What is the PTHrP (Parathyroid Hormone-related Peptide) lab test?

PTHrP (Parathyroid Hormone-Related Peptide) Lab Test

PTHrP is a laboratory test used to detect and measure parathyroid hormone-related peptide, which is an important biomarker for diagnosing humoral hypercalcemia of malignancy (HHM) and evaluating calcium metabolism disorders associated with cancer.

Clinical Utility and Indications

• PTHrP is primarily used in the diagnostic workup of hypercalcemia, particularly to differentiate between hypercalcemia due to malignancy and other causes 1
• It helps identify humoral hypercalcemia of malignancy (HHM), a paraneoplastic syndrome where tumors secrete PTHrP, causing elevated calcium levels without direct bone metastases 2, 3
• PTHrP measurement may assist in distinguishing between primary hyperparathyroidism (elevated PTH) and hypercalcemia of malignancy (elevated PTHrP) 4

Physiological Role

• PTHrP is structurally similar to parathyroid hormone (PTH) and can activate the same receptors, leading to increased calcium levels 1
• Unlike PTH, which is normally produced by the parathyroid glands, PTHrP is produced by various tumors and can cause systemic effects on calcium homeostasis 3
• In normal physiology, PTHrP is present at very low levels in circulation, but becomes significantly elevated in certain pathological conditions 4

Test Characteristics

• Modern PTHrP assays use immunoassay methods (radioimmunoassay, chemiluminescent immunoassay, or LC-MS/MS) to detect the peptide in plasma or serum 2, 5
• Reference intervals vary by assay method, but generally:
  • Normal values are typically ≤0.7 pmol/L with newer chemiluminescent assays 5
  • Clinical decision limits of ≤4.2 pmol/L may be used for increased specificity in diagnosing HHM 5
• Preanalytical considerations:
  • Sample stability is better in EDTA plasma than serum 1
  • Storage at 4°C is preferable to room temperature 1

Clinical Significance of Elevated PTHrP

• Elevated PTHrP levels are found in approximately 47-65% of patients with hypercalcemia associated with malignancy 4, 6
• Common malignancies associated with elevated PTHrP include:
  • Squamous cell carcinomas
  • Breast cancer with bone metastases
  • Various solid tumors with or without bone metastases 6
• PTHrP has prognostic value in cancer patients with hypercalcemia, with elevated levels associated with increased mortality, particularly in patients ≤65 years of age 3

Limitations and Considerations

• Assay variability is significant - different generations and types of assays may yield different results 1
• Kidney function affects PTHrP levels, with an inverse relationship between eGFR and PTHrP concentration 5
• Biotin supplements can interfere with some PTHrP assays, potentially causing falsely elevated or decreased results 1
• Biological variation of PTHrP can be substantial, similar to PTH which has ~20% within-subject variation in healthy individuals 1

Interpretation Challenges

• Standardization of PTHrP assays is still evolving, leading to potential differences in results between laboratories 1
• Newer LC-MS/MS methods have shown that commercial RIAs may substantially underestimate PTHrP concentrations, potentially causing false-negative results 2
• When interpreting results, clinicians should consider:
  • The specific assay method used
  • Patient's clinical context (presence of malignancy, calcium levels)
  • Kidney function 1, 5

PTHrP testing is a valuable tool in the diagnostic workup of hypercalcemia, particularly when malignancy is suspected as the underlying cause. The test helps guide treatment decisions and can provide prognostic information in cancer patients.