Pathogenesis of secondary hyperparathyroidism.

Hyperplasia of the parathyroid glands and increased concentrations of immunoreactive parathyroid hormone are among the earlier alterations of mineral metabolism in patients with chronic renal failure. In the past five years several investigators have demonstrated that phosphorus retention plays a key role in the development of secondary hyperparathyroidism and chief cell hyperplasia of the parathyroid glands. Since phosphorus regulates the production of 1,25D3 by altering the enzyme 1-alpha-hydroxylase it is possible that the effect of phosphorus retention is mediated by a decrease in the synthesis of 1,25D3. This has been shown in patients with early renal insufficiency. However, in patients with advanced renal failure the reduced renal mass may limit the production of 1,25D3. It is clear now that phosphorus per se independent of the levels of ionized calcium and 1,25D3 can increase the synthesis and secretion of PTH in vivo and in vitro. The abnormalities in vitamin D metabolism are not only characterized by low levels 1,25D3 but by low number of vitamin D receptors. Thus, the parathyroid glands are resistant to the action of 1,25D3 and high pharmacological concentrations of 1,25D3 in blood are necessary to suppress the levels of parathyroid hormone in advanced renal failure. The development of monoclonal changes in glands obtained from patients with secondary hyperparathyroidism further complicates the treatment of secondary hyperparathyroidism in patients maintained on haemodialysis. Thus, correction of serum phosphorus is imperative for the success of 1,25D3 to control the levels of parathyroid hormone. Currently several laboratories are studying at the molecular level the mechanisms by which dietary phosphorus induces chief cell hyperplasia.