PSUN19 One-step serum screening for discriminating subtypes of congenital adrenal hyperplasia in metabolic signatures of adrenal steroids

Various metabolic signatures may be associated with individual subtypes of congenital adrenal hyperplasia (CAH). However, the ability of commonly used antibody-based immunoassays is limited to discriminate the different subtypes. To address this, liquid chromatography-mass spectrometry (LC-MS) based quantitative profiling of 34 serum adrenal steroids was developed. The validated LC-MS assay has been then applied to serum samples obtained from 67 CAH patients and 38 healthy subjects to characterize their different subtypes. The significantly increased serum levels of 17α-hydroxyprogesterone (17α-OH-Prog; AUC = 0.997, P < 1×10-16) and 21-deoxycortisol (21-deoxyF; AUC = 0.993, P < 1×10-15) and the increased their metabolic ratios to cortisol (AUC = 1.0, P < 1×10-16 for both) were observed in 21-hydroxylase deficiency (21-OHD; N=63), while the 11-deoxyF/17α-OH-Prog could also be practical marker (AUC = 1.0, P < 1×10-16). Higher levels of mineralocorticoids, including corticosterone (B), 18-hydroxyB, and pregnenolone sulfate (Preg-S) and lower levels of dehydroepiandrosterone sulfate (DHEA-S) indicated 17α-hydroxylase deficiency (17α-OHD; N=3), which was associated with significantly decreased metabolic ratios of 17α-OH-Prog/Prog and DHEA-S/Preg-S. The patient with 11β-hydroxylase deficiency (11β-OHD; N=1) showed remarkably increased levels of 11-deoxyF and tetrahydro-11-deoxyF, while the metabolic ratios of 11β-hydroxytestosterone/testosterone and 11β-hydroxyandrostenedione/androstenedione were characterized. Although both 17α-OHD and 11β-OHD groups included a small number of patients, the present LC-MS screening panel with proposed individual steroids and their metabolic ratios could be valuable for assessing different CAH subtypes in clinical practice through a single run. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.