@phdthesis{Maerz2022,
  author    = {M{\"a}rz, Juliane Elisabeth},
  title     = {Targeted Metabolomics mit Fl{\"u}ssigkeitschromatographie-Massenspektrometrie zur Untersuchung von Stoffwechselver{\"a}nderungen bei Ph{\"a}ochromozytomen und Paragangliomen},
  doi       = {10.25972/OPUS-29061},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290614},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Ph{\"a}ochromozytome und Paragangliome (PPGL) sind seltene, katecholaminproduzierendeTumore des chromaffinen Gewebes. Die Erkrankung ist durch die {\"U}berproduktion von Katecholaminen gekennzeichnet und kann lebensbedrohliche Folgen haben. Die dieser Arbeit zugrunde liegende Studie untersuchte die interindividuellen Unterschiede im Metabolitenprofil bei Patient*innen mit PPGL im Vergleich zu Kontrollen mittels Fl{\"u}ssigchromatographie-Massenspektrometrie und einem Targeted Metabolomic Ansatz. Targeted Metabolomics beschreibt die Messung und Quantifizierung von im Voraus definierten Metaboliten in einer Probe. Von den 188 gemessenen Metaboliten zeigten vier Metabolite eine signifikanten Ver{\"a}nderung zwischen den Gruppen (Histidin, Threonin, LysoPC a C28:0 und Summe der Hexosen). F{\"u}r alle vier Metabolite wurde ein Zusammenhang mit Katecholaminen im Urin beziehungsweise Metanephrinen im Plasma nachgewiesen. Subgruppenanalysen zeigten weitere Hinweise auf geschlechts- und ph{\"a}notypspezifische Unterschiede im Metabolitenprofil zwischen Patient*innen mit PPGL und Kontrollen.},
  subject      = {Ph{\"a}ochromozytom},
  language  = {de}
}
@article{MaerzKurlbaumRocheLancasteretal.2021,
  author    = {M{\"a}rz, Juliane and Kurlbaum, Max and Roche-Lancaster, Oisin and Deutschbein, Timo and Peitzsch, Mirko and Prehn, Cornelia and Weismann, Dirk and Robledo, Mercedes and Adamski, Jerzy and Fassnacht, Martin and Kunz, Meik and Kroiss, Matthias},
  title     = {Plasma Metabolome Profiling for the Diagnosis of Catecholamine Producing Tumors},
  series = {Frontiers in Endocrinology},
  volume    = {12},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2021.722656},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245710},
  year      = {2021},
  abstract  = {Context Pheochromocytomas and paragangliomas (PPGL) cause catecholamine excess leading to a characteristic clinical phenotype. Intra-individual changes at metabolome level have been described after surgical PPGL removal. The value of metabolomics for the diagnosis of PPGL has not been studied yet. Objective Evaluation of quantitative metabolomics as a diagnostic tool for PPGL. Design Targeted metabolomics by liquid chromatography-tandem mass spectrometry of plasma specimens and statistical modeling using ML-based feature selection approaches in a clinically well characterized cohort study. Patients Prospectively enrolled patients (n=36, 17 female) from the Prospective Monoamine-producing Tumor Study (PMT) with hormonally active PPGL and 36 matched controls in whom PPGL was rigorously excluded. Results Among 188 measured metabolites, only without considering false discovery rate, 4 exhibited statistically significant differences between patients with PPGL and controls (histidine p=0.004, threonine p=0.008, lyso PC a C28:0 p=0.044, sum of hexoses p=0.018). Weak, but significant correlations for histidine, threonine and lyso PC a C28:0 with total urine catecholamine levels were identified. Only the sum of hexoses (reflecting glucose) showed significant correlations with plasma metanephrines. By using ML-based feature selection approaches, we identified diagnostic signatures which all exhibited low accuracy and sensitivity. The best predictive value (sensitivity 87.5\%, accuracy 67.3\%) was obtained by using Gradient Boosting Machine Modelling. Conclusions The diabetogenic effect of catecholamine excess dominates the plasma metabolome in PPGL patients. While curative surgery for PPGL led to normalization of catecholamine-induced alterations of metabolomics in individual patients, plasma metabolomics are not useful for diagnostic purposes, most likely due to inter-individual variability.},
  language  = {en}
}