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

Nephrol Dial Transplant. 2003 Jun;18(6):1101-7. doi: 10.1093/ndt/gfg104.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Chloride
  • Disease Models, Animal
  • Dogs
  • Edetic Acid
  • Female
  • Hypercalcemia / chemically induced
  • Hypercalcemia / metabolism*
  • Hypocalcemia / chemically induced
  • Hypocalcemia / metabolism*
  • Immunoradiometric Assay
  • Infusions, Intravenous
  • Kidney / physiology
  • Male
  • Parathyroid Hormone / metabolism*
  • Peptide Fragments / blood

Substances

  • Parathyroid Hormone
  • Peptide Fragments
  • Edetic Acid
  • Calcium Chloride