Assessment of Parathyroid Function in Clinical Practice: Which Parathyroid Hormone Assay Is Better?

Parathyroid hormone (PTH) is a single-chain 84-amino acid polypeptide synthesized by the parathyroid glands. In the blood it is thought to circulate as a mixture of whole molecule [PTH (1–84)] and N- and C-terminal (C-PTH) fragments produced in the parathyroid glands and liver (1)(2). In patients with intact renal function, the non-(1–84) PTH, identified by HPLC, reportedly accounts for ∼21% of PTH(1–84) in hypercalcemia and ∼10% in hypocalcemia (3). C-PTH fragments accumulate in renal failure up to 40–50% of total PTH (4) and may be implicated in the PTH resistance observed in these patients. It is not known whether these fragments can mimic the biological effects of PTH(1–84) or, in contrast, react with distinct receptors (5)(6)(7)(8).The major large C-PTH fragment with partially preserved N-terminal structure is PTH(7–84), often considered to be the likely cross-reacting peptide in “intact PTH” (I-PTH) assays (6)(7)(8)(9). The biological activity of this fragment is not definitively known (10)(11)(12)(13). The large increase of C-PTH fragments in renal failure may complicate monitoring of patients (14)(15).Determination of PTH has also been reported as predictive of different forms of renal osteodystrophy (14). In most laboratories, I-PTH assays from several manufacturers are routinely performed, although the cutoff for PTH concentrations in the classification of adynamic bone in dialysis patients is still controversial (5)(6)(7). These assays use antibodies against amino acids 15–34 and 50–65 of the PTH molecule and, thus, also measure C-PTH fragments with preserved N-terminal structure [such as PTH(7–84)]. A newly available (Bio-Intact) PTH assay measures only the “whole” molecule (residues 1–84) because the antibodies used recognize epitopes in the regions of amino acids 1–5 and 50–65 (16). This assay …