Aim: Recommendations for replacement glucocorticoids in CAH suggest a dose per body surface area (BSA) of glucocorticoids of 10-15mg/m2/day to maintain a 17-OH Progesterone (17OHP) level of 12-36 nmol/l across all ages. We used longitudinal analysis to assess whether biomarkers and dose of hydrocortisone varied with age in children within the I-CAH registry .
Method: This retrospective multi-centre study, including 21 centres (14 countries), analysed data from the International-CAH Registry. We analysed repeated measures using linear mixed-effects modelling (LMEM) (lme4, Rstudio) to obtain insight into the within patients and between centres variability of dose and biomarkers.
Results: A total of 308 patients (50% female) from 21 centres on hydrocortisone replacement with 2707 visits between 2000-2020 were available for modelling, with 1813 visits with biomarker data available. Median age at visit was 3.2 years (Interquartile Range (IQR) 1.7, 6.1), maximum age at visit was 18.7 years, and median number of visits available per patient was 7 (IQR 5,10.5). Androstenedione increased with age in a univariate LMEM (0.86+0.56*age, P < 0.001) whereas 17OHP did not correlate with age within patients (P > 0.05). Weight z-scores increased with age within patients (fixed effects: -2.1+0.35*age). A random intercept multivariate LMEM showed that weight z-score had a significant impact upon dose, increasing weight correlating with a decrease in dose (mg/m2/day) (12.4-1.02*weight+0.085*age, P < 0.001). This equates to a child having a dose decrease of 1.02mg/m2/day with each 1 point increase in their weight z-score. Random effects of this model showed that the patients treating centre had a larger effect on dose than the individual patient effect (Centre Intraclass Correlation Coefficient=0.68).
Conclusions: Repeated measures analysis of real world data shows relative dose of glucocorticoid replacement per body surface area decreases as they experience an increase in weight z-score. The main contributor to dose variability is a difference in practice between centres, with notable interindividual variability in dose between patients within centres, an average increase in Androstenedione with age, but no change in 17OHP with age. Further use of appropriate multivariate and longitudinal analysis, accounting for puberty, will improve our understanding of how the dosing of glucocorticoids should be informed by patient biometrics and biomarkers, and help standardise the management of CAH across centres.
22 Sep 2021 - 26 Sep 2021