Different effects of calcitriol and parathyroidectomy on the PTH—calcium curve in dialysis patients with severe hyperparathyroidism

Abstract

The PTH-calcium sigmoidal curve is shifted to the right, the slope of the curve is steeper, and the set point of calcium is increased in dialysis patients with secondary hyperparathyroidism, compared to patients with low-turnover bone disease. These findings could be related to increased parathyroid cell mass and increased sensitivity of parathyroid cells to serum calcium variations in these patients. Calcitriol therapy has been documented to reduce PTH levels by shifting the 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 investigated. In this study we compared the effects of calcitriol and subtotal parathyroidectomy (PTH) on the dynamics of PTH secretion in response to acute changes of serum calcium in two groups of dialysis patients with severe hyperparathyroidism. Fourteen dialysis patients treated for 6 months with high-dose i.v. calcitriol (1-2 micrograms thrice weekly, and 10 dialysis patients who underwent subtotal PTx were studied. The PTH-calcium relationship obtained by inducing hypo- and hypercalcaemia means of low and high calcium dialysis was evaluated before and 2-6 months after treatment. Both calcitriol and subtotal PTx significantly decreased PTH (respectively from 797 +/- 595 to 380 +/- 244 and from 1036 +/- 250 to 70 +/- 34 pg/ml), as well as maximal PTH response to hypocalcaemia (PTHmax), and maximal PTH suppression during hypercalcaemia ( PTHmin). When the PTH-calcium curves were constructed using PTHmax as 100% to factor for differences in absolute PTH levels and to provide an assessment of individual parathyroid cell function, a shift of the sigmoidal curve to the left and downward, and a significant 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 documented with both treatments. However, the slope of the PTH-calcium curve increased after subtotal PTx indicating that the sensitivity of the parathyroid cell to serum calcium changes increased with PTx, while on the contrary it decreased with calcitriol. 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 hyperplasia.