Diagnosis of adrenal cortical dysfunction by liquid chromatography-tandem mass spectrometry.
Diagnosis of adrenal cortical dysfunction by liquid chromatography-tandem mass spectrometry.
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液相色谱-串联质谱法诊断肾上腺皮质功能障碍。
DOI：
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发表时间：
2001
影响因子：
0.8
通讯作者：
P. Rinaldo
中科院分区：
文献类型：
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作者：
P. Kao;D. Machacek;M. J. Magera;J. Lacey;P. Rinaldo
采用液相色谱-串联质谱 (LC-MS/MS) 对先前根据免疫分析诊断为先天性肾上腺增生症 (CAH)、11 β-羟化酶缺乏症、21-羟化酶缺乏症或阿狄森氏病（肾上腺功能不全）的患者的残留标本同时测量肾上腺皮质类固醇途径的 6 种代谢化合物。两名肾上腺功能正常的受试者的血清皮质醇值为 13.6 和 8.9 微克/dL，血清可的松值为 2.1 和 0.6 微克/dL，但其余化合物未检测到。两名11β-羟化酶缺乏症患者的血清11β-脱氧皮质醇值为14.9和10.0微克/dL，血清11-脱氧皮质酮值为3.9和1.0微克/dL，但血清皮质醇和可的松水平降低。 21-羟化酶缺乏症患者的血清 17-羟基孕酮浓度高度升高，达到 28.5 微克/dL（或 28,500 ng/dL，报告该测定的传统单位），血清 21-脱氧皮质醇浓度为 6.9 ug/dL（这是 21-羟化酶缺乏症的病理标志物，在健康受试者的血清中无法检测到）。该患者的血清皮质醇和可的松浓度也降低（分别为 0.9 和 0.3 微克/分升）。在促肾上腺皮质激素 (ACTH) 刺激后 30 和 60 分钟，血清皮质醇是正常受试者中唯一表现出显着增加的化合物； 21-羟化酶缺乏症患者血清17-羟孕酮水平升高，但血清皮质醇水平没有升高；艾迪生氏病患者的血清皮质醇或其他化合物水平没有增加。 Metyprapone 可阻断 11 β-羟化酶活性，增加血清 11-脱氧皮质类固醇水平并降低血清皮质醇水平。该初步研究表明，使用 LC-MS/MS 进行肾上腺皮质功能障碍的实验室诊断是可行的。作者预计 LC-MS/MS 可能很快成为诊断此类内分泌疾病的理想分析技术。
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measure 6 metabolic compounds of the adrenocorticosteroid pathway simultaneously on residual specimens from patients who had previously been previously diagnosed, on the basis of immunoassays, as having congenital adrenal hyperplasia (CAH), 11 beta-hydroxylase deficiency, 21-hydroxylase deficiency, or Addison disease (adrenal insufficiency). Two subjects with normal adrenal function had serum cortisol values of 13.6 and 8.9 micrograms/dL and serum cortisone values of 2.1 and 0.6 microgram/dL, but the rest of the compounds were undetectable. Two patients with 11 beta-hydroxylase deficiency had serum 11 beta-deoxycortisol values of 14.9 and 10.0 micrograms/dL and serum 11-deoxycorticosterone values of 3.9 and 1.0 microgram/dL, but their serum levels of cortisol and cortisone were diminished. A patient with 21-hydroxylase deficiency had a highly increased serum 17-hydroxyprogesterone concentration of 28.5 micrograms/dL (or 28,500 ng/dL, the traditional unit to report this assay) and a serum 21-deoxycortisol concentration of 6.9 ug/dL (this is a pathologic marker of 21-hydroxylase deficiency that is nondetectable in sera of healthy subjects). This patient also had diminished concentrations of serum cortisol and cortisone (0.9 and 0.3 microgram/dL, respectively). At 30 and 60 min after corticotropin (ACTH) stimulation, serum cortisol was the only compound that showed a dramatic increase in the normal subjects; the patient with 21-hydroxylase deficiency showed an increase of serum 17-hydroxyprogesterone level, but no increase of serum cortisol level; the patient with Addison disease showed no increase in the levels of serum cortisol or other compounds. Metyprapone, which blocks 11 beta-hydroxylase activity, increased the serum 11-deoxycorticosteroid levels and decreased the serum cortisol level. This pilot study demonstrates that it is feasible to use LC-MS/MS for the laboratory diagnosis of adrenal cortical dysfunction. The authors envision that LC-MS/MS may soon become an ideal analytical technique for the diagnosis of such endocrine diseases.