T y r oi d

Dr. M a h a t m a SpPD
Fak.Kedokteran UMS
SURAKARTA

Outline
Latar Belakang
Pendekatan Struma
G AK I
Hipertiroid
Hipotiroid

Outline

Latar Belakang

Pendekatan Struma
G AK I
Hipertiroid
Hipotiroid

Latar Belakang

Hyperthyroidism is a condition too much thyroid hormone.

Thyrotoxicosis: used excess synthesis and secretion of thyroid hormone by the thyroid
gland.
Most common of thyrotoxicosis:
diffuse toxic goiter (Graves disease, ~50-60%)
toxic multinodular goiter (Plummer disease, 15-20%)
toxic adenoma (3-5%).
Gender : Women>men ( Graves : 10 : 1 )
Age
: Graves: 20-40 yrs, Toxic multinodular goiter: > 50yrs
Race : Graves: Caucasians/Asians/Hispanics >> Black population

Toxic Solitary Adenoma

Rare cause (< 2% of patients with hyperthyroidism)

Younger people 30s and 40s
Benign follicular adenomas
Painful (subacute, de Quervains)
Painless (post partum)
Hyperthyroid, hypothyroid and euthyroid phases
Anti thyroid drug therapy does not work

Anatomi / histology

The hypothalamic-hypophyseal-thyroid axis

Mind its feedback mechanism

Biokimia

produksi hormon tiroid

B i o k i m i a produksi hormon tiroid

THIOCYANATES

THIOGLYCOSIDES:
GOITRIN

(CYANOGENIC
GLYCOSIDES)

ISOTHIOCYNATES
DISULFIDES

IODIDE
(SEAWEEDS)
COAST GOITER

WATER BORNE
GOITROGENS

IODIDE
TRANSPORT

OXIDATION

PROTEOLYSIS

ORGANIC BINDING AND

COUPLING

RELEASE AND
DEHALOGENATION

THYROGLOBULIN
I-

I-

(I

2
0

MIT
DIT

T4
T3

MIT
DIT

T4
T3
I-

F i s i o l o g i
HIPOFISIS
TSH
PENGELUARAN
IODIUM

MASUKAN
IODIUM

HORMON TIROID : T3 dan T4

1. METABOLISME
2. PERTUMBUHAN OTAK :
- Kecerdasan
- Saraf

F i s i o l o g i

heat

[Thyroid hormone] oxidative phosphorylation uncoupling (i.e. short circuits the coupling
between the electron transport chain and ATP synthesis) heat production/ inefficient
energy conversion.

HR, contractility CO
O2 consumption, CO2
production Vt, RR

/ PTH levels
bone turnover
(formation/ resorbtion)

Vasodilation
Blood flow

FISIOLOGIS B i o M o l e k u l e r

Mitochondrial effects:
mRNA transcription
Na-K-ATPase synthesis
BMR

Cellular energy use:

GLC absorption
Glycolysis
Gluconeogenesis
Insulin secretion
Cellular-GLC uptake
Lipolysis

Lipids metabolism
Chol to bile serum
Chol/ TG/PL.

Fisiologis : Schematic timing of mature in the human brain

Outline

Latar Belakang

Pendekatan Struma

G AK I
Hipertiroid
Hipotiroid

- Struma Nodusa simple non toksik :

Colloid Nodule

- Struma Nodusa simple toksik :

Adenoma, Carcinoma

- Struma Nodusa multiple non toksik :

GAKI

- Struma Nodusa multiple toksik :

Anamnesis
Sejak

kapan
Nyeri spontan/ tidak
Nyeri berpindah
Membesar cepat / lambat
Keluarga
Radioterapi
Perubahan suara
Tanda toksik

Dx fisik
Morfologi

Nodosa : multi/tunggal
Difusa
Nyeri
Keras, kenyal, kistik, berbenjol
Melekat dengan sekitar
Pendorongan trakea
Pembertons sign
Bising (bruit)

Pemeriksaan penunjang

Sidik tiroid (Scintigrafi)

