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.