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Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency

Bacila, I; Adaway, J; Hawley, J; Mahdi, S; Krone, R; Patel, L; Alvi, S; ... Krone, N; + view all (2019) Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency. The Journal of Clinical Endocrinology & Metabolism , 104 (12) pp. 6417-6429. 10.1210/jc.2019-00031. Green open access

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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.

Type: Article
Title: Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1210/jc.2019-00031
Publisher version: https://doi.org/10.1210/jc.2019-00031
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10086821
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