Dataset Information

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

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.

SUBMITTER: Nebesio TD

PROVIDER: S-EPMC5036261 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

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

Nebesio Todd D TD Renbarger Jamie L JL Nabhan Zeina M ZM Ross Sydney E SE Slaven James E JE Li Lang L Walvoord Emily C EC Eugster Erica A EA

International journal of pediatric endocrinology 20160926

<h4>Background</h4>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.<h4>Methods</h4>Subjects were randomly assigned to three sequential 6-week courses of HC, PDN, and DEX, each followed by ev ...[more]

PMID: 27688786

Similar Datasets

Project description:ObjectiveOutcomes are poor for patients with congenital adrenal hyperplasia (CAH), in part due to the supraphysiological glucocorticoid doses required to control adrenal androgen excess. Hydrocortisone (i.e. cortisol) is the recommended glucocorticoid for treatment of CAH. However, the other endogenous glucocorticoid in humans, corticosterone, is actively transported out of metabolic tissues such as adipose tissue and muscle, so we hypothesized that corticosterone could control adrenal androgens while causing fewer metabolic adverse effects than hydrocortisone.MethodsThirteen patients (8 female, 5 male) with CAH due to 21-hydroxylase deficiency completed a randomised placebo-controlled crossover study comparing 5h intravenous infusions of either hydrocortisone, corticosterone or placebo. 6-6[2H]2-glucose and 1,1,2,3,3-[2H]5-glycerol were infused to measure glucose and glycerol kinetics, and blood samples were collected throughout. Subcutaneous abdominal adipose tissue biopsies were obtained at the end of each infusion.ResultsDuring the infusion, corticosterone and hydrocortisone similarly reduced ACTH, 17α-hydroxyprogesterone, androstenedione, and testosterone (in females only) compared with placebo. Despite achieving circulating corticosterone concentrations ∼2.5-fold higher than hydrocortisone, by T+300 minutes hydrocortisone but not corticosterone increased glucose and insulin concentrations and reduced 6-6-[2H]2-glucose clearance compared with placebo. Hydrocortisone increased mRNA levels of the glucocorticoid regulated transcript PER1 in adipose to a greater extent than corticosterone.ConclusionsCorticosterone acutely controls biochemical markers of androgen excess similarly to hydrocortisone but without inducing markers of glucocorticoid 'toxicity' in CAH. These data demonstrate proof of concept that corticosterone may be a safer glucocorticoid replacement than current medications, although further research is required to assess the longer-term effects of corticosterone replacement.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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