Abstract
ObjectiveUrinary steroid metabolomics by GC-MS is an established method in both clinical and research settings to describe steroidogenic disorders. However, population-based reference intervals for adults do not exist.MethodsWe measured daytime and night time urinary excretion of 40 steroid metabolites by GC-MS in 1128 adult participants of European ancestry, aged 18 to 90 years, within a large population-based, multicentric, cross-sectional study. Age and sex-related patterns in adjacent daytime and night time urine collections over 24 hours were modelled for each steroid metabolite by multivariable linear mixed regression. We compared our results with those obtained through a systematic literature review on reference intervals of urinary steroid excretion.ResultsFlexible models were created for all urinary steroid metabolites thereby estimating sex- and age-related changes of the urinary steroid metabolome. Most urinary steroid metabolites showed an age-dependence with the exception of 6β-OH-cortisol, 18-OH-cortisol, and β-cortol. Reference intervals for all metabolites excreted during 24 hours were derived from the 2.5th and 97.5th percentile of modelled reference curves. The excretion rate per period of metabolites predominantly derived from the adrenals was mainly higher during the day than at night and the correlation between day and night time metabolite excretion was highly positive for most androgens and moderately positive for glucocorticoids.ConclusionsThis study gives unprecedented new insights into sex- and age-specificity of the human adult steroid metabolome and provides further information on the day/night variation of urinary steroid hormone excretion. The population-based reference ranges for 40 GC-MS-measured metabolites will facilitate the interpretation of steroid profiles in clinical practice.
Highlights
Steroid hormones mediate a wide variety of biological processes and analysis of these in serum and their metabolites in urine are used to detect steroid misuse and disorders of reproductive function, sexual development, electrolyte balance, blood pressure and stress response [1,2,3,4,5,6,7]
The population-based reference ranges for 40 GC-MSmeasured metabolites will facilitate the interpretation of steroid profiles in clinical practice
New data about urinary steroid excretion values measured by GC-MS in adults from the general population were published, these data are limited in several respects: 1) the completeness of characterisation of the reference population, 2) the number of analyzed individuals: it ranged from 13 to 120 women and 10 to 120 men per study with overall less than 400 women and less than 400 men in all studies on reference intervals together, 3) the number of analyzed urinary steroids, which remained below 20 in most studies, and 4) the comparability of the laboratory data if several laboratories with different analytical systems were involved in the same study
Summary
Steroid hormones mediate a wide variety of biological processes and analysis of these in serum and their metabolites in urine are used to detect steroid misuse and disorders of reproductive function, sexual development, electrolyte balance, blood pressure and stress response [1,2,3,4,5,6,7]. They are small hydrophobic molecules that are synthesized from cholesterol in the testis and ovary, in the adrenal cortex, the placenta and the brain. While recent decades have seen many new technical developments and enhancements in the field of steroid hormone diagnostics, the method of GC-MS has established itself more and more firmly and is still regarded as the gold-standard allowing a comprehensive analysis of the steroid hormone metabolome [15]
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