From the Guidelines
Hypercalcemia should be worked up with a thorough medical history, physical examination, and laboratory tests to determine the underlying cause.
Initial Evaluation
First, measure the serum calcium level to confirm hypercalcemia, and then assess the patient's volume status and renal function with serum creatinine, electrolytes, and urine output 1.
Next, order the following laboratory tests:
- Parathyroid hormone (PTH) level to differentiate between primary hyperparathyroidism and other causes 1
- Vitamin D levels (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) to evaluate for vitamin D-mediated hypercalcemia
- Phosphate level to assess for hyperparathyroidism or other conditions
- Electrolyte panel, including potassium, sodium, and chloride
- Complete blood count (CBC) to evaluate for underlying hematologic malignancies
- Serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) to evaluate for multiple myeloma
- Thyroid function tests (TFTs) to assess for hyperthyroidism
- Liver function tests (LFTs) to evaluate for liver disease
Imaging Studies
Imaging studies may include:
- Chest X-ray to evaluate for lung malignancies or granulomatous disease
- Bone density scan to assess for osteoporosis or other bone disorders
Treatment
Treatment of hypercalcemia depends on the underlying cause and severity. For mild hypercalcemia, treatment may involve hydration with normal saline and monitoring. For more severe cases, consider the following medications:
- Bisphosphonates (e.g., zoledronic acid 4 mg IV over 15 minutes) for malignancy-related hypercalcemia
- Glucocorticoids (e.g., prednisone 20-50 mg orally per day) for vitamin D-mediated or granulomatous disease-related hypercalcemia
- Calcitonin (e.g., salmon calcitonin 4-8 IU/kg subcutaneously or intramuscularly every 12 hours) for rapid reduction of calcium levels
- Denosumab (e.g., 120 mg subcutaneously on days 1,8,15,29, and every 4 weeks thereafter) for malignancy-related hypercalcemia refractory to bisphosphonates 1.
In severe cases, consider hospitalization for aggressive hydration and monitoring. It is essential to note that accurate measurement of PTH is crucial in identifying patients with normocalcemic primary hyperparathyroidism, and different generations of PTH assays may affect clinical decisions 1.
From the Research
Initial Workup for Hypercalcemia
The initial workup for hypercalcemia should include:
- Measurement of parathyroid hormone (PTH) levels 2, 3
- Discontinuation of any medication likely to be involved in iatrogenic hypercalcemia 2, 3
- Clinical history and physical examination to point towards the correct diagnosis 4
Diagnostic Considerations
The diagnosis of hypercalcemia often involves:
- Excluding other causes before considering parathyroid surgery 3
- Referring patients for parathyroidectomy only if they meet certain criteria 3
- Identifying the underlying etiology, as treatment depends on the cause of hypercalcemia 5
Treatment Options
Treatment for hypercalcemia may include:
- Intravenous rehydration 2, 3, 5
- Antiresorptive agents such as bisphosphonates, denosumab, or calcitonin 2, 3, 5
- Corticosteroids in specific cases 5
- Vigorous intravenous hydration and drugs to reduce bone resorption in critically ill patients 5
Role of Imaging
Imaging plays an important role in: