From the Guidelines
Hypercalcemia testing should begin with a total serum calcium measurement, followed by an ionized calcium test if available, as this is the physiologically active form. If hypercalcemia is confirmed (calcium >10.5 mg/dL), further testing should include parathyroid hormone (PTH) levels to distinguish between PTH-dependent and PTH-independent causes, as PTH is an important regulator of calcium and phosphate homeostasis and bone remodeling 1. Additional tests include:
- 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels
- Phosphorus
- Alkaline phosphatase
- BUN/creatinine
- Complete blood count Urine calcium excretion over 24 hours helps assess renal handling of calcium. If primary hyperparathyroidism is suspected, parathyroid imaging with ultrasound or sestamibi scan may be indicated. For suspected malignancy-related hypercalcemia, appropriate cancer screening tests should be ordered based on symptoms and risk factors, and treatment with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin may be necessary, as recommended by the NCCN MM Panel members 1. Bone scans or skeletal surveys may be needed if metastatic disease is suspected. Testing should be conducted while the patient is adequately hydrated, as dehydration can falsely elevate calcium levels. Patients with severe hypercalcemia (>14 mg/dL) require immediate treatment with IV fluids and possibly bisphosphonates or calcitonin while diagnostic workup continues, as severe hypercalcemia can lead to cardiac arrhythmias, altered mental status, and kidney injury. It is also important to note that accurate measurement of PTH is crucial in identifying patients with normocalcemic primary hyperparathyroidism, and third-generation assays may be more accurate in measuring PTH levels than second-generation assays 1. In patients with chronic kidney disease, serum levels of corrected total calcium should be maintained within the normal range, and therapies that cause serum calcium to rise should be adjusted accordingly 1.
From the Research
Diagnostic Tests for Hypercalcemia
The diagnostic tests for hypercalcemia include:
- Serum intact parathyroid hormone (PTH) assay, which is the most important initial test to evaluate hypercalcemia and distinguishes PTH-dependent from PTH-independent causes 2, 3
- Measurement of serum ionized calcium, which is the most accurate method for detecting hypercalcemia 4, 5
- Measurement of serum total calcium, which can be used as an initial screening test, but may require correction for serum albumin values 6
- Fasting ionized calcium levels, which are recommended for diagnostic purposes 4
Interpretation of Test Results
The interpretation of test results includes:
- Elevated or normal PTH concentration, which is consistent with primary hyperparathyroidism (PHPT) 2, 3
- Suppressed PTH level, which indicates another cause of hypercalcemia 2, 3
- Persistent or frequent total or ionized calcium levels >3 SD above the mean of the normal range, which is diagnostic of hypercalcemia 4
Additional Tests
Additional tests that may be used to evaluate hypercalcemia include:
- Measurement of serum albumin and total protein to correct for serum calcium values 6
- Electrophoresis assessment of albumin concentration, which may be more accurate than colorimetric methods 6
- Measurement of other electrolytes, such as sodium, potassium, and phosphate, to evaluate for other electrolyte abnormalities 5