Abstract
Free thyroxine (T4) has been suggested as the active component available to the cells in vivo for the initiation of the hormonal action and thyrotropin (TSH) regulation. It is known that hypolipemic agent clofibrate displaces T4 from plasma protein in vitro. If the free T4 would be elevated after administration of the drug, the pituitary TSH secretion might be decreased through the negative feedback mechanism, as suggested previously. The present study was undertaken to determine the effect of clofibrate and related compound on serum TSH concentrations in man and experimental animals.
The results obtained herein were as follows :
A single and chronic administration of clofibrate (750mg/day) significantly suppressed serum TSH levels in patients with primary hypothyroidism. There was no change in serum levels of T4-iodine, triiodothyronine (T3) and % free T4 after clofibrate treatment. On the other hand, clofibrate failed to produce discernible changes in serum T4-I, T3, and basal and thyrotropin-releasing hormone (TRH) -induced TSH levels in euthyroid subjects.
Similar results were also obtained with brain-stimulating compound meclofenoxate hydrochloride (750mg drip infusion or 600mg/day x 7days. oral), similar in structure to clofibrate.
In thyroidectomized rats with undetectable levels of serum T4 and T3, both clofibrate and meclofenoxate hydrochloride suppressed elevated serum TSH levels. The pituitary TSH content was lower in these drugs-treated groups than in controls, while no change in the hypothalamic TRH content was observed in these animals.
These observations suggest that clofibrate and structurally related compound suppressed TSH secretion in patients with primary hypothyroidism and in thyroidectomized rats, presumably at the hypothalamic-pituitary levels.
