Plasma Metabolome Profiling for the Diagnosis of Catecholamine Producing Tumors.
Front Endocrinol (Lausanne)
; 12: 722656, 2021.
Article
en En
| MEDLINE
| ID: mdl-34557163
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 C280 p=0.044, sum of hexoses p=0.018). Weak, but significant correlations for histidine, threonine and lyso PC a C280 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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Paraganglioma
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Feocromocitoma
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Células Sanguíneas
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Neoplasias de las Glándulas Suprarrenales
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Metaboloma
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Front Endocrinol (Lausanne)
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania