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T y r oi d

Dr. M a h a t m a SpPD
Fak.Kedokteran UMS
SURAKARTA
Outline
 Pendahuluan
 Pendekatan Struma
GAKI
 Hipertiroid
 Hipotiroid
Anatomi / histology
The hypothalamic-hypophyseal-thyroid axis
Mind its feedback mechanism
Biokimia produksi hormon tiroid
F i s i o l o g i
HIPOFISIS
TSH

MASUKAN PENGELUARAN
IODIUM IODIUM

HORMON TIROID : T3 dan T4

1. METABOLISME
2. PERTUMBUHAN OTAK :
- Kecerdasan
- Saraf
Fisiologis : Schematic timing of mature in the human brain
F i s i o l o g i
Process Examples of Physiological Actions
 Increased basal metabolic rate (BMR)

Thyroid hormone  Stimulate lipolysis/lipogenesis


action  Increase in adaptive thermogenesis
 Stimulate β-oxidation of fatty acids
 TSH measurement for the diagnosis of thyroid disease
Central regulation
 And to monitor treatment
of TRH/TSH
 Central adaptation to fasting, illness, and obesity
 TSH/T4 set point
Local ligand activation
 T4/T3 replacement therapy of hypothyroidism
by D2
 Stimulates adaptive thermogenesis
 Reduces body fat
Thermogenesis and
 Increases β-oxidation of fatty acids
body weight
 Stimulates adaptive thermogenesis
 Reduces serum cholesterol
Cholesterol and triglycerides  Reduces serum triglycerides
 Reduces hepatic steatosis
 Stimulates gluconeogenesis
Carbohydrate
 Reduces insulin sensitivity
metabolism
 Increase in insulin metabolism
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.
Outline
 Pendahuluan

 Pendekatan Struma
 GAKI
 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 :
Adenoma, Plummer disease, Carcinoma
- Struma Diffusa simple non toksik :
- Struma Diffusa simple toksik
- Struma Diffusa multiple non toksik :
Hashimoto, Dishormogenesis, Iatrogenik, OAT
- Struma Diffusa multiple toksik :
Goiter disease
14
Anamnesis Dx fisik
 Sejak kapan  Morfologi
 Nyeri spontan/ tidak Nodosa : multi/tunggal
 Nyeri berpindah  Difusa
 Membesar cepat / lambat  Nyeri
 Keluarga  Keras, kenyal, kistik, berbenjol
 Radioterapi  Melekat dengan sekitar
 Perubahan suara  Pendorongan trakea
 Tanda toksik  Pemberton’s 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
jarum halus
( F N A )
 Padat atau cair  Jarum suntik no 22 –
 Tidak bisa menilai 27
fungsi  Aman, tidak nyeri,
 Kista tiroid dilakukan di poliklinik
 Adenoma tiroid /  Kista : guna untuk
nodul padat diagnostik sekaligus
 Tiroiditis terapeutik
Biokimiawi
 Kadar Free T4 plasma
(peranan tiroglobulin)
 Kadar TSHs plasma
 Tiroglobulin plasma
 Calsitonin
low TSH high  Antibodi mikrosomal (TPO)
nml  Antibodi tiroglobulin (TGO)
Free T4 ? Secondary Free T4
(central) dz high

low high low nml


nml 2o Hyperthyroid
Or Thyroid hormone resistance
1o Hypothyroid

2o Hypothyroid Subclinical
Subclinical 1o Hyperthyroid
Hyperthyroid Hypothyroid

RAIU None
diffuse
focal
Serum Thyroglobulin
homogeneous heterogeneous low high
Functioning
Adenoma
Grave’s Dz Toxic multinodular goiter Thyrotoxicosis factitia Thyroiditis
Iodine load Struma ovarii
Outline
 Latar Belakang
 Pendekatan Struma

