KURIKULUM VITAE :

Nama : Dr. dr.Agus Yuwono, Sp.PD,KEMD,FINASIM

Tempat/tgl.Lahir :Tulung Agung, 13 Mei 1964
Riwayat Pendidikan :
1984 : SD- SMA Di Tulung Agung, JAWA TIMUR
1990 : Lulus Fakultas Kedokteran Universitas Brawijaya
2000 : Lulus Spesialis Penyakit Dalam FK UNDIP Semarang
2007 : Lulus SP2 (konsultan)Endokrinologis FK UNAIR
2012 : Lulus S3-BIOMEDIK FK UNIBRAW

PENGALAMAN ORGANISASI
Sekretaris Badan Perwakilan Mahasiswa FK Unibraw
Sekretaris Umum SEMA FK Unibraw
Ketua IDI Cab Kab Bengkulu Utara
Wakil Ketua I IDI CABANG Banjarmasin
Sekretaris PAPDI CAB.KALSELTENG
Kepala Devisi Endokrin dan Metabolik FK.UNLAM
Kepala Bagian Penyakit Dalam FK UNLAM/RSUD ULIN
 TATALAKSANA TERKINI
HIPERTIROIDISME

Dr.dr. Agus Yuwono, SP.PD, KEMD-FINASIM

BAGIAN/SMF ILMU PENYAKIT DALAM DEVISI ENDOKRIN METABOLIK

FK UNLAM/RSUD ULIN BANJARMASIN
 PENDAHULUAN
Tirotoksikosis merupakan manifestasi klinik
terkait jumlah hormon tiroid yang berlebihan.
Hipertiroidism peningkatan hormon yang
dihasilkan oleh kelenjar tiroid
Tiroiditis : Tirotoksikosis terkait inflamasi kelenjar
tiroid umumnya proses otoimun, pasca infeksi
virus.
Graves Disease (GD) merupakan penyakit
autoimun di mana thyrotropin receptor antibodies
(TRAbs) merangsang reseptor TSH, sehingga
meningkatkan produksi hormon tiroid.
EPIDEMIOLOGI
Di Amerika Serikat, prevalensi hipertiroidisme adalah sekitar
1,2% (0,5% overt dan 0,7% subklinis);
Penyebab paling umum termasuk Graves Disease (GD),
toxic multinodular goiter (TMNG), dan adenoma toksik (TA).
Penyebab tersering dari hipertiroidisme adalah penyakit
Graves (+ 80%)
Eropa prevalensi hipertiroidisme 1 - 2% dari semua
penduduk dewasa.
Hipertiroidisme lebih sering ditemukan pada wanita daripada
laki-laki dengan rasio 5 : 1
organ specific
autoimmune disease REMITTING AND RELAPSING
ILLNESS
anti TSH receptor Only 40 50% cases of
antibody ~ TSH agonist Graves hyperthyroidism will
Synonim : be in complete remission with
Exophthalmos goiter, toxic diffuse goiter, Basedow
disease, Parry disease, ATD.
Immunogenic hyperthyroidism, autoimmune
hyperthyroidism
 Disorders Associated with Thyrotoxicosis
Type of Thyrotoxicosis Pathogenic Mechanism
Thyrotoxicosis Associated with Hyperthyroidism (thyroid radioiodine uptake high)
States pf TSH Excess
Tumor Thyrotroph adenoma
Nontumor Thyrotroph resistance to T4
Abnormal Thyroid Autonomy
Graves disease TSH receptor antibody
Trophopblastic tumor Chorionic gonadotropin
Intrinsic Thyroid Autonomy
Toxic adenoma Benign tumor
Toxic multinodular goiter Foci of functional autonomy
Thyroid cancer Foci of functional autonomy

Thyrotoxicosis Not Associated with Hyperthyroidism (thyroid radioiodine uptake low)

Inflammatory Disease
Silent thyroiditis Release of preformed hormone
Subacute thyroiditis Release of preformed hormone
Extrathyroidal Source of Hormone
Exogenous hormone use Hormone in medication or food
Ectopic thyroid tissue Dermoid tumor (struma ovarii)

(Source : Braverman and Utiger, 1991)

MANIFESTASI KLINIS
Sistem Saraf Manifestasi Kulit
Sistem Kardiovaskular Sistem Reproduksi
Sistem Sistem Metabolik
Muskuloskeletal Sistem Respiratorik
Sistem Kelenjar tiroid
Gastrointestinal
Mata
DIAGNOSIS
Anamnesis yang komperhensif
Pemeriksaan fisik : frekuensi nadi, napas, tekanan darah
dan berat badan.
Tambahan:
ukuran tiroid; nyeri tekan, simetrisitas, nodul;
fungsi pulmonal, kardial dan neuro-muskular;
periferal edema,
tanda-tanda kelainan mata
miksedema pretibial
INDEKS WAYNE
Treatment of Hyperthyroidism
 Which treatment is the
best ?
There is no best
treatment JAPAN ATD
Choice depends on several
factors :
Physicians experience
EUROPE

