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Endocrine Abstracts (2021) 73 PEP1.5 | DOI: 10.1530/endoabs.73.PEP1.5

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

Modified-release hydrocortisone improves androgen excess and facilitates glucocorticoid dose reduction in patients with classic congenital adrenal hyperplasia: non-invasive monitoring in saliva and urine

Alessandro Prete1, 2, 3, Elizabeth S. Baranowski1, 2, 4, Lina Schiffer1, Joanne E. Adaway5, James M. Hawley5, Brian G. Keevil5, John Porter6, Richard J. Ross6, 7 & Wiebke Arlt1, 2, 8


1Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; 2Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK; 3Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 4Department of Paediatric Endocrinology and Diabetes, Birmingham Women’s and Children’s Hospital NHS Foundation Trust, Birmingham, UK; 5Department of Clinical Biochemistry, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 6Diurnal Ltd., Cardiff, UK; 7University of Sheffield, Sheffield, UK; 8NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK


Background

Standard glucocorticoid (GC) therapy in classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD-CAH) is often inadequate in controlling adrenal androgen excess, leading to GC over-exposure and poor health outcomes. A novel modified-release formulation of hydrocortisone (MR-HC, Chronocort® Diurnal Ltd. UK) has been shown to improve circulating adrenal androgen excess in 21-OHD-CAH. We investigated whether saliva and 24-h urine could be used as non-invasive tools to monitor disease control by MR-HC.

Methods

This is a sub-study of the EudraCT 2015-000711-40 and 2015-005448-32 clinical trials. Patients with 21-OHD-CAH were randomised to either MR-HC or their standard GC treatment; at 6 months all were offered MR-HC. Throughout the study, GC replacement was titrated according to serum 17OHP and A4. 24-h urine and saliva day profiles were collected at baseline (standard GC), 6 months (standard GC vs. MR-HC), and 12 months (all on MR-HC). Saliva was collected by passive drool every 2 h between 0700 h and 2300 h. Samples were analysed by LC-MS/MS (saliva) and GC-MS (24-h urine) to measure the 21-OHD-CAH marker 17-hydroxyprogesterone (17OHP in saliva; 17HP, PT, and PTONE in urine), steroids of the classic androgen pathway (A4 in saliva; An and Et in urine), the 11-oxygenated androgen pathway (11OHA4 and 11KT in saliva; 11βOHAn in urine), and the alternative pathway to dihydrotestosterone (3α5α17HP in urine).

Results

12 patients (9 women; median age 42 years, range 21–68) were randomised to MR-HC (n = 4) or standard GC (n = 8). After six months, MR-HC led to a 97% decrease in salivary 17OHP (area under the curve, AUC, P 0.006), A4 (AUC -99%, P 0.029), 11OHA4 (AUC -97%, P 0.001), 11KT (AUC -100%, P 0.004), and urinary 3α5α17HP (97% median reduction, P 0.05) as compared to standard GC. A significant decrease in the 11KT/T ratio also indicated improved control of adrenal androgen excess. Urinary excretion of 17OHP and androgen metabolites also decreased on MR-HC, albeit non-significantly. This improvement in biochemical control was achieved on a lower daily GC dose of MR-HC compared to standard treatment at 6 months (MR-HC 23 mg (15–35 mg); standard GC 32 mg (25–38 mg)). At 12 months, MR-HC maintained excellent biochemical control, despite a further reduction of the median GC dose to 18 mg (10–40 mg).

Conclusions

MR-HC treatment facilitated a significant reduction of GC dose, with non-invasive steroid monitoring comprehensively reflecting biochemical disease control.

Volume 73

European Congress of Endocrinology 2021

Online
22 May 2021 - 26 May 2021

European Society of Endocrinology 

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