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Letters |
1 ARUP Institute for Clinical and Experimental Pathology LLC, Salt Lake City, UT 84108
2 Departments of Pathology and Medicine, University of Utah, School of Medicine, Salt Lake City, UT 84112
aAuthor for correspondence.
To the Editor:
Parathyroid hormone (PTH) is an 84-amino acid peptide secreted by the parathyroid glands that is important in regulating the extracellular calcium concentration in the body. Because this hormone is rapidly metabolized into fragments, its measurement has always been problematic (1).
During the last few years, it has been shown that the current intact PTH, or second-generation, assays will cross-react with a large C-terminal fragment, PTH (7–84), which lacks the six N-terminal amino acids (2)(3). Because of the lack of specificity in these second-generation systems, falsely increased PTH values have been observed (3). New third-generation PTH tests do not detect PTH (7–84) and therefore provide a more accurate measurement of bioactive PTH.
The specificity of third-generation parathyroid assays is important, particularly when evaluating patients with end stage renal disease. In these patients, the clearance of C-terminal PTH fragments is dramatically impaired, leading to increased concentrations of PTH (7–84) fragment. PTH (7–84) has been found to have a weak anticalcemic effect (4)(5). The control of calcium concentrations in dialysis patients poses considerable difficulties as illustrated by the finding that 90% of the patients in a 1995 study had osteodystrophy, either adynamic or low (52%) bone turnover or increased (38%) bone turnover disease (6).
Two third-generation PTH assays that claim PTH (1–84) specificity are the CAP (cyclase-activating PTH) assay from Scantibodies Laboratory and the Bio-Intact PTH assay from Nichols Institute Diagnostics. The Scantibodies CAP assay measures whole (1–84), intact PTH by a manual 125I two-site IRMA. The specificity of the third-generation CAP assay is conferred by the use of an antibody directed toward the (1–4) amino acid epitope of the PTH molecule. The Nichols Bio-Intact assay is an automated PTH test performed on the Nichols Advantage® Specialty System instrument. The methodology consists of a two-site chemiluminescence immunoassay, with one antibody directed toward the first six N-terminal amino acids. Because one antibody of each pair is directed toward the (1–6) N-terminal epitope of PTH, both assay systems should show the desired specificity.
To compare the two assays, we assayed 20 EDTA plasma samples, 10 from healthy volunteers and 10 from renal hemodialysis patients, with the Nichols Advantage Bio-Intact PTH, the Scantibodies CAP, and the Scantibodies total PTH (second-generation) assays.
Deming regression analysis comparing Nichols Advantage and Scantibodies CAP assays (Fig. 1
) yielded a slope of 0.904, which was statistically different from 1.00 (P = 0.001); the y-intercept (13.8 ng/L) also differed statistically from 0.0 (P = 0.001). Although the differences from identity were statistically significant, the Scantibodies CAP and Nichols Bio-Intact assays were still closely correlated. The slope of the regression line between the two third-generation PTH assays was 0.904, indicating that the Scantibodies CAP assay may give values 
10% higher than the Bio-Intact assay, at least for higher values >120 ng/L. The correlation between the Bio-Intact assay and Scantibodies total PTH assay, a second-generation PTH assay, was as follows: Bio-Intact = 0.536(total PTH) + 13.7; R2 = 0.988; n = 20. This Deming regression had a slope of 0.536, illustrating the fact that uremic patients may have nearly equal concentrations of PTH (1–84) and PTH (7–84).
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At low PTH concentrations, the Nichols Advantage gave higher PTH results than those obtained with the Scantibodies CAP. The reason for this may be standardization and/or standard matrix differences, but it does not appear to be related to impaired specificity because at higher concentrations, the Advantage reported lower PTH concentrations than those obtained with the Scantibodies CAP.
The reported interassay CV of the CAP assay is 8.3% at 31 ng/L and 3.4% at 359 ng/L over nine different batches (7). The interassay CVs for the Nichols Bio-Intact assay run on two different instruments on 5 different days were 2.7% at 20.8 ng/L, 2.9% at 143.2 ng/L, and 3.7% at 470.9 ng/L.
Unpublished data from our laboratory have shown that the Bio-Intact PTH assay does not cross-react with the PTH (7–84) fragment. We conclude that although there are minor differences between the assay results, they should produce clinical agreement when used for diagnostic purposes.
References
The following articles in journals at HighWire Press have cited this article:
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  C. Bieglmayer, K. Kaczirek, G. Prager, and B. Niederle Parathyroid Hormone Monitoring during Total Parathyroidectomy for Renal Hyperparathyroidism: Pilot Study of the Impact of Renal Function and Assay Specificity Clin. Chem., June 1, 2006; 52(6): 1112 - 1119. [Abstract] [Full Text] [PDF]
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S. A. Santini, C. Carrozza, C. Vulpio, E. Capoluongo, G. Luciani, P. Lulli, B. Giardina, and C. Zuppi Assessment of Parathyroid Function in Clinical Practice: Which Parathyroid Hormone Assay Is Better? Clin. Chem., July 1, 2004; 50(7): 1247 - 1250. [Full Text] [PDF]
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