The parathyroid glands in chronic renal failure: a study of their growth and other properties made on the basis of findings in patients with hypercalcemia

Abstract

We investigated the growth of hyperplastic parathyroid glands removed at operation from 16 patients with chronic renal failure complicated by hypercalcemia, by incubating fresh tissue with tritiated thymidine. In each gland the proportion of cells synthesizing DNA was determined directly by counting labeled nuclei after autoradiography and indirectly from incorporation of label into DNA, and the mean diameter of chief cell nuclei was measured. Both DNA synthesis and mean nuclear diameter were positively correlated with plasma calcium level. Assuming the mean duration of S phase to be 12 hours, the birthrate of new cells (mean +/- SD) was 18.5% +/- 23.6% per year, significantly (p less than 0.05) greater than the 11.5% +/- 7.4% per year found in 63 parathyroid adenomas previously studied. On the basis of estimated disease duration, the minimum birthrate needed to grow glands of the observed weight was 23.4% +/- 16.5% per year. The similarity between observed and needed birthrates indicates that the glands were growing almost as fast as when renal failure began, and that parathyroid growth was no longer regulated in accordance with normal plasma calcium homeostasis. To account for this, we propose that the disordered growth is a consequence of an increase in secretory set point, which in turn is a consequence of calcitriol deficiency. Because the effectiveness of parathyroid hormone is impaired in renal failure, a large increase in total hormone secretion is needed to raise the plasma calcium level to the new set point, and the necessary increase in gland size can be achieved only by a sustained increase in the rate of cell division.