EVIDENCE FOR A ROLE OF INTRACELLULAR STORED PARATHYROID-HORMONE IN PRODUCING HYSTERESIS OF THE PTH-CALCIUM RELATIONSHIP IN NORMAL HUMANS

OBJECTIVE Despite the clear recognition that extracellular ionized cal cium controls PTH secretion, there have been suggestions of hysteresis in the relationship between extracellular ionized calcium and PM duri ng recovery from induced hypo- and hypercalcaemia in vivo in humans. I n this study, we examined the possibility that release of intracellula r stored PM during induced hypocalcaemia may explain hysteresis. VOLUN TEERS Eleven volunteers, five women and six men, were recruited to par ticipate in the study. DESIGN A series of three protocols of repeated induction of hypocalcaemia or sequential induction of hypo- and hyperc alcaemia. RESULTS We observed in a total of 13 trials that a drastic l owering of blood ionized calcium by 0.20 mmol.l within 30 min elicited an immediate large, transient peak release of PTH amounting to 6-16 t imes the baseline concentration. However, following a steady-state per iod of hypocalcaemia, a subsequent lowering of blood ionized calcium e ither following a brief return to normocalcaemia (protocol 1), from th e initial hypocalcaemic level of blood ionized calcium (protocol 2) or after a brief period of induced hypercalcaemia (protocol 3) gave eith er no peak release of PTH or a markedly blunted peak. Thus, the PTH re sponse during the initial induction of and the first recovery from hyp ocalcaemia in our protocol 3 showed significant hysteresis in the rela tionship between blood ionized calcium and PTH (P<0.001), whereas, no hysteretic relationship could be shown during the second recovery from induced hypocalcaemia in four of five cases (NS). Moreover, no hyster etic relationship was observed during induction, recovery and re-induc tion of hypercalcaemia in protocol 3 (NS). CONCLUSION We believe that the release of what might be preformed, intracellular stored depot PTH can explain, at feast in part, the observed hysteretic PTH-calcium re lationship in normal humans.