Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome
Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome
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DOI：
10.1530/eje-17-0109
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发表时间：
2017-08-01
影响因子：
5.8
通讯作者：
Beuschlein, Felix
中科院分区：
文献类型：
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作者：
Di Dalmazi, Guido;Quinkler, Marcus;Beuschlein, Felix
目的：内源性皮质醇增多症是一种与严重代谢紊乱和心血管后遗症相关的慢性疾病。本研究的目的是通过基于质谱的靶向血浆代谢组学分析来表征不同程度皮质醇增多症患者的代谢改变，并将代谢组学分析与临床和激素数据相关联。设计：横断面研究。方法：根据临床和激素特征对受试者（n = 149）进行分类：库欣综合征46例，肾上腺皮质腺瘤伴自主性皮质醇分泌31例，无皮质醇增多症27例。疑似皮质醇增多症但激素/影像学检查正常的受试者作为对照组（n = 42）。检索所有患者的临床和激素数据，并有针对性的代谢组学profiling performed.Results：皮质醇增多症患者表现出较低水平的短/中链酰基肉毒碱和支链和芳香族氨基酸，但较高的多胺水平，相比对照组。这些变化在排除糖尿病患者后得到证实。回归模型显示地塞米松抑制试验（DST）后皮质醇与31种代谢产物之间存在显著相关性，独立于混杂/促成因素。其中，组氨酸和亚精胺也与皮质醇增多症的分解代谢体征和症状显著相关。根据判别分析，代谢物组能够正确地将受试者分类为主要诊断类别，并在>80%的病例中区分DST后皮质醇改变/未改变的受试者以及有/无糖尿病的受试者。结论：代谢组学分析显示中间代谢的改变与皮质醇增多症的严重程度独立相关，这与蛋白质合成/催化剂紊乱和β-氧化不完全一致，为皮质醇增多症中代谢紊乱的发生提供了证据。
Objective: Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data.Design: Cross-sectional study.Methods: Subjects (n = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome (n = 46), adrenocortical adenomas with autonomous cortisol secretion (n = 31) or without hypercortisolism (n = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls (n = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed.Results: Patients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branched-chain and aromatic amino acids, but higher polyamines levels, in comparison to controls. These alterations were confirmed after excluding diabetic patients. Regression models showed significant correlation between cortisol after dexamethasone suppression test (DST) and 31 metabolites, independently of confounding/contributing factors. Among those, histidine and spermidine were also significantly associated with catabolic signs and symptoms of hypercortisolism. According to an discriminant analysis, the panel of metabolites was able to correctly classify subjects into the main diagnostic categories and to distinguish between subjects with/without altered post-DST cortisol and with/without diabetes in >80% of the cases.Conclusions: Metabolomic profiling revealed alterations of intermediate metabolism independently associated with the severity of hypercortisolism, consistent with disturbed protein synthesis/catabolism and incomplete beta-oxidation, providing evidence for the occurrence of metabolic inflexibility in hypercortisolism.