Does Parathyroid Hormone (PTH) need to be checked in patients with hypercalcemia?

PTH Testing in Hypercalcemia

Yes, PTH should be checked in all patients with hypercalcemia as it is essential for determining the cause of hypercalcemia and guiding appropriate treatment. 1

Rationale for PTH Testing in Hypercalcemia

PTH measurement serves a critical diagnostic purpose in hypercalcemia evaluation:

• It differentiates between hyperparathyroidism (elevated or inappropriately normal PTH) and other causes of hypercalcemia (suppressed PTH) 1
• Approximately 90% of hypercalcemia cases are caused by either primary hyperparathyroidism or malignancy 2
• PTH is the most important initial test in the evaluation of hypercalcemia 2

Diagnostic Algorithm for Hypercalcemia

1. Confirm hypercalcemia with repeat testing
2. Measure intact PTH level to determine if the hypercalcemia is PTH-dependent or PTH-independent
3. Interpret PTH results:
   • Elevated or inappropriately normal PTH: Consistent with primary hyperparathyroidism (PHPT)
   • Suppressed PTH (<20 pg/mL depending on assay): Indicates non-parathyroid causes such as malignancy, granulomatous disease, or medication effects 2

PTH Assay Considerations

• Use assay-specific reference values when interpreting PTH results 1
• Both second-generation and third-generation PTH assays have similar diagnostic sensitivity for primary hyperparathyroidism 1
• Be aware that biotin supplements can interfere with PTH assays, potentially causing false results 1
• Consider measuring PTH in EDTA plasma rather than serum for better stability 1

Special Considerations

Rare Presentations

• In extremely rare cases, primary hyperparathyroidism can present with hypercalcemia and undetectable PTH levels 3, 4
• When PTH is low or undetectable in hypercalcemia, consider measuring parathyroid hormone-related peptide (PTHrP) to evaluate for malignancy-associated hypercalcemia 5

PTH and PTHrP Testing Strategy

• A PTH cutoff of >26 ng/L predicts a non-increased PTHrP result in 100% of patients with hypercalcemia 5
• PTHrP testing should be performed after assessment of PTH, particularly when PTH is low or low-normal 5

Monitoring Recommendations

For patients with chronic conditions affecting calcium metabolism:

• Monitor calcium, phosphorus, and PTH levels with frequency based on clinical context:
  • Mild hypercalcemia: Every 6-12 months
  • More severe cases: Every 1-3 months 6
• Consider vitamin D status when interpreting PTH levels, as vitamin D deficiency can cause secondary hyperparathyroidism 1, 6

Pitfalls to Avoid

• Not checking PTH: Failing to measure PTH can lead to missed diagnoses, particularly in cases where parathyroid disease coexists with malignancy (found in 10% of patients with malignancy and hypercalcemia) 7
• Ignoring vitamin D status: Vitamin D deficiency affects PTH reference values 1
• Relying solely on PTH: In some cases, additional testing such as PTHrP may be needed, especially when PTH is suppressed 5
• Not considering rare presentations: Primary hyperparathyroidism can occasionally present with normal or even undetectable PTH 3, 4

By measuring PTH in all patients with hypercalcemia, clinicians can accurately diagnose the underlying cause and implement appropriate treatment strategies to reduce morbidity and mortality associated with hypercalcemia.