Patients preference
In some situation (e.g.,
in pregnant women, I-131
USA
elderly patients) the
choices are limited.
PENATALAKSANAAN
Guideline tentang tatalaksana tirotiksikosis dan
hipertiroid telah disusun oleh American Thyroid
Association (ATA) bekerja sama dengan
American Association of Clinical
Endocrinologists pada tahun 2011
Berisi 100 evidence-based recommendations
yang diberi tingkatan (grading) berdasarkan
suatu sistem epidemiologi dan uji kualitas bukti
(quality of evidence).
 PENANGANAN DAN EVALUASI TIROTOKSIKOSIS

Symptomatic management
Rekomendasi 2 Beta-adrenergic bloker harus diberikan pada pasien
orang tua dengan tirotoksikosis simptomatik dan pada pasien
tirotoksis dengan denyut nadi istirahat melebihi 90 x/menit atau bila
terdapat penyakit kardiovaskular. 1/++0
Rekomendasi 3 Beta-adrenergic bloker harus dipertimbangkan
pemberiannya pada pasien dengan tirotoksikosis simptomatik. 1/+00
SYMPTOMATIC MANAGEMENT
 PENANGANAN HIPERTIROIDISME YANG DISEBABKAN GD

Rekomendasi 4 Pasien dengan hipertiroidisme Graves harus dirawat

dengan 3 pilihan modalitas berikut: terapi 131II (iodin radioaktif), obat
anti tiroid, atau tiroidektomi. 1/++0
Terapi I:
131

Pada wanita yang merencanakan kehamilan di masa depan

Individu dengan peningkatan komorbid bila dilakukan operasi.
Pasien yang sebelumnya dioperasi pada bagian leher
Kontraindikasikan pada penggunaan Anti thyroid drugs (ATDs).
 PENANGANAN HIPERTIROIDISME YANG DISEBABKAN GD
DENGAN 131I

Rekomendasi 7 Terapi medis dari setiap kondisi komorbiditas harus dioptimalkan

sebelum pemberian yodium radioaktif,methimazole(MMI) harus dihentikan 3-5 hari
sebelum pemberian yodium radioaktif, restart 3-7 hari kemudian, dan umumnya Di-
tapper selama 4-6 minggu.
Rekomendasi 8 Radiasi yang cukup harus diberikan dalam satu dosis (biasanya
10-15 mCi) untuk membuat pasien dengan kondisi GD yang hipotiroid. 1/++0
Rekomendasi 9 Tes kehamilan harus negatif sebelum pemberian radioaktif
yodium. 1 / +00
Rekomendasi 11 Ketika hipertiroidisme karena GD berlanjut 6 bulan setelah terapi 131I, atau
jika respon minimal 3 bulan setelah terapi, disarankan perawatan ulang dengan 131I. 2/+00
 Treatment with
Radioactive Iodine
Indications :
Graves disease Carcinogenesis ?
Toxic multinodular goiter Leukemogenesis ?
Solitary hyperfunctioning nodule Teratogenesis ?
Nontoxic multinodular goiter
Goiter recurrence Infertility ?
Ablation of residual thyroid tissue in malignant
after surgery

Relative
Uncontrolled hyperthyroidism
Contraindications : Active thyroid orbitopathy (especially in
Pregnancy smokers)
Breastfeeding

Stokkel MPM et al. Eur J Nucl Med Imaging 2010;37:2218-2228

 TREATMENT OF HYPERTHYROIDISM
WITH RADIOACTIVE IODINE
Precaution principles

* Absolute contraindication for hyperthyroid

pregnant women and lactating mothers;
* Avoid close contact with children and pregnant
women during the first three days after
radioactive iodine treatment;
* Avoid pregnancy at least in the first 6 months
after radioactive iodine treatment;
* Stop breast feeding or interrupted for many
weeks;
* Flush toilet thoroughly after using it.
 Factors affecting response to
radioactive iodine treatment
Large dose : rapid remission, higher hypothyroidism rate
Side effects of radioactive iodine treatmen

Atrophy, fibrosis, and chronic inflammation result in substantial decrease in the size of
thyroid gland

