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Eur Thyroid J. 2015 Sep;4(Suppl 1):119-24. doi: 10.1159/000381769. Epub 2015 May 28.

Effect of Experimental Thyrotoxicosis onto Blood Coagulation: A Proteomics Study.

Author information

1
Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
2
Experimental and Clinical Endocrinology, Med Clinic I, University of Lübeck, Lübeck, Germany.
3
Institute for Clinical Chemistry and Laboratory Medicine, Greifswald, Germany.
4
Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
5
Clinic for Endocrinology and Metabolic Disorders, University Clinics Essen, Essen, Germany.

Abstract

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 fT4 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 fT4, 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.

KEYWORDS:

Coagulation; Free thyroxine; Label-free quantification; Plasma; Shotgun proteomics

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