Radioimmunoassay for the Middle Region of Human Parathyroid Hormone Using an Homologous Antiserum with a Carboxy-Terminal Fragment of Bovine Parathyroid Hormone as Radioligand*

Abstract

A new type of RIA for human parathyroid hormone (hPTH) is described. The antiserum was generated in a goat against hPTH, and the radioligand is a carboxy-terminal fragment of bovine PTH (bPTH). Although the antiserum is bivalent, use of the fragment as tracer yields an assay monospe-cific for the midregion of the PTH molecule. The assay can detect 0.3 fmol/tube of intact hPTH-(l–84) or 0.1 fmol synthetic hPTH-(44–68), but does not detect hPTH-(l–34), hPTH-(53–84), or bPTH-(28–48). Immunoreactive PTH (iPTH) was detectable in 85 of 92 normal subjects, with a normal range of about 0.1–0.5 µU/ml hPTH Research Standard 75/549. iPTH was undetectable in 22 consecutive severely hypoparathyroid patients and was above normal in 147 of 158 patients with primary hyperparathyroidism. In 60 patients with nonparathy-roid hypercalcemia, iPTH averaged 20% lower than in normal subjects, but was still detectable in 80%. Mean iPTH values in hypercalcemia due to malignancy or other nonparathyroid causes were indistinguishable. When renal insufficiency supervened in those with nonparathyroid hypercalcemia, iPTH tended to increase, and reached levels 3- to 4-fold above normal when serum creatinine was above 5 mg/dl. In chronic renal failure, iPTH levels were 5- to 36-fold above normal in patients just beginning hemodialysis and 60- to 600-fold evaluated in those with severe osteitis fibrosa. The distribution of iPTH values in hypercalcemic chronic hemodialysis patients was bimodal; values were about 600-fold elevated in patients whose hypercalcemia responded to parathyroidectomy (tertiary hyper-parathyroidism), but only 2- to 20-fold increased in those with nonparathyroid hypercalcemias. The assay was sensitive enough t o detect changes that occurred spontaneously in normal subjects or were induced by EDTA infusion. The assay was also useful in detecting venous gradients of PTH. This new assay, with its excellent sensitivity, provides a useful diagnostic and research tool for studies of human parathyroid function. (J Clin Endocrinol Metab54: 1017, 1982)