title: Effect of Experimental Thyrotoxicosis onto Blood Coagulation: A Proteomics Study.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Engelmann
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bischof
authors.affiliation: Experimental and Clinical Endocrinology, Med Clinic I, University of Lübeck, Lübeck, Germany.
authors.forename: Anne-Luise
authors.initials: AL
authors.lastname: Dirk
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, Greifswald, Germany.
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Hammer
authors.affiliation: Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thiele
authors.affiliation: Clinic for Endocrinology and Metabolic Disorders, University Clinics Essen, Essen, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Führer
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.affiliation: Experimental and Clinical Endocrinology, Med Clinic I, University of Lübeck, Lübeck, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Brabant
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
keywords: Coagulation; Free thyroxine; Label-free quantification; Plasma; Shotgun proteomics