What labs should be drawn in a patient with hypercalcemia (elevated calcium level)?

Laboratory Evaluation for Severe Hypercalcemia (>14 mg/dL)

When a patient presents with severe hypercalcemia (calcium >14 mg/dL), essential laboratory tests should include intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, complete blood count, urinalysis, thyroid-stimulating hormone (TSH), liver function tests, serum concentrations of albumin, magnesium, and phosphorus. 1

Initial Diagnostic Approach

1. Confirm hypercalcemia with albumin-corrected calcium calculation:

   • Use formula: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 1
   • Ionized calcium measurement if available

2. First-line laboratory tests:

   • Intact parathyroid hormone (iPTH) - critical for determining PTH-dependent vs. PTH-independent causes 1
   • Parathyroid hormone-related protein (PTHrP) - particularly important when malignancy is suspected 1
   • Serum phosphorus - typically low in primary hyperparathyroidism, variable in malignancy 1
   • Serum albumin - for calcium correction 1
   • Serum creatinine and BUN - to assess renal function 1

3. Additional essential tests:

   • 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D - to evaluate vitamin D metabolism 1
   • Complete blood count - to screen for malignancies 1
   • Urinalysis - to assess for nephrocalcinosis 1
   • Thyroid-stimulating hormone (TSH) - to rule out thyroid disorders 1
   • Liver function tests - to assess liver involvement 1
   • Serum magnesium - often depleted in hypercalcemia 1

Diagnostic Considerations Based on Etiology

• If PTH is elevated or inappropriately normal:

  • Consider primary hyperparathyroidism (accounts for ~90% of outpatient hypercalcemia cases) 2
  • Consider parathyroid imaging studies (sestamibi scan, ultrasound, CT, or MRI) 1

• If PTH is suppressed (<20 pg/mL):

  • Evaluate for malignancy-associated hypercalcemia (accounts for majority of inpatient cases) 2
  • Check PTHrP, which is often elevated in humoral hypercalcemia of malignancy 1
  • Consider additional workup for underlying malignancy

• For specific conditions:

  • If vitamin D toxicity suspected: Check 25-hydroxyvitamin D levels 1
  • If granulomatous disease suspected: Check 1,25-dihydroxyvitamin D levels 1
  • If Williams syndrome: Check urine calcium/creatinine ratio and consider renal ultrasound 3

Common Pitfalls to Avoid

• Failing to correct calcium for albumin levels 1
• Not measuring both PTH and PTHrP when evaluating severe hypercalcemia 1
• Overlooking medication-induced causes (thiazide diuretics, calcium supplements, vitamin D) 2
• Focusing only on laboratory values without addressing the underlying cause 1
• Delaying treatment of severe hypercalcemia while awaiting complete diagnostic workup 1

Special Considerations

• In patients with renal impairment, interpret calcium levels with caution and consider ionized calcium measurement 1
• For patients with Williams syndrome, additional monitoring includes serum blood urea nitrogen, creatinine, vitamin D concentrations, and intact parathyroid hormone 3
• Patients with severe hypercalcemia (>14 mg/dL) often require urgent treatment with IV fluids before completing the diagnostic workup 1, 2

Remember that approximately 90% of hypercalcemia cases are due to either primary hyperparathyroidism or malignancy, with the former being more common in outpatient settings and the latter more common in hospitalized patients 2. The diagnostic approach should be systematic while simultaneously initiating appropriate treatment for severe hypercalcemia.