BSPED2021 Oral Communications Oral Communications 4 (9 abstracts)
The use of urinary steroid profiles in monitoring therapy in children with 21-hydroxylase deficiency – results from the CAH-UK cohort study
Irina Bacila 1 , Neil Lawrence 1 , Sabah Alvi 2 , Timothy Cheetham 3 , Elizabeth Crowne 4 , Urmi Das 5 , Mehul Dattani 6 , Justin H Davies 7 , Evelien Gevers 8,9 , Ruth Krone 10 , Andreas Kyriakou 11 , Leena Patel 12 , Tabitha Randell 13 , Fiona Ryan 14 , Ahmed S Faisal 11 , Brian Keevil 15 , Norman Taylor 16 & Nils Krone 1
1The University of Sheffield, Sheffield, United Kingdom; 2Leeds General Infirmary, Leeds, United Kingdom; 3Great North Children’s Hospital, University of Newcastle, Newcastle, United Kingdom; 4Bristol Royal Hospital for Children, University Hospitals Bristol Foundation Trust, Bristol, United Kingdom; 5Alder Hey Children’s Hospital, Liverpool, United Kingdom; 6Great Ormond Street Hospital, London, United Kingdom; 7University Hospital Southampton, Southampton, United Kingdom; 8Centre for Endocrinology, William Harvey Research Institute, Queen Mary University London, London, United Kingdom; 9Barts Health NHS Trust - The Royal London Hospital, London, United Kingdom; 10Birmingham Women’s & Children’s Hospital, Birmingham, United Kingdom; 11Developmental Endocrinology Research Group, University of Glasgow, Glasgow, United Kingdom; 12Paediatric Endocrine Service, Royal Manchester Children’s Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom; 13Nottingham Children’s Hospital, Nottingham, United Kingdom; 14Oxford Children’s Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; 15Department of Biochemistry, Manchester University NHS Foundation Trust, Manchester, United Kingdom; 16Department of Clinical Biochemistry, King’s College Hospital, London, United Kingdom
Introduction: Monitoring glucocorticoid (GC) replacement in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) remains challenging. There are disease-specific patterns in the plasma and urinary steroid profiles in 21OHD, a key role being played by the 11-oxygenatedC19 androgens.
Aim: To explore the urinary steroid profile in 21OHD in relation to treatment and plasma steroids.
Methods: Participants consisted of 91 patients with 21OHD on hydrocortisone therapy (age 12.5 ± 2.8 years, 53% females), from 14 UK centres. Urinary steroids (24-hour profiles), adjusted for body surface and log10-transformed, were analysed in relation to clinical data and morning plasma steroid panels. Urinary steroids were analysed individually and grouped as cortisol, 17-hydroxyprogesterone (17OHP) and androgen metabolite sums. The 11 β-hydroxysteroid dehydrogenase (HSD-11 β) activity was calculated as (5α-tetrahydrocortisol + tetrahydrocortisol)/ tetrahydrocortisone.
Results: Urinary 17OHP and androgen metabolites correlated well with plasma 17OHP, androstenedione, testosterone, 11-hydroxyandrostenedione and 11-ketotestosterone. The best correlations were found for urinary pregnanetriolone with plasma 17OHP (rs = 0.767, P < 0.001) and urinary 11-hydroxyandrosterone with plasma 11-hydroxyandrostenedione and 11-ketotestosterone (rs = 0.829, P < 0.001 and rs = 0.736, P < 0.001). Urinary pregnanetriolone, 11-hydroxyandrosterone, 17OPH and androgen sums were significantly different (Kruskal-Wallis, P < 0.001) between patient subgroups of <12, 12-36 and >36 nmol/l plasma 17OHP, classified as suppressed, good control and under-treated, respectively. Urinary cortisol metabolites correlated positively with 17OHP and androgen metabolites (rs = 0.634, P < 0.001 and rs = 0.603, P < 0.001), suggesting lack of androgen suppression despite using high GC doses in some patients. A multivariate linear regression showed an increase of the urinary cortisol metabolites with the GC dose, when adjusted for the HSD-11 β activity (R2 = 0.288, P < 0.001). Male patients were receiving higher GC doses (P = 0.031) and had higher urinary cortisol metabolites compared to females (P = 0.020). Patients 12 years and older had higher urinary cortisol (P = 0.025), 17OHP (P = 0.024) and androgen (P = 0.002) metabolites compared to younger children.
Conclusions: The close correlation of urinary 17OHP and androgen metabolites with plasma biomarkers, including 11-oxygenated androgens, support their role as markers of therapy control. Given their relationship with the GC dose, cortisol metabolites may be used to monitor compliance and toxicity. These findings support the use of urinary steroid profiles as an adjuvant non-invasive test in monitoring CAH.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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