Displacement Of T4 Research Articles

Studies of the effects of salicylate in hyperthyroidism.

SUMMARYPrevious studies in rats have shown that salicylate depresses thyroid function by causing a fall in TSH secretion from the pituitary. This fall in TSH secretion has been correlated with a rise in free thyroxine (T4) level due to displacement by salicylate from thyroxine‐binding proteins in the plasma. There is evidence of similar changes following administration of salicylate to man. In view of these findings, the effects of salicylate have now been studied in hyperthyroidism.Consistent depression of the plasma P.B.I. level was noted in 12 hyperthyroid subjects given 6 grammes of salicylate per day for four days. However, there was no improvement in clinical status. A rise in metabolic rate was observed. There was also a rise in free T4 (demonstrated with the dialysis procedure of Christensen). This increase in free T4 was correlated with displacement of T4 from thyroxine‐binding prealbumin (TBPA). The isomer p‐hydroxybenzoate was without effect on free T4 and TBPA.There was a significant depression of three‐hour uptake of radioiodine after salicylate administration (5 grammes per day for 48 hours), but no consistent effect on 24‐hour uptake. The depression in uptake occurred in the presence or absence of long‐acting thyroid stimulator (LATS).A slowing of secretion rate was noted in three of nine hyperthyroid subjects studied after therapeutic doses of 131I. LATS was demonstrated in one of these three subjects.The significance of these findings is discussed. The persistence of clinical hyperthyroidism has been shown to be correlated with a rise in free T4 level, in spite of a fall in the plasma P.B.I. (total T4) concentration. This finding indicates that the free T4 level determines the clinical state of the patient. The reason for the fall in uptake of radioiodine and slowing of secretion rate is uncertain. The possibility of salicylate affecting the action of LATS on the thyroid gland is suggested.