Modified release and conventional glucocorticoids and diurnal androgen excretion in congenital adrenal hyperplasia

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Modified release and conventional glucocorticoids and diurnal androgen excretion in congenital adrenal hyperplasia. / Jones, Christopher; Mallappa, Ashwini; Reisch, Nicole; Nikolaou, Nikolaos; Krone, Nils; Hughes, Beverly; O'Neil, Donna; Whitaker, Martin J; Tomlinson, Jeremy ; Storbeck, Karl-Heinz; Merke, Deborah P; Ross, Richard; Arlt, Wiebke.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 102, No. 6, 15.11.2016, p. 1797-1806.

Research output: Contribution to journalArticlepeer-review

Harvard

Jones, C, Mallappa, A, Reisch, N, Nikolaou, N, Krone, N, Hughes, B, O'Neil, D, Whitaker, MJ, Tomlinson, J, Storbeck, K-H, Merke, DP, Ross, R & Arlt, W 2016, 'Modified release and conventional glucocorticoids and diurnal androgen excretion in congenital adrenal hyperplasia', Journal of Clinical Endocrinology and Metabolism, vol. 102, no. 6, pp. 1797-1806. https://doi.org/10.1210/jc.2016-2855

APA

Jones, C., Mallappa, A., Reisch, N., Nikolaou, N., Krone, N., Hughes, B., O'Neil, D., Whitaker, M. J., Tomlinson, J., Storbeck, K-H., Merke, D. P., Ross, R., & Arlt, W. (2016). Modified release and conventional glucocorticoids and diurnal androgen excretion in congenital adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism, 102(6), 1797-1806. https://doi.org/10.1210/jc.2016-2855

Vancouver

Author

Jones, Christopher ; Mallappa, Ashwini ; Reisch, Nicole ; Nikolaou, Nikolaos ; Krone, Nils ; Hughes, Beverly ; O'Neil, Donna ; Whitaker, Martin J ; Tomlinson, Jeremy ; Storbeck, Karl-Heinz ; Merke, Deborah P ; Ross, Richard ; Arlt, Wiebke. / Modified release and conventional glucocorticoids and diurnal androgen excretion in congenital adrenal hyperplasia. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 102, No. 6. pp. 1797-1806.

Bibtex

@article{b48e80cc2596403c822a489f6d6bb786,
title = "Modified release and conventional glucocorticoids and diurnal androgen excretion in congenital adrenal hyperplasia",
abstract = "CONTEXT: The classic androgen synthesis pathway proceeds via DHEA, androstenedione and testosterone to 5α-dihydrotestosterone (DHT). However, DHT synthesis can also be achieved by an alternative pathway originating from 17α-hydroxyprogesterone (17OHP), which accumulates in congenital adrenal hyperplasia (CAH). Similarly, recent work has highlighted androstenedione-derived 11-oxygenated 19-carbon steroids as active androgens and, in CAH, androstenedione is generated directly from 17OHP. The exact contribution of alternative pathway activity to androgen excess in CAH and its response to glucocorticoid therapy is unknown.OBJECTIVE: We sought to quantify classic and alternative pathway-mediated androgen synthesis in CAH, their diurnal variation and their response to conventional glucocorticoid (GC) therapy and modified release hydrocortisone.METHODS: We employed urinary steroid metabolome profiling by gas chromatography-mass spectrometry for 24-h steroid excretion analysis, studying the impact of conventional GCs (hydrocortisone, prednisolone, dexamethasone) in 55 adults with CAH and 60 controls. We studied diurnal variation in steroid excreton by comparing 8-hourly collections (23:00-7:00h, 7:00-15:00h, 15:00-23:00h) in 16 CAH patients on conventional glucocorticoids and during six months of treatment with modified release hydrocortisone, Chronocort.RESULTS: CAH patients on conventional GCs showed low excretion of classic pathway androgen metabolites but excess excretion of the alternative pathway signature metabolites 3α,5α-17-hydroxypregnanolone and 11β-hydroxyandrosterone. Chronocort reduced 17OHP and alternative pathway metabolite excretion to near normal levels more consistently than other GC preparations.CONCLUSIONS: Alternative pathway mediated androgen synthesis significantly contributes to androgen excess in CAH. Chronocort therapy appears superior to conventional GC therapy in controlling androgen synthesis via alternative pathways through attenuation of their major substrate, 17OHP.",
author = "Christopher Jones and Ashwini Mallappa and Nicole Reisch and Nikolaos Nikolaou and Nils Krone and Beverly Hughes and Donna O'Neil and Whitaker, {Martin J} and Jeremy Tomlinson and Karl-Heinz Storbeck and Merke, {Deborah P} and Richard Ross and Wiebke Arlt",
year = "2016",
month = nov,
day = "15",
doi = "10.1210/jc.2016-2855",
language = "English",
volume = "102",
pages = "1797--1806",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Endocrine Society",
number = "6",

