Li Tiantian, Li Luyang, Wang Xinpan, Li Yue, Gong Yingyun, Zhou Hongwen, Zheng Xuqin
Endocr Connect. 2025 Jun 18;14(6). doi: 10.1530/EC-25-0078. Print 2025 Jun 1.
This study aimed to utilize untargeted metabolomics to analyze changes of serum metabolites before and after methimazole treatment in patients with Graves' disease (GD).
Total 40 GD patients and 30 healthy volunteers were recruited for the study. Metabolomics analysis was conducted using liquid chromatography-mass spectrometry.
A total of 11,590 metabolites were measured. Compared to healthy controls, newly diagnosed untreated GD patients exhibited significant metabolic dysregulation, with 1,805 metabolites upregulated and 1,737 downregulated. After 1 year of methimazole treatment and normalization of thyroid hormone levels, 137 metabolites remained upregulated and 242 remained downregulated, suggesting incomplete metabolic recovery. Pathway enrichment analysis indicated significant alterations in tyrosine metabolism, biosynthesis of alkaloids derived from histidine and purine, and bile secretion pathways in untreated GD patients. In addition, pathways such as ABC transporters, folate biosynthesis, D-amino acid metabolism, anthranilate degradation, and purine metabolism remained significantly dysregulated after treatment. Correlation analysis revealed positive associations between docosatetraenoic acid and citric acid with free triiodothyronine and free thyroxine levels, between 4-hydroxyphenyllactic acid and free triiodothyronine, and between 13Z,16Z-docosadienoic acid and thyroid-stimulating hormone receptor antibody levels.
Significant alterations in plasma metabolomic profiles during the transition from hyperthyroidism to euthyroidism in GD patients were identified using untargeted metabolomics, highlighting persistent metabolic disruptions despite clinical recovery.
本研究旨在利用非靶向代谢组学分析格雷夫斯病（GD）患者甲巯咪唑治疗前后血清代谢物的变化。
共招募40例GD患者和30名健康志愿者进行研究。采用液相色谱-质谱联用技术进行代谢组学分析。
共检测到11590种代谢物。与健康对照相比，新诊断未治疗的GD患者表现出明显的代谢失调，1805种代谢物上调，1737种代谢物下调。甲巯咪唑治疗1年且甲状腺激素水平恢复正常后，仍有137种代谢物上调，242种代谢物下调，提示代谢未完全恢复。通路富集分析表明，未治疗的GD患者在酪氨酸代谢、组氨酸和嘌呤衍生生物碱的生物合成以及胆汁分泌通路中存在显著改变。此外，治疗后ABC转运蛋白、叶酸生物合成、D-氨基酸代谢、邻氨基苯甲酸降解和嘌呤代谢等通路仍存在明显失调。相关性分析显示，二十二碳四烯酸和柠檬酸与游离三碘甲状腺原氨酸和游离甲状腺素水平呈正相关，4-羟基苯乳酸与游离三碘甲状腺原氨酸呈正相关，13Z,16Z-二十二碳二烯酸与促甲状腺激素受体抗体水平呈正相关。
利用非靶向代谢组学鉴定了GD患者从甲亢转变为甲功正常过程中血浆代谢组学谱的显著变化，突出了尽管临床恢复但代谢紊乱仍持续存在。
