CALCITRIOL AND THE PARATHYROID HORMONE-IONIZED CALCIUM CURVE - A COMPARISON OF METHODOLOGIC APPROACHES

Investigations of the effects of calcitriol on the inverse sigmoidal r elationship between parathyroid hormone (PTH) and ionized calcium (iCa ) have yielded contradictory conclusions, possibly because of variatio ns in experimental and analytical approaches. To clarify the existing literature, PTH-iCa curves were constructed by inducing hypo- and hype rcalcemia through alterations in dialysate calcium concentration in ei ght hemodialysis patients with mild to moderate secondary hyperparathy roidism. The effects of low (metabolic acidosis) versus normal bicarbo nate dialysis were compared before and after 4 wk of intravenous calci triol, in a cross-over design. The PTH-iCa curves were primarily evalu ated by using a four-parameter model. In addition, a variety of altern ative published analytic approaches were examined and PTH-iCa curve sl opes were further evaluated after normalization by (maximum - minimum PTH). The latter partially corrects for gland mass and cell-secretory capacity, and therefore yields a purer measure of the sensitivity of s ecretory activity to changes in iCa. The results of the study indicate that calcitriol decreased basal, maximal, and minimal PTH and non-nor malized slope (all P < 0.05), but did not affect set point or normaliz ed slope, independent of the specific analytic approach. Acute metabol ic acidosis did not affect the PTH-iCa curve. Thus, intravenous calcit riol appears to decrease parathyroid gland functional mass, as reflect ed by decreases in maximal and minimal PTH levels, but does not affect the sensitivity of the parathyroid gland to changes in iCa, as set po int and normalized slope were unaffected.