A critical evaluation of simple methods for the estimation of free testosterone in serum

A critical evaluation of simple methods for the estimation of free testosterone in serum
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DOI:
10.1210/jc.84.10.3666
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发表时间:
1999-10-01
影响因子:
5.8
通讯作者:
Kaufman, JM
Kaufman, JM
中科院分区:
医学2区
文献类型:
--
作者:
Vermeulen, A;Verdonck, L;Kaufman, JM

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游离和非特异性结合的血浆激素水平通常比总血浆激素水平更准确地反映临床情况。因此,重要的是要有这些馏分的可靠指标。通过平衡透析(AFTC)获得的表观游离睾酮(T)浓度以及未被50%硫酸铵浓度沉淀的血清T部分(非SHBG-T; SHBG,性激素结合球蛋白),通常称为生物可利用T,似乎代表了生物易利用T的可靠指标,但不太适合临床常规,太耗时。然而,其他几个参数在没有完全验证的情况下使用:用标记的T类似物(aFT)直接免疫测定游离T,从总T和免疫测定的SHBG浓度(iSHBG)计算游离T(FT),以及游离雄激素指数(FAI = 100 T/iSHBG)。鉴于文献中关于游离或生物可利用T水平的实质性差异,我们比较了大量SHBG能力从低(如多毛妇女)到极高(如甲状腺功能亢进)的血清中AFTC、FT、aFT、FAI和非SHBG-T水平。所有这些指标的生物可利用的T与AFTC浓度显着相关; AFTC和FT值几乎相同的所有条件下研究,除了在怀孕期间。然而,aFT的值只是AFTC或FT的一小部分,该部分作为SHBG水平的函数而变化。此外,FAL/AFTC比值作为SHBG水平的函数而变化,因此,aFT和FAI都不是生物可利用T的可靠指标。通过免疫测定法测定T和SHBG计算获得的FT值似乎是生物可利用T的快速,简单和可靠的指标,与AFTC相当,适用于临床常规,但妊娠期除外。在妊娠期间,雌二醇占据了SHBG结合位点的相当一部分,因此通过免疫测定法测定的SWBG高估了实际结合能力,这在妊娠血清中导致计算的FT值低于AFTC。根据FT计算的非特异性结合T与通过硫酸铵沉淀获得的非SHBG-T值高度显著相关且几乎相同,证明了根据iSPBG计算的FT的临床价值。
The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of these fractions. The apparent free testosterone (T) concentration obtained by equilibrium dialysis (AFTC) as well as the fraction of serum T not precipitated by 50% ammonium sulfate concentration (non-SHBG-T; SHBG, sex hormone-binding globulin), often referred to as bioavailable T, appear to represent reliable indexes of biologically readily available T, but are not well suited for clinical routine, being too time consuming. Several other parameters have been used without complete validation, however: direct immunoassay of free T with a labeled T analog (aFT), calculation of free T (FT) from total T and immunoassayed SHBG concentrations (iSHBG), and the free androgen index (FAI = the ratio 100T/iSHBG). In the view of substantial discrepancies in the literature concerning the free or bioavailable T levels, we compared AFTC, FT, aFT, FAI, and non-SHBG-T levels in a large number of sera with SHBG capacities varying from low, as in hirsute women, to extremely high as in hyperthyroidism. All these indexes of bioavailable T correlated significantly with the AFTC concentration; AFTC and FT values were almost identical under all conditions studied, except during pregnancy. Values for aFT, however, were only a fraction of either AFTC or FT, the fraction varying as a function of SHBG levels. Also, the FAL/AFTC ratio varied as a function of the SHBG levels, and hence, neither aFT nor FAI is a reliable index of bioavailable T.The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index of bioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SWBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSPBG.