Background: Treatment of CAH in children is compromised by the pharmacokinetic of available hydrocortisone (HC) preparations resulting in un-physiological early morning rise of ACTH followed by elevated androgens. HC substitution usually follows a fixed dosing scheme (50%25%25%) monitored by blood sampling.
Objective and hypotheses: We describe the individualized optimization of HC treatment by 17-OHP saliva profiles and the effects of the resulting late night dose of HC.
Method: Retrospective analysis in 20 prepubertal children from birth to 5 years (females n=11, males n=9). HC was applied 8-hourly with 1st dose at 68 h, 2nd dose at 1416 h and 3rd dose at (2224 h). Treatment in newborns started using equal dose distribution. Adaptation by timed (prior to medication) saliva profiles started around 6 month of age. Saliva-17OHP outside the target range leads to adaptation of the HC dose before the sampling point. In 16 children (aged 04 years, females n=6, males n=10) blood (ACTH and androgens) was sampled exactly prior to the morning dose.
Results: Newborns (n=15) started with a mean dose of 22.3 mg/m2 per day and equal dose distribution. Individualized dose adaptation by saliva-17OHP levels between the age of 6 month and 2 years resulted in significantly lowered afternoon and increased late-night doses (n=20, HC distribution 44.4%20%38.2%). Similar dose-distribution was found at an age of 34 years (n=7, 38.5%23.1%33.3%) and 45 years (n=3, 38.1%23.1%38.5%). In the cohort with timed blood-sampling children with the highest late-night dose of HC had significant lower ACTH and higher cortisol levels in the morning prior to the next HC dose.
Conclusion: Individualized treatment adaptation by saliva-17OHP-profiles resulted in higher late-night and lower afternoon dose. Adaptation by frequent saliva sampling is able to reduce morning ACTH and androgen levels and thereby able to prevent un-physiologic early morning rise of ACTH and androgens.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology