Plasma metabolomic profile varies with glucocorticoid dose in patients with congenital adrenal hyperplasia.
Plasma metabolomic profile varies with glucocorticoid dose in patients with congenital adrenal hyperplasia.
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DOI：
10.1038/s41598-017-17220-5
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发表时间：
2017-12-06
影响因子：
4.6
通讯作者：
Walker BR
中科院分区：
文献类型：
--
作者：
Alwashih MA;Watson DG;Andrew R;Stimson RH;Alossaimi M;Blackburn G;Walker BR
糖皮质激素替代疗法是治疗先天性肾上腺皮质增生（CAH）的主要方法，但治疗指标狭窄，剂量优化具有挑战性。对117名21-羟化酶缺乏症患者的血浆样本进行了代谢组学分析，这些患者接受了常规的糖皮质激素替代治疗，是CaHASE研究的一部分。样品采用亲水相互作用色谱-高分辨率质谱分析。患者也采用9项常规临床措施进行分析。通过使用临床元数据来选择患者分组，通过多变量和单变量统计对数据进行建模。382种代谢物在接受不同糖皮质激素剂量组之间的比较显示，每日接受≤5mg （n = 64）和bbb5mg （n = 53）泼尼松龙等效剂量的患者之间存在明显差异。其中游离脂肪酸、胆汁酸、氨基酸代谢物等24种代谢物组间差异有统计学意义。使用7种代谢物改善了受试者的工作特性，曲线下面积预测糖皮质激素剂量为>0.9，FDR调整P值在3.3 E-04 -1.9 E-10范围内。七种血浆代谢物生物标志物的组合很容易区分CAH患者的生理上糖皮质激素替代剂量。
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.
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影响因子：
5.6
作者：
Gambino R;Bugianesi E;Rosso C;Mezzabotta L;Pinach S;Alemanno N;Saba F;Cassader M
通讯作者：
Cassader M
DOI：
10.1016/j.numecd.2007.02.017
发表时间：
2008-07-01
影响因子：
3.9
作者：
Paillard, Francois;Catheline, Daniel;Legrand, Philippe
通讯作者：
Legrand, Philippe
DOI：
10.1210/jc.2010-0917
发表时间：
2010-11
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Arlt W;Willis DS;Wild SH;Krone N;Doherty EJ;Hahner S;Han TS;Carroll PV;Conway GS;Rees DA;Stimson RH;Walker BR;Connell JM;Ross RJ;United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE)
通讯作者：
United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE)
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.50.5.912
发表时间：
1963-01-01
影响因子：
11.1
作者：
SEGAL, HL;KIM, YS
通讯作者：
KIM, YS