Effects of long-term l-thyroxine treatment on endothelial function and arterial distensibility in young adults with congenital hypothyroidism

Abstract

Patients with congenital hypothyroidism (CH) display subclinical abnormalities of the cardiovascular system that are related to unphysiological fluctuations of TSH levels and occur despite careful replacement therapy. The aim of the present case-control study was to evaluate the effects of long-term levothyroxine (l-T(4)) replacement therapy on the vascular district in CH patients by assessing endothelial function with flow-mediated dilation (FMD) and brachial artery distensibility with the measurement of the coefficient of distensibility (DC). Thirty-two young adults with CH aged 18.9+/-0.2 years and 32 age- and sex-matched controls underwent brachial Doppler ultrasound examination to measure FMD and DC at the time of the study. Hypothyroidism was diagnosed by neonatal screening, and l-T(4) treatment was initiated within the first month of life. Compared to healthy controls, CH patients had significantly reduced brachial artery reactivity with lower FMD values (8.9+/-5.7 vs 14.1+/-5.1% P=0.003) and decreased vascular distensibility (24.6+/-1.6 vs 27.3+/-3 kPa(-1)x10(-3), P<0.0002). Linear regression analysis revealed that both total and pubertal mean TSH and number of episodes of undertreatment were independent determinants of FMD and DC. Pubertal mean TSH was the best predictor of both FMD and DC (r=0.81 and r=0.87 respectively, P<0.001). Young adults with CH treated with long-term l-T(4) replacement therapy may have significant impairment of both FMD and DC. Our data suggest that high TSH levels, inadequately corrected by l-T(4) replacement therapy in CH patients especially during puberty, can exert significant effects on the elastic and functional vessel properties.