Stikes Akbid tiroid

7/30/2019 Stikes Akbid tiroid

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T y r o i d

Dr. M a h a t m a SpPDSMF Penyakit Dalam FK UMS

SURAKARTAEAGLE FLIES ALONE, MHT


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The hypothalamic-hypophyseal-thyroid axis

Mind its feedback mechanism


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THIOCYANATES

(CYANOGENIC

GLYCOSIDES)

THIOGLYCOSIDES:

GOITRIN

ISOTHIOCYNATES

DISULFIDES

WATER BORNE

GOITROGENS

IODIDE(SEAWEEDS)

COAST GOITER

IODIDE

TRANSPORT

OXIDATIONORGANIC BINDING AND

COUPLING

PROTEOLYSISRELEASE AND

DEHALOGENATION

MITDIT

T4T3

MITDIT

I- I- (I )20

T4T3

I-

THYROGLOBULIN


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Schematic representation of timing of mature formative events in the human brain


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HORMON TIROID

HIPOFISIS

METABOLISMEPERTUMBUHAN

OTAK : - Kecerdasan

- Saraf

MASUKAN

IODIUM

PENGELUARAN

IODIUM

TSH


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PENDEKATANPENDERITA STRUMA


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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)


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Struma difusaToksik: 1. Graves, 2. Hashimoto

Gejala dan tanda klinik toksik

Indeks New Castle

Indeks Wayne

Non toksik(hipotiroidisme atau eutiroidisme)

Struma endemik

Hashimoto

Dishormonogenesis

Iatrogenik

OAT


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Goitre associated with autoimmunity

Most with Graves disease

80% have a diffuse goitre

TSH receptor autoantibodies

15% with Hashimoto disease

Majority have atropic hypothyroidismAccumulation of lymphocytes in the thyroid

gland


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Multi nodular goitre

More prevalence in elderly, female,genetic background

Scintigram most varied, follicle withscattered necrotic area, connectivetissue strands, cyst and evencalcifications

Only few nodules have a true adenoma


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Tanda khas keganasan tiroid

Tumbuh dengan cepat dan sakit Riwayat keluarga kanker tiroid Riwayat radiasi leher masa anak-anak Suara serak Keras Melekat sekitar Limpadenopati Paralisis pita suara


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Pemeriksaan penunjang

Sidik tiroid (Scintigrafi)

USG (ultrasonografi) Biopsi jarum halus (FNA)

Petanda tumor (marker)

Biokimiawi


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Sidik tiroid

Yodium radioaktif

Menilai fungsi dan anatomi Nodul dingin :penangkapan yodium kurang dari sekitarnya

Nodul hangatpenangkapan yodium sama dengan sekitarnya

Nodul panaspenangkapan yodium lebih banyak dari sekitarnya


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Hot, warm and cold spots

Scintigraphy with radioIodine, shows the function

of the respective gland


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Ultrasonografi

Padat atau cair

Tidak bisa menilai fungsiKista tiroid

Adenoma tiroid / nodul padatTiroiditis


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Biopsi aspirasi jarum halusJarum suntik no 22 27

Aman, tidak nyeri,dilakukan di poliklinik

Kista : guna untuk diagnostiksekaligus terapeutik


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Biokimiawi

Kadar Free T4 plasma (peranantiroglobulin)

Kadar TSHs plasmaTiroglobulin plasma CalsitoninAntibodi mikrosomal (TPO) Antibodi tiroglobulin (TGO)


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Subtotal Thyroidectomy.

Isthmus and majority of the oppositelobe

Indikasi

small

non-aggressive thyroid cancers

substernal goiters
http://www.endocrineweb.com/sternal.htmlhttp://www.endocrineweb.com/sternal.html


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Total Thyroidectomy.

Remove all of the thyroid gland.

Choice for all thyroid cancers


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IDD Global Magnitude (1996)

1. At least 1572 million were at risk of IDD

2. At least 655 million affected by goiter ( 27% SEA

15% Europe, 22% Western Pasific etc )

3. Est imated 43 m i l lion people affected by somedegree of IDD-related b rain damage

4. IDD is regarded as P.H. problem in 118 countries

5. IDD is the main cause of potential ly preventable

mental retardation .


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HORMON TIROID

HIPOFISIS

GONDOK METABOLISMEPERTUMBUHAN

OTAK : - Kecerdasan

- SarafKRETIN

HIPOTIROIDI

MASUKAN

IODIUM

PENGELUARAN

IODIUM

TSH


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Apakah GAKI itu ?

