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International Journal of Pediatric Endocrinology
Published in: International Journal of Pediatric Endocrinology 1/2016

Open Access 01-12-2016 | Research

Differential effects of hydrocortisone, prednisone, and dexamethasone on hormonal and pharmacokinetic profiles: a pilot study in children with congenital adrenal hyperplasia

Authors: Todd D. Nebesio, Jamie L. Renbarger, Zeina M. Nabhan, Sydney E. Ross, James E. Slaven, Lang Li, Emily C. Walvoord, Erica A. Eugster

Published in: International Journal of Pediatric Endocrinology | Issue 1/2016

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Abstract

Background

Little is known about the comparative effects of different glucocorticoids on the adrenal and growth hormone (GH) axes in children with congenital adrenal hyperplasia (CAH). We sought to compare the effects of hydrocortisone (HC), prednisone (PDN), and dexamethasone (DEX) in children with classic CAH and to investigate a potential role of pharmacogenetics.

Methods

Subjects were randomly assigned to three sequential 6-week courses of HC, PDN, and DEX, each followed by evaluation of adrenal hormones, IGF-1, GH, and body mass index (BMI). Single nucleotide polymorphism (SNP) analysis of genes in the glucocorticoid pathway was also performed.

Results

Nine prepubertal subjects aged 8.1 ± 2.3 years completed the study. Mean ACTH, androstenedione, and 17-hydroxyprogesterone (17-OHP) values were lower following the DEX arm of the study than after subjects received HC (p ≤ 0.016) or PDN (p ≤ 0.002). 17-OHP was also lower after HC than PDN (p < 0.001). There was no difference in IGF-1, GH, or change in BMI. SNP analysis revealed significant associations between hormone concentrations, pharmacokinetic parameters, and variants in several glucocorticoid pathway genes (ABCB1, NR3C1, IP013, GLCCI1).

Conclusions

DEX resulted in marked adrenal suppression suggesting that its potency relative to hydrocortisone and prednisone was underestimated. SNPs conferred significant differences in responses between subjects. Although preliminary, these pilot data suggest that incorporating pharmacogenetics has the potential to eventually lead to targeted therapy in children with CAH.
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Metadata
Title
Differential effects of hydrocortisone, prednisone, and dexamethasone on hormonal and pharmacokinetic profiles: a pilot study in children with congenital adrenal hyperplasia
Authors
Todd D. Nebesio
Jamie L. Renbarger
Zeina M. Nabhan
Sydney E. Ross
James E. Slaven
Lang Li
Emily C. Walvoord
Erica A. Eugster
Publication date
01-12-2016
Publisher
BioMed Central
Published in
International Journal of Pediatric Endocrinology / Issue 1/2016
Electronic ISSN: 1687-9856
DOI
https://doi.org/10.1186/s13633-016-0035-5

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