Objective

Measurements utilizing commercially available sets of reagents for determination of steroid hormone profiles by liquid chromatography–tandem mass spectrometry (LC-MS/MS) have become increasingly important for routine laboratories. However, method-specific publications of reference intervals obtained from sufficiently large studies are often missing.

Methods

After validation of performance characteristics, a widely available kit for steroid analysis by LC-MS/MS was used to measure concentrations of 15 endogenous steroids (aldosterone, cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, estradiol, testosterone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, 11-deoxycorticosterone, progesterone) in more than 500 blood samples from a population-based study. While randomly selected from a larger cohort, the samples equally represented both sexes and covered a wide range of adult age groups. Age- and sex-specific reference intervals were calculated, and correlation with BMI was assessed.

Results

Performance characteristics of the assay matched expectations for 9 of 15 steroids. For most of them, reference intervals obtained from our study population were comparable to those reported by others, with age and sex being the major determinants. A sex-specific correlation with BMI was found for seven steroids. We identified limitations regarding sensitivity of the method for quantification of progesterone in males and postmenopausal females. Concentrations of aldosterone, 21-deoxycortisol, estradiol, 11-deoxycorticosterone, and dihydrotestosterone could not be quantified in a large percentage of samples.

Conclusions

The reference intervals for nine steroids will support meaningful interpretation for steroid profiles as measured by a widely used kit for LC-MS/MS-based quantification. Laboratories using such kits must be aware of potential limitations in sensitivity for some steroids included in the profile.

Significance Statement

Quantification of steroid hormones is a cornerstone for diagnosis of several diseases. Commonly used immunoassays have limitations in specificity. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is a promising alternative, particularly if methods are harmonized across laboratories. The use of kits from commercial suppliers might support this. Clinical interpretation of steroid concentrations requires availability of appropriate reference intervals (RIs), but studies on RIs reported in the literature differ in preanalytical and analytical procedures. Here, we provide RIs for steroids measured by a widely available kit under preanalytical conditions mirroring common clinical practice. Such RIs might facilitate interpretation for those using the same method and comparable conditions in clinical routine.

中文翻译：

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使用广泛使用的试剂盒通过液相色谱-串联质谱法测量类固醇激素的年龄和性别调整参考区间

客观的

使用市售试剂组通过液相色谱-串联质谱 (LC-MS/MS) 测定类固醇激素谱的测量对于常规实验室来说变得越来越重要。然而，从足够大的研究中获得的参考区间的特定方法的出版物经常缺失。

方法

验证性能特征后，使用广泛使用的 LC-MS/MS 类固醇分析试剂盒来测量 15 种内源性类固醇（醛固酮、皮质醇、可的松、皮质酮、11-脱氧皮质醇、21-脱氧皮质醇、硫酸脱氢表雄酮、雌二醇、一项基于人群的研究对 500 多个血液样本中的睾酮、雄烯二酮、二氢睾酮、脱氢表雄酮、17-羟基孕酮、11-脱氧皮质酮、黄体酮进行了检测。虽然是从更大的队列中随机选择的，但样本平等地代表了两性，并涵盖了广泛的成年人年龄组。计算特定年龄和性别的参考区间，并评估与 BMI 的相关性。

结果

该测定的性能特征符合 15 种类固醇中 9 种的预期。对于大多数人来说，从我们的研究人群中获得的参考区间与其他人报告的参考区间相当，年龄和性别是主要决定因素。研究发现七种类固醇与体重指数存在性别相关性。我们发现男性和绝经后女性孕酮定量方法的敏感性存在局限性。大部分样品中醛固酮、21-脱氧皮质醇、雌二醇、11-脱氧皮质酮和二氢睾酮的浓度无法定量。

结论

九种类固醇的参考区间将支持对通过广泛使用的基于 LC-MS/MS 的定量试剂盒测量的类固醇谱进行有意义的解释。使用此类试剂盒的实验室必须意识到配置文件中某些类固醇敏感性的潜在限制。

意义声明

类固醇激素的定量是诊断多种疾病的基石。常用的免疫测定在特异性方面存在局限性。液相色谱-串联质谱 (LC-MS/MS) 是一种有前途的替代方法，特别是在各个实验室的方法统一的情况下。使用商业供应商提供的套件可能会支持这一点。类固醇浓度的临床解释需要适当的参考区间 (RI)，但文献中报道的 RI 研究在分析前和分析程序方面有所不同。在这里，我们提供了类固醇的 RI，通过广泛使用的试剂盒在反映常见临床实践的分析前条件下进行测量。此类 RI 可能有助于在临床常规中使用相同方法和可比较条件的人进行解释。