Abnormal Regulation of Parathyroid Hormone Release by Calcium in Secondary Hyperparathyroidism due to Chronic Renal Failure*

Abstract

Dispersed parathyroid cells were employed to study calcium-regulated parathyroid hormone (PTH) release in severe secondary hyperparathyroidism due to chronic renal insufficiency. Cell preparations were obtained from 16 parathyroid glands of 6 patients undergoing subtotal parathyroidectomy for parathyroid bone disease and/or hypercalcemia. The effects of increasing ambient calcium concentration on immunoreactive PTH release in vitro were assessed and compared with results observed in cells prepared from 7 adenomas and 6 normal parathyroid glands. There was no difference in maximal PTH release for the 3 types of tissue (mean ± SEM, 8.48 ± 1.9, 8.1 ± 3, and 10.1 ± 0.78 ng/10⁵ cells-h respectively). In 14 of 16 hyperplastic glands, 6 of 7 adenomas, and all of the normal glands, PTH release was inhibited more than 50% by 2–3 mM calcium (suppressible glands). Of the normal glands, half of the maximal inhibition of PTH release (the set-point) occurred at less than 1.03 mM calcium in 5 of 6 cases. In 12 of 14 suppressible hyperplastic glands and all of the 6 suppressible adenomas, on the other hand, the set-point was 1.03 mM or higher (P < 0.01 and P< 0.002, respectively). Thus, in severe secondary parathyroid hyperplasia due to chronic renal insufficiency, there is frequently an increase in the set-point for calcium without a change in the maximal secretory rate per cell. Abnormal calcium-regulated PTH release at the cellular level, therefore, is not limited to parathyroid neoplasia (i.e. adenoma or primary hy-perplasia), but may occur in secondary hyperplasia as well.