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

Abstract

Objective: 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. Design: 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). Methods: Thirty-two young adults with CH aged 18.9G0.2 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. Results: Compared to healthy controls, CH patients had significantly reduced brachial artery reactivity with lower FMD values (8.9G5.7 vs 14.1G5.1% PZ0.003) and decreased vascular distensibility (24.6G1.6 vs 27.3G3 kPa K1 !10 K3 , 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 (rZ0.81 and rZ0.87 respectively, P!0.001). Conclusions: 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.

European Society for Paediatric Endocrinology Consensus Guidelines on Screening, Diagnosis, and Management of Congenital Hypothyroidism

“…In addition to the higher risk of congenital heart malformations [61,62], there is a subtle increase in cardiovascular risk factors in young adults with CH, related to treatment adequacy [132]. …”

ENDOCRINOLOGY AND ADOLESCENCE: Congenital hypothyroidism: a clinical update of long-term outcome in young adults

“…A slight increase in cardiovascular risk factors was found in a small group of young adult patients with CH and impaired diastolic function, low exercise capacity, and a larger than normal intima-media thickness. However, few studies have focused on cardiovascular changes, and most of the existing studies concerned treatment inadequacy (78,79).…”

“…In addition to the higher risk of congenital heart malformations (12, 13), young adults with CH have a slightly higher cardiovascular risk, which may be related to inadequate treatment (79).…”

Von Willebrand Factor, and Soluble Intercellular and Vascular Cell Adhesion Molecules as Indices of Endothelial Activation in Patients with Congenital Hypothyroidism

“…There are several reports on endothelial dysfunction in hypothyroidism in the adult population [28,29], but less information is available on CH patients [30] and there is no study in this field of CH patients during the neonatal period. In a recent study Oliviero et al [30 ]investigated the effects of long-term levothyroxine replacement therapy on the endothelial function in young adults with CH and concluded that young CH patients treated with long-term levothyroxine therapy present endothelial dysfunction which was demonstrated by lower flow-mediated dilation and decreased vascular distensibility.…”

“…In a recent study Oliviero et al [30 ]investigated the effects of long-term levothyroxine replacement therapy on the endothelial function in young adults with CH and concluded that young CH patients treated with long-term levothyroxine therapy present endothelial dysfunction which was demonstrated by lower flow-mediated dilation and decreased vascular distensibility. According to their findings serum TSH level fluctuations during treatment and follow-up could decrease the vascular distensibility and activity.…”