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

Research output: Contribution to journalArticle

  • Irina Bacila
  • Jo Adaway
  • James Hawley
  • Sundus Mahdi
  • Ruth Krone
  • Leena Patel
  • Sabah Alvi
  • Tabitha Randell
  • Evelien Gevers
  • Mehul Dattani
  • Timothy Cheetham
  • Andreas Kyriakou
  • Lina Schiffer
  • Fiona Ryan
  • Elizabeth Crowne
  • Justin H. Davies
  • Syed Faisal Ahmed
  • Brian Keevil
  • Nils Krone
Original languageEnglish
Pages (from-to)6417-6429
Number of pages13
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number12
Early online date30 Jul 2019
DOIs
DateAccepted/In press - 22 Jul 2019
DateE-pub ahead of print - 30 Jul 2019
DatePublished (current) - 1 Dec 2019

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.

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