Zhang Yuwen, Sun Shouyue, Wang Ming, Yu Wenjuan, Chen Peizhan, Yuan Fei, Fang Xuqian
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai, China.
Front Pharmacol. 2021 Jul 8;12:684869. doi: 10.3389/fphar.2021.684869. eCollection 2021.
Hypopituitarism (Hypo-Pit) is partial or complete insufficiency of anterior pituitary hormones. Besides hormone metabolism, the global metabolomics in Hypo-Pit are largely unknown. We aimed to explore potential biomarkers to aid in diagnosis and personalized treatment. Using both univariate and multivariate statistical methods, we identified 72 differentially abundant features through liquid chromatography coupled to high-resolution mass spectrometry, obtained in 134 males with Hypo-Pit and 90 age matched healthy controls. Hypopituitarism exhibits an increased abundance of metabolites involved in amino acid degradation and glycerophospholipid synthesis, but decreased content of metabolites in steroid hormone synthesis and fatty acid beta-oxidation. Significantly changed metabolites included creatine, creatinine, L-alanine, phosphocholines, androstenedione, hydroprenenolone, and acylcarnitines. In Hypo-Pit patients, the increased ratio of creatine/creatinine suggested reduced creatine uptake and impaired creatine utilization, whereas the decreased level of beta-hydroxybutyrate, acetylcarnitine (C2) and a significantly decreased ratio of decanoylcarnitine (C10) to free carnitine suggested an impaired beta-oxidation. Furthermore, the creatine/creatinine and decanoylcarnitine/carnitine ratio were identified as diagnostic biomarkers for Hypo-Pit with AUCs of 0.976 and 0.988, respectively. Finally, we found that the creatinine and decanoylcarnitine/carnitine ratio could distinguish cases that were sensitive vs. resistant to human chorionic gonadotropin therapy. We provided a global picture of altered metabolic pathways in Hypo-Pit, and the identified biomarkers in creatine metabolism and beta-oxidation might be useful for the preliminary screening and diagnosis of Hypo-Pit.
垂体功能减退症（垂体功能减退）是指垂体前叶激素部分或完全缺乏。除了激素代谢外，垂体功能减退症患者的整体代谢组学情况在很大程度上尚不清楚。我们旨在探索潜在的生物标志物，以辅助诊断和个性化治疗。通过液相色谱与高分辨率质谱联用技术，运用单变量和多变量统计方法，我们在134名垂体功能减退症男性患者和90名年龄匹配的健康对照者中，鉴定出72个差异丰度特征。垂体功能减退症表现为参与氨基酸降解和甘油磷脂合成的代谢物丰度增加，但类固醇激素合成和脂肪酸β-氧化中的代谢物含量降低。显著变化的代谢物包括肌酸、肌酐、L-丙氨酸、磷酸胆碱、雄烯二酮、氢化泼尼松和酰基肉碱。在垂体功能减退症患者中，肌酸/肌酐比值升高表明肌酸摄取减少和肌酸利用受损，而β-羟基丁酸、乙酰肉碱（C2）水平降低以及癸酰肉碱（C10）与游离肉碱的比值显著降低表明β-氧化受损。此外，肌酸/肌酐和癸酰肉碱/肉碱比值被确定为垂体功能减退症的诊断生物标志物，其曲线下面积（AUC）分别为0.976和0.988。最后，我们发现肌酐和癸酰肉碱/肉碱比值可以区分对人绒毛膜促性腺激素治疗敏感和耐药的病例。我们提供了垂体功能减退症中代谢途径改变的全貌，并且在肌酸代谢和β-氧化中鉴定出的生物标志物可能有助于垂体功能减退症的初步筛查和诊断。
