IMPROVEMENT OF SECONDARY HYPERPARATHYROIDISM AND REDUCTION OF THE SET-POINT OF CALCIUM AFTER INTRAVENOUS CALCITRIOL

In this study we evaluated the effect of intravenous calcitriol on par athyroid function and ionized calcium/PTH sigmoidal curve obtained dur ing low and high calcium hemodialysis in 10 patients with osteitis fib rosa whose secondary hyperparathyroidism was refractory to conventiona l therapy. After four months of intravenous calcitriol, serum ionized calcium increased from 1.28 +/- 0.08 to 1.37 +/- 0.11 mmol/liter (P < 0.001), serum phosphate from 1.54 +/- 0.18 to 1.79 +/- 0.4 mmol/liter (P = NS), serum calcitriol from 16.7 +/- 9.9 to 34.3 +/- 6.4 pg/ml (P < 0.001), while alkaline phosphatase decreased from 366 +/- 340 to 226 +/- 180 IU/liter (P < 0.05), osteocalcin from 46.4 +/- 20 to 34.5 +/- 15.3 ng/ml (P < 0.05) and basal intact PTH from 1069 +/- 700 to 305 /- 270 (P < 0.01). Basal PTH started to decrease after one month of tr eatment prior to the increase in the ionized calcium. Because of hyper calcemia, the dialysate calcium was decreased from 1.75 to 1.5 mmol/li ter in three of five patients on hemodialysis and calcium-containing s olutions were substituted by calcium-free replacement fluids in four o f five patients on hemodiafiltration. Calcitriol dose at the first mon th of therapy was 5.6 +/- 0.8 mug/week, but successively it was decrea sed because of hypercalcemia to a final dose of 3.6 +/- 1.3 mug/week. After intravenous calcitriol the ionized calcium/PTH sigmoidal curve s hifted to the left and downward. Maximally stimulated PTH and maximall y inhibited PTH obtained during low and high calcium dialysis signific antly decreased as did the ratio of basal PTH/PTH(max) and the set poi nt of calcium. Despite the marked decrease in baseline PTH, two patien ts were considered non-responders as the reduction in PTH was exclusiv ely due to severe hypercalcemia, since the set point of calcium and io nized calcium/PTH curve did not change. In conclusion. intravenous cal citriol is effective in lowering PTH levels and shifting toward normal the ionized calcium-PTH curve in most patients whose secondary hyperp arathyroidism is refractory to conventional therapy. To prevent the de velopment of hypercalcemia, particularly in patients treated with calc ium salts as phosphate binders, the use of low calcium dialysate is ad visable. When, during intravenous calcitriol treatment, despite the de crease in baseline PTH, persistent hypercalcemia or increased calcium- phosphate product develop and the ionized calcium-PTH curve does not s hift toward normal parathyroidectomy should be considered.