title: Hypothyroidism is associated with signs of endothelial dysfunction despite 1-year replacement therapy with levothyroxine.
abstract: OBJECTIVE
  Hypothyroidism is associated with elevated cardiovascular risk, not fully explained by classical risk factors. Instead, endothelial dysfunction may link hypothyroidism to atherosclerosis. The effect of levothyroxine substitution on endothelial function has been sparsely studied and the results are unclear. This study tested endothelial function as estimated by concomitant measurements of endothelial dependent vascular dilatory capacity and plasma concentration of von Willebrand factor antigen in patients with hypothyroidism and further examined the impact of subsequent levothyroxine substitution.
  
  
  METHODS
  Sixteen consecutive patients (13 women, 3 men, aged 46 +/- 11 years) with hypothyroidism were included and compared to 16 matched healthy controls (13 women, 3 men, aged 49 +/- 11 years). Patients with hypothyroidism were reexamined after 3, 6 and 12 months of levothyroxine substitution.
  
  
  METHODS
  Dilatory responses of the brachial artery to post-ischaemic increased blood flow (endothelium-dependent flow-associated dilatation) and to nitroglycerin (endothelium-independent nitroglycerin induced dilatation) were measured by ultrasound. Plasma concentrations of von Willebrand factor antigen were measured by ELISA.
  
  
  RESULTS
  Flow-associated dilatation was impaired in patients with hypothyroidism as compared to controls (102.7 +/- 3.6 vs. 105.6 +/- 3.8%, P = 0.04) whereas no differences in plasma concentration of von Willebrand factor antigen were found. One year levothyroxine substitution did not improve flow-associated dilatation and was associated with an increase of the plasma von Willebrand factor antigen concentration.
  
  
  CONCLUSIONS
  Hypothyroid patients are characterized by endothelial dysfunction sustained despite long-term levothyroxine substitution and potentially increasing the risk of atherosclerosis. Different estimates of endothelial dysfunction seem unequally influenced by hypothyroidism.
authors.affiliation: Department of Nephrology and Endocrinology, Copenhagen University Hospital, Rigshospitalet, Denmark. pclaus@rh.dk
authors.forename: P
authors.initials: P
authors.lastname: Clausen
authors.forename: H
authors.initials: H
authors.lastname: Mersebach
authors.forename: B
authors.initials: B
authors.lastname: Nielsen
authors.forename: B
authors.initials: B
authors.lastname: Feldt-Rasmussen
authors.forename: U
authors.initials: U
authors.lastname: Feldt-Rasmussen
mesh_terms: D000328:Adult; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D013974:Thyroxine / Q000627:therapeutic use*
chemical_list: D013974:Thyroxine