TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Engelmann, Beatrice
A1  - Bischof, Julia
A1  - Dirk, Anne-Luise
A1  - Friedrich, Nele
A1  - Hammer, Elke
A1  - Thiele, Thomas
A1  - Führer, Dagmar
A1  - Homuth, Georg
A1  - Brabant, Georg
A1  - Völker, Uwe
T1  - Effect of Experimental Thyrotoxicosis onto Blood Coagulation: A Proteomics Study
JF  - European Thyroid Journal
N2  - 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.
KW  - -
KW  - Plasma
KW  - Shotgun proteomics
KW  - Label-free quantification
KW  - Free thyroxine
KW  - Coagulation
UN  - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-31257
UR  - www.karger.com/etj
SN  - 2235-0640
SS  - 2235-0640
SN  - 2235-0802
SS  - 2235-0802
U6  - https://doi.org/10.1159/000381769
DO  - https://doi.org/10.1159/000381769
PM  - 26601083
VL  - 4
IS  - Suppl 1
SP  - 119
EP  - 124
PB  - S. Karger AG
CY  - Basel, Switzerland
ER  -