We assessed the post-natal thyroid function in eight infants of mothers with Graves' disease whose thyroid function at birth was suppressed by maternal ingestion of propylthiouracil during pregnancy. These mothers continued taking propylthiouracil after delivery and breast-fed exclusively (two mothers supplemented their breast milk with a small amount of baby food). The cord free T4 level was slightly but uniformly below the normal range in all eight infants, and the cord TSH level was above the normal in seven infants. The dose of propylthiouracil after delivery ranged from 50 to 300 mg daily, which was equal to, or higher than, that before delivery. All these abnormal values normalized in the infant after birth. Serum samples, from seven of the eight mothers, taken at delivery were examined for TSH receptor antibodies; all were positive. The antibody titre, however, was too low, and/or free T4 and TSH levels were examined too long after delivery, for the antibodies to be the cause of the restoration of the infants' thyroid function. These results assure the safety of breast-feeding for the infants of mothers with Graves' disease taking propylthiouracil.

Clinical studies were undertaken of three pairs of monozygotic twin sisters affected by Graves' disease. The evidence that the twins were monozygotic was established by similarity in physical appearance, identical blood-group antigens and identical HLA types. All pairs were female, and the evidence of Graves' disease in both members of the pair was observed in 2 out of 3 pairs. In the remaining pair the disease started in the elder sister, but the younger sister still remained in euthyroidism in spite of the presence of diffuse goiter. The disease occurred in the second decade in all the patients, and the interval between the occurrence of the disease in twin sisters was 1 to 4 years. No common specific type of HLA was found among all three pairs, but DR4 was common in two pairs of twin sisters showing positive MCHA test. Serum TRAb was positive in 2 pairs of twin sisters but negative in the remaining one. However, it became positive in the elder sister of the latter pair during the antithyroid treatment. The effect of antithyroid drug treatment was found to be similar in each of the twin sisters, and the serum TRAb moved almost in parallel with serum FT4 level. These results indicate that a genetic factor may be of great importance in the aetiology of Graves' disease, and there was a strong preponderance for it to occur in women and the second decade was the peak age for its occurrence. The common specific type of HLA for all Graves' patients was not found in this study. A strong relationship was observed between Grave's disease and TRAb.

We employed two different methods of 131I treatment for Graves' disease in 285 patients and compared the results between the two. (We also analyzed the factors affecting the treatment outcome.) A single dose of 131I adjusted to the patients' thyroid weight was administered to 180 patients in group 1, while a relatively lower dose of 131I (approximately 30Gy) was given repeatedly to 105 patients in group 2. A 5-year follow-up showed that in group 1, 34% of the patients were euthyroid, 11% hypothyroid, 11% subclinical hypothyroid and 44% still remained hyperthyroid. In group 2, 43% of the patients were euthyroid, 5% hypothyroid, 35% subclinical hypothyroid and 17% hyperthyroid. The factors affecting the outcome of the treatment in group 1 patients were their thyroid weight, the duration of the disease and TRAb levels. No significant correlation was observed between the efficacy of 131I treatment and the patients' sex, age, 24hr 131I-uptake, effective half life of administered 131I or titers of antithyroid antibodies. We conclude that the repeated low dose administration of 131I provides the best outcome in a 5-year follow-up. However, we suggest that an adjusted dose of 131I in relation to the patients' thyroid weight should be employed to obtain a faster therapeutic response.

Recently, thyroid microsomal antigen was identified as thyroid peroxidase, and thyroid microsomal antibody was found to inhibit thyroid peroxidase activity in vitro. We investigated the possibility that anti-microsomal antibody inhibits the iodination of tyrosine, in vivo. Immunoglobulin G with or without anti-microsomal antibody from hypothyroid patients with goitrous Hashimoto's thyroiditis inhibited thyroid hormone synthesis in cultured slices of normal human thyroid tissue. IgGs with anti-microsomal antibody inhibited 125I thyroidal uptake and thyroid hormone synthesis stimulated by TSH more than normal IgG did. However, the same results were obtained with IgGs without anti-microsomal antibody. This effect did not involve anti-microsomal antibody, anti-thyroglobulin antibody, TSH-binding inhibitor immunoglobulin, thyroid stimulation-blocking immunoglobulin, or the cAMP level of the thyroid tissue. The ratio of organic I to inorganic I with stimulation by TSH in slices incubated with IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis or normal IgG was not significantly different, but was significantly higher in slices incubated with methylmercaptoimidazole. Therefore, IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis mainly suppressed 125I thyroidal uptake, rather than inhibiting thyroid peroxidase activity.In addition, this IgG was present in the serum of 11 of the 12 hypothyroid patients with Hashimoto's thyroiditis studied. This IgG may be involved in the mechanism that causes hypothyroidism in some patients with goitrous Hashimoto's disease. Some patients with Hashimoto's disease become hypothyroid by an unknown mechanism. Possibly the amount of functioning thyroid tissue decreases because of the destruction of follicular cells. In atrophie thyroiditis, the TSH receptor antibody (TR-ab), which blocks the action of TSH, may be responsible for the hypothyroidism (1). However, in hypothyroid patients with goitrous Hashimoto's disease, the mechanism of the hypothyroidism is not known.Thyroid microsomal antigen has now been char¬ acterized (2) and found to be thyroid peroxidase (TPO; 3). Therefore, anti-thyroid microsomal or anti-TPO antibody (Mi-ab, or TPO-ab) may affect thyroid function not only by damaging epithelial cells, but also by inhibiting TPO activity. In fact, Mi-ab inhibits TPO in vitro (4).To explore the possibility that Mi-ab inhibits the iodination of tyrosine in vivo, resulting in hypothy¬ roidism, we here studied slices of healthy human thyroid in tissue culture. Immunoglobulin G with or without Mi-ab was obtained from hypothyroid patients with goitrous Hashimoto's disease and the effects of these IgGs on the incorporation of iodine into the slices and the iodination of tyrosine were investigated. We found an antibody that sup¬ pressed iodine uptake, and also decreased hor¬ mone synthesis. Neither effect involved changes in the cAMP level or inhibition of the iodination of tyrosine in thyroid tissue. The suppression of iodine uptake was not directly related t...