From the Guidelines
The workup for hypercalcemia should begin with confirming the elevated calcium level and initial laboratory tests, including parathyroid hormone (PTH), to guide further evaluation and management, as recommended by recent guidelines 1. The initial step in evaluating hypercalcemia is to confirm the elevated calcium level with a repeat measurement, including ionized calcium if available.
- Initial laboratory tests should include:
- Parathyroid hormone (PTH)
- Phosphorus
- 25-hydroxyvitamin D
- 1,25-dihydroxyvitamin D
- Creatinine
- Albumin
- Complete blood count
- Urinary calcium excretion If PTH is elevated, primary hyperparathyroidism is likely, warranting neck ultrasound or sestamibi scan to locate parathyroid adenomas.
- If PTH is suppressed, evaluate for malignancy with:
- Chest X-ray
- Mammography
- Age-appropriate cancer screening
- Serum protein electrophoresis to detect multiple myeloma, as outlined in the NCCN guidelines for multiple myeloma 1 Consider PTH-related protein measurement if malignancy is suspected.
- For medication-induced hypercalcemia, review all medications, particularly thiazide diuretics, lithium, and excessive vitamin D or calcium supplements.
- Familial hypocalciuric hypercalcemia should be considered in patients with low urinary calcium excretion and family history of hypercalcemia.
- Granulomatous diseases like sarcoidosis may require chest imaging and angiotensin-converting enzyme levels. Treatment of hypercalcemia should be guided by the underlying cause and severity, with options including hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, with zoledronic acid preferred among bisphosphonates 1.
From the Research
Workup for Hypercalcemia
The workup for hypercalcemia typically involves the following steps:
- Measurement of serum intact parathyroid hormone (PTH) to distinguish between PTH-dependent and PTH-independent causes 2
- Evaluation of symptoms and medical history to identify potential underlying causes, such as primary hyperparathyroidism (PHPT), malignancy, granulomatous disease, or medication-induced hypercalcemia 2
- Laboratory tests, including serum calcium, phosphate, and creatinine levels, as well as urine calcium and creatinine levels 2
Diagnostic Considerations
The diagnosis of hypercalcemia is based on the presence of elevated serum calcium levels, which can be classified as mild, moderate, or severe 2. The underlying cause of hypercalcemia should be identified and treated, as the prognosis and treatment approach vary depending on the cause 2.
Treatment Options
Treatment options for hypercalcemia depend on the severity and underlying cause of the condition. For mild hypercalcemia, observation and monitoring may be sufficient, while severe hypercalcemia requires urgent treatment with hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 2, 3. Glucocorticoids may be used as primary treatment for hypercalcemia due to excessive intestinal calcium absorption, such as vitamin D intoxication or granulomatous disorders 2.
Bisphosphonate Therapy
Zoledronic acid is a nitrogen-containing bisphosphonate that inhibits bone resorption and is indicated for the treatment of hypercalcemia of malignancy and skeletal complications of metastatic bone disease 4. It has been shown to be effective in reducing serum calcium levels and improving symptoms in patients with severe hypercalcemia 3, 4, 5. However, its use in patients with preexisting renal dysfunction requires caution, as it may increase the risk of serum creatinine elevations 6.