Diagnosis of Disorders Affecting Steroid Synthesis and Metabolism by Mass Spectrometry

The approach that has been employed for the characterization of almost all disorders of steroid hormone biosynthesis and metabolism is not based on determining the circulating concentration of the hormones, but on the study of the urinary steroid profile. The rationale behind this approach is that most hormonal imbalances caused by enzyme deficiencies or “blocks” lead to the depletion of a steroid product and to the build-up of its upstream precursors. Thus, a ratio of urinary metabolites of the precursor to urinary metabolites of the product should indicate if there is such a block. The ranges for such ratios in normal and affected individuals for most steroid disorders have been traditionally established by GC-MS. Nowadays, this technique is being replaced by superior LC-MS/MS methodologies which allow the simultaneous identification and quantification of both major and minor metabolites.