Graves disease

Graves disease
20-50 5-10
Graves' disease
, ( diffuse goiter ) ,
( ophthalmopathy ) ( dermopathy ) localized myxedema

Graves' disease
Graves' disease
, , , ,

Graves' disease
Graves' disease
Human Leucocyte Antigen ( HlA )
HLA DR3 , HLA-DR4 HLA-DR5 and Gm allotypes HLA
Graves' disease cytotoxic lymphocyte antigen 4 ( CTLA-4
)

Hypothalamic- pituitary- adrenal axis

Suppressoe T cell
5-10

( B- cell lymphocyte )
Yersenia enterocolitica
extracellular domain TSH Receptor
Yersenia enterocolitica ,
Heat Shock Protein ( HSP )

 Graves' disease
TSH receptor ( TSHR ) , thyroid peroxidase ( TPO ) , thyroglobulin ( TG ) thyroidal iodide
transporter
TSHR Graves'
disease 80-100 Graves' disease Ig G TSHR ( TSHRAb )
TSHRAb
Thyroid Stimulating Immunoglobulin ( TSI ) Thyroid Stimualting
Antibody ( TSAb )
TSHR Gprotien , adenylate cyclase
cyclic AMP
TSHR TSH , TSHRAb TSH binding inhibitory immuloglobulin ( TBII )

TSH TSHR TBII

Graves' disease
Thyroid Peroxidase Antibodies ( TPOAb ), Thyrogloblin Antibodies ( TgAb )
( Hashimotos thyroiditis )
Graves' disease



Graves ophthalmopathy ( Thyroid associated orbitopathy ) Graves'
dermopathy localized myxedema

( Hyperthyroidism ) , ( diffuse goiter ) ,
( ophthalmopathy ) ( dermopathy : localized myxedema)
Graves' disease Hyperthyroidism
diffuse goiter Graves' disease
Hyperthyroidism ( ophthalmopathy ) diffuse goiter

( diffuse goiter )
20

2-3 2
2
( exopgthalmos ) / dermopathy Graves' disease
lid lag lid retraction

TSHRAb


Graves' disease

Autoimmune polyglandular syndrome ( Type 1 diabetes, Addisons disease, Hashimotos disease,
premature ovarian failure ) , Rheumatoid arthritis, Sjogren s syndrome, vitiligo, idiopathic
thrombocytopenic purpura, pernicious anemia, myasthenia gravis, systemic lupus erythrematosus
, chronic active hepatitis

Graves' disease 3
1. ( Medical treatment )
2. ( Subtotal thyroidectomy )
3. ( Radioactive iodine: I 131 )
Graves' disease
, 69% , 22%
radioactive iodine ( I 131 )

, , , ,
, , ,



-
1
bruit


40

, ,
( 6 1 )

( Medical treatment )
1. ( Anti-thyroid drugs )

thionamide 3
Propylthiouracil ( 6-propyl-2-thiouracil : PTU )
Methimazole ( 1-methyl-2-mercaptoimidazole : MMI )
Carbimazole ( 1-methyl-2-thio-3-carbethoxy imidazole : CMI ) MMI


5

 5
PTU
MMI
Serum protein binding
75%
nil
Serum half- life
1.5
4-6
Volume of distribution
20
40
Metabolism of drug during illness
Severe liver disease

Severe kidney disease

Transplacental passage

Levels in breast milk

Potency
1
10
Inhibition of peripheral conversion

of T4 to T3
All adverse reactions
7.1%
3.3%
Major adverse reactions
Agranulocytosis
0.4%(idiosyncrasy)
0.1%(dose related)
Hepatotoxicity
hepatocellular damage cholestasis
Vasculitis

substrate iodination intermediate TPO

iodination Tg
iodinate Tg iodinated Tg organification

iodothyronine T3 T4 MMI
PTU 10-50 , PTU ( 600 . )
5 monodeiodinase
T4 T3 ( MMI ) T3
MMI 2

MMI
24 PTU



, cytokine prostacyclin
,

( T cell, B cell, antigen-presenting cell )

Graves' disease PTU 100-300 ./

3 MMI 10-30 ./ 2

PTU 300 ./ MMI 30 ./ 3-4
PTU 150 ./ 3
MMI 15 . euthyroidism

Graves' disease
2 euthyroidism
PTU 150-300 ./ MMI 10-30 ./
euthyroidism

euthyroidism

- MMI
PTU

PTU
MMI MMI aplasia cutis
-
PTU

T4 T3
T3 T3 T4 MMI
PTU
- MMI PTU 10
- MMI ( agranulocytosis ) PTU
PTU ( idiosyncrasy )

MMI
( dose dependent ) MMI
25 .
- MMI ( cholestasis )
PTU PTU
polyarthritis, vasculitis ,
glomulonephritis lupus- like syndrome

-
-

PTU MMI
- euthyroidism
I 131
I131
- thyroid crisis
- I131

-



2
1. 1-15 , , , , , ,
, , 2-3


2. 0.2-0.5 agranulocytosis ( granulocyte
250 /.. ) , (PTU) , cholestatic jaundice ( MMI ) , aplastic anemia ,
thrombocytopenia , vasculitis , hypothrobinemia ( PTU ) , hypoglycemia ( MMI ) , myosistis ( MMI )

