Exogenous subclinical hyperthyroidism impairs endothelial function in nodular goiter patients.

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 microg/day to reach target serum thyroid-stimulating hormone (TSH) levels <0.5 mIU/L. Patients were studied before and after 8 weeks after the target TSH level <0.5 mIU/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 +/- 0.1 mIU/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.