Steroid biosynthesis and metabolism are reflected by the serum steroid metabolome and, in even more detail, by the 24-hour urine steroid metabolome, which can provide unique insights into alterations of steroid flow and output indicative of underlying conditions. Mass spectrometry-based steroid metabolome profiling has allowed for the identification of unique multisteroid signatures associated with disorders of steroid biosynthesis and metabolism that can be used for personalized approaches to diagnosis, differential diagnosis, and prognostic prediction. Additionally, steroid metabolome analysis has been used successfully as a discovery tool, for the identification of novel steroidogenic disorders and pathways as well as revealing insights into the pathophysiology of adrenal disease. Increased availability and technological advances in mass spectrometry-based methodologies have refocused attention on steroid metabolome profiling and facilitated the development of high-throughput steroid profiling methods soon to reach clinical practice. Furthermore, steroid metabolomics, the combination of mass spectrometry-based steroid analysis with machine learning-based approaches, has facilitated the development of powerful customized diagnostic approaches. In this review, we provide a comprehensive up-to-date overview of the utility of steroid metabolome analysis for the diagnosis and management of inborn disorders of steroidogenesis and autonomous adrenal steroid excess in the context of adrenal tumors.

/pdf/steroid-metabolome-analysis-in-disorders-of-adrenal-steroid-7eegnznav4.pdf

Steroid Metabolome Analysis in Disorders of Adrenal Steroid Biosynthesis and Metabolism.

Simultaneous quantitative measurement of fourteen adrenal steroids by capillary column gas chromatographymass spectrometry, and its clinical application

Publisher Summary Steroids include cholesterol, steroid hormones, bile acids, ergosterol, vitamin D, and cardiac glycosides, and they have a cyclopentanoperhydrophenanthrene ring system as the basic common skeleton. Cholesterol, which is synthesized from two-carbon units of acetic acid, is a precursor of steroid hormones, and also bile acids and vitamin D. More than 50 steroids, including many intermediates, have been synthesized from cholesterol via pregnenolone in the adrenal cortex. Progesterone, 17ɑ-hydroxyprogesterone (OHP), and androstenedione also metabolize to pregnanediol, pregnanetriol, and androsterone and etiocholanolone, respectively. These final metabolites are mainly excreted in urine as glucuronide or sulphate conjugates. A variety of analytical methods have been employed for the separation, identification, and quantification of steroid hormones in biological samples. These include spectrophotometry, fluorimetry, paper chromatography (PC), thin-layer chromatography (TLC), competitive protein binding assay (CPBA), radioimmunoassay (RIA), and gas chromatography (GC). The spectrophotometric determination of 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids (17-OHCS) in urine by the Zimmermann reaction and the Porter-Silber reaction, respectively, are the most widely used as routine clinical laboratory methods.

P.G. Marsh

Papers

Determination of steroid profiles in healthy and diseased states: identification and quantitation of a block of 17α-hydroxylase