Understanding iPTH vs PTH Laboratory Tests
The Terms Are Often Used Interchangeably, But Refer to Different Assay Generations
In clinical practice, "iPTH" (intact PTH) and "PTH" are frequently used as synonyms, but they technically refer to different generations of parathyroid hormone assays that measure overlapping but distinct molecular forms of the hormone. 1
Key Differences Between Assay Generations
Second-Generation Assays (Intact PTH or iPTH)
- Use two antibodies in a sandwich immunoassay: one directed against the C-terminal region and another against the N-terminal region (amino acids 12-24 or 26-32) 1
- Measure both full-length PTH (1-84) AND biologically inactive fragments, particularly the 7-84 PTH fragment 1, 2
- Overestimate biologically active PTH because they detect C-terminal fragments that lack the first 6 amino acids but still have a long half-life 1, 3
- Most commonly used in clinical practice, accounting for approximately 90% of assays in some regions 4
Third-Generation Assays (Whole PTH or Bio-intact PTH)
- Use an N-terminal antibody directed against the first four amino acids of PTH, making them specific for full-length 1-84 PTH only 1
- Do not detect 7-84 PTH fragments, providing a more accurate measure of biologically active hormone 1, 5
- Yield approximately 50% lower values compared to intact PTH assays, though the correlation between methods remains high (r > 0.95) 4, 6, 7
Clinical Implications of the Differences
Magnitude of Discrepancy
- Second-generation assays measure 2- to 2.5-fold higher concentrations than third-generation assays in hemodialysis patients 7
- The difference becomes more pronounced as PTH levels increase, particularly in chronic kidney disease patients 4, 3
- In CKD Stage 5 patients, the ratio of biologically active (1-84)PTH to total iPTH is lower than in healthy individuals, meaning iPTH increasingly overestimates parathyroid function as kidney disease progresses 3
Impact on Clinical Decision-Making
- Absolute cutoff values in guidelines become problematic when different assay generations are used 1
- Up to 28% of patients within target iPTH ranges may be misclassified when comparing second- and third-generation assays 4
- Both laboratory experts and clinicians must know which assay generation is being used to correctly interpret results and apply guidelines 1
Practical Recommendations
For Trend Monitoring
- Sequential measurements should always be performed with the same assay in the same laboratory to ensure accurate trend evaluation 1
- Despite different absolute values, all modern PTH assays show excellent correlation (r = 0.87-0.99) for detecting directional changes 4, 7
- Agreement among different assays in detecting significant changes reaches 87% in longitudinal monitoring 7
For Perioperative Use
- Third-generation assays show more rapid PTH decline after parathyroidectomy compared to second-generation assays 1
- In secondary hyperparathyroidism, the 50% decline criterion is reached 20 minutes faster with whole PTH assays versus intact PTH assays 1, 5
- Whole PTH assays may more accurately predict surgical success without false-positive or false-negative results 5
Critical Caveats
Lack of Standardization
- PTH assays are not yet standardized against an internationally recognized reference material, contributing to interlaboratory variability even within the same assay generation 1
- Different second-generation assays can vary by up to 47% depending on whether the N-terminal antibody targets amino acids 12-24 or 26-32 1, 2
Post-translational Modifications
- Both assay generations can detect posttranslationally modified PTH forms (phosphorylated, oxidized) that may lack biological activity 1
- Third-generation assays detect modified PTH forms overproduced in parathyroid carcinoma, which second-generation assays may miss 1