What labs should be ordered for a patient with hypercalcemia?

Laboratory Evaluation for Hypercalcemia

The initial laboratory evaluation for hypercalcemia should include serum intact parathyroid hormone (iPTH), calcium, albumin, magnesium, phosphorus, vitamin D metabolites (25-OH and 1,25-OH2), complete blood count, renal function tests, and urinalysis. 1

Core Laboratory Tests for Hypercalcemia Workup

First-Line Tests

• Serum calcium (total and ionized if available)
• Albumin (for corrected calcium calculation)
• Intact parathyroid hormone (iPTH) - critical for distinguishing PTH-dependent from PTH-independent causes 1, 2
• Renal function panel (BUN, creatinine)
• Serum electrolytes (including magnesium and phosphorus)
• 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels 1
• Complete blood count 3
• Urinalysis 3

Second-Line Tests (Based on Initial Results)

• Parathyroid hormone-related protein (PTHrP) - if iPTH is suppressed, to evaluate for malignancy-associated hypercalcemia 1, 2
• Thyroid-stimulating hormone (TSH) - to rule out thyroid disorders 3
• Liver function tests - to assess for liver involvement 3
• 24-hour urine calcium - to distinguish familial hypocalciuric hypercalcemia from primary hyperparathyroidism 1

Diagnostic Algorithm

1. Measure iPTH level - this is the most critical initial test 2

   • Elevated or inappropriately normal iPTH → Primary hyperparathyroidism (most common cause)
   • Suppressed iPTH (<20 pg/mL) → Consider PTH-independent causes:
     • Malignancy (check PTHrP)
     • Vitamin D toxicity
     • Granulomatous disorders (sarcoidosis)
     • Medications

2. Evaluate calcium-phosphorus relationship:

   • High calcium, low phosphorus → Typical of primary hyperparathyroidism
   • High calcium, high phosphorus → Consider vitamin D toxicity, renal failure, or malignancy

3. Check vitamin D status:

   • High 1,25-OH2 vitamin D with normal/low 25-OH vitamin D → Consider granulomatous disease or lymphoma 3
   • High 25-OH vitamin D → Consider vitamin D intoxication

Special Considerations

• Sarcoidosis patients: Measure both 25-OH and 1,25-OH2 vitamin D levels before vitamin D replacement, as these patients have abnormal calcium metabolism with increased 1α-hydroxylase production 3

• Malignancy workup: If PTH is suppressed and malignancy is suspected, additional tests should include PTHrP, chest imaging, and consideration of age-appropriate cancer screening 2

• Medication review: Always check for medications that can cause hypercalcemia, including thiazide diuretics, lithium, vitamin A supplements, and calcium supplements 2

Monitoring Parameters

• Monitor serum calcium, phosphorus, and renal function during treatment 1
• For patients receiving bisphosphonates or denosumab, regular monitoring of calcium levels is essential to detect hypocalcemia 1
• In chronic hypercalcemia management, calcium levels should be checked at regular intervals based on severity and treatment response

Common Pitfalls to Avoid

• Failing to measure PTH - this is the most important initial diagnostic test 2
• Not correcting calcium for albumin in hypoalbuminemic patients
• Treating laboratory values without identifying the underlying cause 1
• Overlooking medication-induced hypercalcemia
• Not considering familial hypocalciuric hypercalcemia (which typically doesn't require treatment)

Remember that approximately 90% of hypercalcemia cases are due to primary hyperparathyroidism or malignancy, so these conditions should be prioritized in the diagnostic workup 2. The laboratory evaluation should be comprehensive but targeted based on the most likely etiology suggested by the initial PTH result.