Hypothyroidism
 OBAT ANTI TIROID (ATDS)

o Pasien dengan tingkat remisi yang tinggi (terutama perempuan,

dengan penyakit ringan, small goiter, titer TRAb negatif atau
rendah)
o Pasien orang tua atau dengan peningkatan komorbiditas bila
dilakukan operasi atau dengan harapan hidup terbatas.
o Pasien yang tidak bisa mengikuti standar prosedur radiasi
o Pasien yang sebelumnya dioperasi di bagian leher
o Pasien dengan Graves Oftalmopati (GO) aktif sedang hingga
berat.
 PENANGANAN HIPERTIROIDISME YANG
DISEBABKAN GD DENGAN OBAT ANTI TIROID

Rekomendasi 12 Methimazole adalah pilihan pertama setiap pasien yang

memilih terapi obat antitiroid untuk GD, kecuali: selama trimester pertama
kehamilan , krisis tiroid (Thyroid storm), dan pada pasien dengan reaksi
minimal dengan methimazole yang menolak terapi yodium radioaktif atau
operasi. 1/++0
Rekomendasi 19 Jika methimazole dipilih sebagai terapi utama untuk GD,
obat harus dilanjutkan selama kurang lebih 12-18 bulan, kemudian di-tapper
atau dihentikan jika TSH dalam batas normal. 1/+++
Rekomendasi 20 Pengukuran tingkat TRAb sebelum menghentikan obat
antitiroid disarankan, karena membantu dalam memprediksi pasien mana
yang dapat dihentikan obatnya, TRAb normal menunjukkan kesempatan
lebih besar untuk remisi. 2/+00
 Rekomendasi 21 Jika seorang pasien dengan GD relaps
setelah menyelesaikan suatu program methimazole, pengobatan
pilihan adalah yodium radioaktif atau tiroidektomi. Pengobatan
methimazole dosis rendah lebih lama dari 12-18 bulan dapat
dipertimbangkan pada pasien Tidak remisi yang lebih memilih
pendekatan dengan obat ini. 2/+00
Rekomendasi 22 Bila mungkin, pasien dengan GD yang
menjalani tiroidektomi harus dalam kondisi euthyroid dengan
pemberian methimazole. Kalium iodida harus diberikan dalam
periode pra operasi segera. 1/+00
 Which Antithyroid Drugs

Cost : PTU < Methimazole

Pregnant women : PTU > Methimazole

Lactating mother : Dose limited

Rapid onset of action : PTU > Methimazole

Compliance : PTU < Methimazole

Cross allergy : might be

 Short term therapy (weeks-months)

To cool down the patients (toxic adenoma or toxic multinodular goiter) prior
to definitive therapy (radioiodine or surgery)

Long-term therapy (1-2 years)

remission, that may or may not occur, usually followed

by radioiodine therapy or surgery
MMI has a longer duration of action than PTU
 Titration method :

Large initial antithyroid dose

(methimazole 20-30 mg/day; PTU
300-600 mg/day), and gradually
decreasing as low as possible
(depends on thyroid function status)
to maintain euthyroid state.
 First give ATD for 12- 18 months

observe
ATD can be given years or decades (?) as long as no side effects.

If relapse occur

Patients compliance !
start again with ATD consider alternative method

Radioactive
Surgery
iodine
Remission rate 40-50% after 12-18 months ATD for hyperthyroidism Graves;

Toxic adenoma and toxic multinodular : ATD only for preparation before definitive therapy;

Hepatotoxicity for PTU : rare, but serious and fatal;

FDA and ATA recommendations

Do not use PTU as first line PTU

PTU only
only for
for hyperthyroidism
hyperthyroidism in
in pregnant
pregnant women
women in
in 11 st
st

semester,
semester, or
or patients
patients can
can not
not tolerate
tolerate to
to methimazole
methimazole
drug for hyperthyroidism; or
or methimazole
methimazole is
is not
not available
available;;

Methimazole embryopathy in 1stst semester of pregnancy;

When initiating hyperthyroid treatment, propylthiouracil should be reserved for patients

who cannot tolerate methimazole or for patients for whom radioactive iodine therapy or
surgery is not appropriate treatment;

Methimazole : first-line drug for Graves hyperthyroidism;

PTU low cost. Dillema for Indonesia and developing countries.