USG (ultrasonografi)
Biopsi jarum halus (FNA)
Petanda tumor (marker)
Biokimiawi

Sidik tiroid

Yodium radioaktif
Menilai fungsi dan anatomi
Nodul dingin :
penangkapan yodium kurang dari sekitarnya
Nodul hangat
penangkapan yodium sama dengan sekitarnya
Nodul panas
penangkapan yodium lebih banyak dari sekitarnya

Ultrasonografi Biopsi aspirasi

Padat

atau cair
Tidak bisa menilai
fungsi
Kista tiroid
Adenoma tiroid /
nodul padat
Tiroiditis

jarum halus
( F N A )

Jarum

suntik no 22

27
Aman, tidak nyeri,
dilakukan di poliklinik
Kista : guna untuk
diagnostik sekaligus
terapeutik

Kadar Free T4 plasma

(peranan tiroglobulin)
Kadar TSHs plasma
Tiroglobulin plasma
Calsitonin
Antibodi mikrosomal (TPO)
Antibodi tiroglobulin (TGO)

Biokimiawi

TSH

low

high

nml

Free T4
low

nml

Free T4

? Secondary
(central) dz

low

high

high

nml

2o Hyperthyroid
Or Thyroid hormone resistance

1o Hypothyroid
2o Hypothyroid

Subclinical
Hypothyroid

Subclinical
1o Hyperthyroid
Hyperthyroid

diffuse
homogeneous
Graves Dz

None

RAIU
focal

heterogeneous
Toxic multinodular goiter

Functioning
Adenoma

Serum Thyroglobulin
low
Thyrotoxicosis factitia
Iodine load

high
Thyroiditis
Struma ovarii

Outline
Latar Belakang
Pendekatan Struma

G AK I

Hipertiroid
Hipotiroid

IDD Global Magnitude (1996)

1. At least 1,572 billion were at risk of IDD
2. At least 655 million affected by goiter ( 27% SEA
15% Europe, 22% Western Pasific etc )
3. Estimated 43 million people affected by some
degree of IDD-related brain damage
4. IDD is regarded as P.H. problem in 118 countries
5. IDD is the main cause of potentially preventable
mental retardation.

HIPOFISIS
TSH

PENGELUARAN
IODIUM

MASUKAN
IODIUM

HORMON TIROID
GONDOK
HIPOTIROID
CRETINE

METABOLISME
PERTUMBUHAN
OTAK : - Kecerdasan
- Saraf

Apakah GAKI itu ?

Gangguan Akibat Kekurangan Yodium /

Gondok endemik
Kekurangan yodium bukan hanya gondok saja, namun
ada efek yang lebih jauh
Gondok endemik : bukan hanya kekurangan yodium saja.
Misalnya ggn nutrisi, goitrogen, genetik

Mengapa GAKI dipermasalahkan ?

Gangguan yang ditimbulkannya sangat banyak dan

luas
Jumlah penderita masih banyak
Penyakit ini sebenarnya
dapat dicegah

Akibat GAKI pada manusia ?

Yodium : bahan dasar mutlak hormon tiroksin
Tiroksin : pada masa pertumbuhan penting pada perkembangan fisik
dan syaraf (otak)
Penting saat masa fetus, masa kehamilan, masa bayi, masa anak,
masa remaja.
Dampak kekurangan :
1. Kretin endemik
2. Kretin neurologik

Gambaran klinis kretinisme

A. Kretin endemik dan Kretin neurologik :
Lahir di daerah kekurangan yodium, dng dua atau lebih dari :
1. Gangguan kecerdasan
2. Tuli simetrik tipe sensorik
3. Kelainan saraf (gangguan jalan,
gangguan bicara, refleks patologik kelambatan jalan)
B. Keduanya irreversibel, permanen, tidak
dapat diperbaiki dengan obat apapun.

