Recent advances in parathyroid hormone research

The introduction of blood calcium determinations as part of routine health screening procedures in this country has led to the discovery of a much higher incidence of primary hyperparathyroidism than was recognized previously. Research efforts have focused on studies of the cellular defects in the regulation or parathyroid hormone biosynthesis and secretion that are characteristically found in adenomatous and hyperplastic parathyroid glands. The available evidence indicates that the secretory defect probably resides at two levels: (1) a defect in the calcium sensor of the abnormal glands ("set-point" error) and (2) an exaggeration of a small component of autonomous hormone secretion that becomes relevant due to the large mass of glandular tissue. Regulation of parathyroid hormone synthesis appears to be at the level of cell replication (hyperplasia) and at the level of intracellular turnover of hormone. Marked heterogeneity of hormone in the circulation arises as a result of both glandular and extraglandular cleavages of hormone and the predominant circulating form of the hormone are biologically inactive, COOH-terminal fragments. Because most cases of hypercalcemia that accompany cancer are caused by humoral substances other than COOH-terminal fragments should distinguish patients with hypercalcemia due to cancer from those with primary hyperparathyroidism.