Plasma metabolomic profile varies with glucocorticoid dose in patients with congenital adrenal hyperplasia

Mohammad A Alwashih, David G. Watson, Ruth Andrew, Roland H. Stimson, Manal Alossaimi, Gavin Blackburn, Brian R. Walker

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Glucocorticoid replacement therapy is the mainstay of treatment for congenital adrenal hyperplasia (CAH) but has a narrow therapeutic index and dose optimisation is challenging. Metabolomic profiling was carried out on plasma samples from 117 adults with 21-hydroxylase deficiency receiving their usual glucocorticoid replacement therapy who were part of the CaHASE study. Samples were profiled by using hydrophilic interaction chromatography with high resolution mass spectrometry. The patients were also profiled using nine routine clinical measures. The data were modelled by using both multivariate and univariate statistics by using the clinical metadata to inform the choice of patient groupings. Comparison of 382 metabolites amongst groups receiving different glucocorticoid doses revealed a clear distinction between patients receiving ≤5 mg (n = 64) and >5 mg (n = 53) daily prednisolone-equivalent doses. The 24 metabolites which were statistically significantly different between groups included free fatty acids, bile acids, and amino acid metabolites. Using 7 metabolites improved the receiver operating characteristic with area under the curve for predicting glucocorticoid dose of >0.9 with FDR adjusted P values in the range 3.3 E-04 -1.9 E-10. A combination of seven plasma metabolite biomarkers readily discriminates supraphysiological glucocorticoid replacement doses in patients with CAH.

LanguageEnglish
Article number17092
Number of pages7
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 6 Dec 2017

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Congenital Adrenal Hyperplasia
Metabolomics
Glucocorticoids
Therapeutics
Prednisolone
Bile Acids and Salts
Hydrophobic and Hydrophilic Interactions
Nonesterified Fatty Acids
ROC Curve
Area Under Curve
Chromatography
Mass Spectrometry
Biomarkers
Amino Acids

Keywords

  • chromatography
  • glucocorticoid replacement therapy
  • hyperplasia

Cite this

Alwashih, Mohammad A ; Watson, David G. ; Andrew, Ruth ; Stimson, Roland H. ; Alossaimi, Manal ; Blackburn, Gavin ; Walker, Brian R. / Plasma metabolomic profile varies with glucocorticoid dose in patients with congenital adrenal hyperplasia. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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Plasma metabolomic profile varies with glucocorticoid dose in patients with congenital adrenal hyperplasia. / Alwashih, Mohammad A; Watson, David G.; Andrew, Ruth; Stimson, Roland H.; Alossaimi, Manal; Blackburn, Gavin; Walker, Brian R.

In: Scientific Reports, Vol. 7, No. 1, 17092, 06.12.2017.

Research output: Contribution to journalArticle

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