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Effect of Experimental Thyrotoxicosis onto Blood Coagulation: A Proteomics Study

  • Background: Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease. Objectives: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis. Methods: Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT<sub>4</sub> levels were calculated using a Pearson correlation. Results: All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT<sub>4</sub>, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels. Conclusions: The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies.

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Metadaten
Author: Beatrice Engelmann, Julia Bischof, Anne-Luise Dirk, Nele Friedrich, Elke Hammer, Thomas Thiele, Dagmar Führer, Georg Homuth, Georg Brabant, Uwe Völker
URN:urn:nbn:de:gbv:9-opus-31257
URL:http://www.karger.com/etj
DOI:https://doi.org/10.1159/000381769
ISSN:2235-0640
ISSN:2235-0802
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=26601083
Parent Title (English):European Thyroid Journal
Publisher:S. Karger AG
Place of publication:Basel, Switzerland
Document Type:Article
Language:English
Date of first Publication:2015/05/28
Release Date:2020/09/29
Tag:Coagulation, Free thyroxine, Label-free quantification, Plasma, Shotgun proteomics
GND Keyword:-
Volume:4
Issue:Suppl 1
First Page:119
Last Page:124
Faculties:Universitätsmedizin / Institut für Immunologie u. Transfusionsmedizin - Abteilung Transfusionsmedizin
Licence (German):License LogoUrheberrechtlich geschützt