What are the diagnostic tests for primary hyperparathyroidism (PHPT)?

Diagnostic Tests for Primary Hyperparathyroidism

The diagnosis of primary hyperparathyroidism (PHPT) requires simultaneous measurement of serum calcium and intact parathyroid hormone (iPTH), which will show hypercalcemia with an elevated or inappropriately normal PTH level. 1, 2

Initial Diagnostic Tests

• Serum calcium and iPTH: These should be measured simultaneously as the cornerstone of diagnosis 1, 2

  • Hypercalcemia with elevated or inappropriately normal PTH is diagnostic of PHPT 2
  • Total calcium should be corrected for albumin if albumin is abnormal 1

• 25-OH Vitamin D: Should be measured to exclude vitamin D deficiency as a secondary cause of elevated PTH 2, 1

  • Vitamin D deficiency can cause secondary hyperparathyroidism and complicate interpretation of PTH levels 2

• Serum phosphate: Typically low in PHPT due to the phosphaturic effect of PTH 1

• Serum chloride: Can help in differential diagnosis 3

Additional Laboratory Tests

• Calcium-to-creatinine clearance ratio: Helps differentiate PHPT from familial hypocalciuric hypercalcemia 3

• 24-hour urinary calcium: To assess for hypercalciuria, which may influence surgical decisions 2

• Renal function tests: GFR < 60 mL/min/1.73 m² is an indication for surgery in PHPT 2

Preanalytical Considerations for PTH Measurement

• Sample type: PTH is more stable in EDTA plasma than in serum 2

  • The IFCC working group recommends measurement of PTH in EDTA plasma 2

• Timing: PTH has a circadian rhythm; consistent timing of sample collection is important 2

• Storage conditions: PTH is more stable at 4°C than at room temperature 2

Imaging Studies (After Biochemical Diagnosis)

• Ultrasound of the neck: First-line localization study for parathyroid adenomas 2, 1

• Dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT: Highly sensitive when combined with ultrasound 2, 1

  • The combination of these two tests provides the highest sensitivity for localization 2, 1

• MRI or CT scan: Consider if initial imaging is negative or for ectopic parathyroid tissue 2, 1

Special Considerations

• PTH assay generation: Both second- and third-generation PTH assays have similar diagnostic sensitivity for PHPT 2

  • Use assay-specific reference values as recommended by international workshops 2

• Biotin supplements: Can interfere with PTH assays and lead to falsely low or high results 2

• Factors affecting PTH levels: Race, age, BMI, and vitamin D status all influence PTH concentration 2

Atypical Presentations

• Normocalcemic PHPT: Normal calcium with elevated PTH (21% of cases) 4

• Normohormonal PHPT: Elevated calcium with normal PTH (6% of cases) 4

• Both normal calcium and PTH: Rare presentation (3% of cases) but still consistent with PHPT 4

Common Pitfalls to Avoid

• Not assessing vitamin D status: Can lead to misinterpretation of elevated PTH 1

• Using different PTH assays interchangeably: Can affect clinical decisions due to varying sensitivity to PTH fragments 1, 2

• Relying on imaging for diagnosis: Imaging should only be used for localization after biochemical diagnosis is established, not for diagnosis 2

• Missing ectopic parathyroid tissue: Approximately 5% of patients with persistent hyperparathyroidism have ectopically located adenomas 5

By following this diagnostic algorithm, clinicians can accurately diagnose primary hyperparathyroidism and distinguish it from other causes of hypercalcemia or elevated PTH.