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 mu/ml, Group 1 (n = 22) with TSH: 2.1-4.0 mu/ml (upper normal), Group 2 (n=18) with TSH: 4.1-10 mu U/ml (subclinical hypothyroidism), Group 3 (n=22) with TSH > 10 mu U/mI (overt hypothyroidism). One additional group with well-controlled hypothyroidism on L-thyroxine therapy (Group 4, n=11 TSH: 0.3-2.0 mu U/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). Conclusion: 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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.