The Effect of Salicylate and Related Drugs on Thyroxine Binding in Man

Abstract

Summary. Previons studies have demonstrated a fall in circulating thyroid hormone, measured as plasma protein bonnd iodine (PBI), as well as evidence of a suppression of tbyrotropbin (TSH) from the pituitary following the administration of salicylate to nnrnial human subjects. This assoeiation is contrary to the classical concept of the negative feedback regnlatidn of the thyroidpituitary axis.Using the dialysis procedure of Chri.stensen for tlie determination of free thyroxine, it has been demonstrated in aeiite experiments that the administration to normal subjects of sodium salieylate {5 g.) and sodium y-resoreylate (8 g.) produced an increase in circulating free thyroxine within two hours, in spite of the depression in plasma PBI. The admuiistratinn of sodium p-hydroxybenzoate (5 g.) was witbout effect. Displacement of thyroxine from the thyroxine-binding prealbumin site of the serum proteins separated by paper eleetrophoresis in ammnnhnn carbonate buffer (0-12 M at pH 8-4), was demonstrated following saiicylate and y-f'-'sorcylate in vivo, whereas p-hydroxybenzoate was inactive. Tbns, i» civo, salieylatc and y-resorcylate compete for binding sites on jirealbumin displacing bound tbyroxine into tbe free state.Tbe liyptTmetabolism induced by salicyUite as tbe cause of the depression in tliyroid function may now be excluded since 7-resoreylate is witbout ]netabiilie activity. The depression in TSH release produced by these drugs appears to be correlated with an increase hi free thyroxiiie. It is cdnclnded that the level of circulating free thyroxine ser\es as the regulator of the negative feedback system contralhng thyroid-pituitary interrelations.INTRODUCTION.

The interpretation of the serum protein-bound iodine: A review

“…Some batches contaminated with organic iodine (Pileggi, Segal, and Lanchantin, 1963) *Cardivix (= benziodarone) Chlorosane tablets contain iodine (quantity not stated) *C-Van contains 1 5 % available iodine *Darbid (= isopropamide iodide) *Decamethonium iodide contains 49 5 % I *Dimethyltubocurarine iodide contains 35 % I Ekner Seltzer contains 0-01 % Nal Endoiodine contains hexamethyldiaminoisopropanol di-iodide (quantity not stated) Endojodin contains hexamethyldiaminoisopropanol di-iodide (quantity not stated) *Entodon (= hexamethyldiaminoisopropanol di-iodide) *Erythrosine (tetraiodofluorescein) red colorant for food and drugs (Andersen et al, 1964). Eskornade spansule contains 5 mg isopropamide iodide Eskornade syrup contains 15 mg isopropamide iodide per 100 ml *Estomycin (= penethamate hydriodide) *Estopen (penethamate hydriodide) 2, 4-D Florsheim and Velcoff (1962) DOCA Zingg and Perry (1953) Good, Potter, and Hetzel (1965) …”

Studies of the congenitally goitrous sheep. The iodinated compounds of serum, and circulating thyroid-stimulating hormone

“…Assay ofthyroxine-binding proteins was done as described by Good, Potter & Hetzel (1965), with 10,ug. of L-[131I]thyroxine/100ml.…”