Spectrum of IDD:

SPEKTRUM
Fetus

Abortus
Lahir mati
Anomali kongenital
Kematian perinatal
Kematian anak
Kretin endemik
Kretin miksedematosa
Defek psikomotor

Neonatus

Gondok neonatus
Hipotiroidisme neonatus

GAKI

Anak dan remaja

*
*
*
*

Gondok
Hipotiroidisme juvenil
Ggn fungsi mental
Ggn perkembangan fisik

Dewasa

* Gondok dng akibatnya

* Hipotiroidisme
* Gangguan fungsi mental

SURVEY EPIDEMIOLOGI
KRITERIA PEREZ, 1960

Grade O
Grade I
I a
I b
Grade II
Grade III

: tidak teraba
: teraba dan terlihat dengan kepala ditengadahkan
: tidak teraba / jika teraba
tidak lebih besar dari tiroid normal
: jelas teraba dan membesar,
tidak terlihat walau kepala tengadah
: mudah dilihat dengan posisi biasa
: terlihat dari jarak tertentu

KRITERIA ENDEMIK

ENDEMIK GRADE I (RINGAN)

UEI > 50 ug I/gr kreatinin

ENDEMIK GRADE II (SEDANG)

UEI 25 - 50 ug I/gr kreatinin
ENDEMIK GRADE III (BERAT)
UEI < 25 ug I/gr kreatinin

Wanita hipotiroidisme hamil

bagaimana ?
Harus mendapat terapi substitusi tiroksin
Dipantau dengan TSH bukan dengan FT4

Berapa lama diberikan garam yodium ?

Terus menerus,
sepanjang hidup

1. Epidemiological aspect iodine deficiency

2. Clinical aspects neurological and myxedematous
3. Pathologic aspects intrauterine and irreversible

ENDEMIC
ENDEMICCRETINISM
CRETINISM

a. Neurological endemic cretinism

Mental retardation, deaf-mutism
Hearing loss bilateral perceptive
spastic diplegia, squint etc
b. Myxedematous endemic cretinism
Dwarfism, mental retardation,
hypothyroidism

Hypothyroidism
Clinical hypothyroidism
29% in cretins
17% in non cretinous
Biochemical hypothyroidism
41% in cretins
27% in non cretinous

Outline

Latar Belakang
Pendekatan Struma
G AK I

Hipertiroid

Hipotiroid

Etiology
1 Graves disease

Autoimmune disease caused by antibodies to TSH receptors

Can be familial and associated with other autoimmune diseases

2 Toxic multi-nodular goiter

5% of all cases

10 times more common in iodine deficient area

Typically occurs in older than 40 with long standing goiter

3 Toxic adenoma
More common in young patients, Autonomically functioning nodule
4 Thyroiditis Subacute
Abrupt onset due to leakage of hormones
Follows viral infection
Resolves within eight months
Can re-occur
5 Lymphatic and postpartum
Transient inflammation
Postpartum can occur in 5-10% cases in the first 3-6 months
Transient hypothyroidism occurs before resolution

6. Treatment Induced Hyperthyroidism Iodine Induced

Excess iodine indirect
Exposure to radiographic contrast media
Medication
Excess iodine increases synthesis and release of thyroid hormone in iodine
deficient and older patients with pre-existing goiters
7. Amiodarone Induced Thyroiditis

Up to 12% of patients, especially in iodine deficient cases

Most common cause of iodine excess in US.

Two types:
*Type I - due to excess iodine Amiodarone contains 37% iodine.
*Type II occurs in normal thyroid
8. Thyroid Hormone Induced
Factitious hyperthyroidism in accidental or intentional ingestion to lose
weight
Tumors
- Metastatic thyroid cancer
- Ovarian tumor that produces thyriod hormone (struma ovarii)
- Trophoblastic tumor/ molar pregnancy/ chorio carcinoma
- TSH secreting tumor

MORBUS GRAVES

Most common cause in Ireland

Diffuse Goitre
Hyperthyroidism

Ophthalmopathy

Dermopathy

Autoimmune, TSI.

