重新评估液相色谱-串联质谱直接平衡透析法计算游离睾酮。

Reassessing Free-Testosterone Calculation by Liquid Chromatography-Tandem Mass Spectrometry Direct Equilibrium Dialysis.

机构信息

Department of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium.

Andrology Research Unit, Centre for Endocrinology and Diabetes, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.

出版信息

J Clin Endocrinol Metab. 2018 Jun 1;103(6):2167-2174. doi: 10.1210/jc.2017-02360.

DOI:10.1210/jc.2017-02360

PMID:29618085

Abstract

CONTEXT

Assessment of free testosterone (FT) might help evaluate androgen status in patients with borderline total testosterone (T) and/or altered sex hormone-binding globulin (SHBG) levels. However, the validity of different methods to measure FT is debatable.

METHODS

Serum from 183 women and 146 men was analyzed using equilibrium dialysis (ED), with FT directly measured by liquid chromatography-tandem mass spectrometry. FT calculation was re-evaluated for the mass action law-based equation according to Vermeulen (cFT-V), empirical equations according to Ly (cFT-L), and a proposed calculation based on a multistep, dynamic, allosteric model according to Zakharov (cFT-Z).

RESULTS

FT level analyzed by ED [median,13 pmol/L (1.2% of T) in women; 248 pmol/L (1.5% of T) in men] was strongly inversely correlated to SHBG level, significantly to albumin level in women, and only weakly to SHBG level in men. The median [percentile (p) range, 2.5 to 97.5] ratios of calculated FT (cFT) over ED-FT (from European Male Aging Study samples) were 1.19 (0.9 to 1.47), 1.00 (0.69 to 1.42), and 2.05 (1.26 to 3.26) for cFT-V, cFT-L, and cFT-Z, respectively. The ratio for cFT-V was not significantly affected by SHBG, T, or albumin levels (ρ range, 0.17 to -0.01); ratios for cFT-L and cFT-Z were affected (P < 0.05 and P < 0.001, respectively) and strongly correlated with SHBG levels (ρ = 0.72 and 0.75, respectively). Rank correlations between cFT% and ED-FT% (for men) were 0.62, 0.74, and 0.89 for cFT-Z, cFT-L, and cFT-V, respectively.

CONCLUSION

FT results by direct ED confirm prior FT data from indirect ED and ultrafiltration methodologies. Calculations have inherent limitations, with clinically important differences among evaluated equations: cFT-V, although overestimating FT level, appears the most robust approximation, largely independent of SHBG, albumin, and T levels.

摘要

背景

评估游离睾酮（FT）可能有助于评估总睾酮（T）和/或性激素结合球蛋白（SHBG）水平异常的患者的雄激素状态。然而，不同测量 FT 的方法的有效性存在争议。

方法

使用平衡透析（ED）分析了 183 名女性和 146 名男性的血清，通过液相色谱-串联质谱法直接测量 FT。根据 Vermeulen（cFT-V）的质量作用定律方程、根据 Ly（cFT-L）的经验方程以及根据 Zakharov（cFT-Z）的多步骤、动态、变构模型提出的计算方法，重新评估了 FT 计算值。

结果

ED 分析的 FT 水平[中位数，女性 13 pmol/L（T 的 1.2%）；男性 248 pmol/L（T 的 1.5%）]与 SHBG 水平呈强烈负相关，与女性白蛋白水平显著相关，与男性 SHBG 水平仅弱相关。计算的 FT（cFT）与 ED-FT（来自欧洲男性老龄化研究样本）的比值中位数（2.5%至 97.5%的百分位范围）分别为 1.19（0.9 至 1.47）、1.00（0.69 至 1.42）和 2.05（1.26 至 3.26），分别用于 cFT-V、cFT-L 和 cFT-Z。cFT-V 的比值不受 SHBG、T 或白蛋白水平的显著影响（ρ范围，0.17 至-0.01）；cFT-L 和 cFT-Z 的比值受影响（P<0.05 和 P<0.001），并与 SHBG 水平呈强相关（ρ=0.72 和 0.75）。cFT-Z、cFT-L 和 cFT-V 的 cFT%与 ED-FT%（男性）的秩相关系数分别为 0.62、0.74 和 0.89。