Parathyroid sensing of the direction of change of calcium in uremia.

It could be advantageous for the parathyroids to be able to sense not only the absolute concentration of extracellular Ca2+, but also the rate and direction of change of Ca2+, thereby allowing the parathyroids to respond earlier to threats to Ca2+ homeostasis. By using high and low Ca2+ dialysis in a single session, we examined the parathyroid response to direction of change of Ca2+ during acute Ca2+ perturbation in nine hemodialysis patients. Separate PTH/ionized calcium (PTH/iCa) response curves were generated for rising Ca2+ and falling Ca2+. Significant directional hysteresis (higher PTH level during falling than during rising Ca2+) was found. During hypercalcemia, PTH levels were between 2.2 and 1.6 times higher at iCa concentrations of between 0 and +0.1 mM above the baseline iCa, when Ca2+ was falling than when it was rising. During the phase of induced hypocalcemia, parathyroid fatigue was seen in six of the nine patients. Fatigue patients tended to have higher basal PTH (1-84) levels than those not showing fatigue. The existence of fatigue provides an explanation for directional hysteresis during hypocalcemia, and therefore parathyroid sensing of the direction of change of Ca2+ could not be assessed during hypocalcemia. These studies demonstrate a capacity of the parathyroids to sense the direction of movement of Ca2+ during hypercalcemia.