Gangguan Akibat Kekurangan Yodium /

Gondok endemik

Kekurangan yodium bukan hanya gondoksaja, namun ada efek yang lebih jauh

Gondok endemik : bukan hanya kekuranganyodium saja.

Misalnya ggn nutrisi, goitrogen, genetik


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Mengapa GAKI

dipermasalahkan ?

Gangguan yang ditimbulkannya sangat

banyak dan luas Jumlah penderita masih banyak

Penyakit ini sebenarnya

dapat dicegah


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Akibat GAKI

pada manusia ?

Yodium : bahan dasar mutlak hormon tiroksin

Tiroksin : pada masa pertumbuhan penting padaperkembangan fisik dan syaraf (otak) Penting saat masa fetus, masa kehamilan, masa

bayi, masa anak, masa remaja. Dampak kekurangan :

1. Kretin endemik2. Kretin neurologik


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Gambaran klinis kretinisme

A. Kretin endemik dan Kretin neurologik :Lahir di daerah kekurangan yodium, dngdua atau lebih dari :

1. Gangguan kecerdasan2. Tuli simetrik tipe sensorik3. Kelainan saraf (gangguan jalan,

gangguan bicara, refleks

patologik kelambatan jalan)B. Keduanya irreversibel, permanen, tidak

dapat diperbaiki dengan obat apapun.


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f DD


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Spectrum of IDD:


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SPEKTRUM GAKI

Fetus Anak dan remaja Abortus * Gondok Lahir mati * Hipotiroidisme juvenil Anomali kongenital * Ggn fungsi mental

Kematian perinatal * Ggn perkembangan fisik Kematian anak Kretin endemik Kretin miksedematosa Defek psikomotor

Neonatus Dewasa Gondok neonatus * Gondok dng akibatnya Hipotiroidisme neonatus * Hipotiroidisme

* Gangguan fungsi mental


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B h n b k


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Bahan bakuyodium manusia

Tanaman, air tanah yang mengandung yodium(kecuali terkikis)

Kebutuhan : 100-300 mikrogram sehari Harus cukup terus menerus sepanjang hidup

Makin berat kekurangannya, makin beratmanifestasi klinisnya

Tolok ukur :Kadar yodium urine

Kadar yodium dalam darahTangkapan radioaktif oleh leherJumlah klinik gondok di masyarakatJumlah kretin endemik di masyarakat


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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


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SURVEY EPIDEMIOLOGI

KRITERIA PEREZ, 1960Grade O : tidak teraba

Grade I : teraba dan terlihat dengankepala ditengadahkan

I a : tidak teraba / jika terabatidak lebih besar dari tiroidnormal

I b : jelas teraba dan membesar,umumnya tidak terlihat walau

kepala tengadahGrade II : mudah dilihat dengan posisi

biasaGrade III : terlihat dari jarak tertentu


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Wanita hipotiroidisme hamil

bagaimana ?

Harus mendapat terapi substitusitiroksin

Dipantau dengan TSH bukan denganFT4


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Apakah ada hubungan antaraberatnya endemik dengan

beratnya gangguan ?

Ya Makin berat endemik, makin tinggi

prevalensi gondok, makin banyakkretinisme

Mengingat : kretinisme adalah

irreversibel Maka : harus garam beryodium Alasan : kebutuhan sehari-hari

konsumsinya tertentu


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Pemberian garam beryodium akanmerubah apa saja ?

Prevalensi gondok menurun Komplikasi metabolik membaik Hipotiroidisme normal kembali Gangguan pendengaran berkurang Tidak lahir bayi kretin lagi Putus sekolah menurun Refleks abnormal anak menghilang Rekaman otak membaik Angka kematian bayi menurun Perbaikan gangguan kecerdasan


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Berapa lama diberikan garam

beryodium ?

Terus menerus,sepanjang hidup


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ENDEMIC CRETINISM

1. Epidemiological aspect iod ine defic iency2. Clinical aspects neurolog ical and myxedematous3. Pathologic aspects intrauter ine and irreversible


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Table.2. Symptomatologyof endemiccretinism from Sengi and Papua NewGuinea (in%)

Sengi Papua

A. Hearing loss 93 93.6

Deaf-mutism 12 79.9

B. Mental retardation 95 >90

C. Neuromotor abnormalities 76 79.9

Impaired speech 37 13.7Specific gait 46 ?

