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

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 ）

Assay for anti-microsomal antiboby using hemagglutination method

Solubilized microsomal antigen by sonication

Tanned sheep red cell

+

Antibody(MCHA)

Agglutinationgatin

（ Yamada N, Amino N ）

Anti-microsamal antibody(MCHA) and -thyroglobulin antibody(TGHA) in thyroid diseases

Negative

204080

160320640

128025605120

10240204804096081920

163840

Euthyroid Hypothyroid

Hashimoto’s thyroiditis

MCHA

TGHA

Amino N et al. Clinical Endocrinology 5: 115 , 1976

Graves’ disease

Subacute thyroidits

(Amino, The Thyroid 5th ed, Chapter 24, 1986.)

Prevalence of anti-thyroid microsomal antibodies in healthy adults

18 ～ 29 30 ～ 49 50 ～ 69 70 ～ 89 Age(years)

20

15

10

5

%： Female

： Male

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

Intensity of immunofluorescence

Negative

16000080000400002048010240

512025601280

64032016080

4020

Negative + ++ +++

Examination of anti-microsomal antibodies ：Comparison between hemagglutination and

immunofluorescence testsTi

ter o

f MCH

A

(Amino N et al. Clin Endocrinol 5: 115 , 1976 )

Presence of anti-thyroid antibodies and lymphocytic infiltration in thyroid gland

Autopsy study in 70 cases without thyroid disease

Serum antibodies

lymphocytic infiltration

No Yes

Negative 57 2

Positive* 1 10* 　 MCHA 9 cases, TGHA 2 cases

Yoshida H, Amino N et al. J Clin Endocrinol Metab 46: 859 , 1978

MCHA titer 1000

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.

Significance of thyroid microsomal antibodies

Nobuyuki Amino, Hidemitsu Mori, Yoshinori Iwatani, Minoru Kawashima, Kiyoshi Miyai

Lancet 　 2: 1369, 1980

High TSH cases in positive MCHAtotal 　 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 　％

Start of autoimmune abnormality

Aggravating factorsActivating event

in immunity

NormalSubclinical

autoimmune state

Clinical autoimmune disease

Reversible Irreversible

Activ

ity o

f aut

oim

mun

ity

Time

Time course of autoimmune abnormality

(Amino et al. Thyroid 9:705, 1999)

Subclinical Autoimmune Thyroiditis(10% in adult females)

Delivery

Aggravation

Postpartum Thyroid Dysfunction

Systemic Immune Reaction in PregnancyImmune Rebound After Delivery

Activation

Supression

Non pregnant

Pregnant

Parturition

Postpartum (months)

3 6 9 12

Cellularimmunity

(Th1)

Humoral immunity (Th2)

Th1predominant

Th2predemonant

Imm

une

activ

ity

( Amino et al. Endocr J 47: 645,2000 )

2 4 6

Delivery

Postpartum Thyroid Dysfunction(5-10 % of postparum momen)

Incr

ease

Dec

reas

e

months

（ II） Transient thyrotoxicosis

（ I） Persistent thyrotoxicosis (4.5%)

（ III） Destructive thyrotoxicosis (52.1%)（ IV） Transient hypothyroidism (20.5%)

（ V） Persistent hypothyroidism (0.1%)

PostpartumGraves’ disease

Postpartumexacerbation

of autoimmune thyroiditis

elevated RAIU (6.8%)

Seru

m th

yroi

d ho

rmon

e

low RAIU (16.0%)

Amino N et al. New Engl J Med 306:849,1982Amino et al. Thyroid 9: 705,1999

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.

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

Dr Hakaru Hashimoto Dr Shizuo Kuma,The first president of Kuma Hospital

Founded in 1932

Kobe, Japan

We are very happy to continue the traditional thyroid clinic and research in Kuma Hospital

Thank you very much for your attention