What labs should be ordered for a patient presenting to the Emergency Room (ER) with hypercalcemia?

Laboratory Evaluation for Hypercalcemia in the Emergency Room

For patients presenting to the ER with hypercalcemia, initial laboratory evaluation should include complete blood count, urinalysis, serum electrolytes (including calcium, phosphorus, and magnesium), blood urea nitrogen, serum creatinine, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D levels, and liver function tests. 1

Initial Laboratory Panel

Essential Tests:

• Calcium levels:

  • Total serum calcium
  • Ionized calcium (if available)
  • Corrected calcium calculation: Corrected calcium = Total calcium + 0.8 × (4.0 - serum albumin) 1

• Parathyroid function:

  • Intact parathyroid hormone (iPTH) - critical for differentiating PTH-dependent from PTH-independent causes 1, 2

• Renal function:

  • Blood urea nitrogen (BUN)
  • Serum creatinine 1

• Other electrolytes:

  • Phosphorus
  • Magnesium
  • Sodium
  • Potassium 1

• Vitamin D metabolism:

  • 25-hydroxyvitamin D
  • 1,25-dihydroxyvitamin D 1

• Additional baseline tests:

  • Complete blood count (CBC)
  • Urinalysis
  • Liver function tests
  • Urinary calcium/creatinine ratio 1

Second-tier Testing Based on Initial Results

If the initial evaluation doesn't reveal the cause, consider:

• Malignancy workup:

  • Serum protein electrophoresis
  • Urine protein electrophoresis
  • PTH-related protein (PTHrP) 2

• Specific conditions:

  • Thyroid-stimulating hormone (TSH) to rule out hyperthyroidism 1
  • Angiotensin-converting enzyme (ACE) for sarcoidosis 1

Diagnostic Algorithm

1. Determine if PTH-dependent or PTH-independent:

   • Elevated/normal PTH with hypercalcemia → Primary hyperparathyroidism
   • Suppressed PTH (<20 pg/mL) → Consider malignancy, vitamin D toxicity, granulomatous disorders 2

2. If PTH-dependent:

   • Check calcium/creatinine clearance ratio to distinguish primary hyperparathyroidism from familial hypocalciuric hypercalcemia (FHH) 3
   • Ratio ≤0.020 suggests FHH, which requires no treatment 3

3. If PTH-independent:

   • Evaluate 25-OH vitamin D and 1,25-OH vitamin D levels 1
   • Check for evidence of malignancy
   • Review medication list for calcium, vitamin D supplements, thiazides 2

Common Pitfalls to Avoid

• Failing to correct calcium for albumin levels 1
• Not measuring both 25-OH and 1,25-OH vitamin D levels when assessing vitamin D status 1
• Overlooking familial hypocalciuric hypercalcemia, which requires genetic testing but no treatment 3
• Treating laboratory values without addressing the underlying cause 1
• Delaying treatment of severe symptomatic hypercalcemia while waiting for diagnostic results 1

Clinical Pearls

• Primary hyperparathyroidism and malignancy account for 90% of hypercalcemia cases 2
• Severe hypercalcemia (total calcium ≥14 mg/dL) requires immediate treatment while diagnostic workup continues 2
• The combination of serum calcium, phosphorus, and chloride with intact PTH achieves 99% accuracy in identifying hyperparathyroidism 4
• Vitamin D toxicity typically occurs when 25(OH)D levels exceed 150 ng/mL 1

By following this systematic approach to laboratory evaluation, you can efficiently diagnose the cause of hypercalcemia and initiate appropriate treatment while in the emergency room setting.