Effects of thyroxine replacement on endothelial function and carotid artery intima-media thickness in female patients with mild subclinical hypothyroidism

BACKGROUND Previous studies have suggested an association between subclinical hypothyroidism and coronary artery disease that could be related to changes in serum lipids or endothelial dysfunction. METHODS Thirty-two female subclinical hypothyroidism patients were randomly assigned to 12 months of L-thyroxine replacement or no treatment. Endothelial function was measured by the flow-mediated vasodilatation of the brachial artery, as well as mean carotid artery intima-media thickness, and lipid profiles were studied at baseline and after 12 months of follow-up. RESULTS The mean ( ± SD) serum thyroid-stimulating hormone levels in the L-thyroxine replacement and control groups were 6.09 ± 1.32 and 6.27 ± 1.39 μUI/ml, respectively. No relationship between carotid artery intima-media thickness or brachial flow-mediated vasodilatation and free T4 and serum thyroid-stimulating hormone was found. The median L-T4 dose was 44.23 ± 18.13 μg/day. After 12 months, there was a significant decrease in the flow-mediated vasodilatation in the subclinical hypothyroidism control group (before: 17.33 ± 7.88 to after: 13.1 ± 4.75%, p =0.03), but there were no significant differences in flow-mediated vasodilatation in the L-thyroxine treated group (before: 16.81 ± 7.0 to after: 18.52 ± 7.44%, p = 0.39). We did not find any significant change in mean carotid intimamedia thickness after 12 months of L-thyroxine treatment. CONCLUSION Replacement therapy prevents a decline in flow-mediated vasodilatation with continuation of the subclinical hypothyroidism state. Large prospective multicenter placebo-controlled trials are necessary to investigate endothelial physiology further in subclinical hypothyroidism patients and to define the role of L-thyroxine therapy in improving endothelial function in these patients.