Treatment of subclinical hypothyroidism with L-thyroxine improves endothelial function due to increase in free T4 levels
S Razvi1 CP Oates2 & JU Weaver3
Background: Subclinical hypothyroidism (SCH) has been reported as a potent risk factor for cardiovascular disease, independent of cholesterol levels. Endothelial dysfunction, which is the earliest manifestation of atherosclerosis, may account for some of this cardiovascular risk. It has never been studied in a randomised controlled manner whether L-thyroxine therapy improves endothelial function.
Methods: 100 patients with SCH (mean TSH of 6.6 mIU/L and normal free T4 and free T3 levels) were studied in a randomised placebo controlled fashion in a cross-over study of L-thyroxine (100 mcg) and matching placebo for a period of 3 months each. Endothelial function was assessed by brachial artery flow mediated dilatation (FMD). The local research ethics committee approved the study.
Results: L-thyroxine therapy improved FMD significantly by [mean (95% CI)] 1.6% (1.2 to 2.1). Non-endothelial mediated dilatation did not show any significant change (as measured response to GTN). There was also significant reduction in total cholesterol (TC) levels by −0.35 mmol/L (−0.52 to −0.16). Multivariate regression showed that the improvement in FMD and reduction in TC levels was due to increase in free T4 levels.
Conclusion: Treatment of SCH with L-thyroxine leads to a clinically significant improvement in endothelial function, which may influence cardiovascular risk status. It remains to be shown whether these improvements will lead to a reduction in cardiovascular events in the future. Monitoring of treatment of SCH should also include free T4 levels as the benefits in FMD and TC are determined more by an increase in free T4 levels than level of TSH.