PTHrP and PTH Assay Cross-Reactivity
Modern PTH assays do not cross-react with PTHrP, as these are distinct proteins measured by separate immunoassays with specific antibodies that do not recognize the other molecule. 1, 2
Technical Basis for Lack of Cross-Reactivity
PTH and PTHrP are structurally different proteins that require distinct assays:
PTH assays use antibodies directed against specific PTH epitopes (amino acids 1-4 or 12-24/26-32 for N-terminus, and 34-84 for C-terminus in second- and third-generation assays) that are designed to measure only PTH and its fragments 3
PTHrP assays use completely different antibodies with epitopes typically targeting regions like amino acids 20-29 of PTHrP, which do not exist in the PTH molecule 2
Direct validation studies confirm no cross-reactivity: PTHrP assays show no detection of PTH even at concentrations up to 2000 pmol/L, demonstrating complete specificity 2
Clinical Evidence Supporting Assay Specificity
Multiple clinical studies demonstrate the independent measurement of these hormones:
In hypercalcemic patients with primary hyperparathyroidism, PTH levels are elevated while PTHrP is undetectable in 92% of cases, proving the assays measure different molecules 1
In malignancy-associated hypercalcemia, PTHrP is elevated (detectable in 76-88% of cases) while PTH levels remain suppressed or normal, again confirming no cross-reactivity 1, 2, 4
Combined measurement of both PTH and PTHrP is recommended specifically because they provide complementary diagnostic information—this would be unnecessary if cross-reactivity existed 1, 4
Important Clinical Caveats
PTH Assay Internal Cross-Reactivity Issues
While PTH assays don't cross-react with PTHrP, different PTH assay generations do cross-react with various PTH fragments and modified forms:
Second-generation PTH assays cross-react with C-terminal PTH fragments (particularly PTH 7-84) and oxidized PTH 3
Third-generation PTH assays cross-react with amino-PTH and oxidized PTH but not with C-terminal fragments 3
This internal PTH assay variability can cause up to 47% difference in measured PTH concentrations between assay generations, which is clinically significant 3
Practical Implications
Always use the same PTH assay type (same generation, same laboratory) for serial measurements in individual patients to ensure accurate trend evaluation 3, 5
When evaluating hypercalcemia, measure both PTH and PTHrP as they provide distinct diagnostic information—elevated PTH suggests primary hyperparathyroidism while elevated PTHrP suggests malignancy-associated hypercalcemia 1, 4
Biotin supplements can interfere with both PTH and PTHrP assays depending on assay design, potentially causing falsely elevated or decreased results 3, 5