Whole or Fragmentary Information on Parathyroid Hormone?

Abstract

More than a decade ago, Brossard et al. (1) drew attention to the fact that the so-called “intact,” second-generation parathyroid hormone (PTH) assays measured not only the PTH-(1-84) molecule but also large PTH fragments in patients with chronic kidney disease (CKD). One of the major problems is that the proportion of PTH-(1-84) and its fragments in the circulation changes in response to the serum level of ionized calcium; therefore, in presence of hypercalcemia, the parathyroid gland releases less PTH-(1-84) but more PTH fragments. The reverse is true in the presence of hypocalcemia, where more active PTH-(1-84) is needed. The difference is particularly striking in patients with CKD. When considering the potential biologic relevance of this finding, it is even more disturbing that at least one of the fragments, namely PTH-(7-84), has been shown to act as a partial antagonist of PTH-(1-84), with opposite biologic activities (2–4). Progressive awareness of these methodologic problems and the underlying biologic complexity went along with the development of third-generation PTH assays that recognize only PTH-(1-84), also called “whole,” “bio-intact,” or “biologically active” PTH (5). Theoretically, the assessment of second- and third-generation PTH assays combined should reflect parathyroid activity more adequately than second-generation assays alone, reflecting the sum of potentially opposing effects of PTH-(1-84) and its fragments. …