What is the workup for hypercalcemia?

From the Guidelines

The initial workup for hypercalcemia should include confirmation of hypercalcemia, PTH level measurement, renal function assessment, and evaluation for underlying causes such as malignancy or primary hyperparathyroidism, as these conditions can significantly impact morbidity, mortality, and quality of life. The workup for hypercalcemia involves several key steps:

• Confirm hypercalcemia with repeat testing of total and ionized calcium levels, as recommended by recent clinical guidelines 1.
• Order parathyroid hormone (PTH) level to differentiate between PTH-dependent and PTH-independent causes, taking into account the importance of accurate PTH measurement in identifying patients with normocalcemic primary hyperparathyroidism 1.
• Check renal function with serum creatinine and estimated glomerular filtration rate (eGFR) to assess for potential kidney damage or disease, which can be a complication of hypercalcemia 1.
• Measure 25-hydroxyvitamin D level to assess vitamin D status, as hypovitaminosis D can be a concomitant secondary cause of hyperparathyroidism 1.
• Order serum and urine protein electrophoresis to screen for multiple myeloma, a common cause of hypercalcemia, especially in older adults 1.
• Obtain a complete blood count (CBC) to evaluate for hematologic malignancies, which can also cause hypercalcemia 1.
• Check thyroid-stimulating hormone (TSH) to rule out hyperthyroidism, a potential underlying cause of hypercalcemia 1.
• Perform chest X-ray to screen for lung cancer or sarcoidosis, both of which can cause hypercalcemia 1. Additional tests may be necessary based on initial results and clinical suspicion, and prompt evaluation is crucial to prevent serious complications such as renal failure, cardiac arrhythmias, and altered mental status. The most recent and highest quality study, published in 2019, emphasizes the importance of accurate PTH measurement and comprehensive workup in managing hypercalcemia 1.

From the FDA Drug Label

Patients who receive zoledronic acid injection should have serum creatinine assessed prior to each treatment Consideration should be given to the severity of, as well as the symptoms of, tumor-induced hypercalcemia when considering use of zoledronic acid injection. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i. e., saline hydration, with or without loop diuretics)

The workup for hypercalcemia includes:

• Assessing serum creatinine prior to treatment
• Evaluating the severity and symptoms of tumor-induced hypercalcemia
• Initiating vigorous saline hydration to restore urine output
• Considering conservative measures such as saline hydration with or without loop diuretics for mild or asymptomatic cases 2

From the Research

Workup for Hypercalcemia

The workup for hypercalcemia involves several steps to determine the underlying cause of the condition.

• The initial test to evaluate hypercalcemia is serum intact parathyroid hormone (PTH) levels, which distinguishes PTH-dependent from PTH-independent causes 3.
• An elevated or normal PTH concentration is consistent with primary hyperparathyroidism (PHPT), while a suppressed PTH level indicates another cause 3.
• Fasting ionized calcium levels should be used for diagnostic purposes, as ingestion of calcium supplements or calcium-containing nutrients can cause transient elevations in blood calcium levels 4.
• A repeat fasting total and ionized calcium measurement should be obtained before further investigations if there is an isolated high total calcium level 4.

Diagnostic Considerations

The diagnosis of hypercalcemia is based on serum calcium concentration, with levels above 10.5 mg/dL considered hypercalcemic 5.

• Hypercalcemia can be classified into mild, moderate, and severe, depending on calcium values 5.
• The majority of patients with hypercalcemia are asymptomatic and diagnosed during routine exams, while a small percentage present with severe manifestations 5.
• Clinical manifestations are related to calcium levels, with higher values leading to more pronounced symptoms 5.

Treatment Approach

The treatment approach for hypercalcemia depends on the underlying cause and severity of the condition.

• Initial treatment involves vigorous intravenous hydration and drugs to reduce bone resorption, such as bisphosphonates 5, 6.
• Denosumab, corticosteroids, and calcitonin can be used in specific cases 5, 6.
• Haemodialysis with low calcium bath can be effective in reducing calcium levels in patients with extreme hypercalcaemia and life-threatening complications 7.
• Treatment of the underlying cause, such as surgical resection of a parathyroid adenoma, is also crucial in managing hypercalcemia 3, 7.