Analysis of TSH receptor antibody and studies of effects of it upon thyroid development and function.

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1. We were distributed rat thyroid FRTL-5 cell from Dr. Kohn of NIH and using FRTL-5 cell , we have established the methods for detection of TSH-receptor antibody activities, that is, TSH-binding inhibitor immunoglobulins(TBII),Thyroid-stimulating antibody(TSAb),Thyroid-stimulation blocking antibody(TSBAb),antibody which inhibit iodine transport or thysidine incorporation into FRTL"5 cells. We have determined these activities in patients with various auto-immune thyroid diseases to find out any etiological significance of the diseases.1) Chronic thyroiditis: We couldn't detected TSH-receptor blocking antibodies(TBII and TSBAB) in patients with atrophic autoinsune thyroiditis(AAT) of childhood onset which suggested the pathogenesis of AAT in childhood is different from that of postpubertal onset. It is well known that mother who possessed TSH-receptor blocking antibody give birth hypothyroid infant however,the correlation between mother's TSH-receptor blocking antibody activities and ou … More tcome of their offspring have not fully elucidated. We have established the method to predict thyroid dysfunction of newborn infants with diluting mother's serum with normal pooled serum to obtained 50% inhibition of labeled TSH binding to its receptor which enable us to prenatal diagnosis of hypothyroidism and ultra-early start of treatment.2) Graves' disease: Both TBII and TSAB antibody activity were detected at diagnosis and these activities were decreased with anti-thyroid treatment. We have evaluated these activity.whether it might be a good indicator of long-term prognosis of Grave's disease and found that TSAB is the most useful indicator of remission or relapse of the disease. To elucidate the relationship between the mother's TSH-receptor antibody activities and the status of thyroid dysfunction in their offspring, We have studies TSII and TSAB activities in mother's sera. We found that TBII and TSAB activities were responsible for development neonatal thyrotoxicosis, while on the other hand very weak TSAB activities regardless of TBII were detected in mothers who gave birth infants with transient hypothyroxinemia which is a new thyroid dysfunction proposed by us.3) Cretinism: It was reported that there are some autoantibodies in mothers who gave birth sporadic cretinism. We have evaluated TSH-receptor blocking antibody and antibodies which inhibit iodine transport or thysidine incorporation into DNA using FRTL-5 cell, however, we could not found any difference between normal controls.2. Neonatal screening for congenital hypothyroidism: More than ten years has passed since we start screening for congenital hypothyroidism. Nationwide study of mental development was performed and found there is a significant difference between normal control and cretinism who were over 6 years of age. It is necessary to continue future evaluation and improvement of treatment.We have conducted population-basis study of cretinism in Hokkaido and reported the incidence and types of disease. We also evaluated iodine metabolism in prenatal period to improve sensitivity and accuracy of screening. Less