Measurement of salivary adrenal-specific androgens as biomarkers of therapy control in 21-hydroxylase deficiency

Bacila, I. et al. (2019) Measurement of salivary adrenal-specific androgens as biomarkers of therapy control in 21-hydroxylase deficiency. Journal of Clinical Endocrinology and Metabolism, 104(12), pp. 6417-6429. (doi: 10.1210/jc.2019-00031) (PMID:31361321)

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Abstract Background Monitoring of hormonal control represents a key part of the management of congenital adrenal hyperplasia (CAH). Monitoring strategies remain suboptimal because they rely on frequent blood tests and are not specific for adrenal-derived hormones. Recent evidence suggests the crucial role of adrenal-specific 11-oxygenated-C19 androgens in the pathogenesis of CAH. Objective To establish a correlation between plasma and salivary adrenal-specific androgens in CAH as a noninvasive monitoring strategy. Design This prospective cross-sectional study recruited patients between 2015 and 2018. Setting Multicenter study including 13 tertiary centers in the United Kingdom. Participants Seventy-eight children with CAH and 62 matched healthy controls. Methods Using liquid chromatography–tandem mass spectrometry, plasma and salivary concentrations of five steroids were measured: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11-hydroxyandrostenedione (11OHA4), and 11-ketotestosterone (11KT). The correlation between plasma and salivary steroids was analyzed to assess their use in clinical practice. Results Strong correlations between plasma and salivary steroid concentrations in patients with CAH were detected: 17OHP (rs = 0.871; P < 0.001), A4 (rs = 0.931; P < 0.001), T (rs = 0.867; P < 0.001), 11OH4A (rs = 0.876; P < 0.001), and 11KT (rs = 0.944; P < 0.001). These results were consistent for patient subgroups based on sex and age. Analysis of patient subgroups based on 17OHP concentrations established clear correlations between plasma and salivary concentrations of the adrenal-specific androgen 11KT. Conclusions The current study identified tight correlations between plasma and saliva for the adrenal-derived 11-oxygenated C19 androgen 11KT, as well as 17OHP and A4, which are widely used for monitoring treatment in CAH. This combination of steroid hormones will serve as an improved noninvasive salivary test for disease monitoring in patients with CAH.

Item Type:Articles
Additional Information:This study was supported by the National Institutes of Health Research Rare Disease Translational Research Collaboration (NIHR RD TRC; to N.P.K.), the Chief Scientist Office of Scotland, and Diurnal Ltd.
Glasgow Author(s) Enlighten ID:Kyriakou, Dr Andreas and Ahmed, Professor Syed Faisal
Authors: Bacila, I., Adaway, J., Hawley, J., Mahdi, S., Krone, R., Patel, L., Alvi, S., Randell, T., Gevers, E., Dattani, M., Cheetham, T., Kyriakou, A., Schiffer, L., Ryan, F., Crowne, E., Davies, J. H., Ahmed, S. F., Keevil, B., and Krone, N.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Clinical Endocrinology and Metabolism
Publisher:Oxford University Press
ISSN (Online):1945-7197

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