlying causes of hypercalcemia, such as hypercalcemia of malignancy, and determining the pathophysiologic mechanism involved (e.g. humoral hypercalcemia or hypercalcemia due to tumor invasion of bone) 1
From the Research
For a serum calcium level of 17.3 mg/dL, which represents severe hypercalcemia, immediate workup and treatment are necessary, starting with aggressive IV hydration with normal saline at 200-300 mL/hour, followed by IV bisphosphonates such as zoledronic acid 4 mg or pamidronate 60-90 mg, as recommended by the most recent and highest quality study 2.
Initial Assessment and Workup
The initial assessment should include confirming the elevated calcium with a repeat measurement including ionized calcium, and evaluating for symptoms like confusion, lethargy, nausea, constipation, or cardiac abnormalities. Essential laboratory tests include:
- Parathyroid hormone (PTH)
- Phosphorus
- Vitamin D levels (25-OH and 1,25-OH)
- Complete blood count
- Comprehensive metabolic panel
- Urinary calcium
- Serum protein electrophoresis Imaging should include chest X-ray and skeletal survey to evaluate for malignancy.
Treatment Approach
The treatment approach should prioritize reducing serum calcium levels and managing symptoms.
- Aggressive IV hydration with normal saline at 200-300 mL/hour is the first step.
- IV bisphosphonates such as zoledronic acid 4 mg or pamidronate 60-90 mg should be administered to reduce calcium levels, as supported by the study 3.
- Calcitonin 4 IU/kg every 12 hours may provide temporary relief while bisphosphonates take effect. In severe cases, hemodialysis may be necessary, especially if there is evidence of renal dysfunction, as noted in the study 4.
Underlying Cause Identification
It is crucial to identify the underlying cause of hypercalcemia, with primary hyperparathyroidism and malignancy being the most common causes, accounting for about 90% of cases, as stated in the study 5. The prognosis and management strategy will depend on the underlying cause, with asymptomatic primary hyperparathyroidism having an excellent prognosis with medical or surgical management, and hypercalcemia of malignancy being associated with poor survival, as discussed in the study 2.
Safety Considerations
When using IV bisphosphonates, it is essential to consider the safety profile, particularly in patients with preexisting renal dysfunction, as highlighted in the study 4. The use of furosemide in the management of hypercalcemia is not recommended, as there is limited evidence supporting its effectiveness, as stated in the study 6.