Elevated reflexes 29 40

Babinsky sign 5

Squint 2 25.5

Later walker 22

D. Clinical hypothyroidism 29 0

Short stature 29 10-50E. Goiter 70 10-50

____________________________________________________

Djokomoeljanto 1974, Pharoah 1972.


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Endemic cretinism

a.Neurological endemic cretinism

Mental retardation , deaf-mutism

Hearing lo ss bi lateral percept ive

spast ic diplegia, squ int etc

b. Myxedematous endemic cretinism

Dwarf ism , mental retardat ion,

hypothyro id ism


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HypothyroidismClinical hypothyroidism

29% in cretins

17% in n on cretinous

Biochemical hypothyroidism

41% in cretins

27% in n on cretinous


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Spectrum of Iodine Deficiency Disorders (I)

Fetus Abortions, Stillbirths, Congenital

abnormalities, Increased perinatal mor

tality, Increased infant mortality,

Neurologicalcret in ism:mental def, deaf

mutism, spastic diplegia, squintMyxedematouscret in ism: dwarfism ,

mental deficiency, hypothyroidism

Psychomotor defects

Neonate Neonatal goiter, Neonatal hypothyroidism

Increased susceptibility to nuclear radiation


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One mililiter of iodinated oil injection reversed thefate of the whole family


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Diagnosis: fungsi, anatomi, etiologi

Sinonim :morbus Basedow , morbus Parry

Pengertian :

a. hipertiroidisme

b. tirotoksikosis

MORBUS GRAVES

Causes of Hyperthyroidism


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Main causesGraves disease and variants

toxic multinodular goitre

toxic nodule

Rarer causesJod-Basedowdisseminated thyroid autonomythyroiditis:

de Quervains

silentfactitioushypothalamicpituitary:

with or without apituitary tumour

post-partum:probably variant

of silentmolar pregnancyChoriocarninoma


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Organ-Spesific Autoimmune Disease

chronic hepatitis

Hashimotos disease

myxoedema

lymphocytic thyroidistis

Graves disease

pernicious anaemia

Addisons disease

hypoparathyroidism(some forms)

diabetes mellitus (some

forms)

vitiligo

premature ovarian failure

allergic alveolitis

Table of the organ-spesific autoimmune diseases. All of these disorderss

are characterised by the presence of circulating antibodies and lymphocytic

infiltration of the gland or tissue


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Hipertiroidisme

Tirotoksikosis


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A COOH

TSH

TSHR antibody

B COOH

TSH and TSHR-Ab induced activation. Although similar conformational changes are

assumed to apply in these cases, the extent of similarity with whole and cleaved

receptor remains to be established (Graves 2000)


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pathogenesis of Graves Opthalmopathy

Mechanism of IGO protrusion and oedema with fibrous tissues


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Gejalah serta tanda hipertiroidisme pada penyakit Graves

Sistem Gejala dan tanda Sistem Gejala dan tanda

Umur tak tahan hawa panas Susunan saraf pusat labil, intitabelHiperkinesis, bapai, berat badan psikosis, tremor, nervo-

Menurun, percepatan pertumbuhan sitasperiodic paralysis

Drug tolerance, youthfullness (*)

Gastrointestin hiperdefekasi, kelaparan, makan Cardiorespirasi dyspnoea, hipertensi

Banyak, haus, muntah aritmi, palpitasi, gagal

jantung

Muskular rasa lemah Darah / limfatik limfositosis, anemia

Genitourinaria oligomenoroe, amenoroe Splenomegali

Libido menurun pembesaran l.n.leher

Kulit rambut rontok, berkeringat Skelet osteoporosis

Kulit basah, onycholysis epifisis cepat menutup

Nyeri tulang

Spesifik untuk penyakit Graves, ditambah :

Optalmopati (50%) udema pretibial, kemosis, proptosis, diplopia, visus < ulkus kornea

Dermopati (0.5-4%)Akropaki ( 1 % )

Sumber McDougall.1991. Huruf miring jarang * hampir khusus bagi Oriental.


