{
    "abstract": "Pheochromocytomas and Paragangliomas (PPGL) result in chronic catecholamine excess and serious health complications. A recent study obtained a metabolic signature in plasma from PPGL patients; however, its targeted nature may have generated an incomplete picture and a broader approach could provide additional insights. We aimed to characterize the plasma metabolome of PPGL patients before and after surgery, using an untargeted approach, and to broaden the scope of the investigated metabolic impact of these tumors.\nA cohort of 36 PPGL patients was investigated. Blood plasma samples were collected before and after surgical tumor removal, in association with clinical and tumor characteristics.\nPlasma samples were analyzed using untargeted nuclear magnetic resonance (NMR) spectroscopy metabolomics. The data were evaluated using a combination of uni- and multi-variate statistical methods.\nBefore surgery, patients with a nonadrenergic tumor could be distinguished from those with an adrenergic tumor based on their metabolic profiles. Tyrosine levels were significantly higher in patients with high compared to those with low BMI. Comparing subgroups of pre-operative samples with their post-operative counterparts, we found a metabolic signature that included ketone bodies, glucose, organic acids, methanol, dimethyl sulfone and amino acids. Three signals with unclear identities were found to be affected.\nOur study suggests that the pathways of glucose and ketone body homeostasis are affected in PPGL patients. BMI-related metabolite levels were also found to be altered, potentially linking muscle atrophy to PPGL. At baseline, patient metabolomes could be discriminated based on their catecholamine phenotype.",
    "authors": [
        {
            "affiliation": "Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, the Netherlands. nick.bliziotis@radboudumc.nl.",
            "firstname": "Nikolaos G",
            "initials": "NG",
            "lastname": "Bliziotis"
        },
        {
            "affiliation": "Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, the Netherlands.",
            "firstname": "Leo A J",
            "initials": "LAJ",
            "lastname": "Kluijtmans"
        },
        {
            "affiliation": "Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, the Netherlands.",
            "firstname": "Sebastian",
            "initials": "S",
            "lastname": "Soto"
        },
        {
            "affiliation": "Department of Analytical Chemistry, Institute for Molecules and Materials, Radboud University, Nijmegen, the Netherlands.",
            "firstname": "Gerjen H",
            "initials": "GH",
            "lastname": "Tinnevelt"
        },
        {
            "affiliation": "Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany.",
            "firstname": "Katharina",
            "initials": "K",
            "lastname": "Langton"
        },
        {
            "affiliation": "Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.",
            "firstname": "Mercedes",
            "initials": "M",
            "lastname": "Robledo"
        },
        {
            "affiliation": "Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany.",
            "firstname": "Christina",
            "initials": "C",
            "lastname": "Pamporaki"
        },
        {
            "affiliation": "Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, the Netherlands.",
            "firstname": "Udo F H",
            "initials": "UFH",
            "lastname": "Engelke"
        },
        {
            "affiliation": "Klinik f\u00fcr Endokrinologie, Diabetologie und Klinische Ern\u00e4hrung, Universit\u00e4tsspital Z\u00fcrich, Z\u00fcrich, Switzerland.",
            "firstname": "Zoran",
            "initials": "Z",
            "lastname": "Erlic"
        },
        {
            "affiliation": "Biometris, Wageningen UR, Wageningen, The Netherlands.",
            "firstname": "Jasper",
            "initials": "J",
            "lastname": "Engel"
        },
        {
            "affiliation": "Schwerpunkt Endokrinologie/Diabetologie, Medizinische Klinik und Poliklinik I, Universit\u00e4tsklinikum W\u00fcrzburg, Z\u00fcrich, Germany.\nMedicover Oldenburg MVZ, Oldenburg, Germany.",
            "firstname": "Timo",
            "initials": "T",
            "lastname": "Deutschbein"
        },
        {
            "affiliation": "Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t, M\u00fcnchen, Munich, Germany.",
            "firstname": "Svenja",
            "initials": "S",
            "lastname": "N\u00f6lting"
        },
        {
            "affiliation": "Department of Hypertension, Institute of Cardiology, Warsaw, Poland.",
            "firstname": "Aleksander",
            "initials": "A",
            "lastname": "Prejbisz"
        },
        {
            "affiliation": "Institut f\u00fcr Klinische Chemie und Labormedizin, Universit\u00e4tsklinikum Carl Gustav Carus, Dresden, Germany.",
            "firstname": "Susan",
            "initials": "S",
            "lastname": "Richter"
        },
        {
            "affiliation": "Helmholtz Zentrum M\u00fcnchen, Research Unit Molecular Endocrinology and Metabolism, Neuherberg, Germany.",
            "firstname": "Cornelia",
            "initials": "C",
            "lastname": "Prehn"
        },
        {
            "affiliation": "Helmholtz Zentrum M\u00fcnchen, Research Unit Molecular Endocrinology and Metabolism, Neuherberg, Germany.\nInstitute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.\nInstitute of Experimental Genetics, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Neuherberg, Germany.\nDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.",
