Schneider M A, Honour J W
Department of Chemical Pathology, Cobbold Laboratories, Middlesex Hospital, UCMSM, London, England.
Steroids. 1992 Jan;57(1):7-12. doi: 10.1016/0039-128x(92)90089-r.
A method is reported for the measurement of the urine excretion rates of tetrahydro-11-deoxycorticosterone (3 alpha,5 beta-THDOC), an important metabolite of 11-deoxycorticosterone (DOC). Quantification using gas chromatography/mass spectrometry (GC/MS) was achieved by comparing the ion fragment response for the molecular ion (m/z 507) of the analyte (as methyloxime trimethylsilyl ether derivative) to that of a fixed amount of an isomer of THDOC added to urine as internal standard. To improve the specificity of measuring THDOC in clinical samples, an additional Sephadex LH-20 chromatography step was introduced to separate 11-deoxycortisol and some progesterone metabolites. In the luteal phase of the menstrual cycle, THDOC excretion was higher than in the follicular phase; it was also higher than in women taking oral contraceptives. The correlation of THDOC with progesterone production, independent of a constant cortisol output, supports an ovarian or peripheral conversion of progesterone to DOC. The assay proved useful (1) in monitoring for the recurrence of a mineralocorticoid-secreting tumor and (2) when adrenal production of DOC was not fully suppressed in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Under the latter circumstances, the renin-angiotensin system seemed to be an important regulator of DOC production.
本文报道了一种测量四氢-11-脱氧皮质酮(3α,5β-THDOC)尿排泄率的方法,3α,5β-THDOC是11-脱氧皮质酮(DOC)的一种重要代谢产物。通过将分析物(作为甲基肟三甲基硅醚衍生物)的分子离子(m/z 507)的离子碎片响应与添加到尿液中作为内标的固定量的THDOC异构体的离子碎片响应进行比较,实现了气相色谱/质谱联用(GC/MS)定量分析。为提高临床样本中THDOC测量的特异性,增加了Sephadex LH-20色谱步骤,以分离11-脱氧皮质醇和一些孕酮代谢产物。在月经周期的黄体期,THDOC排泄量高于卵泡期;也高于服用口服避孕药的女性。THDOC与孕酮生成的相关性,与恒定的皮质醇产量无关,支持孕酮向DOC的卵巢或外周转化。该检测方法被证明在以下方面有用:(1)监测分泌盐皮质激素肿瘤的复发;(2)在因11β-羟化酶缺乏导致的先天性肾上腺皮质增生症中,当肾上腺DOC生成未被完全抑制时。在后一种情况下,肾素-血管紧张素系统似乎是DOC生成的重要调节因子。