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Endocrine Abstracts (2021) 73 PEP1.1 | DOI: 10.1530/endoabs.73.PEP1.1

ECE2021 Presented Eposters Presented ePosters 1: Adrenal and Cardiovascular Endocrinology (8 abstracts)

Salivary steroid and 11‑oxygenated androgen profiles in patients with congenital adrenal hyperplasia on various glucocorticoid replacement regimens

Matthias Auer 1 , Hanna Nowotny 1 , Marcus Quinkler 2 , Martin Bidlingmaier 1 , James M Hawley 3 , Jo Adaway 3 , Brian Keevil 3 , Richard Ross 4 , John Porter 5 & Nicole Reisch 1


1Medizinische Klinik and Poliklinik IV, Endocrinology, Munich, Germany; 2Endocrinology in Charlottenburg, Berlin, Germany; 3Manchester University Foundation NHS Trust, Department of Clinical Biochemistry, Manchester, UK; 4University of Sheffield, Department of Oncology and Metabolism, Sheffield, UK; 5Diurnal Ltd., Cardiff, UK


Context

11-oxygenated C19 steroids have recently gained attention as markers of androgen control in congenital adrenal hyperplasia (CAH) due to 21hydroxylase deficiency (21OHD). However, they have not yet been systematically investigated in the context of different glucocorticoid (GC) replacement regimens and in particular not in patients receiving new modified-release formulations.

Methods

Cross-sectional single center study including 26 men and 48 women with CAH and 14 male and 9 female controls. Saliva samples were collected at four times during the day starting with a morning sample after awakening. 24 patients were receiving conventional hydrocortisone three times a day, 15 patients Plenadren once in the morning, 19 patients twice-daily prednisolone and 16 patients twice-daily Chronocort. Salivary concentrations of 17hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11βhydroxyandrostenedione (11OHA4) and 11ketotestosterone (11KT) were analyzed by LC–MS/MS. Sex-specific linear mixed-effects models corrected for hydrocortisone (HC) equivalence dosage and age were calculated to compare steroid profiles between groups.

Results

Once daily plenadren resulted in poor androgen control in both sexes in comparison to other GC replacement regimens as it was not able to suppress nightly rise of adrenal androgens. All investigated steroids in the Plenadren group were higher in the morning than in any other group. Mean overall salivary T levels in women on Plenadren (102.0 ng/ml; 95% CI 82.0–126.9) were actually as high as in control men (111.1 ng/ml; 95% CI 81.9–150.5) whereas on Chronocort they were comparable to controls and on prednisolone even lower. 11-oxygenated C19 steroids were only elevated on plenadren, where 11KT levels were greatly increased in both sexes. Females on chronocort and HC had lower 11KT levels compared to controls and 11KT was similar to controls on prednisolone. There was a strong natural diurnal rhythm in 11OHA4 and 11KT in healthy controls that was independent of 17OHP. Diurnal variance for 11-oxygenated C19 steroids was lowest in patients receiving chronocort. In accordance with the half-life of prednisolone and HC, most steroids showed a small peak around lunchtime in these groups, an effect that was limited to men.

Conclusions

Once daily Plenadren cannot mimic physiological cortisol secretion in CAH and therefore fails in suppressing the nocturnal androgen surge. Chronocort in contrast controls the overnight rise in 17OHP and the subsequent pathological generation of 11OHA4 and 11KT seen in CAH.

Volume 73

European Congress of Endocrinology 2021

Online
22 May 2021 - 26 May 2021

European Society of Endocrinology 

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