1. Hashimoto’s disease was initially recognized by characteristic histopathological abnormalities in the thyroid gland, different from thyroid cancer but concept has been expanded on the basis of autoimmune thyroiditis

2. Assay development for detection of anti –thyroid antibodies 1957 USA Witebsky UK Roitt, Doniach 1958 UK Roitt, Doniach 1959 UK Holborow ， Doniach 1976 Japan Amino, Yamada 1985 USA Portmann, DeGroot ： Anti-thyroglobulin antibody （ Tanned red cell hemagglutination ）（ TRC ） → （ TGHA ） ： Anti-microsomal antibody （ Complement fixation ）（ MCF ） ： Immunofluorescent antibody (Cytoplasmic antibody) （ Fab ） ： Anti-microsomal antibody （ Tanned red cell hemagglutination ）（ TRC ） （ MCHA ） ： Anti-peroxidase antibody （ TPOAb ）

3. Assay for anti-microsomal antiboby using hemagglutination method Solubilized microsomal antigen by sonication Tanned sheep red cell + Antibody (MCHA) Agglutinationgatin （ Yamada N, Amino N ）

4. Anti-microsamal antibody(MCHA) and -thyroglobulin antibody(TGHA) in thyroid diseases Negative 20 40 80 160 320 640 1280 2560 5120 10240 20480 40960 81920 163840 EuthyroidHypothyroid Hashimoto’s thyroiditis MCHA TGHA Amino N et al. Clinical Endocrinology 5: 115, 1976 Graves’ disease Subacute thyroidits

5. (Amino, The Thyroid 5th ed, Chapter 24, 1986.) Prevalence of anti-thyroid microsomal antibodies in healthy adults 18 ～ 29 30 ～ 4950 ～ 6970 ～ 89 Age (years) 20 15 10 5 % ： Female ： Male

6. Examination into specificity of anti-microsamal hema ｇｇ lutination antibody 1) Thyroid specificity ： Comparison with immunofluresence antibody 2)Autoimmune change in thyroid gland ： Relation to lymphocytic infiltration ３） Relation to thyroid dysfunction

8. Intensity of immunofluorescence Negative 160000 80000 40000 20480 10240 5120 2560 1280 640 320 160 80 40 20 Negative + +++++ Examination of anti-microsomal antibodies ： Comparison between hemagglutination and immunofluorescence tests Titer of MCHA (Amino N et al. Clin Endocrinol 5: 115, 1976 )

9. Presence of anti-thyroid antibodies and lymphocytic infiltration in thyroid gland Autopsy study in 70 cases without thyroid disease Serum antibodies lymphocytic infiltration NoYes Negative572 Positive*110 * MCHA 9 cases, TGHA 2 cases Yoshida H, Amino N et al. J Clin Endocrinol Metab 46: 859, 1978

10. MCHA titer 1000

11. Association of serum antithyroid antibodies with lymphocytic infiltration of the thyroid gland: Studies of seventy autopsied cases Yoshida H, Amino N, Yagawa K, Uemura K, Satoh M, Miyai K, Kumahara Y J Clin Endocrinol Metab 46: 859 – 862, 1978 These data suggest that positive serum antithyroid antibodies in subjects without overt thyroid disease may indicate the existence of lymphocytic infiltration in the thyroid gland, that is presumably subclinical autoimmune thyroiditis.

12. Significance of thyroid microsomal antibodies Nobuyuki Amino, Hidemitsu Mori, Yoshinori Iwatani, Minoru Kawashima, Kiyoshi Miyai Lancet 2: 1369, 1980 High TSH cases in positive MCHA total 9.1 ％ Less than 50 years old 2.2 ％ 50 years old and more 16.2 ％ Health examination 1024 adult cases Positive MCHA ： Adult female 10.2 ％ Adult male 6.0 ％

13. Start of autoimmune abnormality Aggravating factors Activating event in immunity Normal Subclinical autoimmune state Clinical autoimmune disease Reversible Irreversible Activity of autoimmunity Time Time course of autoimmune abnormality (Amino et al. Thyroid 9:705, 1999)

14. Subclinical Autoimmune Thyroiditis (10% in adult females) Delivery Aggravation Postpartum Thyroid Dysfunction

15. Systemic Immune Reaction in Pregnancy Immune Rebound After Delivery Activation Supression Non pregnant Pregnant Parturition Postpartum (months) 36912 Cellular immunity (Th1) Humoral immunity (Th2) Th1 predominant Th2 predemonant Immune activity ( Amino et al. Endocr J 47: 645,2000 )

16. 2 46 Delivery Postpartum Thyroid Dysfunction (5-10 % of postparum momen) Increase Decrease months （ II ） Transient thyrotoxicosis （ I ） Persistent thyrotoxicosis (4.5%) （ III ） Destructive thyrotoxicosis (52.1%) （ IV ） Transient hypothyroidism (20.5%) （ V ） Persistent hypothyroidism (0.1%) Postpartum Graves’ disease Postpartum exacerbation of autoimmune thyroiditis elevated RAIU (6.8%) Serum thyroid hormone low RAIU (16.0%) Amino N et al. New Engl J Med 306:849,1982 Amino et al. Thyroid 9: 705,1999

17. The classical concept of Hashimoto’s disease has been expanded on the basis of the concept of autoimmune thyroiditis, and subclinical or mild cases of Hashimoto’s disease are thought to exist in one of 10-30 adult women in the general population.

19. Alumni meeting of the first department of surgery, Kyushu University in 1928

21. Dr Hakaru HashimotoDr Shizuo Kuma, The first president of Kuma Hospital

22. Founded in 1932

23. Kobe, Japan

24. We are very happy to continue the traditional thyroid clinic and research in Kuma Hospital Thank you very much for your attention