 GAKI
 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

MASUKAN PENGELUARAN
IODIUM IODIUM

HORMON TIROID

GONDOK
METABOLISME
HIPOTIROID PERTUMBUHAN
OTAK : - Kecerdasan
- Saraf
CRETINE
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 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
SURVEY EPIDEMIOLOGI
KRITERIA PEREZ, 1960
Grade O : tidak teraba
Grade I : teraba dan terlihat dengan kepala ditengadahkan
I a : tidak teraba / jika teraba
tidak lebih besar dari tiroid normal
I b : jelas teraba dan membesar,
tidak terlihat walau kepala tengadah
Grade II : mudah dilihat dengan posisi biasa
Grade III : 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
 GAKI

 Hipertiroid
 Hipotiroid
Etiology
1 Grave’s 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 Clinical signs Laboratory tests
• Diffuse Goitre
• Hyperthyroidism diffuse goitre
• Ophthalmopathy
eye signs thyroid-stimulating
• Dermopathy
antibodies (TSAb)
• Autoimmune, TSI.
localised
 Older myxoedema
Usually less severe
acropachy thyroglobulin
May have subclinical antibodies (TgAb)
 May have long history of goitre (anti-Tg Ab)
vitiligo

family history microsomal


antibodies
(anti-M Ab)
Organ-Spesific Autoimmune Disease

chronic hepatitis hypoparathyroidism


(some forms)
Hashimoto’s disease
diabetes mellitus
myxoedema type 1 (some forms)

lymphocytic thyroidistis Rheumatoid Arthritis

vitiligo
Graves’ disease
premature ovarian
pernicious anaemia
failure
Addison’s disease
allergic alveolitis
Thyroid Hormone Excess Clinical Features
 General  Genitourinary
– Heat intolerance, fatigue, – Amenorrhea, infertility.
tremor.
 Neuromuscular
 Cardiovascular
– Proximal muscle weakness
– Tachycardia, heart failure.  Psychiatric
 Gastrointestinal – Irritability, agitation, anxiety,
– Weight loss, diarrhoea psychosis
 Ophthalmological  Dermatological
– Lid lag, ophthalmopathy – 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 Grave’s 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  Asymmetrical opthalmopathy
Exopthalmos retroblubar tumor
Diagnosis Low TSH Diagnosis
Measure Free T4 Level

Normal High

- Subclinical Hyperthyroidism
hyperthyroidism Thyroid uptake
- Resolving
Hyperthyroidism
Low High
- Medication
- Pregnancy Measure thyroglobulin
DIffuse Nodular
- New thyroid
illness decreased Increased Graves Multiple One “hot” area
disease areas
Thyroiditis Toxic
Exogenous Iodide exposure Toxic multinodular adenoma
hormone 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 Skor Tanda – tanda Skor
atau bertambah berat
ada tidak ada tidak

Sesak bila bekerja +1 Kelenjar tiroid teraba +3 -3


Berdebar debar +2 Bising klenjar tiroid +2 -2
Kelelahan +2 Exophtha;mos +2
Lebih suka udara panas -5 Kelopak mata tertinggal +1 -2
Lebih suka udara dingin +5 Gerakan hiperkinetik +4
Tak dipengaruhi suhu - - Tremor halus jari +1 -2
-1
Keringat berlebihan +3 Tangan yang ‘panas’ +2
Keguguran +2 Tangan yang ‘basah’ +1
Nafsu makan bertambah +3 Fibrilasi atrium +4 -3
Nefasu makan kurang -3 Nadi teratur 0
Berat badan naik -3 - < 80 /menit
Berat badan turun +3 - - 80-90 /menit 0
- > 90 /menit +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 0 Age of onset 45-55 12
25-34 4 > 55 16
35-44 8
Psychological Present -5 Exopthalmos Present 9
precipitant Absent 0 Absent 0
Frequent checking Present -3 Lid retraction Present 2
Absent 0 Absent 0
Severe anticipatory Present -3 Hyperkinesia Present 4
anxiety Absent 0 Absent 0
Increased appetite Present 5 Fine finger tremor Present 7
Absent 0 Absent 0
Goitre Present 3 Pulse rate > 90 / m 16
Absent 0
Thyroid bruit Present 18 Pulse rate 80-90/m 8
Absent 0 < 80/m 0

