Endocrine Abstracts

The cell surface calcium receptor (CaR) in the parathyroid gland plays a central role in the regulation of serum calcium homeostasis. Activation and inactivation mutations in the CaR lead to chronic hypocalcemia and hypercalcemia states (Brown, EM. Mutations in the calcium-sensing receptor and their clinical implications. Horm Res 1997 48 199–208). Type 11 calcimimetics are a novel class of compounds that directly reduce PTH secretion from the parathyroid cell by binding to the CaR and increasing its sensitivity to extracellular ionized calcium, thus causing a left-shift in the Ca-PTH setpoint (Nemeth, EF et al. Calcimimetics with potent and selective activity on the parathyroid calcium receptor. PNAS USA 1998 95 4040–4045). Cinacalcet is an oral calcimimetic that has been shown to reduce serum PTH and calcium in secondary hyperparathyroidism of renal failure (Block, GA et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 2004 350 1516–1525), in primary hyperparathyroidism (Peacock et al. Cinacalcet Hydrochloride maintains long-term normocalcemia in patients with hyperparathyroidism. J Clin Endocrinol 2005), and in parathyroid cancer (Silverberg, SJ et al. Cinacalcet reduces hypercalcemia in patients with parathyroid carcinoma. J Bone Min Res 2006 21 Suppl. 1 S440).

Cinacalcet therapy is well tolerated long-term, and current studies indicate that it may play a valuable role in the medical management of diseases of hyperparathyroidism.