Reverse circadian glucocorticoid treatment in prepubertal children with congenital adrenal hyperplasia

Ilja Dubinski; Susanne Bechtold Dalla-Pozza; Martin Bidlingmaier; Nicole Reisch; Heinrich Schmidt

doi:10.1515/jpem-2021-0540

Article

Reverse circadian glucocorticoid treatment in prepubertal children with congenital adrenal hyperplasia

Ilja Dubinski , Susanne Bechtold Dalla-Pozza , Martin Bidlingmaier , Nicole Reisch and Heinrich Schmidt

Published/Copyright: September 15, 2021

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 34 Issue 12

Abstract

Objectives

Children with salt-wasting congenital adrenal hyperplasia (CAH) have an impaired function of steroid synthesis pathways. They require therapy with glucocorticoid (GC) and mineralocorticoid hormones to avoid salt-wasting crisis and other complications. Most commonly, children receive hydrocortisone thrice daily with the highest dose in the morning, mimicking the regular physiology. However, reverse circadian treatment (RCT) had been suggested previously. In this study, we aimed to determine the efficacy of RCT in prepubertal children with CAH by comparing the salivary 17-hydroxyprogesterone (s17-OHP) levels individually.

Methods

In this retrospective study, we analyzed the records of children with classical CAH and RCT who were monitored by s17-OHP levels. The study included 23 patients. We identified nine prepubertal children with RCT schemes (three boys and six girls) and compared the s17-OHP levels in the morning, afternoon, and evening. The objective of this study was to demonstrate the non-effectiveness of RCT in terms of lowering the morning s17-OHP concentration. In addition, we compared s17-OHP day profiles in six patients on RCT and non-RCT therapy (intraindividually).

Results

Eight of nine children with RCT showed higher s17-OHP levels in the morning compared to the evening. In addition, none of the children showed a significant deviation of development. Three children were overweight. No adrenal crisis or pubertal development occurred. Comparison of RCT and non-RCT regimens showed no difference in 17-OHP profiles.

Conclusions

Our data do not support the use of RCT schemes for GC replacement in children with CAH due to lack of benefits and unknown long-term risks.

Keywords: 17-hydroxyprogesterone; circadian rhythms of hormones; congenital adrenal hyperplasia; reverse circadian steroid treatment; steroid hormone metabolism

Corresponding author: Ilja Dubinski, MD, Division for Pediatric Endocrinology, Dr. von Hauner Children’s Hospital University Hospital, LMU Munich, Lindwurmstrasse 4, D-80337 Munich, Bavaria, Germany, Phone: +49 89440052780, E-mail: ilja.dubinski@med.uni-muenchen.de

Research funding: No funding to declare.
Author Contributions: I. Dubinski analyzed the data and wrote the manuscript. H. Schmidt and S. Bechtold Dalla-Pozza provided the patients´ clinical data. H. Schmidt, S. Bechtold Dalla-Pozza, and N. Reisch contributed to study concept and data analysis. M. Bidlingmaier performed the biochemical analysis. All of the authors have significantly contributed to this study providing intellectual input to the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Competing interests: The authors declare that there is no conflict of interest regarding the publication of this article.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Received: 2021-06-21

Accepted: 2021-09-03

Published Online: 2021-09-15

Published in Print: 2021-12-20

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Articles in the same Issue

https://doi.org/10.1515/jpem-2021-0540

Keywords for this article

17-hydroxyprogesterone; circadian rhythms of hormones; congenital adrenal hyperplasia; reverse circadian steroid treatment; steroid hormone metabolism