APPLIED STUDY OF SCREENING SYSTEM FOR ADRENOCORTICAL HYPERTENSION

肾上腺皮质高血压筛查系统的应用研究

• 批准号: 09557128
• 负责人: CHIBA Hitoshi
• 金额: $ 2.62万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557128/
• 关键词: hypertension; adrenal; 18-hydroxycortisol; immunoassay; aldosteronism; screening; chemiluminescence

We established a monoclonal antibody-based chemiluminescent immunoassay for 18-hydroxycortisol, using chemically synthesized 18-hydroxycortisol and its acridinium ester-conjugate, in order to detect patients with primary aldosteronism (adenoma) and hereditary glucocorticoid-remediable aldosteronism. This system enabled measuring 0.1 to 10 ng steroid per tube, or 2 to 200nglml in serum) in 15 minutes. We also developed a filter paper-based immunoassay and also a gel matrix-based immunoassay for convenient bed-side measurement. Serum 18-hydroxycortisol levels in patients with primary aldosteronism were 10.6 * 3.5 ng/ml, and were lowered below 2 ng/ml after adrenalectomy. Urinary 18-hydroxycortisol in patients with hypertension (n=261) were screened for 18-hydroxycortisol by measuring the steroid in spot urine samples, and two with the highest 18-hydroxycortisol levels were diagnosed as primary aldosteronism (0.8%). Glucocorticoid-remediable hyperaldosteronism was not found in this study, suggesting its low frequency in Japan. However, a high urinary 18-hydroxycortisol was demonstrated in an established family with glucocorticoid-remediable hyperaldosteronism. We conclude that our chemiluminescent immunoassay for 18-hydroxycortisol is useful for screening adrenocortical hypertension.

为了检测原发性醛固酮增多症（腺瘤）和遗传性糖皮质激素可修复性醛固酮增多症患者，我们建立了一种基于化学合成的18-羟基皮质醇及其吖啶酸酯偶联物的单克隆抗体化学发光免疫分析法。该系统能够在15分钟内测量每管0.1至10ng类固醇（或血清中2至200ng）。我们还开发了一种基于滤纸的免疫分析法和一种基于凝胶基质的免疫分析法，用于方便的床边测量。原发性醛固酮增多症患者血清18-羟基皮质醇水平为10.6 * 3.5 ng/ml，肾上腺切除术后降至2 ng/ml以下。对261例高血压患者的尿中18-羟基皮质醇进行检测，通过测定尿样中的类固醇来筛查18-羟基皮质醇，其中2例18-羟基皮质醇水平最高的患者诊断为原发性醛固酮增多症（0.8%）。本研究未发现糖皮质激素可补救性高醛固酮增多症，提示其在日本发病率较低。然而，高尿18-羟基皮质醇在糖皮质激素可补救的高醛固酮增多症家族中被证实。我们的结论是，我们的化学发光免疫测定18-羟基皮质醇是有用的筛选肾上腺皮质高血压。

项目成果

Fukada H.: "A Chemiluminescent immunoassay for salmon growth hormone." Journal of Bioluminescence and Chemiluminescence. 12. 271-275 (1997)

Fukada H.：“鲑鱼生长激素的化学发光免疫分析。”

Fukada H.: "Immune complex transfer two-site chemiluminescent immunoassay for serum growth hormone in alevin chum salmon." Journal of Bioluminescence and Chemiluminescence. 13. 107-111 (1998)

Fukada H.：“免疫复合物转移双位点化学发光免疫分析法测定鲑鱼血清生长激素。”

千葉 仁志: "18-ヒドロキシコルチゾール,18-オキソコルチゾール,6β-ヒドロキシコルチゾール" 日本臨床. 印刷中. (1999)

Hitoshi Chiba：“18-羟基皮质醇、18-氧化皮质醇、6β-羟基皮质醇”日本临床杂志（1999 年）。

Matteo R.D.: "In vestigation of the mineralo corticoid and hypertensinogenic activity of 18-hydroxycortisol in conscious sheep." Steroids. 62. 351-357 (1997)

Matteo R.D.：“在有意识的绵羊中研究盐皮质激素和 18-羟基皮质醇的致高血压活性。”