}

RIS

TY - JOUR

T1 - Modified release and conventional glucocorticoids and diurnal androgen excretion in congenital adrenal hyperplasia

AU - Jones, Christopher

AU - Mallappa, Ashwini

AU - Reisch, Nicole

AU - Nikolaou, Nikolaos

AU - Krone, Nils

AU - Hughes, Beverly

AU - O'Neil, Donna

AU - Whitaker, Martin J

AU - Tomlinson, Jeremy

AU - Storbeck, Karl-Heinz

AU - Merke, Deborah P

AU - Ross, Richard

AU - Arlt, Wiebke

PY - 2016/11/15

Y1 - 2016/11/15

N2 - CONTEXT: The classic androgen synthesis pathway proceeds via DHEA, androstenedione and testosterone to 5α-dihydrotestosterone (DHT). However, DHT synthesis can also be achieved by an alternative pathway originating from 17α-hydroxyprogesterone (17OHP), which accumulates in congenital adrenal hyperplasia (CAH). Similarly, recent work has highlighted androstenedione-derived 11-oxygenated 19-carbon steroids as active androgens and, in CAH, androstenedione is generated directly from 17OHP. The exact contribution of alternative pathway activity to androgen excess in CAH and its response to glucocorticoid therapy is unknown.OBJECTIVE: We sought to quantify classic and alternative pathway-mediated androgen synthesis in CAH, their diurnal variation and their response to conventional glucocorticoid (GC) therapy and modified release hydrocortisone.METHODS: We employed urinary steroid metabolome profiling by gas chromatography-mass spectrometry for 24-h steroid excretion analysis, studying the impact of conventional GCs (hydrocortisone, prednisolone, dexamethasone) in 55 adults with CAH and 60 controls. We studied diurnal variation in steroid excreton by comparing 8-hourly collections (23:00-7:00h, 7:00-15:00h, 15:00-23:00h) in 16 CAH patients on conventional glucocorticoids and during six months of treatment with modified release hydrocortisone, Chronocort.RESULTS: CAH patients on conventional GCs showed low excretion of classic pathway androgen metabolites but excess excretion of the alternative pathway signature metabolites 3α,5α-17-hydroxypregnanolone and 11β-hydroxyandrosterone. Chronocort reduced 17OHP and alternative pathway metabolite excretion to near normal levels more consistently than other GC preparations.CONCLUSIONS: Alternative pathway mediated androgen synthesis significantly contributes to androgen excess in CAH. Chronocort therapy appears superior to conventional GC therapy in controlling androgen synthesis via alternative pathways through attenuation of their major substrate, 17OHP.

AB - CONTEXT: The classic androgen synthesis pathway proceeds via DHEA, androstenedione and testosterone to 5α-dihydrotestosterone (DHT). However, DHT synthesis can also be achieved by an alternative pathway originating from 17α-hydroxyprogesterone (17OHP), which accumulates in congenital adrenal hyperplasia (CAH). Similarly, recent work has highlighted androstenedione-derived 11-oxygenated 19-carbon steroids as active androgens and, in CAH, androstenedione is generated directly from 17OHP. The exact contribution of alternative pathway activity to androgen excess in CAH and its response to glucocorticoid therapy is unknown.OBJECTIVE: We sought to quantify classic and alternative pathway-mediated androgen synthesis in CAH, their diurnal variation and their response to conventional glucocorticoid (GC) therapy and modified release hydrocortisone.METHODS: We employed urinary steroid metabolome profiling by gas chromatography-mass spectrometry for 24-h steroid excretion analysis, studying the impact of conventional GCs (hydrocortisone, prednisolone, dexamethasone) in 55 adults with CAH and 60 controls. We studied diurnal variation in steroid excreton by comparing 8-hourly collections (23:00-7:00h, 7:00-15:00h, 15:00-23:00h) in 16 CAH patients on conventional glucocorticoids and during six months of treatment with modified release hydrocortisone, Chronocort.RESULTS: CAH patients on conventional GCs showed low excretion of classic pathway androgen metabolites but excess excretion of the alternative pathway signature metabolites 3α,5α-17-hydroxypregnanolone and 11β-hydroxyandrosterone. Chronocort reduced 17OHP and alternative pathway metabolite excretion to near normal levels more consistently than other GC preparations.CONCLUSIONS: Alternative pathway mediated androgen synthesis significantly contributes to androgen excess in CAH. Chronocort therapy appears superior to conventional GC therapy in controlling androgen synthesis via alternative pathways through attenuation of their major substrate, 17OHP.

U2 - 10.1210/jc.2016-2855

DO - 10.1210/jc.2016-2855

M3 - Article

C2 - 27845856

VL - 102

SP - 1797

EP - 1806

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 6

ER -