Older
Usually less severe
May have subclinical
May have long history of goitre

Clinical signs

Laboratory tests

diffuse goitre
eye signs

thyroid-stimulating
antibodies (TSAb)

localised
myxoedema
acropachy

thyroglobulin
antibodies (TgAb)
(anti-Tg Ab)

vitiligo
family history

microsomal
antibodies
(anti-M Ab)

Organ-Spesific Autoimmune Disease

chronic hepatitis
Hashimotos disease

hypoparathyroidism
(some forms)

myxoedema

diabetes mellitus
type 1 (some forms)

lymphocytic thyroidistis

Rheumatoid Arthritis

Graves disease

vitiligo

pernicious anaemia

premature ovarian
failure

Addisons disease

allergic alveolitis

Thyroid Hormone Excess Clinical Features

General
Heat intolerance, fatigue,
tremor.
Cardiovascular

Tachycardia, heart failure.

Gastrointestinal
Weight loss, diarrhoea
Ophthalmological
Lid lag, ophthalmopathy

Genitourinary
Amenorrhea, infertility.
Neuromuscular
Proximal muscle weakness
Psychiatric
Irritability, agitation, anxiety,
psychosis
Dermatological
Pruritus, hair thinning,
onycholysis, vitiligo.

Spesifik untuk penyakit Graves, ditambah :

Optalmopati (50%) udema pretibial, kemosis, proptosis, diplopia,
visus < ulkus kornea
Dermopati (0.5-4%)
Akropaki
(1%)

Eyes
Stare
Lid lag
Due to sympathetic over activity
Only Graves disease has ophthalmopathy
- Inflammation of extraocular muscles, connectivetissue
- This results in exopthalmos
- More common in smokers

Impaired eye muscle function (Diplopia)

Periorbital and conjunctival edema
Gritty feeling or pain in the eyes
Corneal ulceration due to lid lag and proptosis
Optic neuritis and even blindness

Lid retraction
Exopthalmos

Asymmetrical opthalmopathy
retroblubar tumor

Diagnosis

Diagnosis

Low TSH
Measure Free T4 Level

Normal

High
Hyperthyroidism

- Subclinical
hyperthyroidism

Thyroid uptake

- Resolving
Hyperthyroidism

Low

- Medication
- Pregnancy

Measure thyroglobulin

- New thyroid
illness decreased
Exogenous
hormone

High
DIffuse

Nodular

Increased Graves Multiple

One hot area
disease areas
Thyroiditis
Toxic
Iodide exposure
Toxic multinodular
adenoma
Exrtraglandular
goiter
production

Diagnosis klinis kecurigaan hipertiroidisme:

Indeks Wayne, Indeks New Castle
Diagnosis pasti dengan memeriksa :
kadar hormon beredar fT4, TSH
nilai tangkap yodium radioaktif leher ( )
etiologi : antibodi, ultrasonografi, scintigrafi
Membedakan morbus Graves dengan sebab lain
dengan menggunakan uji tangkap 1-131
Tinggi
Rendah
Morbus Graves
Masukan tiroksin berlebihan
Gondok Noduler toksik tunggal
medikamentosa, faktisia
Gondok Multinodulaer toksik
health food, hamburger mix
Thyroiditis Silent, Postpartum,
De Quervain, Ca infiltratif
Sebab lain : mola, struma ovarii. TSH
Secreting tumor, metasis Ca follic

Hyperthyroid Iodine uptake

A.

Normal
B. Graves Dz
C. Toxic Multinodular
D. Toxic Adenoma
E. Thyroiditis

Indeks diagnostik WAYNE hipertiroidisme

Gejala yang baru timbul
atau bertambah berat

Sesak bila bekerja

Berdebar debar
Kelelahan
Lebih suka udara panas
Lebih suka udara dingin
Tak dipengaruhi suhu
Keringat berlebihan
Keguguran
Nafsu makan bertambah
Nefasu makan kurang
Berat badan naik
Berat badan turun

