ESPE Abstracts (2016) 86 P-P1-15

Individualized Optimization with 17OHP-Saliva Profiles Leads to Changes in Hydrocortisone Dosing Pattern in Children with Congenital Adrenal Hyperplasia

Uta Neumanna,b, Erwin Lankesb, Franziska Bathelt-Toka, Heiko Krudea & Oliver Blankensteina,b

aInstitute for Experimental Paediatric Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany; bSozialpädiatrisches Zentrum, Charité-Universitätsmedizin Berlin, Berlin, Germany

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 6–8 h, 2nd dose at 14–16 h and 3rd dose at (22–24 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 0–4 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 3–4 years (n=7, 38.5%–23.1%–33.3%) and 4–5 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.

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