HYPOTHYROIDISM :

ETIOLOGY,
PATHOPHYSIOLOGY AND
TREATMENT
Dr. I Gede palgunadi, SpPD
SMF Penyakit Dalam
Rumah Sakit Umum Mataram
1

Introduction
The hypothalamic-hypohyseal-thyroid axis

INTRODUCTION
Hypothyroidism
Clinical syndrome ~ TH deficiency
metabolic process
Accumulation of glycosaminoglycans
Myxedema (adult), cretin (new born)
Myxedema coma (severe)
3

INTRODUCTION
Hypothyroidism
Primary, secondary, tertiary and peripheral
resistance to TH
Most common : Primary Hypo
In iodine deficient areas : IDD
In iodine sufficient areas : Hashimoto
(Chronic Autoimmune Thyroiditis)
4

ETIOLOGIC CLASSIFICATION
I. Primary Hypothyroidism
Destruction of thyroid tissue

A.
1.
2.
3.
4.

Thyroiditis (chronic autoimmune thyroiditis, subacute

thyroiditis, postpartum thyroiditis)
I131 therapy, external radiation (neck)
Thyroidectomy : subtotal, total
Infiltrative

Defect in TH biosynthesis

B.
1.
2.
3.
4.

Iodine deficiencies
Thyroid gland agenesis / dysgenesis
Hereditary defects in TH biosynthesis
Drugs with Antithyroid effect
5

ETIOLOGIC CLASSIFICATION
II. Central Hypothyroidism
A.

B.

Thyrotropin deficiency pituitary diseases

(Secondary Hypo)
Thyrotropin Releasing Hormone Deficiency
Hypothalamic Disorders (Tertiary Hypo)

III. Generalized Resistance to

Thyroid Hormone (GRTH)
6

PATHOPHYSIOLOGY
Normal :

T4 , T3 , T4 T3 (peripher)
T4 : 100 125 mcg/day

Sub Clinical : small in T4 (but still in N range) :

adequate source of T3 symptom (-)
stimulating TSH secretion
hyperplasia, hypertrophy
T4 & T3 still Normal, TSH , symptoms (-)
Overt Hypo : frank in T4 :
T3 symptom (+)
TSH
T4 & T3 , TSH , symptoms (+)
7

PATOPHYSIOLOGY
T3

metabolic process
Hypothermic, hypercholesterolemia
Accumulation of glycosaminoglycans
Edema : skin, muscles
heart muscle contractility,
Cardiomegaly, pericardial effusion,
Stroke volume / COP
Reproduction :
Anovulation, irregular cycles,
infertility
8

THYROID

rT3
T3

T4

T4

T4

T4

TR
T3

rT3
T3

T4

TR

MATERNAL
TISSUES

MOTHER

T3

TR

PLACENTA

T3

TR

FETUS

Possible sites of action of maternal thyroid hormone during early pregnancy.

(Pickard et al, 2002)

Iodine is the essential element for thyroid hormones, thyroid hormone is

indispensable for every living cells, thyroid hormone is a must for DNA
synthesis

Fatal circulation

Maternal circulation

THYROID
Pituitary/Chorionic TSH controlled
T4 synthesis and release

T4

FETUS

Chorionic
TSH

T4 deiodination
and metabolism

T4

free T4

free T4

TBG bound T4

TBG
LIVER
Estrogen/fT4 controlled
TBG synthesis
and release

Estrogen

Feedback control
of T4 delivery

PLACENTA
TBG/T4 controlled
T4 deiodination and transport,
and chorionic TSH secretion

Hypothetical control system governing fetal exposure to

maternal T4 during pregnancy
10

DIAGNOSIS
Importance of Etiologic Diagnosis
1. The hypo may be transient
2. The hypo may be reversible by
alleviating responsible drugs
3. The hypo may be the first and the only
manifestation of hypothalamopituitary disorders
11

DIAGNOSIS
I. CLINICAL SUSPICION
1. Symptoms, signs, Lab.
2. Deficiencies, exposures, diseases
3. Diseases ~ chronic autoim. thyroiditis

