Endocrine Abstracts

Techniques of analysis of urinary steroid metabolites evolved rapidly in the 1960 s from paper via thin layer and gas-liquid chromatography (GC) to GC-mass spectrometry. Formation of trimethylsilyl derivatives was a critical development for GC. This enabled all the major analytes to be identified and quantified in one run and the term ‘steroid profile’ for this first emerged in 1968. The use of capillary columns in place of packed columns, pioneered in the UK in the early ‘70 s by CHL Shackleton at the Clinical Research Centre, Northwick Park, greatly improved resolution. The following years were a fruitful time for the application of this technique to disorders of steroid synthesis and catabolism and increasing referral of clinical samples to Shackleton’s group resulted in the de facto development of a national service, which later gave rise to both of the present SAS services. Urinary steroid profiling has an especially important place in identification of steroid synthesis abnormalities in the newborn, since it is non-invasive and not subject to interference by steroids unique to this period, in contrast to blood assays. All known inborn errors of steroid metabolism, with the exception of 17-hydroxysteroid dehydrogenase deficiency, can be unambiguously identified. Profiling has enabled definition of cortisol-cortisone inter-conversion defects and prenatal diagnosis of several disorders including steroid sulphatase deficiency and 7-dehydrocholesterol reductase deficiency (Smith Lemli Opitz syndrome). The combined application of genomics and steroid profile analysis, now reborn as ‘metabolomics’ has proved powerful. A recently described new form of CAH, in which the profile resembles a mixed 17 and 21-hydroxylase deficiency has been identified as due to a mutation of cytochrome P450 oxoreductase. Tandem MS may permit limitations of interference in blood steroid assays to be overcome, so that steroid profiling in the future may encompass blood as well as urine.