Ouseph R, Leiser JD, Moe SM
Calcitriol and the parathyroid hormone -- ionized calcium
curve: a comparison of methodologic approaches
J Am Soc Nephrol
(Mar) 7:497-505 1996

Objective: To clarify the effect of calcitriol on the inverse
sigmoidal relationship between parathyroid hormone (PTH) and
ionized calcium (iCa).
Methods: PTH-iCa curves were constructed in 8 chronic hemodialysis
patients with mild to moderate secondary hyperparathyroidism (PTH
289-839 pg/mL, nl < 65) by inducing hypo- and hypercalcemia through
alterations in dialysate calcium concentrations. Studies were
performed during treatment with low-bicarbonate (25 mM) and
standard-bicarbonate (35-40 mM) dialysate in order to determine the
effect of acute metabolic acidosis on the PTH-iCa curve.
Subsequently, patients were treated with 0.02 ug/kg calcitriol
intravenously after each HD session for 4 weeks and the PTH-iCa
curves repeated. The inverse sigmoidal relationship between PTH
and iCa was analyzed using a full curve four-parameter fit (max
PTH, min PTH, set point and slope) as well as a graphical fit. The
slope of the curve was expressed as a non-normalized slope as well
as a normalized slope (i.e., non-normalized slope divided by
(maxPTH - minPTH)) to correct for different magnitudes of PTH
response. Use of the normalized slope thus partially corrects for
gland mass and cell-secretory capacity, thereby allowing
determination of the sensitivity of secretory activity to changes
in iCa level.
Results: Calcitriol decreased basal, maximal and minimal PTH and
non-normalized slope, but did not affect set point or normalized
slope. Acute metabolic acidosis did not affect the PTH-iCa
relationship.
Conclusion: Caclitriol appears to decrease parathyroid gland
functional mass (i.e., decreases PTH levels) but does not affect
the sensitivity of the gland to changes in iCa concentration.
Comment: This is a rigorously performed study that clarifies the
realtionship between PTH and iCa in secondary hyperparathyrodism.
Increased PTH in uremia may be due to several mechanisms, including
1) increased tissue mass, resulting in increased secretion of
hormone; 2) increased tissue mass plus altered calcium set-point,
i.e., the iCa concentration required to inhibit 50% of maximal PTH
secretion, necessitating higher iCa levels to inhibit PTH
secretion; 3) increased tissue mass, set-point, plus a change in
the slope of the sigmoid curve, possibly indicating heterogeneity
of set-points among parathyroid cells (this is the most often cited
mechanism). The data of Ouseph et al. do not support an alteration
in set-point; rather, these authors conclude that calcitriol
appears to lower PTH levels by decreasing functioning tissue mass.
Their data are consistent with the observation that the iCa level
that maximally suppresses PTH secretion (10.4-11.2 mg/dl total
calcium) is unchanged in ESRD patients with secondary
hyperparathyroidism. (David J. Leehey, M.D., Loyola University School of
Medicine)