Intravenous 1,25(OH)2D therapy increases the intact parathyroid hormone secretion set point in hemodialyzed patients

We have studied the effect of intravenous calcitriol [1,25(OH)2D] therapy (1 microgram at the end of each dialysis session) on parathyroid secretory curves of hemodialyzed patients with near-normal basal intact (< 10 pmol/l, n = 7; NNBI) or elevated basal intact (> 10 pmol/l, n = 6; EBI) parathyroid hormone (PTH; iPTH) levels. These results were compared with those obtained in matched normal individuals (N). Our main objective was to define the influence of intravenous 1,25(OH)2D therapy on the set point of iPTH stimulation in relation to the severity of secondary hyperparathyroidism. A complete parathyroid function was obtained by CaCl2 and Na2EDTA infusions in 14 N and by modification of the dialysate calcium content in 13 hemodialyzed patients. Ionized calcium (Ca2+) and iPTH were measured regularly during hypo- and hypercalcemia. Parathyroid secretory curves were derived from these data. Both groups of patients had lower basal Ca2+ (NNBI 1.16 +/- 0.05; EBI 1.10 +/- 0.03; N 1.25 +/- 0.04 mmol/l; p < 0.001) and higher basal iPTH (NNBI 6.3 +/- 2.5; EBI 49.2 +/- 39.5; N 2.5 +/- 0.8 pmol/l; p < 0.01) levels than N with more extreme values in EBI than in NNBI patients (p < 0.001). NNBI patients had stimulated iPTH levels similar to N (18.4 +/- 7.1 vs. 17.3 +/- 7.2 pmol/l), while these levels were markedly increased in EBI patients (80.7 +/- 46.0 pmol/l; p < 0.001). After 1,25(OH)2D therapy, Ca2+ increased to 1.16 +/- 0.03 mmol/l in EBI and normalized in NNBI patients (1.25 +/- 0.07 mmol/l). Stimulated iPTH decreased by 30% in NNBI (p < 0.05) and by 21% in EBI patients (NS). These two factors contributed to a decrease in basal iPTH by 52% in NNBI (p < 0.05) and by 40% in EBI (p < 0.01). The set point of iPTH stimulation was lower than in N (1.18 +/- 0.04 mmol/l) and increased with intravenous 1,25(OH)2D therapy from 1.09 +/- 0.03 to 1.16 +/- 0.05 mmol/l in NNBI (p < 0.05) and from 1.08 +/- 0.04 to 1.12 +/- 0.04 mmol/l in EBI patients (p < 0.05). The set points and changes in set point were correlated with basal Ca2+ (r = 0.56; p = 0.003) and changes in basal Ca2+ (r = 0.64; p = 0.04) observed before and during therapy. The starting position of each patient on his secretory curve before and after 1,25(OH)2D therapy was inversely related to his starting Ca2+ concentration (n = 26; r = -0.66; p = 0.0003). Taking this into account improved the relationship between Ca2+ concentration and the set point of iPTH stimulation by Ca2+ in a stepwise regression (R2 = 0.62; p = 0.0003). However, no correlation was found between set points and stimulated iPTH values. We concluded that 1,25(OH)2D therapy induced an increase in the set point of PTH stimulation in hypocalcemic hemodialyzed patients related to a similar increase in basal Ca2+ concentration. This is in part related to the starting position of each patient on his secretory curve which will affect his set point in relation to the hysteresis phenomenon in iPTH secretion. But the set point of PTH stimulation is also related to the basal ionized calcium concentration by mechanisms yet to be elucidated.