Pathogenesis of secondary hyperparathyroidism.
The past 20 years has witnessed a dramatic improvement in our understanding of the factors involved in the pathogenesis of secondary hyperparathyroidism in chronic renal insufficiency. The major causes are retention of phosphorus, relatively low levels of serum calcium, and decreased 1,25-(OH)2D3 (calcitriol) levels. Abnormalities in vitamin D metabolism are responsible for a series of events that result in a state of abnormal calcium-regulated parathyroid hormone (PTH) secretion. In patients with a moderate degree of renal insufficiency, phosphate restriction suppresses PTH secretion by increasing serum calcitriol. However, studies in patients and dogs with advanced renal insufficiency have clearly demonstrated that phosphate per se, independent of the levels of calcitriol or ionized calcium, has an important effect on the secretion of PTH. In addition, low levels of calcitriol, characteristically seen in patients with advanced renal insufficiency, may affect the response of the parathyroid glands to serum ionized calcium. A shift in the set-point for calcium-regulated PTH secretion requires a much higher concentration of serum calcium to suppress the release of PTH. Studies evaluating the administration of intravenous calcitriol have clearly demonstrated that the parathyroid glands become more sensitive to calcium and the suppression of PTH secretion can be achieved with physiologic levels of ionized calcium. In addition, the number of calcitriol receptors in the parathyroid glands of patients and experimental animals with advanced renal failure is low. Investigators have shown that the administration of calcitriol to normal rats increases the mRNA of the vitamin D receptor. Thus, calcitriol upregulates the number of its own receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Slatopolsky
E
E
Chromalloy American Kidney Center, St. Louis, MO.
Delmez
J A
JA
D000818:Animals; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000150:complications*