From the Guidelines
Testing for hypercalcemia involves measuring serum calcium levels, with total calcium above 10.5 mg/dL (2.6 mmol/L) or ionized calcium above 5.6 mg/dL (1.4 mmol/L) indicating hypercalcemia, and initial evaluation should include a comprehensive metabolic panel, intact parathyroid hormone (PTH), 25-hydroxyvitamin D, and phosphorus levels, as recommended by recent guidelines 1.
Initial Evaluation
The initial evaluation of hypercalcemia should include:
- Comprehensive metabolic panel
- Intact parathyroid hormone (PTH)
- 25-hydroxyvitamin D
- Phosphorus levels If PTH is elevated, primary hyperparathyroidism is likely the cause, and further testing should focus on confirming this diagnosis, as suggested by 2.
Additional Tests
If PTH is suppressed, additional tests should include:
- PTH-related protein
- Serum and urine protein electrophoresis
- Thyroid function tests
- Possibly a chest X-ray to evaluate for malignancy or granulomatous disease, as recommended by 3.
Importance of PTH Measurement
PTH measurement is crucial in the diagnostic workup of hypercalcemia, as it differentiates between hyperparathyroidism and other causes of hypercalcemia, and its measurement is important for monitoring development and degree of metabolic bone disease, as highlighted by 3.
Treatment
For patients with confirmed hypercalcemia, treatment depends on severity and cause, and may include:
- Monitoring for mild asymptomatic hypercalcemia
- Immediate intervention with IV fluids, bisphosphonates, and calcitonin for moderate to severe hypercalcemia or symptomatic cases, as suggested by recent clinical guidelines 1.
From the Research
Tests for Hypercalcemia
The following tests are used to evaluate hypercalcemia:
- Serum intact parathyroid hormone (PTH) assay: This is the most important initial test to evaluate hypercalcemia, as it distinguishes PTH-dependent from PTH-independent causes 4, 5, 6, 7, 8.
- Measurement of total calcium and ionized calcium: These tests are used to confirm the diagnosis of hypercalcemia 4, 6.
- Measurement of phosphate, creatinine, and alkaline phosphate: These tests are used to evaluate the underlying cause of hypercalcemia 6.
- Measurement of vitamin D metabolites: This test is used to evaluate vitamin D-related causes of hypercalcemia 6.
- Parathyroid hormone-related peptide (PTHrP) measurement: This test is used to evaluate hypercalcemia of malignancy 7.
- 1,25-dihydroxyvitamin D measurement: This test is used to evaluate granulomatous diseases and other causes of hypercalcemia 7.
Interpretation of Test Results
The results of these tests are used to determine the underlying cause of hypercalcemia:
- Elevated PTH levels: Confirm primary hyperparathyroidism 4, 5, 7.
- Low-normal or decreased PTH levels: Suggest malignancy or granulomatous disease 5, 7.
- Mildly elevated PTH levels: May be observed in familial hypocalciuric hypercalcemia 7.
- Suppressed PTH level: Indicates another cause of hypercalcemia, such as vitamin D intoxication or granulomatous disease 4.