Skor
ada
+1
+2
+2
+5
+3
+2
+3
+3

tidak

-5
-

-3
-3
-

Skor

Tanda tanda

Kelenjar tiroid teraba

Bisig klenjar tiroid
Exophtha;mos
Kelopak mata tertinggal
Gerakan hiperkinetik
Tremor halus jari
Tangan yang panas
Tangan yang basah
Fibrilasi atrium
Nadi teratur
- < 80 /menit
- 80-90 /menit
- > 90 /menit

ada

tidak

+3
+2
+2
+1
+4
+1
+2
+1
+4

-3
-2
-2
-2
-1
-3
0

0
+3

Hiper: >20, <10 tidak ada, 10-19 meragukan

Indeks diagnostik klinik NEW CASTLE

Item

Grade

Score

Item

Grade

Score

Age of onset

15-24
25-34
35-44

0
4
8

Age of onset

45-55
> 55

12
16

Psychological
precipitant

Present
Absent

-5
0

Exopthalmos

Present
Absent

9
0

Frequent checking

Present
Absent

-3
0

Lid retraction

Present
Absent

2
0

Severe anticipatory
anxiety

Present
Absent

-3
0

Hyperkinesia

Present
Absent

4
0

Increased appetite

Present
Absent

5
0

Fine finger tremor

Present
Absent

7
0

Goitre

Present
Absent

3
0

Pulse rate

> 90 / m

16

Thyroid bruit

Present
Absent

18
0

Pulse rate

80-90/m
< 80/m

8
0

Euthyroid : 11 to +23, doubtful :+ 24 to + 39, toxic +40 to +80

medical
Treatments available
For Graves disease

surgical
radioiodine

Indication for Medical

Treatment
patient preference
small goitre
mild disease
other disease
children
pregnancy
opthalmopathy
pre-operative
pre-radioiodine
thyrotoxic crisis
relapse after thyroidectomy

Antithyroid Drugs
carbimazole choice in Europe
methimazole
propylthiouracil (PTU)
potassium perchlorate
lithium
iodides
proppanolol
sodium ipodate

Dosis awal dan maintenance OAT yang sering digunakan

Obat

Dosis awal (mg)

Maintenance (mg)

Neomercazol

30-60

5-20 (10)

Methimazol

30-60

5-20 (10)

Propiltiourasil

200-600

50-200 (100)

Skema hormonogenesis dan efek pengobatan

MMI, PTU
release

I-

I+

T1

T3

T2

transpor Oxidative
iodination

Coupling

Rantai peptid tiroglobulin

operasi

SEL TIROID

T4
T3

T4
Li

PTU
propanlol
Na-ipodate
C.steroid

I131
T3

Sel somatik
Beta-blocker

Guna beta blockers pada hipertiroidisme

Telah terbukti pada:
pelengkap pengobatan OAT
pelengkap pengobatan radioiodine
pada krisis tiroid
selama dilakukan tes diagnostik

Kemungkinan penggunaan lain:

persiapan tiroidektomi
sebagai obat tunggal tirotoksikosis
sebagai obat tunggal pada kehamilan
pengobatan hiperkalsemia pada tirotoksikosis
pada hipertiroidi neonatal
- pengobatan /pencegahan thyrotoxic periodic paralysis

Metoda pemberia
A. Decremental cara tritasi, dosis makin menurun
sesuai dengan respons pasien
B. Block-suplemen .Obat diberi hingga ada supresi
kemudian diberi suplemen dosis fisiologis.
Cara ini tidak dianjurkan ada wanita hamil.

dan Ablasi,

Indications for surgical treatment

Absolute

Relative

1.suspicious of harboring malignancy

2.pregnant case uncontrolled with ATD/ allergy
3.wish to be pregnant soon after treatment
4.compressive symptoms, reject RAI exposure
1.poor compliance
2.rapid control is desired
3.patient with Graves opthalmopathy
4.larger/ goiter with low uptake

Indication for radioiodine therapy and associated complication.

Radioiodine is the most effective treatment in cases of recurrence after
surgery. It is suitable for older patients in severe disease, and when
patient cooperation is poor. Radioiodine is also useful in the presence of
other disorders. The only problematic complication is hypothyroidism,
which is relatively easy to control.

