A Goitrous Subject with Defective Synthesis of Diiodotyrosine Due to Thyroglobulin Abnormalities

Abstract

A study of a 51-yr-old goitrous woman with positive thiocyanate discharge of 131I by the thyroid is reported. Activities of thyroid peroxidase, NADPH-cytochrome c reductase, catalase, protease, and iodotyrosine deiodinase were normal. The thyroid protein of the patient seemed to be a protein indistinguishable from the authentic thyroglobulin in so far as it had been studied by electrophoresis, immunodiffusion, and by precipitation with ammonium sulphate. The iodine content was 0.28%. However, more than one-half of the goiter thyroglobulin in saline dissociated irreversibly into 3S component. A very small amount of it dissociated into 12S and 6S components. This dissociation took place during a Spinco analytical ultracentrifugation. This suggests that the binding of the subunits is extremely labile, and that, therefore, more than one half of the goiter thyroglobulin does not contain the specific globular form with covalent bonds. In the goiter thyroglobulin the concentration of monoiodotyrosyl residues was at a normal level whereas that of diiodotyrosyl and thyroxyl residues was very low. When the protein was iodinated in vitro by the addition of I2, the formation of diiodotyrosyl residues and the concomitant decrease in tyrosyl residues in the goiter thyroglobulin were less than one half of that in the normal thyroglobulin. It has been declared that a specific globular form of the protein appears to be required to promote the synthesis of diiodotyrosyl residues. Thus, in the patient's thyroid, the formation of diiodotyrosine from monoiodotyrosine in the protein appeared to be defective because of the structural abnormality of the thyroglobulin.