Selective determination of C-terminal (70–84) hPTH: elevated concentrations in cholestatic liver disease

Abstract

In order to obtain a better resolution of circulating PTH-fragments, we developed a radioimmunoassay with an antiserum raised against the synthetic 70-84 hPTH molecule in a sheep. [125I](69 Tyr) 70-84 hPTH was used as the radioactive tracer with the antiserum at a final dilution of 1:200,000. Displacement curves showed that only the 70-84 hPTH. (69 Tyr) 70-84 hPTH and 53-84 hPTH fragments were able to compete with the tracer. Synthetic 28-48 hPTH, 44-68 hPTH, (61 Tyr) 62-68 hPTH, purified 1-84 hPTH and 53-84 bPTH showed no ability to displace the tracer indicating that the idiotype of the antibody is directed against the 70-84 portion that is usually hidden within the globular structure of the intact molecule. Healthy adults revealed PTH-peptide levels of 153 .+-. 86 pg/ml (mean .+-. 2 SD); 2 SD range: 67-239 pg/ml. C-terminal PTH-peptide (70-84 hPTH) concentration was normal in patients with primary hyperparathyroidism and chronic renal failure, thus excluding that neither the kidney nor the parathyroid gland is involved in the generation of this C-terminal PTH-peptide sequence. Increased levels of 70-84 hPTH immunoreactivity were found in most individuals with severe cholestatic liver disease. Since the liver appears to be responsible for part of the peripheral PTH metabolism, this assay system might be used as an indicator of altered liver function.