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

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

doi:10.1210/jc.2019-00031

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

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

Bristol Medical School (THS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

31 Citations (Scopus)

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.

Original language	English
Pages (from-to)	6417-6429
Number of pages	13
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	104
Issue number	12
Early online date	30 Jul 2019
DOIs	https://doi.org/10.1210/jc.2019-00031
Publication status	Published - 1 Dec 2019

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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., & Krone, N. (2019). Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency. Journal of Clinical Endocrinology and Metabolism, 104(12), 6417-6429. https://doi.org/10.1210/jc.2019-00031

@article{6f4c74717d6a45b4a69e0d64b24be9b8,

title = "Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency",

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.",

author = "Irina Bacila and Jo Adaway and James Hawley and Sundus Mahdi and Ruth Krone and Leena Patel and Sabah Alvi and Tabitha Randell and Evelien Gevers and Mehul Dattani and Timothy Cheetham and Andreas Kyriakou and Lina Schiffer and Fiona Ryan and Elizabeth Crowne and Davies, {Justin H.} and Ahmed, {Syed Faisal} and Brian Keevil and Nils Krone",

year = "2019",

month = dec,

day = "1",

doi = "10.1210/jc.2019-00031",

language = "English",

volume = "104",

pages = "6417--6429",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "12",

}

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, JH, Ahmed, SF, Keevil, B & Krone, N 2019, 'Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency', Journal of Clinical Endocrinology and Metabolism, vol. 104, no. 12, pp. 6417-6429. https://doi.org/10.1210/jc.2019-00031

TY - JOUR

T1 - Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency

AU - Bacila, Irina

AU - Adaway, Jo

AU - Hawley, James

AU - Mahdi, Sundus

AU - Krone, Ruth

AU - Patel, Leena

AU - Alvi, Sabah

AU - Randell, Tabitha

AU - Gevers, Evelien

AU - Dattani, Mehul

AU - Cheetham, Timothy

AU - Kyriakou, Andreas

AU - Schiffer, Lina

AU - Ryan, Fiona

AU - Crowne, Elizabeth

AU - Davies, Justin H.

AU - Ahmed, Syed Faisal

AU - Keevil, Brian

AU - Krone, Nils

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85073725192&partnerID=8YFLogxK

U2 - 10.1210/jc.2019-00031

DO - 10.1210/jc.2019-00031

M3 - Article (Academic Journal)

C2 - 31361321

SN - 0021-972X

VL - 104

SP - 6417

EP - 6429

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 12

ER -

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

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