Effects of Dextrothyroxine on the Pituitary-Thyroid Axis in Hypercholesterolemic Children and Goitrous Adults

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Abstract
To evaluate the effects of dextrothyroxine (D-T4) on the pituitary-thyroid axis, the secretion of TSH [thyrotropin] in response to TRH [thyroliberin] in 6 goitrous adults and 6 euthyroid children with familial hypercholesterolemia was measured. 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 [triiodothyroine] 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; this results 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.

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