Full-length versus intact PTH concentrations in pseudohypoparathyroidism type 1 and primary hyperparathyroidism: clinical evaluation of immunoassays in individuals from China

Abstract

Purpose: The application of the third-generation parathyroid hormone (PTH) assay [PTH(1-84) assay] for evaluating PTH levels in patients with pseudohypoparathyroidism type-1 (PHP1) is less popular than the second-generation assay. Therefore, we aimed at examining the conformity between the PTH(1-84) assay and the intact PTH (iPTH) assay, specifically examining their performance in individuals with PHP1 versus individuals with primary hyperparathyroidism (PHPT), compared to healthy controls.

Methods: PTH(1-84) and iPTH assay were performed in patients with PHP1, patients with PHPT, and healthy volunteers. ∆PTH%, PTH(1-84)/iPTH (3^rd/2^nd ratio), iPTH/upper limit of normal (ULN), and PTH (1-84)/ULN of each group were calculated for comparison. Linear regression, Kappa conformity test, and Bland-Altman analysis of ∆PTH/mean of iPTH and PTH(1-84) (percent bias) plotted against the mean of iPTH and PTH(1-84) were performed to determine the conformance of PTH(1-84) assay with iPTH assay.

Results: A total of 54 patients with PHP1, 127 patients with PHPT, and 65 healthy volunteers were enrolled in this study. All the three groups showed strong linear relationship between iPTH and PTH (1-84) (r² = 0.9661, 0.7733, and 0.9575, respectively). No significant differences were noted in 3^rd/2^nd ratio (median 0.76 vs. 0.72) between the PHP1 and PHPT groups (p > 0.05). Conformity examination showed the Kappa value was 0.778 and 0.395 for PHP1 and PHPT groups respectively. No difference in the Kappa values was found between PHP1A and PHP1B subgroups. Bland-Altman plot demonstrated that the proportion of data points that were plotted within mean ± 1.96 SD in PHP1, PHPT and normal control groups were 96.3%, 93.7%, and 98.5%, respectively. The mean percent bias of the three groups were 26.1%, 31.2%, and 17.0%, respectively. The range of mean ± 1.96 SD of percent bias of the three groups were 2.2%-50.0%, -14.3%-76.6%, and 6.7%-27.2%, respectively.

Conclusion: Although iPTH and PTH(1-84) values were both lower in the present PHP1 cohort than in the PHPT cohort, there appear to be differences in the relative agreement between both immunoassays, and in the relationship between the two values, especially in comparison to healthy controls. Whether these differences are due to differential accumulation of C-terminal fragments or other factors requires further study.

Keywords: PTH assay; Pseudohypoparathyroidism; Third-generation PTH assay.