Indication for, and Complications of, Radioiodine Treatmen

Indications

Complications

patient preference

permanent hypothyroidism

patients over 45 years

transient hypothyroidism

treatment choice for recurrence after

thyroidectomy

thyroiditis

severe uncontrolled disease

sialadentis

large goitre

thyrotoxic crisis

poor patient cooperation

nodule formation

presence of other disease

malignancy (not proven)

Graves dan kehamilan

T4 ,T3 amat sedikit sedang TSAb dan PTU lewat plasenta
Hipotiroidisme fetus perlu dihindari
200 mg PTU masih tidak memberi dampak jelek
Deteksi hipotiroidisme fetus :
a. Nadi janin normal sekitar 120-150/m
b. >150 mungkin hiper dan < 120 mungkin hipotiroidi.
c. Dengan serial USG, melihat besar janin
d.Menentukan bone age

Trias krisis tiroid hipertermi, kesadaran turun, gejala

toksikosis meningkat
Check dengan indeks klinik Burch-Wartofsky
Medikal

Surgikal

Infeksi
Emboli paru
Ketoasidosis diabetik
Kelebihan hormon tiroid
Terapi dengan 1- 131
Iodium (obat. zat warna )
Stroke

Pembedahan tiroid
Operasi besar
Operasi minor
Ekstraksi gigi
Melahirkan
Dilatasi. kuretase

Thyroid storm is a rare presentation, occurs after stressful illness

in under treated or untreated patient.
Characteristics
-Delirium
-Dehydration
-Severe tachycardia
-Vomiting
-Fever
-Diarrhea

Indeks klinik krisis tiroid BURCH WARTOFSKY

Thermoregulatory dysfunction
Temperature 99-99.9 F
5
100-100.9
10
101-101.9
15
102-102.9
20
103-103,9
25
140
30
Central nervous system effects
Absent
0
Mild (agitation)
10
Moderate(delirium,psychosis,letargy 20
Severe (seizure, coma)
30
Gastrointestinal hepatic dysfunction
Absent
0
Moderate(diarrhea,vomit, abdpain)
Severe (unexplained jaundice)

10
20

Cardiovascular dysfunction
Tachycardia
99 109
110 119
120 - 129
130 - 139
140
Congestive heart failure
Absent
Mild (pedal edema)
Moderate ( bibasilar rales)
Severe (pulmonary edema)
Atrial fibrillation Absent
Present
Precipitant history
Negative
Positive

5
10
15
20
25
0
5
10
15
10

0
10

For severe thyrotoxicosis award the highest score, with intercurrent illness choose
which favor the diagnosis of thyroid storm . Score 45 highly suggestive, 25-44
suggestive impending and below 25 is unlikely to respresent thyroid storm. Note:
hyperthermia, consciousness, toxic signs

Prinsip pengobatan krisis tiroid

1.
2.
3.
4.
5.

Cairan dan oksigen

Menurunkan kadar hormon (sol Lugol, PTU)
Mengelola hipertermi jangan aspirin
Memberi corticosteroid
Inderal atau betablocker non spesifik lain

Outline

Latar Belakang
Pendekatan Struma
G AK I
Hipertiroid

Hipotiroid

Hypothyroidism
1. decrease function of thyroid gland
2. the effect of thyroid hormone in tissues

a. Central (secondary or tertiary)

b. Primary (thyroid gland itself)
Primary: (a) postoperative, (b) postradiation (c) autoimmune, (d)
postpartum thyroiditis (e) de Quervains, (f) dyshormonogenesis
(g) carcinoma thyroid, (h) transient and (i) pharmacologic drugs.

Hypothyroid cases as seen in Iodine

Deficiency Areas some belongs to
endemic cretinism

Characteristic feature of
a hypothyroid woman

Billewicz index for hypothyroidism

Clinical index
Yes(score)

No (score)

Symptoms

Sweat scarcely
Dry skin
Cold intolerance
Weight gain
Constipation
Husky voice
Tingling sensation
Hearing loss

+6
+3
+4
+1
+2
+4
+5
+2

-2
-6
-5
-1
-1
-6
-1
-1

Physical signs

Slow movement
Coarse skin
Cold skin
Periorbital oedema
Heart rate < 60 / minutes
Slow Achilles reflex

+11
+7
+3
+4
+4
+15

-3
-7
-2
-6
-4
-6

Hypotiroid> 25,No hypothyroid <-30, Equivocal between 29 and +24