Measurement of Parathyroid Hormone

Abstract

Interpretation of serum immunoreactive PTH measurements requires an understanding of the secretion, metabolism, and heterogeneity of circulating immunoreactive PTH. Both intact hormone and biologically inactive carboxyl fragments containing the middle and C-terminal regions are secreted by the parathyroid glands. Inactive fragments also are produced peripherally by metabolism of intact hormone by liver and kidney. Inactive fragments represent 75 to 95% of the total immunoreactivity in serum, a consequence of their long half-life in vivo as compared with intact hormone. Immunoassays for PTH can be divided into those measuring intact hormone (N-terminal, intact) and those measuring both inactive fragments and intact hormone (mid-region, C-terminal, polyvalent). The latter principally measures inactive fragments because of their greater concentration as compared with intact hormone in peripheral serum. The clinical utility of PTH assays varies considerably because of differences in their specificity and sensitivity. Serum PTH levels have been more often observed to be elevated in individuals with primary hyperparathyroidism with the use of research quality radioimmunoassays that recognize both inactive fragments and intact hormone than with conventional N-terminal or intact assays. Homologous mid-region assays have provided exceptional clinical sensitivity in confirming primary hyperparathyroidism. Comparison of a sensitive mid-region radioimmunoassay with a recently developed two-site, noncompetitive chemiluminescent immunoassay for intact PTH indicated that both methods were highly useful in the differential diagnosis of hypercalcemia. The mid-region assay provided the best diagnostic sensitivity in primary hyperparathyroidism with more elevated levels of PTH. The sensitivity of the intact assay was good, a significant improvement over conventional N-terminal and intact assays. The specificity of the intact assay was clearly superior, with measured PTH levels found to be suppressed to below normal in most subjects with hypercalcemia associated with malignancy. In contrast, measured levels were primarily normal with the mid-region assay. The higher levels of immunoreactive PTH observed in nonparathyroid hypercalcemia with the mid-region assay are in agreement with the measurement of biologically inactive carboxyl fragments, which continue to be secreted in hypercalcemia.