Plasma Metabolome Profiling for the Diagnosis of Catecholamine Producing Tumors

März J, Kurlbaum M, Roche-Lancaster O, Deutschbein T, Peitzsch M, Prehn C, Weismann D, Robledo M, Adamski J, Fassnacht M, Kunz M, Kroiss M (2021)

Publication Language: English

Publication Type: Journal article

Publication year: 2021


Book Volume: 12

Article Number: 722656

DOI: 10.3389/fendo.2021.722656


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.

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März, J., Kurlbaum, M., Roche-Lancaster, O., Deutschbein, T., Peitzsch, M., Prehn, C.,... Kroiss, M. (2021). Plasma Metabolome Profiling for the Diagnosis of Catecholamine Producing Tumors. Frontiers in Endocrinology, 12.


März, Juliane, et al. "Plasma Metabolome Profiling for the Diagnosis of Catecholamine Producing Tumors." Frontiers in Endocrinology 12 (2021).

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