Abnormal endothelial function in female patients with hypothyroidism and borderline thyroid function.
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.
Dagre
Anna G
AG
Vascular Laboratory, Department of Clinical Therapeutics, Alexandra University Hospital, 23 Ikarias Street, 14578 Ekali, Athens, Greece. annadagre@hotmail.com
Lekakis
John P
JP
Protogerou
Athanassios D
AD
Douridas
Gerassimos N
GN
Papaioannou
Theodoros G
TG
Tryfonopoulos
Dimitrios J
DJ
Papamichael
Christos M
CM
Alevizaki
Maria
M
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
D009569:Nitric Oxide