Steroid Profiling for Adrenocortical Disorders: A Pathway for Omics-Based Diagnostics.

During the past 15 years, a considerable investment of effort and funds has been directed to the use of omics-based technologies for biomarker identification and development. The outcome in terms of laboratory tests applicable to the routine environment has been slow to materialize, in some cases corrupted by poorly conceived and conducted work (1, 2). This disappointing return is in part attributable to the time and expertise required to meet the many steps and processes required from biomarker discovery to validation and acceptance for clinical use. Compounding the problem, application of an omics-based panel of multiple measurements requires considerably more complex approaches for test validation and interpretation than those required for more commonly used single biomarkers. In this issue of Clinical Chemistry , two groups, one at King's College (3) and a second at the Mayo Clinic (4), highlight the potential applications of mass spectrometry-based steroid profiling (“steroidomics”) for disorders of the adrenal cortex. With respective panels of 13 and 26 steroids, the outlined methods illustrate pathways for validation of omics-based signatures for diagnostics and stratification of disease for therapeutic intervention. Application of steroid profiling for the diagnosis of adrenocortical disorders has a history spanning >50 years, first using laborious chromatographic separation and colorimetric or immunoassay procedures (5–7) subsequently replaced by methods using gas chromatography or liquid chromatography combined with mass spectrometry (8, 9). GC-MS methods, in particular, have proven extremely useful for steroid profiling, but because of the need for complex sample preparation, they are not well suited for the routine laboratory environment. Consequently, methods using liquid chromatography at the front end of mass spectrometry instruments have come to the forefront for routine laboratories. Whereas the King's College panel of 13 serum steroids uses an LC-MS/MS instrument common to many routine laboratories, the Mayo Clinic …