DIFFERENT EFFECTS OF CALCITRIOL AND PARATHYROIDECTOMY ON THE PTH-CALCIUM CURVE IN DIALYSIS PATIENTS WITH SEVERE HYPERPARATHYROIDISM

Background. The PTH-calcium sigmoidal curve is shifted to the right, t he slope of the curve is steeper, and the set point of calcium is incr eased in dialysis patients with secondary hyperparathyroidism, compare d to patients with low-turnover bone disease. These findings could be related to increased parathyroid cell mass and increased sensitivity o f parathyroid cells to serum calcium variations in these patients. Cal citriol therapy has been documented to reduce PTH levels by shifting t he curve to the left and downward. The effect of a surgical reduction of parathyroid gland mass on the PTH-calcium curve has not yet been in vestigated. In this study we compared the effects of calcitriol and su btotal parathyroidectomy (PTH) on the dynamics of PTH secretion in res ponse to acute changes of serum calcium in two groups of dialysis pati ents with severe hyperparathyroidism. Methods. Fourteen dialysis patie nts treated for 6 months with high-dose i.v. calcitriol (1-2 mu g thri ce weekly), and 10 dialysis patients who underwent subtotal PTx were s tudied. The PTH-calcium relationship obtained by inducing hypo- and hy percalcaemia by means of low and high calcium dialysis was evaluated b efore and 2-6 months after treatment. Results. Both calcitriol and sub total PTx significantly decreased PTH (respectively from 797+/-545 to 380+/-244 and from 1036+/-250 to 70+/-34 pg/ml), as well as maximal PT H response to hypocalcaemia (PTHmax), and maximal PTH suppression duri ng hypercalcaemia (PTHmin). When the PTH-calcium curves were construct ed using PTHmax as 100% to factor for differences in absolute PTH leve ls and to provide an assessment of individual parathyroid cell functio n, a shift of the sigmoidal curve to the left and downward, and a sign ificant decrease in the set point of ionized calcium (from 1.31+/-0.05 to 1.26+/-0.05 and from 1.36+/-0.09 to 1.22+/-0.07 mmol/l) was docume nted with both treatments. However, the slope of the PTH-calcium curve increased after subtotal PTx indicating that the sensitivity of the p arathyroid cell to serum calcium changes increased with PTx, while on the contrary it decreased with calcitriol. Conclusions. PTH secretion decreases proportionally more with calcitriol than with surgery for a given decrease in the functional mass of parathyroid cells. The change in the PTH-ICa sigmoidal curve induced by subtotal PTx is due to the removal of a large mass of parathyroid tissue with advanced hyperplasi a.