ESPE2024 Poster Category 1 Adrenals and HPA Axis 2 (8 abstracts)
Non-invasive biochemical monitoring for Congenital Adrenal Hyperplasia: use of urinary steroid metabolites and salivary 17α-Hydroxyprogesterone
Joseph J Tonge 1,2 , Irina Bacila 1,3 , Neil Richard Lawrence 1,3 , Sabah Alvi 4 , Timothy D Cheetham 5 , Elizabeth Crowne 6 , Urmi Das 7 , Mehul Tulsidas Dattani 8 , Justin H Davies 9,10 , Evelien Gevers 11,12 , Brian Keevil 13 , Ruth E Krone 14 , Leena Patel 15 , Tabitha Randell 16 , Fiona J Ryan 17 , Ajay Thankamony 18 , S Faisal Ahmed 19 , Norman Taylor 20 & Nils P Krone 1,3
1University of Sheffield, Sheffield, United Kingdom. 2Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom. 3Sheffield Children's Hospital, Sheffield, United Kingdom. 4Leeds General Infirmary, Leeds, United Kingdom. 5Great North Children's Hospital, Newcastle, United Kingdom. 6Bristol Royal Hospital for Children, University Hospitals Bristol Foundation Trust, Bristol, United Kingdom. 7Alder Hey Children's Hospital, Liverpool, United Kingdom. 8Great Ormond Street Hospital, London, United Kingdom. 9University Hospital Southampton, Southampton, United Kingdom. 10University of Southampton, Southampton, United Kingdom. 11The Royal London Hospital, London and Barts Health NHS Trust, London, United Kingdom. 12Queen Mary University London, London, United Kingdom. 13Manchester University NHS Foundation Trust, Manchester, United Kingdom. 14Birmingham Women's & Children's Hospital, Birmingham, United Kingdom. 15Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 16Nottingham Children’s Hospital, Nottingham, United Kingdom. 17Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. 18Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. 19University of Glasgow, Glasgow, United Kingdom. 20King’s College Hospital, London, London, United Kingdom
Background: Monitoring disease control in congenital adrenal hyperplasia (CAH) by random serum 17a-Hydroxyprogesterone (17OHP) measurements is invasive and fails to capture total daily adrenal steroid synthesis. Urinary steroid analysis may provide a more suitable, non-invasive method of assessing treatment response in children with CAH, by estimating the total daily excretion of 17OHP metabolites.
Method: Urine was collected over 24-hours from CAH patients in 13 centres across the United Kingdom and analysed at Kings College Hospital, London, by gas chromatography-mass spectrometry (GC-MS). Single paired serum and salivary samples were collected from patients between 8-10am, after their first morning glucocorticoid dose, and analysed by light chromatography-tandem mass spectrometry (LC-MS/MS). Urinary samples collected in the 24 hours prior to the study visit were obtained. We analysed results using multiple regression in R Studio accounting for missing data using mean imputation. We evaluated the direct urinary metabolites of 17OHP, pregnanetriol and pregnanetriol-20b, to assess how well they predicted serum 17OHP while accounting for sex, body surface area (BSA) and salivary 17OHP as covariates.
Results: A total of 96 CAH patients (53 female and 43 male) aged 8 - 18 years were included, with 95% taking hydrocortisone two to four times per day. Mean total hydrocortisone equivalent was 18.7 mg/day (SD=6.7), 13.5 mg/m2/day (SD=3.8). Urinary 17OHP metabolites, pregnanetriol and pregnanetriol-20b, both predicted serum 17OHP (R2adj=0.21, 0.09), with improved predictions when combined (R2adj=0.22). Salivary 17OHP was superior at predicting serum 17OHP compared with urinary metabolites (R2adj=0.55). However, combining both urinary 17OHP metabolites and salivary 17OHP in a multiple regression model improved prediction of serum 17OHP compared to urine or saliva alone [loge(Serum17OHP) = -2.80 + 1.51 x (loge(Pregnanetriol) + 7.19 x (loge(Saliva17OHP)/10), R2adj of 0.66]. Adding sex or BSA as covariates did not improve prediction of serum 17OHP (P >0.05).
Discussion: The use of urinary profiles alongside salivary steroid analysis offers improved prediction of serum 17OHP while being a non-invasive way to assess disease control in CAH. Further studies and individual participant data meta-analysis using these markers would allow development of a robust prediction model that combines non-invasive techniques to reliably predict serum 17OHP.
Conclusion: Urinary steroid profiles are a useful non-invasive way of predicting overall adrenal steroid synthesis when used alongside salivary analysis. This has the potential to improve non-invasive and remote monitoring of CAH.
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