2.
2.1 ( Beta adrenergic antagonist )


cathecolamine Beta receptor Beta receptor

peripheral conversion T4 T3
peripheral tissue

PTU MMI
PTU MMI propranolol
20-60 . 2-3 atenolol ,metoprolol

1-2 propranolol


thyroid crisis

asthma, chronic obstructive pulmonary disease, heart block, congestive heart failure, pregnancy ( 2 nd,
3rd trimester ) diltiazem, reserpine
2.2 Lugols solution SSKI ( Saturated Solution of Potassium Iodine )

2-4

escaped phenomenon
5- 10 8
:
( thyroid storm )
, , , , ,
, , leukemoid eosinophillic
granulocytosis
2.3 Dexamethasone

, preipheral
conversion T4 T3 ( immunosuppression )
peripheral conversion T4 T3

PTU

PTU SSKI T3 24-48 2 . 6
( thyroid storm)

2.4 Lithium carbonate

thionamide iodide 300-450 . 8
radioactive iodine ( diabetic
insipidus )

1-2
euthyroidism 6-8

4-8 2-4
euthyroidism ( 4-8 )

euthyroidism 4-12 PTU 50 . MMI .
5 . euthyroidism
PTU 50 . MMI 2.5-5 .
6


Hashimotos thyroiditis, Subacute thyroiditis




-

-
-
-
-
- , bruit
2

-
-
-

1 . ( Thyroid function test )

- 2-3 euthyroidism

- 6
euthyroidism
- 11/2 2
-


T3
T4 T3 T4 sTSH
T3 T4
T3 toxicosis
T3
T4 s TSH T4
sTSH
2.
complete blood count ( CBC ) ,
CBC agranulocytosis
TSI , HLA DR3, TRH test T3 suppression test

Graves' disease

(
subtotal thyroidectomy )

I 131

1.

2. ,
3.
(
cosmetic effect )
4. I 131
5.

6. ( Relapse )
I131
7.
8. ( poor compliance ) I 131

9.

Graves' disease
2

- 0- 3.1

( asphyxia )


- ( vocal cord paralysis ) 0-4.4
Recurrrent laryngral nerve
-
0-3.6

1-7

- ( permanent hypothyroidism )
4.0-29.7
- ( relapse hyperthyroidism )

0.6-17.9

- ,
( keloid ) ,


1.



recurrent laryngeal nerve ,
2.
euthyroidism
Lugols solution
SSKI follicular , colloid


7-10 bruits thrills

3.

( Radioactive Iodine : I 131 )
I 131





I131
-
-
I131

- ,

-
- 20-40

I 131

-

-
- subclinical hyperthyroidism I 131
( Atrial fibrillation )
I 131
1.

congenital malformation
( congenital hypothyroidism )
pregnancy test
I 131 10
I 131

6
2.
3.

17 25
2. Radioiodine uptake
3.
4. Graves' ophthalmopathy
5.
6.

7. poor compliance
I 131
1. I131
euthyroidism I
131

 2 I 131 I 131


euthyroidism

I131
3 7 propranolol


thyroxine
thyroxine I 131 4
2. Graves ophthalmopathy I 131
ophthalmopathy
prednisolone 0.4-0.5 . . 1 I131

2-3 ophthalmopathy
I 131
I 131
I131 I 131
1. Repeated small dose regimen I 131 2 millicurie ( mCi )
3-6 Euthyroidism
2. Fixed dose regimen ( 5-10 mCi )
3. Sliding scale regimen I 131
4. Standard formular regimen RAIU

( 50-75 uCi ), (
100 uCi ) , ( 150-200 uCi )
hypothyroidism
= 100 uCi x ( )
% uptake




I 131

 I 131

7

7 I 131
I 131
I131 2

( Radiation thyroiditis )

I131

8
4
propanolol I131

ohthalmopathy
T3, T4 TSH 12
euthyroidism 8-12 euthyroidism
6 1 3-6
I131
Lugol s solution 3 SSKI 1 1 6-12
euthyroidism
euthyroidism

I 131
,
I131

( Pregnancy induced hypertension ) , , , , ,
,
, , , ,

1.

Hyperdynamic , , ,
, , , , ,

2.

TBG ( Thyroid Binding Globulin )

( total T4 total T3 )

,
( lid lag , exophthalmos ) , onycholysis , , 100
Valsava Maneuver , bruits

total T4 total T3 TBG

total T4
22 ug% total T3 350 ng%
total T4 total T3
total T4 total T3

FT4 / FT3I
FT4I / FT3I sTSH FT4 single step

 2 3 FT4I FT3

FT4I
TSH

1 2
physiologic transient hyperthyroxinemia hCG ( human Chorionic Gonadotropin )
RAIU

FT4 TSH
Graves disease
( transient hyperthyroidism of hyperemesis
gravidarum ) Graves disease T3
ophthalmopathy , dermopathy / TSHR Ab

30-70
hCG , hCG ( TSHR
TSH TSH ) desialylated hCG
TSHR hCG T3 w
non-thyroidal illness ,

16-20
TSH

Graves disease

1. Graves disease

3
2. Graves disease

32-36

TSH

3.

PTU
MMI aplasia cutis
MMI

MMI PTU

1.

Graves disease

FT4 ( High normal )

150 PTU 3
euthyroidism 3-6 50-100
MMI
PTU aplasia cutis

FT4 2-4


Intrauterine growth retardation ,postnatal bradycardia syndrome,
, ,
6-12

2
( Lugols solution SSKI ) (
Neonatal goiter )

2.

premature
labor 2
PTU
agranulocytosis
3. ( I 131 )
Graves disease

( congenital malformation )
2

PTU 100
MMI PTU PTU

2 Graves disease RAIU
( postpartum thyroiditis ) RAIU
bruit 2
RAIU Graves disease