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Classical and the many faces of Graves disease


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Classical and the many faces of Graves disease

Asymmetrical opthalmopathy DD: retroblubar tumor


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Asymmetrical opthalmopathy, DD: retroblubar tumor


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Lid retractionExopthalmos


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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)

Diagnosis of Graves Disease


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Diagnos is kl inis kecurigaanhipertiroidisme:

Indeks Wayne

Indeks New Castle

Diagnosis past idengan memeriksa :

kadar hormon beredar (T4, fT4, T3, fT3, TSH )

nilai tangkap yodium radioaktif leher ( )etiologi : antibodi, ultrasonografi, scintigrafi

I d k di tik kli ik WAYNE


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Indeks diagnostik klinik WAYNE

(eutiroidisme hipertiroidisme)

Gejala yang baru timbulatau bertambah berat

Skor Tanda tanda Skor

ada tidak ada tidak

Sesak bila bekerjaBerdebar debarKelelahanLebih suka udara panasLebih suka udara dinginTak dipengaruhi suhuKeringat berlebihanKeguguranNafsu makan bertambahNefasu makan kurangBerat badan naik

Berat badan turun

+1+2+2

+5-+3+2+3

+3

-5

-

-3-3

-

Kelenjar tiroid terabaBisig klenjar tiroidExophtha;mosKelopak mata tertinggalGerakan hiperkinetikTremor halus jariTangan yang panasTangan yang basahFibrilasi atriumNadi teratur- < 80 /menit

- 80-90 /menit- > 90 /menit

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

0+3

-3-2

-2

-2-1

-3

0

Wayne EJ. Brit Med J 1:78, 1960. Hiper: >20,


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Indeks diagnostik klinik NEW CASTLE

Item Grade Score Item Grade Score

Age of onset 15-2425-3435-44

048

Age of onset 45-55> 55

1216

Psychologicalprecipitant

PresentAbsent

-50

Exopthalmos PresentAbsent

90

Frequent checking Present

Absent

-3

0

Lid retraction Present

Absent

2

0Severe anticipatory

anxietyPresentAbsent

-30

Hyperkinesia PresentAbsent

40

Increased appetite PresentAbsent

50

Fine finger tremor PresentAbsent

70

Goitre Present

Absent

3

0

Pulse rate > 90 / m 16

Thyroid bruit PresentAbsent

180

Pulse rate 80-90/m< 80/m

80

Euthyroid range11 to +23, doubtful range + 24 TO + 39, toxic range +40 to +80.

Gurney, Owen, Hall et al. Lancet ii: 1275, 1970.


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Membedakan morbus Graves dengan sebab lain

dengan menggunakan uji tangkap 1-131

Tinggi Rendah

Morbus Graves Masukan tiroksin berlebihan

Gondok Noduler toksik tunggal medikamentosa, faktisiaGondok Multinodulaer toksik health food, hamburger mix

Thyroiditis Silent, Postpartum,

De Quervain, Ca infiltratif

Sebab lain : mola, struma ovarii. TSH

Secreting tumor, metasis Ca follic


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Treatments available

For Graves disease

medical

surgical

radioiodine

Methods of treating Graves disease. Graves disease may be

treated with antithyroid drugs, by partial thyroidectomy or by

means ofradioiodine


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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

methimazole

propylthiouracil (PTU)

potassium perchlorate

lithium

iodides

proppanolol

sodium ipodate

Indication for Medical Treatment in

Graves disease

Table of anthithyroid drugs.

Carbimazole is the drug of choice in Europe.Some clinicians add thyroxine to the

carbimazole in a blocking-replacement

regime, once the patient is clinically

euthyroid. Carbimazole is rapidly converted

to methimazole (10 mg carbimazole = 6 mg

methimazole)


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MMI, PTU

I- I+

transpor Oxidative

iodination

T1 T2

Coupling

T3 T4

release

I2

Li

Rantai peptid tiroglobulin

operasi SEL TIROID I131

T4

T3

PTUpropanlol

Na-ipodate

C.steroid

T3Sel somatik

Beta-blocker

Skema hormonogenesis dan efek pengobatan

M k i k j b t l ti id


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Mekanisme kerja obat golongan tionamide

INTRATIROIDAL

1. Menghambat yodinasi tiroglobulin dengan mencegah yodium

tiroksidasi dari residu tirosin

2. Menghambat reaksi coupling yodotirosin > yodotironin

3. Mengikat tiroglobulin dan merubah strukturnya (?)

4. Menghambat sintesis tiroglobulin (?)EXTRATIROIDAL

1. Menghambat konvesi T4 > T3 di perifer (hanya PTU)

2. Mempengaruhi sistem imun.

a. mengurangi respon limfosit in vitrob. mengurangi kadar titer autoantibodi tiroid

c. menormalkan aktifitas sel supresor

d. dapat langsung mengenai autoimunitas intratiroidal


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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


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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)


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Metoda pemberianA. Decrementalcara tritasi, dosis makin menurun

sesuai dengan respons pasien

B. Block-suplemen.Obat diberi hingga ada supresi dan

Ablasi, kemudian diberi suplemen dosis fisiologis.

