Increase in IDDM incidence in Bulgarian children (1974-1995)

OBJECTIVE: Despite the clear recognition that extracellular ionized calcium controls PTH secretion, there have been suggestions of hysteresis in the relationship between extracellular ionized calcium and PTH during recovery from induced hypo- and hypercalcaemia in vivo in humans. In this study, we examined the possibility that release of intracellular stored PTH during induced hypocalcaemia may explain hysteresis. VOLUNTEERS: Eleven volunteers, five women and six men, were recruited to participate in the study. DESIGN: A series of three protocols of repeated induction of hypocalcaemia or sequential induction of hypo- and hypercalcaemia. RESULTS: We observed in a total of 13 trials that a drastic lowering 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 times the baseline concentration. However, following a steady-state period of hypocalcaemia, a subsequent lowering of blood ionized calcium either following a brief return to normocalcaemia (protocol 1), from the initial hypocalcaemic level of blood ionized calcium (protocol 2) or after a brief period of induced hypercalcaemia (protocol 3) gave either no peak release of PTH or a markedly blunted peak. Thus, the PTH response during the initial induction of and the first recovery from hypocalcaemia in our protocol 3 showed significant hysteresis in the relationship 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 hysteretic relationship was observed during induction, recovery and re-induction of hypercalcaemia in protocol 3 (NS). CONCLUSION: We believe that the release of what might be preformed, intracellular stored depot PTH can explain, at least in part, the observed hysteretic PTH-calcium relationship in normal humans.