Dynamics of secretion and metabolism of PTH during hypo- and hypercalcaemia in the dog as determined by the 'intact' and 'whole' PTH assays

Abstract

Background. Recent evidence has shown that the assay for 'intact' parathyroid hormone (I-PTH) not only reacts with 1-84 PTH but also with large non-1-84 PTH fragments, most of which is probably 7-84 PTH. As a result, an assay specific for 1-84 PTH named 'whole' PTH (W-PTH) has been developed. The present study was designed: (i) to determine whether the W-PTH assay reliably measures PTH values in the dog; (ii) to evaluate differences between the W-PTH and I-PTH assays during hypo- and hypercalcaemia; and (iii) to assess the peripheral metabolism of W-PTH and I-PTH. Methods. In normal dogs, hypocalcaemia was induced by EDTA infusion and was followed with a 90 min hypocalcaemic clamp. Hypercalcaemia was induced with a calcium infusion. Results. I-PTH and W-PTH values increased from 36±8 and 13±3 pg/ml (P=0.01) at baseline to a maximum of 158±40 and 62±15 pg/ml (P=0.02 vs I-PTH) during hypocalcaemia. The W-PTH/I-PTH ratio, 38±4% at baseline, did not change during the induction of hypocalcaemia, but sustained hypocalcaemia increased (P<0.05) this ratio. During hypercalcaemia, maximal suppression for I-PTH was 2.0±0.5 and only 5.7±0.6 pg/ml for W-PTH, due to a decreased sensitivity of the W-PTH assay at values < 5 pg/ml. The disappearance rate of PTH was determined in five additional dogs which underwent a parathyroidectomy (PTX). At 2.5 min after PTX, W-PTH was metabolized more rapidly, with a value of 25±2% of the pre-PTX value vs 30±3% for I-PTH (P<0.05). Conclusions. (i) The W-PTH/I-PTH ratio is less in the normal dog than in the normal human, suggesting that the percentage of non-1-84 PTH measured with the I-PTH assay is greater in normal dogs than in normal humans; (ii) the lack of change in the W-PTH/I-PTH ratio during acute hypocalcaemia is different from the situation observed in humans; and (iii) the dog appears to be a good model to study I-PTH and W-PTH assays during hypocalcaemia.