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Open Access 01-12-2017 | Research article

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

Authors: Maik Pietzner, Beatrice Engelmann, Tim Kacprowski, Janine Golchert, Anna-Luise Dirk, Elke Hammer, K. Alexander Iwen, Matthias Nauck, Henri Wallaschofski, Dagmar Führer, Thomas F. Münte, Nele Friedrich, Uwe Völker, Georg Homuth, Georg Brabant

Published in: BMC Medicine | Issue 1/2017

Abstract

Background

Determinations of thyrotropin (TSH) and free thyroxine (FT₄) represent the gold standard in evaluation of thyroid function. To screen for novel peripheral biomarkers of thyroid function and to characterize FT₄-associated physiological signatures in human plasma we used an untargeted OMICS approach in a thyrotoxicosis model.

Methods

A sample of 16 healthy young men were treated with levothyroxine for 8 weeks and plasma was sampled before the intake was started as well as at two points during treatment and after its completion, respectively. Mass spectrometry-derived metabolite and protein levels were related to FT₄ serum concentrations using mixed-effect linear regression models in a robust setting. To compile a molecular signature discriminating between thyrotoxicosis and euthyroidism, a random forest was trained and validated in a two-stage cross-validation procedure.

Results

Despite the absence of obvious clinical symptoms, mass spectrometry analyses detected 65 metabolites and 63 proteins exhibiting significant associations with serum FT₄. A subset of 15 molecules allowed a robust and good prediction of thyroid hormone function (AUC = 0.86) without prior information on TSH or FT₄. Main FT₄-associated signatures indicated increased resting energy expenditure, augmented defense against systemic oxidative stress, decreased lipoprotein particle levels, and increased levels of complement system proteins and coagulation factors. Further association findings question the reliability of kidney function assessment under hyperthyroid conditions and suggest a link between hyperthyroidism and cardiovascular diseases via increased dimethylarginine levels.

Conclusion

Our results emphasize the power of untargeted OMICs approaches to detect novel pathways of thyroid hormone action. Furthermore, beyond TSH and FT₄, we demonstrated the potential of such analyses to identify new molecular signatures for diagnosis and treatment of thyroid disorders. This study was registered at the German Clinical Trials Register (DRKS) [DRKS00011275] on the 16th of November 2016.

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Title: Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model
Authors: Maik Pietzner
Beatrice Engelmann
Tim Kacprowski
Janine Golchert
Anna-Luise Dirk
Elke Hammer
K. Alexander Iwen
Matthias Nauck
Henri Wallaschofski
Dagmar Führer
Thomas F. Münte
Nele Friedrich
Uwe Völker
Georg Homuth
Georg Brabant
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-016-0770-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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