Serum thyroid hormone levels may not accurately reflect thyroid tissue levels and cardiac function in mild hypothyroidism

The link between thyroid dysfunction and cardiovascular diseases has been recognized for more than 100 years. Although overt hypothyroidism leads to impaired cardiac function and possibly heart failure, the cardiovascular consequences of borderline low thyroid function are not clear. Establishment of a suitable animal model would be helpful. In this study, we characterized a rat model to study the relationship between cardiovascular function and graded levels of thyroid activity. We used rats with surgical thyroidectomy and subcutaneous implantation of slow release pellets with three different T(4) doses for 3 wk. In terminal experiments, cardiac function was evaluated by echocardiograms and hemodynamics. Myocardial arteriolar density was also quantified morphometrically. Thyroid hormone levels in serum and heart tissue were determined by RIA assays. Thyroidectomy alone led to cardiac atrophy, severe cardiac dysfunction, and a dramatic loss of arterioles. The low T(4) dose normalized serum T(3) and T(4) levels, but cardiac tissue T(3) and T(4) remained below normal. Low-dose T(4) failed to prevent cardiac atrophy or restore cardiac function and arteriolar density to normal values. All cardiac function parameters and myocardial arteriolar density were normalized with the middle dose of T(4), whereas the high dose produced hyperthyroidism. Our results show that thyroid hormones are important regulators of cardiac function and myocardial arteriolar density. This animal model will be useful in studying the pathophysiological consequences of mild thyroid dysfunction. Results also suggest that cardiac function may provide valuable supplemental information in proper diagnosis of mild thyroid conditions.