ALTERED INSTANTANEOUS AND CALCIUM-MODULATED OSCILLATORY PTH SECRETIONPATTERNS IN PATIENTS WITH SECONDARY HYPERPARATHYROIDISM

The relative contributions of increased parathyroid cell mass and alte red control mechanisms of parathyroid hormone (PTH) secretion in secon dary hyperparathyroidism are still controversial. In this study, endog enous pulsatile PTH secretion was analyzed by the multiparameter decon volution technique to differentiate alterations in cell mass-dependent (PTH burst mass) and regulation-dependent (frequency, synchrony, calc ium responsiveness) PTH release in uremic patients. PTH concentration versus time profiles were obtained in 13 uremic and 16 healthy adults under baseline conditions and during acute hypo- and hypercalcemia. Pl asma PTH half-life was increased in patients compared with control sub jects (4.7 +/- 1.9 versus 2.6 +/- 0.1 min, P < 0.005). The baseline PT H secretion rate was elevated eightfold in the patients as a result of an increased PTH mass secreted per burst (17.1 +/- 4.7 versus 2.0 +/- 0.4 pM, P = 0,0001), higher burst frequency (8.0 +/- 0.3 versus 6.8 /- 0.3 h(-1), P < 0.01), and a higher tonic secretion rate (343 +/- 99 versus 30 +/- 4 pM/h, P = 0.0001). Acute hypocalcemia elicited an imm ediate, frequency- and amplitude-mediated selective increase in the pu lsatile secretory component, which was fractionally weaker in patients (+595%) than control subjects (+1755%, P < 0.001). The acceleration a nd the amplification of PTH bursts were 35 and 60% lower in the patien t group. Acute hypercalcemia suppressed total PTH secretion by 79% in control subjects but only by 63% in patients (P < 0.002). PTH burst fr equency vt as reduced during hypercalcemia by 30% in control subjects, bur remained unchanged in patients. In conclusion, uremic hyperparath yroidism is mediated by a marked increase in glandular secretion, but also by reduced PTH elimination. The increased spontaneous PTH burst f requency and the blunted responsiveness to changes in Ca2+ indicate pa rtial uncoupling of hyper plastic parathyroid glands from the physiolo gic regulatory mechanisms that direct pulsatile PTH release.