Radio immuno-assay of thyroxine-binding globulin

Abstract

Thyroxine-binding globulin (TBG), the major extracellular thyroid hormone binding protein, is a glycoprotein with a single binding site for thyroxine. The serum concentration of TBG is known to vary over a wide range in normal subjects, to be raised during pregnancy and oestrogen therapy, and lowered in old age, malnutrition, cirrhosis, androgen therapy and nephrotic syndrome, and is also dependent on genetic factors. Thyroxine-binding globulin has been purified from pooled human sera by a three-step procedure consisting of affinity chromatography on thyroxine-Sepharose, followed by chromatography on Con A-Sepharose and finally ion exchange chromatography on DEAE Sephadex A-50. The final product gives a single stained band on analytical disc gel electrophoresis. A sensitive radioimmunoassay for thyroxine-binding globulin has been developed. The assay is specific, being unaffected by human serum proteins other than TBG. TBG levels in normal adults were found to range between 10 and 23.5 mg/l (mean 17.2 mg/l). In 15 women receiving oral contraceptives, the TBG levels were significantly raised (20.5–35 mg/l, mean 26 mg/l). There was no significant difference in hyperthyroid subjects (range 12–46 mg/l, mean 19.4 mg/l). In pregnancy, TBG levels were increased up to 18 weeks' gestation and thereafter maintained at the maximal level. A linear correlation was shown between total serum thyroxine and TBG levels in euthyroid subjects. A positive correlation between Free Thyroxine Index and a ratio of total thyroxine to TBG was demonstrated.