Arakawa Toshio, D'Amour Pierre, Rousseau Louise, Brossard Jean-Hugues, Sakai Makoto, Kasumoto Hiroomi, Igaki Naoya, Goto Takeo, Cantor Tom, Fukagawa Masafumi
Division of Nephrology & Dialysis Center, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017 Japan.
Clin J Am Soc Nephrol. 2006 May;1(3):525-31. doi: 10.2215/CJN.01391005. Epub 2006 Apr 5.
Measurement of bioactive parathyroid hormone (PTH) is essential for optimal management of bone abnormalities in dialysis patients. This can be accomplished by PTH measurements using third-generation PTH assays, which detect more or less of the first six amino acids of the PTH structure. Such assays do not detect non-(1-84) PTH fragments, such as human PTH (7-84), which are recognized by the second-generation PTH assays that use a detection antibody that recognizes an epitope within the 13-34 region of the PTH structure. Therefore, third-generation PTH results are expected to be lower than those that are obtained with second-generation PTH assays. Rare exceptions to this rule have been reported for patients with severe primary hyperparathyroidism or parathyroid cancer. Sera and gland extracts were analyzed from a dialysis patient with high bone turnover disease and with surprising higher PTH levels by a third-generation assay than by a second-generation assay. This finding normalized after the surgical removal of an enlarged gland with a single nodule, an advanced type of nodular hyperplasia. HPLC fractionation of sera and gland extracts revealed the overproduction and secretion of a PTH molecule with an intact amino-terminus structure distinct from (1-84) PTH. This form of PTH was readily detectable by third-generation PTH assays but was poorly reactive in second-generation PTH assays. Therefore, parathyroid glands with advanced uremic nodular hyperplasia may overproduce and secrete a novel, biologically active form of PTH with an intact 1-6 region but a presumably modified 12-18 region required for the detection in second-generation PTH assays.
测量生物活性甲状旁腺激素（PTH）对于透析患者骨骼异常的最佳管理至关重要。这可以通过使用第三代PTH检测方法来完成，该方法可检测PTH结构前六个氨基酸的或多或少情况。此类检测方法无法检测非（1-84）PTH片段，如人PTH（7-84），而第二代PTH检测方法使用能识别PTH结构13-34区域内表位的检测抗体，可识别这些片段。因此，预计第三代PTH检测结果会低于第二代PTH检测方法所得结果。对于患有严重原发性甲状旁腺功能亢进或甲状旁腺癌的患者，已报道有该规则的罕见例外情况。对一名患有高骨转换疾病的透析患者的血清和腺体提取物进行分析，发现通过第三代检测方法测得的PTH水平比第二代检测方法测得的结果出人意料地更高。在手术切除一个有单个结节的增大腺体（一种晚期结节性增生类型）后，这一发现恢复正常。血清和腺体提取物的HPLC分级分离显示，产生并分泌了一种氨基末端结构完整、不同于（1-84）PTH的PTH分子。这种形式的PTH很容易被第三代PTH检测方法检测到，但在第二代PTH检测方法中反应性较差。因此，患有晚期尿毒症结节性增生的甲状旁腺可能会产生并分泌一种新型的、具有生物活性的PTH形式，其1-6区域完整，但在第二代PTH检测方法中检测所需的12-18区域可能经过修饰。
