Akiyo Shiroozu

Predominant T3 synthesis in the metastatic thyroid carcinoma in a patient with T3-toxicosis

A metastatic mixed papillary and follicular thyroid carcinoma synthesizing predominantly triiodothyronine (T3) producing thyrotoxicosis is described. There was a concentration of 131I in numerous masses on the lung as well as a mass in the neck. BMR was +38%. Serum T4, T3-RU and T3 were 6.6 microgram/100 ml, 35.1% and 9.0 ng/ml, respectively. Serum TSH was not detectable and was not increased by the injection of 500 microgram of synthetic TRH. Decompressive surgery, performed while the patient was receiving no thyroid medication, yielded tumor tissue for chemical analysis. The mass measured 4.5 cm X 4.0 cm X 3.0 cm. The normal thyroid tissue was found to be atrophic. Sedimentation pattern of the soluble protein revealed a small peak at 18 S without a 27 S peak, suggesting an accelerated hydrolysis of thyroglobulin (Tg). Both the Tg content of the tumor and the degree of iodination of the Tg were low, 0.53% (based on wet weight of tissue) and 0.07%, respectively. DIT-I, MIT-I, T4-I, and T3-I in hydrolysate of the tumor tissue were 17.8%, 29.1%, 7.1%, and 41.7%, respectively. Therefore, the high T3 in the serum in this case seems to arise mainly from the cancer tissue. Possible mechanisms for this predominant T3 production are discussed.

TSH DEPENDENT ELEVATION OF SERUM THYROGLOBULIN IN REVERSIBLE PRIMARY HYPOTHYROIDISM

Serum levels of thyroglobulin (Tg) were measured using immunoradiometric assay in 18 patients with primary hypothyroidism, whose serum levels of thyroid stimulating hormone (TSH) were higher than 40 mU/1 and anti‐Tg antibodies were negative. In 12 patients, serum Tg levels were extremely elevated above the upper limit of normal (30 ng/ml) and the levels were more than 800 ng/ml in 10 of them. In all of these 12 patients, thyroid function recovered spontaneously with only iodide restriction and the serum Tg levels declined concomitantly with the decrease in serum TSH concentrations, events suggesting the TSH dependency of this Tg elevation. In the other 6 patients without elevated Tg levels, thyroid function did not recover and replacement therapy with l‐thyroxine had to be given. Data from our study show that the TSH dependent Tg secretion is observed in reversible type primary hypothyroidism and that it may proceed vigorously even though thyroid hormone production is subnormal. Measurement of serum Tg may be valuable for predicting the prognosis of primary hypothyroidism.

Defective iodide transport and normal organification of iodide in cold nodules of the thyroid.

Eleven thyroid follicular adenomas, cold on scintigram were analysed to determine whether defect in iodide organification or iodide transport causes low iodide uptake in cold nodules of the thyroid. The results were compared with perinodular tissue samples used as controls.

Acid thyroglobulin protease activities in human diseased thyroid glands.

The lysosomal acid protease is thought to be a main enzyme in hydrolysis of thyroglobulin. The protease activity of lysosome‐rich fractions of various diseased thyroid glands were assayed by the sensitive and reproducible method developed in our laboratory. They included 78 diseased thyroid glands; 37 thyrotoxic goitres, five irradiated thyroids, five Hashimotos thyroiditis, one granulomatous thyroiditis, six multinodular goitres, 14‘cold’ adenomas, four‘hot’ adenomas with three paranodular tissues, and six carcinomas. Fifteen paranodular tissues of cold and solitary thyroid nodules were served as controls. The protease activities were significantly increased in thyroid tissues of thyrotoxic goitres, Hashimotos thyroiditis, adenomas and adenocarcinomas. In thyrotoxic goitres, the protease activity correlated well with the mean area size of colloid follicles. The‘hot’ adenomas had higher protease activity than‘cold’ ones. The protease activity of multinodular goitres was nearly normal. Only the irradiated thyroid glands had low protease activities. Therefore the high protease activities in hyperfunctioning goitres seem to reflect hormone secretory activities. On the other hand, cold neoplastic goitres seem to have lysosomal protease activities which are not associated with thyroidal secretory process. The assay of acid protease activity will be useful to understand the pathophysiology of lysosomal system in diseased thyroid glands.

The Adverse Effects of Thioureylene Antithyroid Drugs

The aims of the present study were to investigate the incidence of adverse effects of thioureylene antithyroid drugs and to see if there were any factors related to the development of the adverse effects. Methimazole or propylthiouracil was administered to 151 patients with Graves disease; 76 untreated cases and 75 treated cases. The overall incidence was 22.4% among the 76 untreated cases. The incidences were 26.7% (13/45 cases) for methimazole and 16.1% (5/31 cases) for propylthiouracil, respectively, which were significantly higher than those previously reported. Fourteen out of 17 cases with the adverse effects were given the other thioureylene. The successive incidence of the adverse effects was 28.6% (4 cases), which was not significantly different from that under the drug of first choice. The result suggests that methimazole and propylthiouracil may not have cross-reaction each other. On the other hand, antinuclear antibody and anti-DNA antibody became positive in 2 out of the 4 cases. It would be a significant phenomenon, since antinuclear antibody was positive in only 3% of cases before the drug treatment. Thus, an immunological mechanism seemed to be involved in the problems, although there was no correlation between antithyroid autoantibodies and the development of the adverse effects. The adverse effects were observed within 2 months of administration of less than 250 tablets in total in most of the cases. The results imply that allergic mechanism rather than accumulating or toxic effect may concern the development of adverse effects of the thioureylenes.

Residual Capacity for Iodide Organification in Human Thyroid Slices Provoked by Hydrogen Peroxide

Iodination of tyrosyl residues in thyroglobulin is one of the essential steps of biosynthesis of thyroid hormones. In 1944, Dempsy demonstrated a peroxidase in the thyroid histochemically (1). Since then, the study concerned with thyroid hormone production has progressed greatly. So far, evidence has been provided, indicating that thyroid peroxidase is the key enzyme for iodide organification in the thyroid. Subsequently, it was also demonstrated that the process of thyroid hormone synthesis involves hydrogen peroxide.