What are the initial steps to diagnose and treat hypercalcemia?

Initial Diagnostic and Treatment Approach for Hypercalcemia

The initial steps to diagnose and treat hypercalcemia should include measuring serum calcium, albumin, intact parathyroid hormone (iPTH), and other key laboratory tests to determine the underlying cause, followed by appropriate hydration therapy and specific treatments based on severity and etiology. 1

Diagnostic Approach

First-Line Laboratory Tests

• Measure serum calcium (total and ionized) to confirm hypercalcemia 1
• Check albumin levels for corrected calcium calculation 1
• Measure intact parathyroid hormone (iPTH) to distinguish PTH-dependent from PTH-independent causes 1
• Assess renal function with serum creatinine and blood urea nitrogen 1
• Check serum phosphorus and magnesium levels 1

Second-Line Laboratory Tests (Based on Initial Results)

• If PTH is elevated or inappropriately normal: measure 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels 1
• If PTH is suppressed: measure parathyroid hormone-related protein (PTHrP) to evaluate for malignancy-associated hypercalcemia 1, 2
• Consider additional tests based on clinical suspicion (e.g., malignancy markers if PTH is suppressed) 2

Classification of Severity

• Mild: >5.0 to <5.5 mEq/L (usually asymptomatic) 1, 3
• Moderate: 5.5 to 6.0 mEq/L (may present with polyuria, polydipsia, nausea, vomiting) 1, 2
• Severe: >6.0 mEq/L or >14.0 mg/dL (associated with mental status changes, dehydration, acute renal failure) 1, 2

Treatment Algorithm

1. Hydration Therapy (First-Line for All Patients)

• Administer IV normal saline to correct hypovolemia and promote calciuresis 4
• Target urine output of at least 100 ml/hour (3 ml/kg/hour in children <10 kg) 4
• Consider loop diuretics only in patients with renal or cardiac insufficiency to prevent fluid overload 4

2. Bisphosphonate Therapy (For Moderate to Severe Hypercalcemia)

• Administer IV bisphosphonates as first-line pharmacologic treatment, especially for malignancy-associated hypercalcemia 4, 3
• Zoledronic acid is preferred over pamidronate according to the National Comprehensive Cancer Network 4, 5
• Do not delay bisphosphonate therapy in moderate to severe hypercalcemia 4

3. Additional Treatments Based on Cause and Severity

• For vitamin D-mediated hypercalcemia (granulomatous disorders, vitamin D intoxication): administer glucocorticoids 2, 6
• For rapid, short-term calcium reduction: consider calcitonin (200 IU per day as nasal spray or 100 IU subcutaneously/intramuscularly every other day) 4, 5
• For patients with renal failure: consider denosumab or dialysis 3, 5
• For primary hyperparathyroidism: consider parathyroidectomy based on age, calcium level, and evidence of end-organ damage 3

Special Considerations

• Avoid vitamin D supplements in patients with hypercalcemia 4, 2
• Avoid NSAIDs and intravenous contrast media in patients with renal impairment 4
• In patients with kidney disease, interpret PTH levels with caution as secondary hyperparathyroidism can coexist with other causes of hypercalcemia 1
• For mild, asymptomatic hypercalcemia due to primary hyperparathyroidism in patients >50 years with calcium <1 mg/dL above normal limit and no evidence of skeletal or kidney disease, observation may be appropriate 3
• Treat the underlying cause, especially in malignancy-associated hypercalcemia 2

Common Pitfalls to Avoid

• Don't attribute slightly elevated calcium levels to pathology without checking hydration status, as dehydration can concentrate blood components 1
• Don't rely solely on total calcium levels; confirm with albumin-adjusted or ionized calcium measurements 7
• Don't forget to monitor serum calcium, renal function, and electrolytes regularly to assess treatment effectiveness 4, 2
• Don't use temporary measures like insulin and beta-agonists as primary therapy as they provide only short-term benefit (1-4 hours) 4