Effects of dextrothyroxine on the pituitary-thyroid axis in hypercholesterolemic children and goitrous adults

To evaluate the effects of dextrothyroxine (D-T4) on the pituitary-thyroid axis, we have measured the secretion of TSH in response to TRH in six goitrous adults and six euthyroid children with familial hypercholesterolemia. Since the effects of thyroid hormones appear to be mediated by specific nuclear receptors, the binding affinity of D-T4 was also studied. In both groups of subjects, D-T4 completely abolished the expected TRH stimulation of TSH and T3 secretion. The in vitro binding of D-T4 to rat pituitary nuclear receptors is only 3% that of L-T3, but the binding of D-T3 was similar to that of L-T4 (13% and 11%, respectively). The high circulating levels of D-T4 and possibly of D-T3 after chronic administration of D-T4 may be responsible for the saturation of pituitary nuclear T3 receptors, resulting in the suppression of the TRH-induced TSH response. During the treatment period, total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol were significantly decreased by 18%, 18%, and 19%, respectively. Plasma triglyceride levels and the ratio of total to high density lipoprotein cholesterol were not affected. Although D-T4 lowers cholesterol levels, in view of its suppressive effect on the pituitary-thyroid axis, caution must be exercised with regard to its long term use in children.