ESPE2019 Rapid Free Communications Adrenals and HP Axis (12 abstracts)
Development of Novel Non-Invasive Strategies for Monitoring of Treatment Control in Patients with Congenital Adrenal Hyperplasia
Irina-Alexandra Bacila 1 , Jo Adaway 2 , James Hawley 2 , Sundus Mahdi 1 , Carlo L Acerini 3 , Ruth Krone 4 , Leena Patel 5 , Sabah Alvi 6 , Tabitha Randell 7 , Evelien Gevers 8 , Mehul Dattani 9 , Timothy Cheetham 10 , Andreas Kyriakou 11 , Lina Schiffer 12 , Fiona Ryan 13 , Elizabeth Crowne 14 , Justin H Davies 15 , S Faisal Ahmed 11 , Brian Keevil 2 & Nils P Krone 1
1Academic Unit of Child Health, Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom. 2Department of Biochemistry, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 3Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom. 4Birmingham Women's & Children's Hospital, Birmingham, United Kingdom. 5Paediatric Endocrine Service, Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 6Leeds General Infirmary, Leeds, United Kingdom. 7Nottingham Children's Hospital, Nottingham, United Kingdom. 8Centre for Endocrinology, William Harvey Research Institute, Queen Mary University London, London and Barts Health NHS Trust - The Royal London Hospital, London, United Kingdom. 9Great Ormond Street Hospital, London, United Kingdom. 10Great North Children's Hospital, University of Newcastle, Newcastle, United Kingdom. 11Developmental Endocrinology Research Group, University of Glasgow, Glasgow, United Kingdom. 12Institute of Metabolism and System Research, University of Birmingham, Birmingham, United Kingdom. 13Oxford Childrens Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. 14Bristol Royal Hospital for Children, University Hospitals Bristol Foundation Trust, Bristol, United Kingdom. 15University Hospital Southampton, Southampton, United Kingdom
Introduction: Glucocorticoid treatment remains a challenging aspect in the management of congenital adrenal hyperplasia (CAH). Current strategies for monitoring treatment are suboptimal and rely largely on frequent blood tests, which are traumatising in children and young persons (CYP). Recent evidence indicates a crucial role of 11-oxygenatedC19 androgens in the pathogenesis of CAH.
Aim: To explore the use of 11-oxygenatedC19 androgens in non-invasive clinical tests to monitor glucocorticoid treatment in CAH.
Objective: To establish the correlation between plasma and salivary androgens in CYP with CAH.
Patients and Methods: We conducted a prospective multi-centre study recruiting CYP with CAH across the United Kingdom. Participants included 78 patients (43 females, 35 males, 8-18 years (12.87+/-3.04 years)) and 62 matched controls. Using liquid chromatography tandem mass spectrometry, we measured plasma and salivary concentrations for five steroid hormones: 17-hydroxyprogesterone, androstenedione, testosterone, 11-hydroxyandrostenedione and 11-ketotestosterone. The relationship between plasma and salivary steroids was analysed by Spearman correlation to assess their usefulness in clinical practice.
Results: Salivary and plasma concentrations correlated well for all the five steroids measured, with the strongest correlations found for androstenedione and 11-ketotestosterone: androstenedione(rs=0.931, P<0.001), testosterone (rs=0.867, P<0.001), 17-hydroxyprogesterone(rs=0.871, P<0.001), 11-hydroxyandrostenedione(rs=0.876, P<0.001), 11-ketotestosterone (rs=0.944, P<0.001). In addition, high correlations were found in CYP with CAH when analysing subgroups based on gender and age. Plasma and salivary steroid concentrations were significantly raised in patients compared to controls for all hormones, with the exception of testosterone which was higher in healthy individuals compared to CAH patients for the subgroup of pubertal boys. Analysing patients subgroups of CAH control based on 17-hydroxyprogesterone concentrations (<15 nmol/L; 15-30 nmol/L; >30 nmol/L), the strongest correlations between plasma and saliva were found for androstenedione and 11-ketotestosterone in both overtreated (androstenedione(rs=0.797, P=0.002), 11-ketotestosterone (rs=0.888, P<0.001)) and undertreated(androstenedione(rs=0.924, P<0.001), 11-ketotestosterone (rs=0.878, P<0.001)) CAH patients.
Conclusions: We have established that salivary concentrations correlate well with plasma concentrations for androgens used as markers of therapy control in CAH patients. Importantly, the best correlations were found for adrenal-derived 11-oxygenatedC19 androgen 11-ketotestosterone as well as 17-hydroxyprogesterone and androstenedione, which are widely used for CAH monitoring. Thus, we believe that this novel and improved combination of salivary steroid hormones can serve as non-invasive monitoring tool in CAH providing a significant amount of additional information and will ultimately improve management and outcomes in CAH.
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