Endocrine Abstracts

Surgical parathyroidectomy remains the most cost effective treatment for primary hyperparathyroidism but where surgery is inappropriate because of significant co-morbidity there is a place for medical therapy. Calcimimetics are type II agonists (requiring calcium for activity) of the calcium sensing receptor (CaSR). The first compound of this class is cinacalcet which reduces PTH by about 50% at 4 h with recovery to within 20% of baseline over the next 8 h. Despite these fluctuations in PTH it is possible to achieve stable normocalcaemia over a 24 h period without loss of effect in studies extending out to 4 years. Most patients with modest HPTH (<2.85 mmol/l) will require 60–90 mg/day although those with hypercalcaemia > 3 mmol/l will require 90 mg twice daily or more to achieve normocalcaemia.

Despite the achievement of normocalcaemia calcium excretion does not fall because the reduced filtered load of calcium (Ca⁺⁺× GFR) is balanced by loss of distal renal tubular calcium reabsorption consequent on the fall in PTH. Serum concentrations of 1,25 (OH)₂ D are also maintained because a reduction due to the fall in PTH is balanced by direct stimulation of theproximal convoluted tubular CaSR which activates the 1 α hydroxylase. A disappointing finding is that bone turnover and BMD are notimproved by cinacalcet. This may be due to the transientnature of the control of PTH since BMD increases when PTH is reduced by parathyroidectomy. It is also likely that the changes in PTH produced by cinacalcet have a more prolonged time course than, for example, the short spike of concentration produced by teriparatide which is anabolic to bone. However several studies have shown that bisphosphonates protect the skeleton from HPTH and in patients with osteoporosis due to HPTH co-prescription with cinacalcet will be needed.