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


medical

Treatments available
surgical
For Graves’ disease

radioiodine
Indication for Medical
Treatment Antithyroid Drugs

patient preference carbimazole choice in Europe


small goitre methimazole
mild disease propylthiouracil (PTU)
other disease potassium perchlorate
children lithium
pregnancy iodides
opthalmopathy proppanolol
pre-operative sodium ipodate
pre-radioiodine
thyrotoxic crisis
relapse after thyroidectomy

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 T2 T3 T4 T4
T3
transpor Oxidative Coupling
iodination
Li
PTU
propanlol
Rantai peptid tiroglobulin Na-ipodate
C.steroid
operasi SEL TIROID 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 dan Ablasi,
kemudian diberi suplemen dosis fisiologis.
Cara ini tidak dianjurkan ada wanita hamil.

Indications for surgical treatment


Absolute 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
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 thyroiditis


thyroidectomy

severe uncontrolled disease sialadentis

large goitre thyrotoxic crisis

poor patient cooperation nodule formation

presence of other disease malignancy (not proven)


Advantages and disadvantages of treatment
modalities in Graves’ disease

Mode of treatment Advantages Disadvantages

Anti Thyroid Drugs Possibility to obtain - high relapse rate


remission in the long run - longterm treatment with
without hypothyroidsm tight control by doctor

Thyroidectomy - substantial number of - surgical expertise


cases remit (euthyroid) necessary
- relatively quick and - morbidity exist
‘simple’ - 40% hypothyroid within
- relapse is relatively 10y
scarce

Radio Active Iodine ( I131) - ‘simple’ - slow clinical action


- rarely relapse (depends - 50% hypothyroids post-
on the dose) radiation
Graves dan kehamilan
T4 ,T3 , TSAb 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 hipertiroid , < 120 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 Pembedahan tiroid


Emboli paru Operasi besar
Ketoasidosis diabetik Operasi minor
Kelebihan hormon tiroid Ekstraksi gigi
Terapi dengan 1- 131 Melahirkan
Iodium (obat. zat warna ) Dilatasi. kuretase
Stroke
 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 Cardiovascular dysfunction
Temperature 99-99.9 F 5 Tachycardia 99 – 109 5
100-100.9 10 110 – 119 10
101-101.9 15 120 - 129 15
102-102.9 20 130 - 139 20
103-103,9 25 ≥ 140 25
≥ 140 30 Congestive heart failure
Central nervous system effects Absent 0
Absent 0 Mild (pedal edema) 5
Mild (agitation) 10 Moderate ( bibasilar rales) 10
Moderate(delirium,psychosis,letargy 20 Severe (pulmonary edema) 15
Severe (seizure, coma) 30 Atrial fibrillation Absent 0
Gastrointestinal hepatic dysfunction Present 10
Absent 0 Precipitant history
Moderate(diarrhea,vomit, abdpain) 10 Negative 0
Severe (unexplained jaundice) 20 Positive 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. Cairan dan oksigen
2. Menurunkan kadar hormon (sol Lugol, PTU)
3. Mengelola hipertermi jangan aspirin
4. Memberi corticosteroid
5. Inderal atau betablocker non spesifik lain
Outline
 Latar Belakang
 Pendekatan Struma
 GAKI
 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 +6 -2


Dry skin +3 -6
Cold intolerance +4 -5
Weight gain +1 -1
Constipation +2 -1
Husky voice +4 -6
Tingling sensation +5 -1
Hearing loss +2 -1

Physical signs Slow movement +11 -3


Coarse skin +7 -7
Cold skin +3 -2
Periorbital oedema +4 -6
Heart rate < 60 / minutes +4 -4
Slow Achilles reflex +15 -6

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