Differential effects of hydrocortisone, prednisone, and dexamethasone on hormonal and pharmacokinetic profiles: a pilot study in children with congenital adrenal hyperplasia.
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.
Department of Pediatrics, Division of Pediatric Endocrinology/Diabetology, Indiana University School of Medicine, 705 Riley Hospital Drive, Room 5960, Indianapolis, IN 46202 USA.
Todd D
TD
Nebesio
Department of Pediatrics, Division of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN USA ; Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN USA.
Jamie L
JL
Renbarger
Department of Pediatrics, Division of Pediatric Endocrinology/Diabetology, Indiana University School of Medicine, 705 Riley Hospital Drive, Room 5960, Indianapolis, IN 46202 USA.
Zeina M
ZM
Nabhan
Department of Pediatrics, Division of Pediatric Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN USA.
Sydney E
SE
Ross
Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN USA.
James E
JE
Slaven
Department of Medical and Molecular Genetics, Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN USA.
Lang
L
Li
Department of Pediatrics, Division of Pediatric Endocrinology/Diabetology, Indiana University School of Medicine, 705 Riley Hospital Drive, Room 5960, Indianapolis, IN 46202 USA.
Emily C
EC
Walvoord
Department of Pediatrics, Division of Pediatric Endocrinology/Diabetology, Indiana University School of Medicine, 705 Riley Hospital Drive, Room 5960, Indianapolis, IN 46202 USA.
Erica A
EA
Eugster
Congenital adrenal hyperplasia; Dexamethasone; Hydrocortisone; Pharmacogenetics; Prednisone
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