title: Abnormal endothelial function in female patients with hypothyroidism and borderline thyroid function.
abstract: BACKGROUND
  It has been suggested that hypothyroidism is associated with an increased risk for cardiovascular disease. The aim of this study was to assess non-invasively NO-dependent endothelial function of resistance arteries in subjects with hypothyroidism of varying severity.
  
  
  METHODS
  Ninety-six female subjects (aged: 42+/-13 years) comprised the study population. Subjects were divided into five groups based on TSH levels at presentation: Group 0 (n=23) with TSH: 0.3-2.0 microU/ml, Group 1 (n=22) with TSH: 2.1-4.0 microU/ml (upper normal), Group 2 (n=18) with TSH: 4.1-10 microU/ml (subclinical hypothyroidism), Group 3 (n=22) with TSH >10 microU/ml (overt hypothyroidism). One additional group with well-controlled hypothyroidism on L-thyroxine therapy (Group 4, n=11, TSH: 0.3-2.0 microU/ml) was also studied. Endothelial function of resistance arteries was assessed by measuring forearm blood flow response during reactive hyperemia utilizing venous occlusion strain-gauge plethysmography.
  
  
  RESULTS
  Duration of reactive hyperemia was significantly different among groups of subjects with varying hypothyroidism (83.7+/-58.3 s, 53.2+/-35.7 s, 52.8+/-47.5 s, 12.9+/-13.3 s and 69.5+/-26.2 s in Groups 0, 1, 2, 3 and 4, respectively, p<0.001, ANOVA). Duration of reactive hyperemia was significantly shorter in subjects with upper normal TSH values (Group 1) compared to controls (53.2+/-35.7 s vs. 83.7+/-58.3 s, p=0.013), while it was comparable to that of subjects with subclinical hypothyroidism (Group 2) (52.8+/-47.5 s). However, duration of reactive hyperemia in Group 1 was significantly longer compared to Group 3 (overt hypothyroidism) (53.2+/-35.7 s vs. 12.9+/-13.3 s, p=0.002). Similarly, duration of reactive hyperemia in subjects with subclinical hypothyroidism was significantly longer compared to subjects with overt hypothyroidism (52.8+/-47.5 s vs. 12.9+/-13.3 s, p=0.003). Duration of reactive hyperemia in Group 4 (well-controlled hypothyroidism on L-thyroxine therapy) did not differ significantly compared to controls. There was a highly significant linear correlation between duration of reactive hyperemia and TSH (r=-0.383, p<0.001).
  
  
  CONCLUSIONS
  Endothelial dysfunction was detected in the microvasculature of patients with hypothyroidism. Duration of reactive hyperemia decreased with increasing TSH levels. Since endothelial dysfunction is a factor leading to atherosclerosis, this abnormality may partly explain predisposition of patients with thyroid failure to cardiovascular disease.
authors.affiliation: Vascular Laboratory, Department of Clinical Therapeutics, Alexandra University Hospital, 23 Ikarias Street, 14578 Ekali, Athens, Greece. annadagre@hotmail.com
authors.forename: Anna G
authors.initials: AG
authors.lastname: Dagre
authors.forename: John P
authors.initials: JP
authors.lastname: Lekakis
authors.forename: Athanassios D
authors.initials: AD
authors.lastname: Protogerou
authors.forename: Gerassimos N
authors.initials: GN
authors.lastname: Douridas
authors.forename: Theodoros G
authors.initials: TG
authors.lastname: Papaioannou
authors.forename: Dimitrios J
authors.initials: DJ
authors.lastname: Tryfonopoulos
authors.forename: Christos M
authors.initials: CM
authors.lastname: Papamichael
authors.forename: Maria
authors.initials: M
authors.lastname: Alevizaki
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001783:Blood Flow Velocity; D002318:Cardiovascular Diseases / Q000503:physiopathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004198:Disease Susceptibility; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007037:Hypothyroidism / Q000378:metabolism / Q000503:physiopathology*; D016014:Linear Models; D008833:Microcirculation; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D012307:Risk Factors; D013960:Thyroid Function Tests; D014655:Vascular Resistance
chemical_list: D009569:Nitric Oxide