Schmitt C P, Huber D, Mehls O, Maiwald J, Stein G, Veldhuis J D, Ritz E, Schaefer F
Department of Pediatrics, University of Heidelberg, Germany.
J Am Soc Nephrol. 1998 Oct;9(10):1832-44. doi: 10.1681/ASN.V9101832.
The relative contributions of increased parathyroid cell mass and altered control mechanisms of parathyroid hormone (PTH) secretion in secondary hyperparathyroidism are still controversial. In this study, endogenous pulsatile PTH secretion was analyzed by the multiparameter deconvolution technique to differentiate alterations in cell mass-dependent (PTH burst mass) and regulation-dependent (frequency, synchrony, calcium 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. Plasma PTH half-life was increased in patients compared with control subjects (4.7+/-1.9 versus 2.6+/-0.1 min, P < 0.005). The baseline PTH 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 immediate, frequency- and amplitude-mediated selective increase in the pulsatile secretory component, which was fractionally weaker in patients (+595%) than control subjects (+1755%, P < 0.001). The acceleration and the amplification of PTH bursts were 35 and 60% lower in the patient group. Acute hypercalcemia suppressed total PTH secretion by 79% in control subjects but only by 63% in patients (P < 0.002). PTH burst frequency was reduced during hypercalcemia by 30% in control subjects, but remained unchanged in patients. In conclusion, uremic hyperparathyroidism is mediated by a marked increase in glandular secretion, but also by reduced PTH elimination. The increased spontaneous PTH burst frequency and the blunted responsiveness to changes in Ca2+ indicate partial uncoupling of hyperplastic parathyroid glands from the physiologic regulatory mechanisms that direct pulsatile PTH release.
在继发性甲状旁腺功能亢进中，甲状旁腺细胞质量增加和甲状旁腺激素（PTH）分泌控制机制改变的相对作用仍存在争议。在本研究中，采用多参数去卷积技术分析内源性PTH的脉冲式分泌，以区分尿毒症患者中细胞质量依赖性（PTH脉冲质量）和调节依赖性（频率、同步性、钙反应性）PTH释放的改变。在基线条件下以及急性低钙血症和高钙血症期间，对13名尿毒症成年人和16名健康成年人进行了PTH浓度随时间变化曲线的测定。与对照组相比，患者的血浆PTH半衰期延长（4.7±1.9分钟对2.6±0.1分钟，P<0.005）。由于每次脉冲分泌的PTH质量增加（17.1±4.7对2.0±0.4 pM，P = 0.0001）、脉冲频率更高（8.0±0.3对6.8±0.3 h⁻¹，P<0.01）以及基础分泌率更高（343±99对30±4 pM/h，P = 0.0001），患者的基线PTH分泌率升高了8倍。急性低钙血症引发了脉冲分泌成分的立即、频率和幅度介导的选择性增加，患者的增加幅度（+595%）比对照组（+1755%）小（P<0.001）。患者组中PTH脉冲的加速和放大分别降低了35%和60%。急性高钙血症使对照组的总PTH分泌减少79%，但患者仅减少63%（P<0.002）。高钙血症期间，对照组的PTH脉冲频率降低了30%，但患者组保持不变。总之，尿毒症性甲状旁腺功能亢进是由腺体分泌显著增加介导的，但也与PTH清除减少有关。自发PTH脉冲频率增加以及对Ca²⁺变化的反应迟钝表明增生的甲状旁腺与指导PTH脉冲式释放的生理调节机制部分解耦。
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