Mass Spectrometric Immunoassay Raises Doubt for the Existence of Parathyroid Hormone Fragment 7–84

To the Editor: Parathyroid hormone (PTH)1 plays an important role in the regulation of systemic calcium and phosphate homeostasis and bone remodeling, and its measurement in serum or plasma is used to diagnose hyperparathyroidism. Traditionally, PTH has been quantified using 2-site immunochemical assays. Previous comparisons of immunoassays demonstrated significant proportional biases as well as sample-specific discrepancies between immunoassays, due to differences in calibration, interferences, or both (1–3). Biochemically, PTH is a heterogeneous collection of molecules with posttranslational modifications that include phosphorylation, oxidation, and proteolytic cleavage. Different assays variably detect these modified PTH molecules. Previous experiments used HPLC to fractionate serum and identify a peak that cross-reacts with many PTH immunoassays. This peak did not coelute with intact PTH (1–84), but did coelute with PTH fragment (7–84) (4). It has been proposed and generally accepted that this fragment (and to a lesser extent other PTH fragments) interferes with most second-generation immunoassays (those that target amino acid residues proximal to the amino terminus). We aimed to evaluate whether PTH fragments interfere with 2 commonly used US Food and Drug Administration (FDA)-approved second-generation clinical immunoassays: the Roche Elecsys/Cobas e601 and the Beckman Access DxI 800 intact PTH assays. The monoclonal capture antibody in the Roche assay detects amino …