Radeke H H, Auf'mkolk B, Jüppner H, Krohn H P, Keck E, Hesch R D
J Clin Endocrinol Metab. 1986 Feb;62(2):393-402. doi: 10.1210/jcem-62-2-393.
Three different pathophysiological mechanisms are probably responsible for hereditary pseudohypoparathyroidism: 1) a defect at the prereceptor-level, 2) a defective membrane N-protein accounting for diminished second messenger production, and 3) a defect in the cytosolic response to the hormone. In a cooperative, study 24 patients (mean age, 13 yr; range, 3-23 yr, 8 girls, 16 boys) receiving vitamin D metabolites (5,000-80,000 U/day) were examined and compared to a control group of 36 normal children. Immunoreactive N-terminal PTH (N-PTH), mid-C-regional PTH (mid-C-PTH), intact PTH and bio-PTH, vitamin D metabolites, and serum calcium and phosphate, alkaline phosphatase activity, and the N-protein activity of erythrocyte membranes were measured in each subject. By clinical and biochemical criteria three groups were differentiated. Eight patients had the completely expressed features of Albright's Hereditary Osteodystrophy (AHO+), including brachydactyly and/or sc calcifications, and increased N-PTH, mid-C-PTH, and alkaline phosphatase activity. Bio-PTH, intact PTH, and N-protein were normal. Nine additional patients with complete (AHO+) had elevated levels of bio-PTH, N-PTH, and mid-C PTH, normal hydroxylation of vitamin D, but decreased N-protein activity. Seven patients with pseudohypoparathyroidism had no features of AHO (AHO-), no increase of urinary cAMP excretion after exogenous PTH, normal PTH peptide levels and N-protein activity, but elevated 25-hydroxyvitamin D and decreased 1,25-dihydroxyvitamin D concentrations. In conclusion, we identified three subpopulations of PsHP: group a had a dissociation of N-PTH and bio-PTH suggesting a defective N-PTH causing renal resistance, whereas their bones respond to PTH. Group b had defective N-protein causing generalized PTH resistance. Group c was characterized by high 25-hydroxyvitamin D and relatively low 1,25-dihydroxyvitamin D levels, thus providing evidence for a defect in the cytosolic interaction of the two different second messengers for PTH, cAMP, and calcium.
1）受体前水平缺陷；2）膜N蛋白缺陷导致第二信使生成减少；3）细胞溶质对激素的反应缺陷。在一项合作研究中，对24例接受维生素D代谢物（5000 - 80000 U/天）治疗的患者（平均年龄13岁；范围3 - 23岁，8名女孩，16名男孩）进行了检查，并与36名正常儿童的对照组进行比较。检测了每个受试者的免疫反应性N端甲状旁腺激素（N - PTH）、中段C区域甲状旁腺激素（mid - C - PTH）、完整甲状旁腺激素和生物活性甲状旁腺激素、维生素D代谢物、血清钙和磷、碱性磷酸酶活性以及红细胞膜的N蛋白活性。根据临床和生化标准将患者分为三组。8例患者具有完全表达的奥尔布赖特遗传性骨营养不良（AHO +）特征，包括短指畸形和/或皮下钙化，以及N - PTH、mid - C - PTH和碱性磷酸酶活性升高。生物活性甲状旁腺激素、完整甲状旁腺激素和N蛋白正常。另外9例完全性（AHO +）患者的生物活性甲状旁腺激素、N - PTH和mid - C PTH水平升高，维生素D羟化正常，但N蛋白活性降低。7例假性甲状旁腺功能减退患者无AHO特征（AHO -），外源性甲状旁腺激素后尿cAMP排泄无增加，甲状旁腺激素肽水平和N蛋白活性正常，但25 - 羟维生素D升高，1,25 - 二羟维生素D浓度降低。总之，我们确定了假性甲状旁腺功能减退的三个亚群：a组N - PTH和生物活性甲状旁腺激素解离，提示N - PTH缺陷导致肾脏抵抗，而其骨骼对甲状旁腺激素有反应。b组N蛋白缺陷导致全身性甲状旁腺激素抵抗。c组的特征是25 - 羟维生素D水平高，1,25 - 二羟维生素D水平相对较低，从而为甲状旁腺激素、cAMP和钙的两种不同第二信使在细胞溶质中的相互作用缺陷提供了证据。