            "firstname": "Jerzy",
            "initials": "J",
            "lastname": "Adamski"
        },
        {
            "affiliation": "Department of Hypertension, Institute of Cardiology, Warsaw, Poland.",
            "firstname": "Andrzej",
            "initials": "A",
            "lastname": "Januszewicz"
        },
        {
            "affiliation": "Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t, M\u00fcnchen, Munich, Germany.",
            "firstname": "Martin",
            "initials": "M",
            "lastname": "Reincke"
        },
        {
            "affiliation": "Schwerpunkt Endokrinologie/Diabetologie, Medizinische Klinik und Poliklinik I, Universit\u00e4tsklinikum W\u00fcrzburg, Z\u00fcrich, Germany.\nCore Unit Clinical Mass Spectrometry, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany.\nComprehensive Cancer Center Mainfranken, Universit\u00e4t W\u00fcrzburg, W\u00fcrzburg, Germany.",
            "firstname": "Martin",
            "initials": "M",
            "lastname": "Fassnacht"
        },
        {
            "affiliation": "Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany.\nInstitut f\u00fcr Klinische Chemie und Labormedizin, Universit\u00e4tsklinikum Carl Gustav Carus, Dresden, Germany.",
            "firstname": "Graeme",
            "initials": "G",
            "lastname": "Eisenhofer"
        },
        {
            "affiliation": "Klinik f\u00fcr Endokrinologie, Diabetologie und Klinische Ern\u00e4hrung, Universit\u00e4tsspital Z\u00fcrich, Z\u00fcrich, Switzerland.\nMedizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t, M\u00fcnchen, Munich, Germany.",
            "firstname": "Felix",
            "initials": "F",
            "lastname": "Beuschlein"
        },
        {
            "affiliation": "Schwerpunkt Endokrinologie/Diabetologie, Medizinische Klinik und Poliklinik I, Universit\u00e4tsklinikum W\u00fcrzburg, Z\u00fcrich, Germany.\nMedizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t, M\u00fcnchen, Munich, Germany.\nCore Unit Clinical Mass Spectrometry, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany.\nComprehensive Cancer Center Mainfranken, Universit\u00e4t W\u00fcrzburg, W\u00fcrzburg, Germany.",
            "firstname": "Matthias",
            "initials": "M",
            "lastname": "Kroiss"
        },
        {
            "affiliation": "Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, the Netherlands.",
            "firstname": "Ron A",
            "initials": "RA",
            "lastname": "Wevers"
        },
        {
            "affiliation": "Department of Analytical Chemistry, Institute for Molecules and Materials, Radboud University, Nijmegen, the Netherlands.",
            "firstname": "Jeroen J",
            "initials": "JJ",
            "lastname": "Jansen"
        },
        {
            "affiliation": "Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.",
            "firstname": "Jaap",
            "initials": "J",
            "lastname": "Deinum"
        },
        {
            "affiliation": "Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. henri.timmers@radboudumc.nl.",
            "firstname": "Henri J L M",
            "initials": "HJLM",
            "lastname": "Timmers"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2021. The Author(s).",
    "doi": "10.1007/s12020-021-02858-z\n10.1677/ERC-10-0211.Catecholamine\n10.1016/j.physbeh.2017.03.040\n10.1016/S0300-595X(85)80070-0\n10.1055/a-0649-0960\n10.1007/s10545-017-0131-6\n10.1039/b906712b\n10.1016/j.copbio.2016.08.001\n10.1038/nrm3314.Metabolomics\n10.1530/EJE-19-0589\n10.1007/s11306-020-01686-y\n10.1373/clinchem.2018.291369\n10.1210/jc.2016-3829\n10.1016/j.jmoldx.2017.04.009\n10.1021/ac060209g\n10.1038/nbt0208-162\n10.1002/pro.3715\n10.1007/s11306-009-0185-z\n10.1111/j.2517-6161.1995.tb02031.x\n10.1210/jc.2005-0859\n10.1016/S0026-0495(96)90238-3\n10.1371/journal.pone.0056827\n10.1038/s41598-017-00467-3\n10.1038/s41366-020-0565-z\n10.7759/cureus.4551\n10.2337/db15-1272\n10.1002/jcsm.12270\n10.1016/j.mehy.2006.04.048\n10.1007/s00774-018-0959-3",
    "journal": "Endocrine",
    "keywords": [
        "Metabolomics",
        "NMR",
        "Operation",
        "PPGL",
        "Paired",
        "Plasma"
    ],
    "methods": null,
    "publication_date": "2021-09-19",
    "pubmed_id": "34536194\n21051559\n28162975\n31294942\n33001846\n16112304\n30011405\n29453510\n20717559\n27580257\n21359215\n22436749\n31614337\n32358672\n30097498\n28324046\n28552549\n16808451\n29140435\n18259166\n31441146\n29099853\n20339442\n16303838\n8843175\n23451094\n17713401\n28341846\n32203114\n31275775\n27207556\n29464940\n16797873\n30238430",
    "results": "Before surgery, patients with a nonadrenergic tumor could be distinguished from those with an adrenergic tumor based on their metabolic profiles. Tyrosine levels were significantly higher in patients with high compared to those with low BMI. Comparing subgroups of pre-operative samples with their post-operative counterparts, we found a metabolic signature that included ketone bodies, glucose, organic acids, methanol, dimethyl sulfone and amino acids. Three signals with unclear identities were found to be affected.",
    "title": "Pre- versus post-operative untargeted plasma nuclear magnetic resonance spectroscopy metabolomics of pheochromocytoma and paraganglioma.",
    "xml": "<Element 'PubmedArticle' at 0x788502de5620>"
}