Influence of immunoheterogeneity of circulating parathyroid hormone on results of radioimmunoassays of serum in man

We describe the practical consequences of the immunoheterogeneity of circulating parathyroid hormone (PTH) in the routine evaluation of patients by radioimmunoassay of serum PTH, based on our experience with two radioimmunoassays of PTH using antiserums of widely different specificities. One antiserum is directed against the COOH-terminal region of the human PTH molecule, and it recognizes a major portion of the immunoreactive PTH in hyperparathyroid serum. The other antiserum is directed against the NH₂-terminal region of human PTH, and it recognizes only “native” molecules (molecular weight 9,500 daltons) and a low molecular weight form of the hormone; these comprise a relatively small proportion of the total immunoreactive species of PTH in hyperparathyroid serum. Assays of “total serum PTH” using the COOH-terminal antiserum correlated much better with the presence of suspected or proved hyperparathyroidism as well as with osteoclast counts in bone biopsy specimens from patients with primary hyperparathyroidism. On the other hand, results of assays using the NH₂-terminal antiserum better reflected acute changes in glandular secretion of PTH.