Dilantin and salicylate effects on hepatic thyroxine bio-availability and dialyzable thyroxine

Earlier studies have shown that drugs such as dilantin inhibit T4 binding by thyroid hormone binding globulin (TBG) and cause a displacement of T4 from TBG to prealbumin with no change in the albumin-bound T4 fraction. Since recent studies have shown albumin-bound T4 is freely transported into liver, the present studies are designed to investigate drug effects on T4 transport in liver. The effect of salicylate and diphenylhydantoin (Dilantin) on T4 in human serum were examined both in vitro by using equilibrium dialysis and in vivo in the rat liver by using a tissue sampling single injection technique. Serum was obtained from 6 healthy normal volunteers and was made either 0 or 0.5 mM Dilantin and either 0 or 10 mM sodium salicylate. The portal vein injection vehicle contained 125I-T4/3H-water (highly diffusible internal reference) mixed with either a) Ringer's (0.1 g/dl albumin), b) 5% T4 antiserum, or c) 80% human serum. The free dialyzable fraction in vitro was raised by 40 and 125% after the addition of Dilantin and salicylate respectively. However, the percent of total T4 that was transported into liver on one pass, 17 +/- 1%, was not different in the control, the salicylate treated, or the Dilantin-treated sera. Therefore, in contrast to the in vitro dialyzable measurement of free T4, which is elevated by toxic concentrations of Dilantin or salicylate, the bio-available fraction of T4 as determined by the single pass perfusion technique, is unchanged in rat liver in vivo. These drug-induced changes in free T4 in vitro and bio-available T4 in vivo are similar to the ones reported previously in non-thyroidal illness.     

Schistosomatium douthitti: effects of thyroxine

Thyroxine-treated flukes showed increased tetrazolium reductase and cytochrome oxidase activities in histochemical preparations. Single male, single female, and pairs of S. douthitti, as well as cercariae of this species, consumed more oxygen when treated with thyroxine than did controls. The same effect was observed in all other invertebrates examined (Haematoloechus sp., Dugesia sp., Tetrahymena pyriformis, and an unidentified strigeoid species of cercaria).Both male and female schistosomes from hyperthyroid hosts are significantly larger than flukes from normal mice (P < 0.025). This condition prevailed whether the hyperthyroid state was established prior to cercarial penetration or after schistosomular migration through the lungs. S. douthitti adults from surgically thyroidectomized rats were significantly smaller than flukes from sham-operated sibling controls (P < 0.01). An accelerated death rate was also observed in hyperthyroid mice infected with S. douthitti.Female schistosomes from unisexual infections were significantly smaller (P < 0.1) than those from bisexual infections, confirming Short's (1952) report.     

Ion chromatographic determination of thyroxine in urine

Thyroxine (3,5,3',5'-tetraiodo thyronine) is administered to patients suffering from endemic goiter as also in cases of non-iodine deficient ethiology and hypothyroidism. It is suggested that the uptake of thyroxine can be monitored by assessing the levels of the same in the urine of patients under treatment. For the purpose, a highly sensitive and selective ion chromatographic procedure is developed. The sample of urine is treated with sodium hydroxide and UV irradiated to convert iodine in thyroxine to iodide. Subsequently, iodide is separated on an anion exchanger AS 4A column using 50 mM NaOH as the eluent and determined spectrophotometrically at 226 nm.