Gas chromatography/mass spectrometry (GC/MS) remains a pre-eminent discovery tool in clinical steroid investigations even in the era of fast liquid chromatography tandem mass spectrometry (LC/MS/MS)
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Liquid chromatography tandem mass spectrometry (LC/MS/MS) is replacing classical methods for steroid hormone analysis. It requires small sample volumes and has given rise to improved specificity and short analysis times. Its growth has been fueled by criticism of the validity of steroid analysis by older techniques, testosterone measurements being a prime example. While this approach is the gold-standard for measurement of individual steroids, and panels of such compounds, LC/MS/MS is of limited use in defining novel metabolomes. GC/MS, in contrast, is unsuited to rapid high-sensitivity analysis of specific compounds, but remains the most powerful discovery tool for defining steroid disorder metabolomes. Since the 1930s almost all inborn errors in steroidogenesis have been first defined through their urinary steroid excretion. In the last 30 years, this has been exclusively carried out by GC/MS and has defined conditions such as AME syndrome, glucocorticoid remediable aldosteronism (GRA) and Smith–Lemli–Opitz syndrome. Our recent foci have been on P450 oxidoreductase deficiency (ORD) and apparent cortisone reductase deficiency (ACRD).
In contrast to LC/MS/MS methodology, a particular benefit of GC/MS is its non-selective nature; a scanned run will contain every steroid excreted, providing an integrated picture of an individual's metabolome. The “Achilles heel” of clinical GC/MS profiling may be data presentation. There is lack of familiarity with the multiple hormone metabolites excreted and diagnostic data are difficult for endocrinologists to comprehend. While several conditions are defined by the absolute concentration of steroid metabolites, many are readily diagnosed by ratios between steroid metabolites (precursor metabolite/product metabolite). Our work has led us to develop a simplified graphical representation of quantitative urinary steroid hormone profiles and diagnostic ratios.
In contrast to LC/MS/MS methodology, a particular benefit of GC/MS is its non-selective nature; a scanned run will contain every steroid excreted, providing an integrated picture of an individual's metabolome. The “Achilles heel” of clinical GC/MS profiling may be data presentation. There is lack of familiarity with the multiple hormone metabolites excreted and diagnostic data are difficult for endocrinologists to comprehend. While several conditions are defined by the absolute concentration of steroid metabolites, many are readily diagnosed by ratios between steroid metabolites (precursor metabolite/product metabolite). Our work has led us to develop a simplified graphical representation of quantitative urinary steroid hormone profiles and diagnostic ratios.
Date Issued
2010-08-01
Date Acceptance
2010-04-15
Citation
Journal of Steroid Biochemistry and Molecular Biology, 2010, 121 (3-5), pp.496-504
ISSN
0960-0760
Publisher
Elsevier
Start Page
496
End Page
504
Journal / Book Title
Journal of Steroid Biochemistry and Molecular Biology
Volume
121
Issue
3-5
Copyright Statement
© 2010 Elsevier Ltd. Open access under CC BY license.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/20417277
PII: S0960-0760(10)00210-4
Subjects
ACRD
Apparent cortisone reductase deficiency
Biochemistry & Molecular Biology
CONGENITAL ADRENAL-HYPERPLASIA
CORTISONE
DEFICIENCY
Endocrinology & Metabolism
Gas chromatography/mass spectrometry
GC/MS
Life Sciences & Biomedicine
MATERNAL URINE
MUTANT P450 OXIDOREDUCTASE
NEWBORN
ORD
P450 oxidoreductase deficiency
PATHWAY
PRENATAL-DIAGNOSIS
Science & Technology
SERUM
Tandem mass spectrometry
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2010-04-22