ESPE Abstracts (2019) 92 P1-6

Health status of children with Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency in the United Kingdom: results of a multi-centre cohort study

Irina-Alexandra Bacila1, Sundus Mahdi1, Carlo L Acerini2, Ruth Krone3, Leena Patel4, Sabah Alvi5, Tabitha Randell6, Evelien Gevers7, Mehul Dattani8, Timothy Cheetham9, Andreas Kyriako10, Fiona Ryan11, Elizabeth Crowne12, Justin H Davies13, S. Faisal Ahmed10, Nils P Krone1


1Academic Unit of Child Health, Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom. 2Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom. 3Birmingham Women's & Children's Hospital, Birmingham, United Kingdom. 4Paediatric Endocrine Service, Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 5Leeds General Infirmary, Leeds, United Kingdom. 6Nottingham Children's Hospital, Nottingham, United Kingdom. 7Centre for Endocrinology, William Harvey Research Institute, Queen Mary University London, London and Barts Health NHS Trust - The Royal London Hospital, London, United Kingdom. 8Great Ormond Street Hospital, London, United Kingdom. 9Great North Children's Hospital, University of Newcastle, Newcastle, United Kingdom. 10Developmental Endocrinology Research Group, University of Glasgow, Glasgow, United Kingdom. 11Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. 12Bristol Royal Hospital for Children, University Hospitals Bristol Foundation Trust, Bristol, United Kingdom. 13University Hospital Southampton, Southampton, United Kingdom


Introduction: Congenital adrenal hyperplasia (CAH) is associated with long-term health problems. However, little is known about co-morbidities and their onset in children and young persons (CYP).

Objective: To establish the health status of CYP with CAH across the United Kingdom.

Methods: A multi-centre prospective study recruited 102 patients with 21-hydroxylase deficiency targeting CYP aged 8-18 years (54 females, 48 males, 13.0±2.92 years) from 13 centres across the United Kingdom and 83 matched controls. Recruitment took place between September 2016 and March 2019. Demographic, clinical, and metabolic data were explored by descriptive statistics and analysis of variance.

Results: Most CAH patients were of White (72.5%) or Southeast Asian (19.6%) ethnicity. Glucocorticoid treatment (hydrocortisone 94.1%, prednisolone 5.9%) exceeded 15mg/m2/day in 27% of patients. 84.3% of patients received 3-4 doses/day with a higher am dose (50-70% of total daily dose in 32% patients; 30-50% of total daily dose in 35%). Glucocorticoid doses (mg/m2/day, median with interquartile range) were significantly higher in boys (14 (11.8-15.6)) compared to girls (11 (8.1-14.2))(P=0.002). 75% of patients received fludrocortisone with a median dose 90(64-133) mg/m2/day. 34.3% of patients required admission for adrenal crisis after diagnosis (1-2 episodes for 87.1%). Advanced bone age (>1.5 years) was not different between girls (23%) and boys (20%). Delta-SDS for target height was 1.2±1.4 for children younger than 12 years and 0.3±1.6 for 12-18 year-olds. Comparing height-SDS, patients younger than 12 years were taller (P=0.02) and patients aged 12-18 years shorter (P=0.03) than controls. Patient weight-SDS (0.87; 0.03-1.35) and body-mass-index-SDS (0.98; -0.04-1.94) were significantly higher than in controls, 27.7% of patients were overweight and 22.8% obese. Five patients had high blood pressure. Post-glucocorticoid dose androstenedione was normal in 32%, supressed in 7%, and elevated in 50% of patients; 17-hydroxyprogesterone was within target range in 20%, supressed in 19%, and increased in 43% of patients. Biochemistry indicated normal sodium in all patients, low potassium in 1 patient, mildly raised creatinine in 9.8%, abnormal high lipids in 9.8%, and normal fasting glucose in all patients. Associated behavioural and mental health problems were reported for 11.3% patients aged 12-18 years, similar to the general population.

Conclusion: Our findings suggest that children with CAH have increased prevalence of growth problems, excessive weight, and metabolic co-morbidities compared to controls. Improved standardised treatment and personalised strategies for the management and monitoring of CAH in childhood are required to improve long-term patient outcomes.