[Homeostatic adaptation to iodine deficiency].
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As a tool with which to detect iodinated compounds in human thyroid specimens, we have reevaluated a nonincineration technique which has so far been employed in the determination of thyroxine-iodine in peripheral blood. The catalytic action of iodoamino acids in the Ce-As reaction was enhanced by a small amount of Cl2. On the contrary, a large amount of Cl2 inhibited the reaction unexpectedly. Among iodide, iodotyrosine and iodothyronine, iodide was the most effective catalyst in the Ce-As reaction and iodothyronine was the least effective one. Protein seemed to inhibit this reaction of thyroglobulin. But the result of iodine content in thyroglobulin by this technique agreed well with that by incineration when measured 127I was corrected by percent activity of dializable part of the total activity of 131I-thyroglobulin with the same protein concentration, after the NaClO treatment. The results of human thyroid specimens were as follows: the thyroglobulin content of five normal subjects was 8.0 +/- 1.5% of wet thyroid weight. That of Hashimoto's disease was significantly decreased which seemed compatible with the decrease in iodine content of thyroglobulin, whereas thyroglobulin content of Graves disease treated with 1-methyl, 2-mercaptoimidazole followed by a large dose of iodide was well preserved in spite of a lower degree of iodination of thyroglobulin. As for the distribution of iodoamino acids-iodine in normal thyroid, T4 was 20.5 +/- 0.7%. This technique ultimately looks promising as a tool with which to study intrathyroidal iodine metabolism in human.
Acetylation of porcine thyroglobulin with N-acetyl imidazole was performed at various temperatures in the presence of urea. In the medium without urea, the number of O-acetylated iodoamino acid residues formed was constantly 15 above 10 degrees C (originating from all diiodotyrosyl and a few of monoiodotyrosyl residues), while the number of O-acetyl tyrosyl residues increased gradually from 15 at 0 degrees C to a maximum of 70 at 70 degrees C. All (about 25) iodoamino acid residues were acetylated at 20 degrees C in 2 M urea, while the presence of 8 M urea was necessary to acetylate all tyrosyl residues at 20 degrees C. Experiments on the nitration of thyroglobulin with tetranitromethane showed that diiodotyrosyl and thyroxyl residues were easily nitrated even at low temperatures and the low ratio of the reagent to the protein, while tyrosyl residues consisted of three groups: the first group (about 14%) which was very easily nitrated even at 0 degrees C and the low ratio of the reagent to the protein, the second group (about 45%) which was nitrated depending on temperature and the molar ratio of the reagent, the remaining which was definitely unreactive even under extreme conditions. In addition, the ionization of tyrosyl and iodoamino acid residues was studied by spectrophotometric titration at various temperatures in the presence and absence of 8 M urea. It was found that diiodotyrosyl and thyroxyl residues did not change very much with respect to ionization behaviour by the addition of urea, in contrast to clear dependence of tyrosyl residues on urea. Based on these observations, the location of these residues and the structural change of the protein with temperature are discussed.
A girl who had a nontoxic diffuse goiter with a congenital organification defect of iodide was first seen at the age of 8 years, and since then she has been followed up for a long period. The nodularity of the thyroid gland had gradually progressed, because of intermittent failure of ingestion of thyroid hormone preparation which was followed by excess TSH secretion. 18 years later, a nodular goiter developed and the patient underwent subtotal thyroidectomy. In order to prevent the development of nodular change in the thyroid gland in this disorder, supplemental thyroid hormone medication should be started as soon as the diagnosis is confirmed, and the therapy should be carried out regularly.
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