Reverse circadian glucocorticoid treatment in prepubertal children with congenital adrenal hyperplasia
Related Experiment Video
Updated: Oct 20, 2025
Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids
Published on: April 25, 2016
Ilja Dubinski1, Susanne Bechtold Dalla-Pozza1, Martin Bidlingmaier2
1Division for Pediatric Endocrinology, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.
Insights
Reverse circadian treatment (RCT) for congenital adrenal hyperplasia (CAH) in children did not lower morning 17-hydroxyprogesterone (s17-OHP) levels and showed no benefits over standard therapy. Long-term risks of RCT remain unknown.
Area of Science:
- Pediatric Endocrinology
- Endocrinology
- Genetics
Background:
- Congenital adrenal hyperplasia (CAH) is a group of genetic disorders affecting steroid synthesis.
- Salt-wasting CAH requires glucocorticoid (GC) and mineralocorticoid hormone replacement therapy.
- Standard GC therapy involves thrice-daily hydrocortisone, mimicking physiological rhythms.
Purpose of the Study:
- To evaluate the efficacy of reverse circadian treatment (RCT) in prepubertal children with CAH.
- To compare salivary 17-hydroxyprogesterone (s17-OHP) levels in children receiving RCT versus standard therapy.
- To determine if RCT effectively lowers morning s17-OHP concentrations.
Main Methods:
- Retrospective analysis of 23 pediatric CAH patients' records.
- Focused on nine prepubertal children on RCT, comparing s17-OHP levels at different times of day.
- Intra-individual comparison of s17-OHP profiles in six patients on RCT versus non-RCT therapy.
Main Results:
- Eight of nine children on RCT had higher morning s17-OHP levels than evening levels.
- No significant developmental deviations, adrenal crises, or pubertal development were observed.
- No difference in 17-OHP profiles was found between RCT and non-RCT regimens.
Conclusions:
- Current data do not support the use of RCT for GC replacement in pediatric CAH.
- RCT demonstrated a lack of benefits in managing s17-OHP levels.
- Unknown long-term risks associated with RCT warrant caution.
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.
Related Concept Videos
01:27Adrenal Gland Disorders
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
01:21Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
01:15Hypoglycemia and Glucagon
01:15Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
01:31Hormones of the Adrenal Glands
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...
01:25Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...