From the Guidelines
The workup for elevated calcium (hypercalcemia) should begin with confirmation of the elevated level through repeat testing, followed by assessment of parathyroid hormone (PTH) levels to determine if the hypercalcemia is PTH-dependent or independent, as recommended by the most recent guidelines 1. The initial laboratory evaluation should include serum calcium, ionized calcium, phosphorus, magnesium, creatinine, albumin, PTH, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D levels.
- A 24-hour urine collection for calcium and creatinine helps assess renal calcium handling.
- If PTH is elevated or inappropriately normal with hypercalcemia, primary hyperparathyroidism is likely, warranting parathyroid imaging with ultrasound and sestamibi scan, as suggested by recent studies 1.
- If PTH is suppressed, evaluation for malignancy is appropriate, including serum protein electrophoresis, chest X-ray, and age-appropriate cancer screening. Some key points to consider in the workup of hypercalcemia include:
- Bone-specific alkaline phosphatase and urinary N-telopeptide may help assess bone turnover.
- Additional tests based on clinical suspicion include thyroid function tests, cortisol levels, and screening for granulomatous diseases.
- Patients with severe hypercalcemia (>14 mg/dL) or symptomatic presentations require urgent treatment with IV fluids, calcitonin, bisphosphonates, or denosumab while the diagnostic workup proceeds, as indicated by recent guidelines 1. This systematic approach helps identify the underlying cause, which is essential for appropriate long-term management of hypercalcemia, and is supported by recent evidence 1.
From the Research
Workup for Elevated Calcium
The workup for elevated calcium involves several steps to determine the underlying cause of hypercalcemia.
- Primary hyperparathyroidism and malignancy are responsible for greater than 90% of all cases of hypercalcemia 2.
- The initial approach to hypercalcemia includes measuring serum calcium levels and parathyroid hormone (PTH) levels to distinguish between PTH-dependent and PTH-independent causes 3, 4.
- Serum intact PTH is the most important initial test to evaluate hypercalcemia, and an elevated or normal PTH concentration is consistent with primary hyperparathyroidism, while a suppressed PTH level indicates another cause 4.
- Other tests that may be performed include:
- Kidney function tests to evaluate for kidney damage or disease
- Bone density tests to evaluate for osteoporosis or other bone disorders
- Imaging tests such as X-rays, CT scans, or MRI scans to evaluate for bone lesions or other abnormalities
- Biopsy or fine-needle aspiration to evaluate for malignancy
Diagnostic Criteria
The diagnostic criteria for primary hyperparathyroidism include:
- Persistent hypercalcemia
- Elevated serum parathyroid hormone level 5
- Other causes of hypercalcemia are rare and usually associated with low or normal parathyroid hormone levels
Treatment
Treatment for hypercalcemia depends on the underlying cause and severity of symptoms.
- Mild hypercalcemia usually does not require acute intervention, but may be monitored with regular check-ups and laboratory tests 4.
- Symptomatic or severe hypercalcemia is typically treated with:
- Hydration to help flush out excess calcium
- Intravenous bisphosphonates such as zoledronic acid or pamidronate to reduce bone resorption
- Glucocorticoids to reduce intestinal calcium absorption
- Calcitonin to reduce bone resorption and lower calcium levels
- Parathyroidectomy (surgery to remove the parathyroid gland) for primary hyperparathyroidism 2, 4, 5