 Possible
Possible binding
binding of
of drug
drug
metabolite
metabolite to
to hepatocellular
hepatocellular
proteins(s)
proteins(s)

Serious side-effect from PTU

liver transplantation fatal

FDA and ATA recommendation (2009-2010)

Williams JCEM 1997, Cooper the Endocrinologist 1999

 Antithyroid Drug Toxicity
PTU MMI
M in o r
R e a c tio n s (fe v e r ,
5 -2 0 % 5 - 2 0 % ( d o s e - r e la te d )
ra s h )

M A J O R R E A C T IO N S
0 .2 -0 .5 % 0 .2 -0 .5 %
A g r a n u lo c y to s is ( n o t c le a r ly d o s e - ( d o s e - r e la te d )
r e la te d )

H e p a t it is ( 2 5 % )
H e p a to to x ic ity C h o le s ta tic ( fe w d e a th s )
(? < 1 % s e v e re )

V a s c u litis A N C A + (v e ry ra re )
Bar ber o et al . 2008

Choanal atresia
associated with
maternal
hyperhytoidism
treated with
methimazole
Barbero et al
2008
 PEMBEDAHAN

Penekanan sehingga menimbulkan gejala atau large goiters (80 g);

Uptake radioaktif iodine yang rendah.
Curiga malignansi tiroid.
Nodul besar yang nonfungsional atau hipofungsional
Hiperparatiroidisme yang membutuhkan pembedahan
Wanita yang merencanakan kehamilan dalam < 4-6 bulan terutama bila
TRAb levelnya tinggi.
Pasien dengan Graves Oftalmopati (GO) aktif sedang hingga berat.
SURGERY
Hyperthyroidism with large goiter;
need good pre-operative preparation
(normalization of thyroid hormone levels with
antithyroid drugs);
In good hands: high volume surgeon minimal
surgical risk;
Hypothyroidism and relapse : depends on how
big the rest thyroid tissue.
 Rekomendasi 26 Setelah tiroidektomi untuk GD,
disarankan kalsium serum atau tingkat hormon paratiroid
intak diukur, dan kalsium oral dan suplemen calcitriol dapat
diberikan berdasarkan hasil ini. 2/+00
 PENANGANAN HIPERTIROIDISME KARENA TOXIC
MULTINODULAR GOITER (TMNG) DAN TOXIC ADENOMA (TA)

Rekomendasi 31 disarankan bahwa pasien dengan

TMNG atau TA diobati dengan terapi 131I atau
tiroidektomi. Bila tidak memungkinkan pengobatan
dosis rendah dengan methimazole jangka panjang
mungkin sudah cukup. 2/++0
 HYPERTHYROIDISM IN SPECIAL CONDITIONS
Hyperthyroidism & Pregnancy
In pregnancy and breast feeding
mothers PTU is preferable;

Maintain maternal thyroid hormone

levels for
fT4 in trimester-specific normal
range (if available)
in the upper non-pregnant
reference range
No alteration in thyroid function in newborns
breast fed by mothers treated with PTU < 300
mg/day or MMI < 20mg/day
Kampmann, 1980; Lamberg, 1984; Momatani, 1989; Azizi, 2000;
MMI is not absolutely contraindicated in
pregnant women, although there have been
reports of teratogenic effects such as aplasia
cutis and choanal / esophageal atresia.

total T4 at 1.5 times the normal

reference range
 Timing of diagnosis Specific circumstaces
GD Diagnosed during Diagnosed during first trimester
pregnancy
Diagnosed after first trimester
GD diagnosed and Currently taking methimazole
treated prior to pregnancy
In remission after stopping antithyroid
medication
Previous treatment with radioiodine or
surgery
Hyperthyroidism Management Guidelines, Endocr Pract.2011;17(No.3)
Recommendation
Begin propylthiouracil
Measure TRAb at diagnosis and, if elevated, repeat at 22 26
weeks of gestation
If thyroidectomy is required, it is optimally performed during the
second trimester
Begin Methimazole
Measure TRAb at diagnosis and, if elevated, repeat at 22-26
weeks of gestation
If thyroidectomy is required, it is optimally performed during the
second trimester
Switch to propylthiouracil as soon as pregnancy is confirmed
with early testing
Measure TRAb either initially at 22-26 weeks of gestation, or
initially during the first trimester and, if elevated, again at 22-
26 weeks of gestation
TRAb measurement not necessary
Measure TRAb either initially at 22-26 weeks of gestation, or
initially during the first trimester and, if elevated, again at 22-
26 weeks of gestation
Treatment of Subclinical Hyperthyroidism

Hyperthyroidism Management Guidelines, Endocr Pract.2011;17(No

 During the last 60 years there is no
There is no standard treatment for
breakthrough in the treatment of (Graves)
(Graves) hyperthyroidism. The alternatives
hyperthyroidism, despite recent advance
are still antithyroid drugs, surgery, and
in our understanding of the pathogenesis
radioactive iodine.
and immune system regulation.

The choice of treatment varies according to :

Immunosuppressive therapy of Graves hyperthyroidism is still an elusive goal.

TERIMA KASIH