Examination of Circulating Parathyroid Hormone in Pseudohypoparathyroidism*

We examined characteristics of circulating PTH in three patients with pseudohypoparathyroidism type I. All patients were normocalcemic while receiving vitamin D therapy at the time of study. In all three, immunoreactive PTH levels were elevated, whereas bioactive levels were low or low normal. Analysis of plasma immunoreactivity by high performance liquid chromatography revealed a relative increase in hydrophobic moieties compared to patterns in patients with other hyperparathyroid states. Plasma or serum from these patients inhibited the stimulatory action of exogenous bovine PTH in an in vitro renal cytochemical bioassay and an in vitro renal adenylate cyclase assay. Such inhibition persisted after partial reduction, in one patient, of circulating immunoreactive PTH levels by an acute calcium challenge. Patient plasma did not bind bioactive 125I-labeled PTH in vitro. The results demonstrate abnormal persistence of elevated immunoreactive PTH levels in normocalcemic patients with pseudohypoparathyroidism, indicate that this circulating hormone may be altered, and suggest that a defect in PTH release and/or metabolism may accompany the other biochemical abnormalities known to occur in this disorder.