madman
Super Moderator
Abstract
In clinical practice, it is fundamental to compare the results of hormonal examinations obtained in the laboratory with reliable reference values. This is particularly difficult when faced with rare conditions, such as disorders of sex development, where not routinely assayed peptide hormones as well as intermediate steroid metabolites are often needed and local reliable reference values are not available. There are considerable differences among techniques and assays used in clinical and research laboratories. In fact, laboratory hormonology is undergoing a critical transition between techniques for quantitative determination: established immunoassays and mass spectrometry. Harmonizing results from different laboratories is a major challenge along the path leading to the establishment of consensus reference intervals for steroid hormones. Most of the efforts are being concentrated on testosterone, with very encouraging results being provided by the harmonization of liquid chromatography-tandem mass spectrometry results. However, this goal is still far from being achieved for the other steroid and small-molecule hormones, and a much more challenging perspective is foreseeable for protein hormones. In addition to technical issues, the importance of the definition and of the characterization of the reference population as well as sampling and processing methodology should not be underestimated, as these aspects may impact on hormonal axis and compound stability. The aim of the present review is to provide a comprehensive overview of the circulating reference values in basal condition of the hormones and proteins involved in sex development reported to date in the peer reviewed literature. We present a series of tables where we have collected the reference intervals for each specific hormone and protein.
Laboratory hormonology is undergoing a critical period of transition between milestone techniques for quantitative determination: established immunoassays, mainly in their direct and automated versions, and mass spectrometry in its latest hyphenation with liquid chromatography (LC-MS/MS) [Taylor et al., 2015]. There are clear differences between the 2 techniques in terms of analytical principles, benefits, drawbacks, and potential, which have been extensively described elsewhere in the present issue.
LC-MS/MS is seen as the first real opportunity to achieve a global harmonization of results generated across laboratories worldwide. Considerable advancements have been achieved, as promoted by health agencies as well as scientific communities [Rosner et al., 2007, 2013; Vesper et al., 2009; Auchus, 2014; Wierman et al., 2014; Büttler et al., 2015, 2016]. The recent initiative of the Endocrine Society on the harmonization of results from large epidemiologic studies on male hypogonadism represents a milestone, as for the first time it established consensus reference intervals for testosterone [Travison et al., 2017]. Nonetheless, this goal is still far from being achieved for the other steroid and small-molecule hormones, and a much more challenging perspective is foreseeable for protein hormones [Sabbagh et al., 2016]. The techniques and assays used in clinical and research laboratories differ considerably. The choice of assay is too often dominated by convenience and financial reasons but rarely by an evaluation of the quality and reliability of the results. This situation is further exacerbated by the high workload faced by the laboratories. Thus, it is of key importance that each laboratory uses assay-specific reference values.
Nonetheless, the accuracy of reference intervals does not only rely on the assay used, since important aspects concerning the “reference” definition for the cohort and the sampling conditions need to be taken into account when generating normative limits, as well as when interpreting patients’ results according to these normative levels. Reference values provided by ready-to-use kit vendors do not provide exhaustive information on such issues. On the other hand, it is very difficult for laboratories to have the resources to build up their own values [Fanelli et al., 2013a]
The aim of the present review is to provide a comprehensive overview of the circulating reference values in basal conditions of hormones involved in sex development and of sex hormone binding globulin reported to date in the peer-reviewed literature.
Table 2. Total testosterone (TT) reference intervals according to age and testicular volume in the male population
Table 8. Sex hormone binding globulin (SHBG) reference intervals according to age in the male population
Table 10. Dihydrotestosterone (DHT) reference intervals according to age and testicular volume in the male population
Table 14. Dehydroepiandrosterone (DHEA) reference intervals according to age and Tanner stage in the male population
Table 36. Estradiol (E2) and estrone (E1) reference intervals according to age and Tanner stage in the male population
In clinical practice, it is fundamental to compare the results of hormonal examinations obtained in the laboratory with reliable reference values. This is particularly difficult when faced with rare conditions, such as disorders of sex development, where not routinely assayed peptide hormones as well as intermediate steroid metabolites are often needed and local reliable reference values are not available. There are considerable differences among techniques and assays used in clinical and research laboratories. In fact, laboratory hormonology is undergoing a critical transition between techniques for quantitative determination: established immunoassays and mass spectrometry. Harmonizing results from different laboratories is a major challenge along the path leading to the establishment of consensus reference intervals for steroid hormones. Most of the efforts are being concentrated on testosterone, with very encouraging results being provided by the harmonization of liquid chromatography-tandem mass spectrometry results. However, this goal is still far from being achieved for the other steroid and small-molecule hormones, and a much more challenging perspective is foreseeable for protein hormones. In addition to technical issues, the importance of the definition and of the characterization of the reference population as well as sampling and processing methodology should not be underestimated, as these aspects may impact on hormonal axis and compound stability. The aim of the present review is to provide a comprehensive overview of the circulating reference values in basal condition of the hormones and proteins involved in sex development reported to date in the peer reviewed literature. We present a series of tables where we have collected the reference intervals for each specific hormone and protein.
Laboratory hormonology is undergoing a critical period of transition between milestone techniques for quantitative determination: established immunoassays, mainly in their direct and automated versions, and mass spectrometry in its latest hyphenation with liquid chromatography (LC-MS/MS) [Taylor et al., 2015]. There are clear differences between the 2 techniques in terms of analytical principles, benefits, drawbacks, and potential, which have been extensively described elsewhere in the present issue.
LC-MS/MS is seen as the first real opportunity to achieve a global harmonization of results generated across laboratories worldwide. Considerable advancements have been achieved, as promoted by health agencies as well as scientific communities [Rosner et al., 2007, 2013; Vesper et al., 2009; Auchus, 2014; Wierman et al., 2014; Büttler et al., 2015, 2016]. The recent initiative of the Endocrine Society on the harmonization of results from large epidemiologic studies on male hypogonadism represents a milestone, as for the first time it established consensus reference intervals for testosterone [Travison et al., 2017]. Nonetheless, this goal is still far from being achieved for the other steroid and small-molecule hormones, and a much more challenging perspective is foreseeable for protein hormones [Sabbagh et al., 2016]. The techniques and assays used in clinical and research laboratories differ considerably. The choice of assay is too often dominated by convenience and financial reasons but rarely by an evaluation of the quality and reliability of the results. This situation is further exacerbated by the high workload faced by the laboratories. Thus, it is of key importance that each laboratory uses assay-specific reference values.
Nonetheless, the accuracy of reference intervals does not only rely on the assay used, since important aspects concerning the “reference” definition for the cohort and the sampling conditions need to be taken into account when generating normative limits, as well as when interpreting patients’ results according to these normative levels. Reference values provided by ready-to-use kit vendors do not provide exhaustive information on such issues. On the other hand, it is very difficult for laboratories to have the resources to build up their own values [Fanelli et al., 2013a]
The aim of the present review is to provide a comprehensive overview of the circulating reference values in basal conditions of hormones involved in sex development and of sex hormone binding globulin reported to date in the peer-reviewed literature.
Table 2. Total testosterone (TT) reference intervals according to age and testicular volume in the male population
Table 8. Sex hormone binding globulin (SHBG) reference intervals according to age in the male population
Table 10. Dihydrotestosterone (DHT) reference intervals according to age and testicular volume in the male population
Table 14. Dehydroepiandrosterone (DHEA) reference intervals according to age and Tanner stage in the male population
Table 36. Estradiol (E2) and estrone (E1) reference intervals according to age and Tanner stage in the male population