II. CONFIRMATIVE EXAM

1. T4 (FT4) , Normal FT4 : 0.8-2.8 ng/dl
2. TSH (Primary Hypo), Normal : 0.4-4 mu/l
12

Severe primary hypothyroidism

A: A patient with unrecognised severe primary hypothyroidism who became severely obtunded after surgery
for fractured neck of femur. Marked myxoedema is evident. B: Several months later, after therapy including
thyroid hormone replacement.
13

DIAGNOSIS
SUSPICION
SYMPTOMS

SIGNS

LAB, ETC

Weakness, fatique,
Cold intolerance,
Weight , constip.,
Hoarseness,
Menorraghia,
Depression

Dry skin
Bradycardia
Prolonged relaxation time of tendon
reflex

Hypercholest.
Hyponatremia
Pericard Effusion
Myocardial
contractility
14

CLINICAL SUSPICION
T4 (FT4), TSH
T4 , TSH

T4 N, TSH

T4 , TSH

T4 N, TSH N

Primary hypo

Sub clinical
hypo

Central hypo

Normal

TRH Test
T4 , TSH

T4 , TSH

Resp. (-)

Primary hypo

Tertiary
hypo

Secondary
hypo

Figure 1. Algorithm Diagnosis of Hypothyroidism

15

DIAGNOSIS
I. IODINE DEFICIENCY
1. Radioactive iodine uptake
2. Urinary iodine excretion
3. TSH

II. CHRONIC AUTOIMMUNE

THYROIDITIS
1. T4 , TSH
2. Autoantibody anti TPO
3. Autoantibody anti TG

16

DIAGNOSIS

Increased TSH in some central Hypo ~

Immunoreactive (but bioinactive) TSH

Decreased TSH, T4, T3 in severe

non thyroidal illness

17

TREATMENT
Lifelong levothyroxine (T4) except in :
transient Hypo
reversible Hypo
Goal : Clinical euthyroidism, Normal T4 and TSH
Levothyroxine :
- Half life 7 days once daily dosage
- dosage :
- Substitution (adult) : 1.6 mcg/BW/day
x 100 mcg/day (range 50-200 mcg/day)
Evaluation / Adjustment : T4 & TSH 3-6 wkly
18

TREATMENT
DOSAGE VARIATION
Lower

: Hashimoto, post radioiodine

High

: Total thyroidectomi, central hypo,

severe hypo, BW, pregnancy,
estrogen therapy, malabsorption,
excretion (nephrotic syndrome),
metabolism

Small initial dose : increase gradually : elderly

19

TREATMENT
PREGNANCY
Higher dose due to :
1.
2.
3.
4.
5.

maternal clearance of T4
T4 transfer to fetus
Placental degradation of T4 (deiodinase)
TBG ~ estrogen
absorption ~ Fe, Calcium
20

TREATMENT
ELDERLY / CAD

- Initial dose :
- Elderly : 50 mcg/day orally
- CAD : 25 mcg/day orally
- Increase by 25 mcg/day every 3-6 weeks until
normal TSH or arrhytmia
21

TREATMENT
SUBCLINICAL HYPO

- T4 to prevent conversion to overt hypo

- Especially :
- TSH > 10 mu/L
- anti TPO
- Goiter or non specific symptoms
22

TREATMENT
CENTRAL HYPO

- Deficiency of other trophic hormone ?

- ACTH defic Adrenal insuff

- T4 : + Glucocorticoid to prevent adrenal crisis

23

TREATMENT
POST TOTAL THYROIDECTOMY
- Higher dose T4 for :
1. Substitution
2. Erradicate metastasis / prevent relaps
- Target : TSH < 0,01 mU/L
24

TREATMENT
MYXEDEMA COMA
- Aggressive, dose, IV T4
- After blood sample (T4, TSH, Cortisol)
- IV T4 : 200-300 mcg 50-100 mcg/day
(+ IV T3: 5-20 mcg 2,5-10 mcg/8 hours
- IV Hydrocortisone 100 mg/8 hr (2 days)
decreased
- Supportive :
- Mech. Ventilation, O2
- IVFD
- Correct : Hypo Na, Hypothermia
- Antibiotics
25

.for the children..

