Abstract
Background: Metabolomics—the novel science that evaluates the multitude of low-molecular-weight metabolites in a biological system, provides new data on pathogenic mechanisms of diseases, including endocrine tumors. Although development of metabolomic profiling in pituitary disorders is at an early stage, it seems to be a promising approach in the near future in identifying specific disease biomarkers and understanding cellular signaling networks.Objectives: To review the metabolomic profile and the contributions of metabolomics in pituitary adenomas (PA).Methods: A systematic review was conducted via PubMed, Web of Science Core Collection and Scopus databases, summarizing studies that have described metabolomic aspects of PA.Results: Liquid chromatography tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) spectrometry, which are traditional techniques employed in metabolomics, suggest amino acids metabolism appears to be primarily altered in PA. N-acetyl aspartate, choline-containing compounds and creatine appear as highly effective in differentiating PA from healthy tissue. Deoxycholic and 4-pyridoxic acids, 3-methyladipate, short chain fatty acids and glucose-6-phosphate unveil metabolite biomarkers in patients with Cushing's disease. Phosphoethanolamine, N-acetyl aspartate and myo-inositol are down regulated in prolactinoma, whereas aspartate, glutamate and glutamine are up regulated. Phosphoethanolamine, taurine, alanine, choline-containing compounds, homocysteine, and methionine were up regulated in unclassified PA across studies. Intraoperative use of ultra high mass resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which allows localization and delineation between functional PA and healthy pituitary tissue, may contribute to achievement of complete tumor resection in addition to preservation of pituitary cell lines and vasopressin secretory cells, thus avoiding postoperative diabetes insipidus.Conclusion: Implementation of ultra high performance metabolomics analysis techniques in the study of PA will significantly improve diagnosis and, potentially, the therapeutic approach, by identifying highly specific disease biomarkers in addition to novel molecular pathogenic mechanisms. Ultra high mass resolution MALDI-MSI emerges as a helpful clinical tool in the neurosurgical treatment of pituitary tumors. Therefore, metabolomics appears to be a science with a promising prospect in the sphere of PA, and a starting point in pituitary care.
Highlights
Metabolomics, one of the newest “omics” sciences, assesses small molecules with molecular mass below 1,500 Da [1] within various bio-fluids or tissues, to potentially set correlates to physiological or pathological status of an organism
A range of analytical techniques is applied, with either nuclear magnetic resonance (NMR), known as magnetic resonance spectroscopy (MRS), or, more frequently, mass spectrometry (MS)-based platforms being routinely employed in assessing the metabolic fingerprint, the later method as a combination with other analysis techniques (i.e., gas-chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) [2, 3], ultra-performance liquid-chromatography tandem mass spectrometry (UPLC–MS/MS) [4, 5], ultra-high performance liquid chromatography-quadrupole timeof-flight mass spectrometry (UHPLC/Q-TOF-MS) [6, 7], capillary electrophoresis (CE-MS) [8, 9] or matrix-assisted laser desorption/ionization mass spectrometry (MALDIMS) [10, 11] etc.) to overcome the limitations of MS, such as erroneous interpretation of the metabolomic analysis in presence of impurities or modest reproducibility of the method [12, 13]
Secretion of these peptides was confirmed by MALDI in-source decay (ISD) fragmentation, by identification of c-series ion fragments of GH (c13), adrenocorticotrophic hormone (ACTH) (c10) and neurophysin 2 (c16) in the anterior and posterior pituitary gland
Summary
Metabolomics, one of the newest “omics” sciences, assesses small molecules with molecular mass below 1,500 Da [1] within various bio-fluids (e.g., serum, plasma, cerebrospinal fluid, urine, saliva etc.) or tissues, to potentially set correlates to physiological or pathological status of an organism. Given its contribution to the understanding of cellular signaling mechanisms, in addition to identification and quantification of novel biomarkers in various clinical conditions, metabolomics is underpinning the development of personalized medicine. Metabolomics—the novel science that evaluates the multitude of low-molecular-weight metabolites in a biological system, provides new data on pathogenic mechanisms of diseases, including endocrine tumors. Development of metabolomic profiling in pituitary disorders is at an early stage, it seems to be a promising approach in the near future in identifying specific disease biomarkers and understanding cellular signaling networks
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