Exogenous subclinical hyperthyroidism impairs endothelial function in nodular Goiter patients

Abstract

Background: Exogenous subclinical hyperthyroidism is associated with cardiovascular and metabolic changes. The aim of this study was to evaluate the effect of levothyroxine ( LT4) suppression on endothelial function and insulin sensitivity in euthyroid nodular goiter patients. Methods: Twenty-two euthyroid patients with multinodular goiter (MNG) and 22 matched healthy controls were studied. LT4 was administered in doses ranging from 50 to 150 mu g/day to reach target serum thyroid-stimulating hormone ( TSH) levels < 0.5mIU/L. Patients were studied before and after 8 weeks after the target TSH level < 0.5mIU/L. The control group was studied twice, 16 weeks apart. Flow mediated vasodilatation ( FMD), insulin sensitivity index (ISI), lipid peroxidation, and high-sensitivity C-reactive protein (hsCRP) were the outcome measures. Results: LT4 treatment significantly suppressed TSH levels to 0.2 +/- 0.1mIU/L ( minimum and maximum range was 0.05-0.3 mIU/L). FMD decreased from 10.7 +/- 2.7% to 5.4 +/- 1.7% ( p < 0.001) and mean ISI decreased from 2.56 +/- 1.10 to 1.41 +/- 0.50 ( p < 0.001) with LT4 treatment in the MNG group. Lipid peroxidation measured as thiobarbituric acid reactive substances ( Tbars) ( p < 0.05), and hsCRP ( p < 0.001) levels significantly increased compared to the baseline in the MNG group. FMD measurement inversely correlated with free T4 ( p =0.008) and Tbars ( p = 0.004), and positively correlated with ISI ( p 0.004). Serum Tbars and hsCRP were independent predictors of FMD ( p= 0.004) in multivariate analysis. All results expressed as mean +/- SD. Conclusions: TSH suppression therapy with LT4 leading to subclinical hyperthyroidism may cause impaired endothelial function, increased oxidative stress, and decreased insulin sensitivity in euthyroid nodular goiter patients.