Cara ini tidak dianjurkan ada wanita hamil.


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Indications for surgical treatment

Abso lu te 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

Relative 1.poor compliance

2.rapid control is desired

3.patient with Graves opthalmopathy

4.larger/ goiter with low uptake


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Indication for, and Complications of, Radioiodine Treatmen

Indications

patient preference

patients over 45 years

treatment choice for recurrence afterthyroidectomy

severe uncontrolled disease

large goitre

poor patient cooperation

presence of other disease

Complications

permanent hypothyroidism

transient hypothyroidism

thyroiditis

sialadentis

thyrotoxic crisis

nodule formation

malignancy (not proven)

Indication for radioiodine therapy and associated complication. Radioiodine is the mosteffective 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.


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- high relapse rate

- longterm treatment with

tight control by doctor

- surgical expertise

necessary

- morbidity exist

- 40% hypothyroid within

10y

- slow clinical action

- 50% hypothyroids post-

radiation

Possibility to obtain

remission in the long run

without hypothyroidsm

- substantial number of

cases remit (euthyroid)

- relatively quick and

simple- relapse is relatively

scarce

- simple- rarely relapse (depends

on the dose)

Anti Thyroid Drugs

Thyroidectomy

Radio Active Iodine ( I131)

DisadvantagesAdvantagesMode of treatment

Advantages and disadvantages of treatment

modalities in Graves disease


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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 janind.Menentukan bone age


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Trias krisis tiroid hipertermi, kesadaran turun, gejala

toksikosis meningkatCheck dengan indeks klinik Burch-WartofskyTidak ada indikator kimiawi yang memadaiFaktor presipitas krisis tiroid

Medikal Surgikal

Infeksi Pembedahan tiroid

Emboli paru Operasi besar

Ketoasidosis diabetik Operasi minor

Kelebihan hormon tiroid Ekstraksi gigi

Terapi dengan 1- 131 MelahirkanIodium (obat. zat warna ) Dilatasi. kuretase

Strok


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Prinsip pengobatan krisis tiroid

1. Cairan dan oksigen

2. Menurunkan kadar hormon (sol Lugol, PTU)

3. Mengelola hipertermijangan asp ir in

4. Memberi corticosteroid

5. Inderal atau betablocker non spesifik lain


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Indeks klinik krisis tiroid BURCH WARTOFSKY

Thermoregulatory dysfunction

Temperature 99-99.9 F 5100-100.9 10

101-101.9 15

102-102.9 20103-103,9 25

140 30Central nervous system effects

Absent 0Mild (agitation) 10Moderate(delirium,psychosis,letargy 20Severe (seizure, coma) 30Gastrointestinal hepatic dysfunctionAbsent 0Moderate(diarrhea,vomit, abdpain) 10

Severe (unexplained jaundice) 20

Cardiovascular dysfunction

Tachycardia 99 109 5110 119 10120 - 129 15130 - 139 20

140 25Congestive heart failureAbsent 0

Mild (pedal edema) 5Moderate ( bibasilar rales) 10Severe (pulmonary edema) 15Atrial fibrillation Absent 0

Present 10Precipitant historyNegative 0Positive 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 impendingand below 25 is

unlikely to respresent thyroid storm. Note: hyperthermia, consciousness, toxic signs

Burch HB, Wartofsky L., Endocrinol Metab Clin North Am, 22 : 263, 1993

Hypothyroidism


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yp y

1. decrease function of thyroid gland2. 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.


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Hypothyroid cases as seen in IodineDeficiency Areas some belongs toendemic cretinism


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Characteristic feature of a hypothyroid woman


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Billewicz index (1969) for hypothyroidism


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Clinical index for hypothyroidism

Yes(score) No (score)

Symptoms Sweat scarcelyDry skin

Cold ntolerance

Weight gain

ConstipationHusky voice

Tingling sensation

Hearing loss

+6

+3

+4

+1

+2+4

+5

+2

-2

-6

-5

-1

-1-6

-1

-1

Physical signs Slow movementCoarse 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, Not hypothyroid < - 30, Equivocal between

29 and +24


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Stikes Akbid tiroid