Every child has the right to an adequate supply of iodine
to ensure his (or her) normal developments.

..for the unborn child..

Every mother has the right to an adequate iodine nutrition
to ensure her unborn child experiences normal mental
development

Declarations from:
Convention on the Rights of the Child, UN Assembly, New York 1989, World Summit for Children, UN New York
1990, The Survival, Protection and Development of Children , World Conference on Micronutrients: Eliminating
the Hidden Hunger, Montreal 1991 (Unicef, FAO,WHO, ICCIDD), World Conference on Nutrition, Rome 1992
WHO, FAO
26

SUMMARY
Hypothyroidism ~ TH deficiency ~HypothalamoPituitary-Thyroid Axis Disorders
Most common etiology : Primary Hypo
Iodine deficiency, Hashimoto thyroiditis
Patophysiology : metabolic process and glycosaminoglycans accumulation
Diagnosis
Therapy
Prognosis

: Clinical + T4 + TSH
: Levothyroxine (T4)
: reversible (T4)
poor in myxedema coma
27

Hipertiroid = Thyrotoxicosis

Batasan
Merupakan keadaan/perubahan2 fisiologis dan
biokemis yang kompleks dari jaringan, sebagai
akibat kenaikan kadar hormon tiroid dalam
sirkulasi

Insidens
Lebih serig pada wanita dibanding pria (8:1) sering
pada dekade ke-3 dan 4
Pembagian :
- Disfus toxic goiter = morbus
basedow =
Penyakit Graves =
penyakit Parry
- Toxic adrenoma = Single toxic noduler
- Multinodular toxic goiter
- Toxic ectopic goiter

Penyebab

Mula-mula diduga oleh karena produksi TSH yang

berlebihan oleh kelenjarhipofisis anterior. Ternyata teori
ini tdk seluruhnya benar
Autonum hyperfunction dari kelenjar gondok itu
sendiri
Long Acting Thyroid Stimulator (LATS) : efek thd
kelenjar gondok hampir sama dgn TSH, ttp jauh lbh
lama.
Thyroid Stimulating Immunoglobulin (TSI) : proses
auto immune.

Gejala klinis hipertiroid tergantung pada

Umur penderita
- muda : nervositas yang lebih
menonjol
- Tua : kardiovaskular yang lebih menonjol
2. Ada / tidaknya kelainan organ-organ
lain sebelumnya
1.

Gejala-gejalanya antara lain

Tremor halus (terutama jari-jari dan lidah)

Nervous
Goiter
Emotional irritability mudah tersinggung
Von Mullers Paradoxx (makan banyak tetapi badan
tambah kurus)
Tak tahan udara panas
Kulit banyak berkeringat dan hangat

Palpasi (Berdebar-debar) sinus takikardi, Atrial Fibrilasi dan

kadang2 decompensasi cordis
Rambut jarang, halus, dan mudah rontok
Hiperdefekasi (sehari BAB beberapa kali)
Lekas lelah (terutama otot2 paha)

3. Dernopati
4. Gejala pada mata :
* Ok sympathetic over stimulation (spatis) :
a. Mobius sign
: sukar mengadakan
konvergensi
b. Von Graves sign : Sclera antara limbus &
kelompok mata bag.
Atas terlihat
c. Joffreys sign
: dahi tak dapat berkerut
d. Tellwags sign : mata jarang berkedip
e. Lid Lag
: Palpebra superior tertinggal
waktu melirik kebawah
f. Ok. Faktor mekanis : pendesakan retro orbital

g. Exofthalmus dan gejala akibatnya :

