What blood tests are used to diagnose hyperparathyroidism?

Blood Tests for Diagnosing Hyperparathyroidism

The essential blood tests for diagnosing hyperparathyroidism include serum calcium, phosphorus, and intact parathyroid hormone (iPTH), with iPTH being the most critical diagnostic test that distinguishes hyperparathyroidism from other causes of hypercalcemia. 1, 2

Primary Diagnostic Tests

Core Laboratory Panel

• Serum calcium: Almost always elevated in primary hyperparathyroidism (PHPT)
• Intact parathyroid hormone (iPTH): Elevated or inappropriately normal in the presence of hypercalcemia
• Serum phosphorus: Often low or low-normal in PHPT due to PTH's phosphaturic effect

Additional Important Tests

• 25-OH Vitamin D: To exclude vitamin D deficiency as a concomitant cause of secondary hyperparathyroidism 1
• Serum creatinine/GFR: To assess kidney function and help distinguish between primary and secondary hyperparathyroidism 1

Specialized Testing

For Equivocal Cases

• Ionized calcium: More sensitive than total serum calcium and more linearly associated with adenoma size 3
• Calcium-to-phosphorus (Ca/P) ratio: A ratio above 2.55 has high sensitivity (85.7%) and specificity (85.3%) for identifying PHPT 4
• 24-hour urinary calcium: To assess for hypercalciuria, which may indicate PHPT 1

For Differential Diagnosis

• Parathyroid hormone-related peptide (PTHrP): To rule out hypercalcemia of malignancy, especially when PTH is low or suppressed (≤26 ng/L) 5
• Serum chloride: Can help distinguish PHPT from other causes of hypercalcemia 6

Testing Considerations

Preanalytical Factors

• Sample type: PTH is more stable in EDTA plasma than in serum
• Storage conditions: PTH is more stable at 4°C than at room temperature
• Sampling time: PTH has a circadian rhythm, though optimal sampling time is not established 1

Analytical Factors

• Assay generation: Both second and third-generation PTH assays have similar diagnostic sensitivity for PHPT
• Reference ranges: Use assay-specific reference values as recommended by international workshops 1

Monitoring Recommendations

For patients with confirmed hyperparathyroidism:

• CKD patients: Frequency of testing based on CKD stage:

  CKD Stage	Calcium & Phosphorus	PTH
  Stage 3	Every 6-12 months	Every 6-12 months
  Stage 4	Every 3-6 months	Every 3-6 months
  Stage 5	Every 1-3 months	Every 3 months
  Dialysis	Monthly	Every 3 months
  1, 2

• Post-treatment: Monitor calcium, phosphorus, and PTH within 1 week of treatment initiation or dose adjustment for calcium and phosphorus, and 1-4 weeks for iPTH 2

Pitfalls to Avoid

• Relying solely on serum calcium: Some patients with PHPT may have normal serum calcium but elevated ionized calcium 3
• Ignoring vitamin D status: Vitamin D deficiency can cause secondary hyperparathyroidism and affect PTH levels 1
• Misinterpreting PTH levels: PTH may be inappropriately "normal" (not suppressed) in PHPT despite hypercalcemia 6
• Failing to consider biotin interference: Depending on assay design, biotin supplements can cause falsely high or low PTH results 1

By following this diagnostic approach, clinicians can accurately diagnose hyperparathyroidism and distinguish between its primary, secondary, and tertiary forms, leading to appropriate treatment decisions that will improve patient outcomes related to mortality, morbidity, and quality of life.