Levothyroxine Therapy on Ventricular Function in Neonates with Congenital Hypothyroidism

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Decreased thyroid hormone levels are associated with poor left ventricular contractility and relaxation in hypothyroid adults. These abnormalities can be reversed by levothyroxine substitution therapy. Few studies have been done in neonates with congenital hypothyroidism and to date the results have been conflicting. Only standard echocardiography has been used to assess left ventricular function. Tissue Doppler echocardiography (TDE) is a new method that permits evaluation of regional and global left and right systolic and diastolic ventricular function and color codes the velocity of myocardial movement allowing for more accurate quantification.

Fifty neonates (17 to 28 days of age) who were full term and diagnosed with congenital hypothyroidism (TSH >5.6 mIu/L) with a depressed serum free thyroxine (FT4 <10 pmol/L) or total thyroxine (TT4 <54 mmd/L) were studied. A control group of 35 healthy neonates with normal thyroid function levels matched for age, sex, body surface area, and BMI were studied. None of the subjects had congenital heart disease as assessed by clinical and routine echocardiographic studies. Each neonate was studied with both conventional M-mode pulsed wave Doppler and with TDE. The infants were sedated with oral chloral hydrate for the studies. M-mode echocardiography measured left atrial aortic diameter, left atrial/aortic ratio, left ventricular fractional shortening, and left ventricular ejection fraction. In addition diastolic mitral and tricuspid inflow velocity was measured. The TDE permitted measurement of peak early diastolic mitral annular velocity, peak late diastolic mitral annular velocity, and peak systolic mitral annular velocity, as well as similar measurements for tricuspid velocity.

Using conventional Doppler echocardiography, markers of left ventricular systolic global function were significantly lower in the infants with congential hypothyroidism. In addition, early and late mitral and tricuspid valve diastolic function were significantly lower in the infants with congential hypothyroidism. After a month of levothyroxine (L-T4) therapy several of the left ventricular parameters improved, but left atrial and aortic diameter did not change. Significantly reduced mitral systolic and early diastolic velocity was found by TDE in the group with congenital hypothyroidism. These significantly increased after therapy, while the peak annular mitral and tricuspid velocity remained unchanged.

Mao et al pointed out that their study was the first comprehensive report of systolic and diastolic function of both ventricles in neonates with congenital hypothyroidism and their data showed impaired left ventricular systolic function which normalized with L-T4 therapy. Their data also showed that infants with congenital hypothyroidism do not have abnormal left atrial structure. The use of the TDE confirms subclinical impairment of both left and right ventricular contractile function in neonates with congenital hypothyroidism, as well as diastolic dysfunction of both ventricles. The authors concluded that their data underscore the importance of early detection and treatment of infants with hypothyroidism.

Mao S, Wang Y, Jiang G, Zhao Z. Effects of levothyroxine therapy on left and right ventricular function in neonates with congenital hypothyroidism: a tissue Doppler echocardiography study. Eur J Pediatr. 2007;166:1261-5.

Editor’s Comment

This is a very interesting and comprehensive study which shows convincing evidence that there is significant cardiac dysfunction in neonates with congenital hypothyroidism. The presence of a control group adds to the significance of the findings. It is interesting that this study, conducted in China, was performed on infants aged 17 to 28 days, prior to the initiation of L-thyroxine therapy. Details of screening for congenital hypothyroidism in China were not presented. It is disturbing that treatment of a hypothyroid infant would be delayed as long as 28 days. One would hope that with improvement in screening techniques such a delay could be reduced. Clearly the authors have presented significant information demonstrating the need for early identification and treatment of this disorder.

William L. Clarke, MD

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Last Updated: 04/30/2008