- Konjungtivitis
- Ulkus koma
- Palpebra bengkak
- Optic neuritis
- Optic atropi

Pemeriksaan laboratorium

BMR jarang dipakai lagi

I131 uptake yang meningkat : > 60% /24 jam
Thyroid scaning = sidikin kelenjar tiroid hot nodule
Kadar kolesterol yang rendah (kurang dan 160 mg%)
T3 dan T4 serum yang meningkat, FT4 meningkat; TSH5 :
menurun
Uric acid sering menurun
Tes Toleransi Glukosa Oral kadang2 terganggu
X-foto dada dan leher : mencari adanya struma aberrant
Dari pemeriksaan laboratorium tsb FT4 dan TSH5 yg
terpenting untuk mendiagnosis hyperthyroid

Diagnosis Pasti : TSHs : Bila tak dapat menentukan

TSHs, dpt ggn indeks WAYNE/NEW CASTLE

Goiter
Tanda2 pd mata
Von Mulers paradox
Kulit basah & hangat
Tremor halus pd tangan, kelopak mata (bila ditutup)
Takikardi/aritmia
Defecative yg sering

Pengobatan
1.

2.
3.

Konservatif = dengan obat-obatan

Pembedahan = subtotal thyroidectomy
Radioaktif
= I131

Konservatif

Obat2 yg menekan produksi hormon tiroid :

Obat2 yg menekan pengaruh symphatetic over

stimulations

P.T.U. = Prophylthiouracil dosis 200-600 mg/hr

Mthimazole (mis. Neomercazole) dosis 1/10-nya PTU

Beta-blocker-propanolol
Sedativa/minor tranquilizer

Roborantia : multivitamin dengan mineral

Diet TKTP

Pembedahan
Indikasi
1. Relaps
2. Struma yg besar
3. Tak dpt diobati secara konservatif
4. Evaluasi pengobatan konservatif sukar
5. Kosmetik

Penyulit

Akut :
- Penyulit pembiusan
- Perdarahan
- Paralysa
- Thyroid crisis
2. Kronis :
- Infeksi
- Hipoparatiroidi
- Hipotiroidi
- Relaps

Radioaktif memakai Iodium -131(I131)

Indikasi
- Umur tua
- Menolak pembedahan
- Karena kondisinya tak dapat dibedah

Pengobatan exopthalmus
Bila ada exopthalmus :
- Hindari iritasi pada corne (+ salep
mata)
- Kalau perlu, kortikosteroid lokal dan
per oral

Krisis Tiroid = Thyroid Storm

Adalah keadaan gawat yg terjadi jika gejala2

hipertiroidi mendadak meningkat dgn hebat.
Dapat terjadi pada penderita yg tak terkontrol
dgn baik dan ada faktor-faktor penctusnya,
seperti infeksi dan trauma (fisik/psikis)

Gejala
1.
2.
3.

4.
5.
6.
7.
8.

Semua gejala hypertiroidi tampak dalam gradasi

yg lebih hebat/berat
Fibris tinggi (=hyperpyrexia)
Muntah-muntah diarrhea, sakit perut
Tachycardia, aritmia, Atrial, Fibrilasi hingga
ventricular fibrilasi
Bendungan paru dan dekompensasi kordis
kengestif
Hipotensi
Delirium
Koma

Pengobatan
Harus segera, tanpa menunggu hasil
Laboratorium :
1. Pemberian cairan dan kalori
2. Menekan hormon tiroid dengan PTU 200 mg600 mg/4 jam atau methimazole 20 mg/jam

Menekan pengaruh Sympathetic over

stimulation dengan

Beta-blocker (propranolol) IV 2 mg dan per oral 10-40

mg/6-8 jam
Febris diturunkan (dgn obat dan kompres dingin)
Larutan Kj jenuh 5 tetes tiap 4 jam lewat sonde
Hidrokortison : 100-300 mg/hr
Bila ada kelemahan jantung dan kandungan paru,
diberikan digitalis dan diuretika
Hilangkan faktor-faktor pencetus

Biasanya bila pengobatan berhasil, dalam waktu

1-2 hari sudah terjadi perbaikan dan sembuh pd
hari ke-7
Angka kematian (dengan pengobatan yg baik)
masih 20 %

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