title: The Hypercoagulable state in Hyperthyroidism is mediated via the Thyroid Hormone β Receptor pathway.
abstract: OBJECTIVE
  Hyperthyroidism is associated with a hypercoagulable state, but the underlying mechanism is unknown. Patients with resistance to thyroid hormone (RTH) due to defective thyroid hormone receptor β (TRβ) exhibit elevated circulating thyroid hormones (TH) with refractoriness to TH action in TRβ-expressing tissues. We tested the hypothesis that the hypercoagulable state in hyperthyroidism is mediated via the TRβ.
  
  
  METHODS
  We conducted a cross-sectional study from November 2013 to January 2015 in 3 hospitals in the Netherlands and the United Kingdom.
  
  
  METHODS
  Patients with RTH due to defective TRβ (n=18), patients with hyperthyroidism (n=16) and euthyroid subjects (n=18) were included. TH concentrations and markers of coagulation and fibrinolysis were measured. Data are expressed as median [interquartile range].
  
  
  RESULTS
  Free thyroxine (FT4) levels were slightly higher in hyperthyroid patients than in RTH patients (53.9 [30.5-70.0] and 34.9 [28.4-42.2]pmol/l, respectively, P=0.042). Both groups had raised FT4 levels compared to euthyroid subjects (14.0 [13.0-15.8] pmol/l, P≤0.001). Levels of von Willebrand factor (VWF), factor (F) VIII, fibrinogen, and D-dimer were significantly higher in hyperthyroid patients than in RTH patients (VWF 231 [195-296] vs. 111 [82-140]%, FVIII 215 [192-228] vs. 145 [97-158]%, fibrinogen 3.6 [3.0-4.4] vs. 2.8 [2.5-3.2]g/L, D-dimer 0.41 [0.31-0.88] vs. 0.20 [0.17-0.26]mg/L, respectively, P≤0.001), while there were no differences between RTH patients and euthyroid controls.
  
  
  CONCLUSIONS
  Parameters of coagulation and fibrinolysis were elevated in hyperthyroid patients compared to patients with RTH due to defective TRβ, whereas these parameters were not different between euthyroid controls and RTH patients, despite elevated FT4 concentrations in RTH patients. This indicates that the procoagulant effects observed in hyperthyroidism are mediated via the TRβ.
authors.affiliation: L Elbers, Internal Medicine, Medical Center Slotervaart, Amsterdam, Netherlands l.p.elbers@amc.uva.nl.
authors.forename: Laura P B
authors.initials: LP
authors.lastname: Elbers
authors.affiliation: C Moran, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, United Kingdom of Great Britain and Northern Ireland.
authors.forename: Carla
authors.initials: C
authors.lastname: Moran
authors.affiliation: V Gerdes, Internal Medicine, Medical Center Slotervaart, Amsterdam, Netherlands.
authors.forename: Victor Ea
authors.initials: VE
authors.lastname: Gerdes
authors.affiliation: B van Zaane, Internal Medicine, Medical Center Slotervaart, Amsterdam, Netherlands.
authors.forename: Bregje
authors.initials: B
authors.lastname: van Zaane
authors.affiliation: J Meijers, Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Meijers
authors.affiliation: E Endert, Laboratory of Endocrinology and Radiochemistry, Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Endert
authors.affiliation: G Lyons, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, United Kingdom of Great Britain and Northern Ireland.
authors.forename: Greta
authors.initials: G
authors.lastname: Lyons
authors.affiliation: V Chatterjee, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, United Kingdom of Great Britain and Northern Ireland.
authors.forename: V Krishna
authors.initials: VK
authors.lastname: Chatterjee
authors.affiliation: P Bisschop, Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Bisschop
authors.affiliation: E Fliers, Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers