HIPOTHYROID

DALAM KEHAMILAN
Andi cakra

Divisi Fetomaternal, Departemen Obgin FK UNHAS/

RS Dr.Wahidin Sudirohusodo
Makassar



• Kelenjar tiroid menghasilkan Tiroksin (T4) dan
triyodotironin (T3)
• Biosintesis hormon tersebut:
1. Uptake ion iodida oleh tiroid
2. Oksidasi yodida dan yodida gugus tirosil
3. Perubahan radikal yodotirosil menjadi radikal
• Hypothyroidism is characterized by
inadequate thyroid hormone production, and
usually requires for diagnosis elevated thyroid
stimulating hormone (TSH) and low free
thyroxine (FT4)
 Kehamilan akan Perubahan fisiolofis
menyebabkan perubahan peningkatan hormon tiroid
40-100% untuk keperluan ibu
struktur dan fungsi dan janin
kelenjar tiroid ibu

Menyulitkan penegakan diagnosis penyakit

atau menentukan adanya kelainan tiroid

Gejala seperti mudah lelah, konstipasi, dispneu,

takikardi, muscle cram juga sering ditemukan pada
kehamilan normal
• Insiden: 1% in popularion 0,2 -0,3% kasus hipothyroid dan 2,3 % kasus
hipothyroid subklinis in pregnant women. General screening of obstetric
patients reveals an incidence of 2,5% of elevated serum TSH. There is an
increased incidence with concurrent autoimmune disease, that is 5 % to
8% incidence in patients with dm type 1. Up to 25 % of dm type 1 develop
postpartum thyroid dysfunction.
• May occur more frequently in pregnant women with type 1 diabetes and
T4 replacement therapy can increase insulin requirements.
• Characteristic by insidious nonspesific clinical findings that include:
- fatigue, constipation, cold intolerance, muscle cramps, and weight
gain,decreasein exercise capacity,lethargy, intoleranceto cold
- Edema, dry skin, hair loss, and prolonged relaxation phase of deep tendon
reflexes, hoarseness,britttle nail
- A pathologically enlarged thyroid gland depens on the etiology of
hypothyroidism
• Physical signs may include a goiter,a thyroidectomy
scar, and delay in the relaxation phase of deep tendon
reflexes
• Laboratory finding: Abnormal high serum TSH level,
with or without a suppresed free T4 value. For thyroid
autoantibodies (i.e., antithyroglobulin and peroxidase)
may be positive. Other laboratory abnormalities
elevated levels of creatinin phosphokinase, cholesterol,
and carotene and liver function abnormalities. Patients
may have macrocytic or normocytic, normocytic
anemia.
• Etiologi:
Two most common
-Sufficient dietary iodine supply autoimmune thyroiditis
(Hashimoto thyroiditis)
- Post thyroid ablation therapy, either surgical or I induced
Other causes include
congenital (about 1 in 3000 births in US)
Drug induced( lithium, amiodarone, iodine excess, antithyroid
drugs)
Prior head and neck radiation for nonthyroid malignant
disease,
Congenital defects in thyroid hormone biosynthesis.
• Regardless of the etiology
- Primary hypothyroidism:
a. Subclinical hypothyroidism(normal serum T4
and elevated serum TSH)
b. Overt or clinical hypothyrodism (low serum T4
and elevated TSH)
- Secondary hypothyroidism includes:
a. Disease of pituitary gland or hypothalamus.
b. Autoimmune hypophysitis  sheehan syndrome
• Hypothyroxinemia: Normal TSH and low FT4
• SERUM THYROID ANTIBODIES (TPOAbs, also
known as antimicrosomal antibodies) are
elevated in almost 95% of patiens with
autoimmune hypothyroidism
• Serum antithyroglobulin antibodies(TGAbs)
elevated in about 60% chronic thyroiditis
• The titer of antibodies doesn’t correlate with the
size of the goiter or the clinical severity of
hypothyroidism but could be a predictor for the
development of postpartum thyroiditis
• The spectrum of pregnant women diagnosed:
1.Subclinical and overt hypothyroidism diagnosed for the first time
during pregnancy;
2. Hypothyroid women who discontinue thyroid therapy before or at
the time of conception because of poor medical advice or
misconception that thyroid medications may affect the fetus
3. Women on thyroid replacement therapy requiring larger doses in
pregnancy
4. Women previously diagnosed but not concisistent in taking their
medication
5. Hyperthyroid patients on excessive amounts of antithyroid drug
therapy
6. Some patients on lithium or amiodaronetherapy  affect thyroid
function chronic thyroiditis
Risk Factor
• Riwayat hipo atau hipertiroid, PPT (post partum tiroiditis), atau lobektomi
tiroid
• Riwayat keluarga dengan penyakit tiroid
• Wanita dengan goiter
• Memiliki antibodi tiroid
• Terdapat tanda dan gejala yang mengarah pada kekurangan dan kelebihan
hormon
• tiroid
• Diabetes melitus tipe I
• Penyakit autoimun lain
• Infertilitas
• Riwayat radiasi pada kepala dan leher
• Riwayat keguguran atau melahirkan Premature
• Screening/diagnosis
• Universal screening for maternal
hypothyroidism is not usually recommended
even if some have proposed it. Women at
hight risk for hypothyroidism should be
screened. Tests used for screening and
diagnosis include TSH (most sensitive) and FT4
• Indication for thyroid testing in pregnancy
• 1. History of thyroid dysfunction or prior thyroid surgery
• 2.Age>30 years
• 3.Symptons of thyroid dysfunction or the presence of goiter
• Thyroid peroxidase antibody positive
• Type 1 diabetes or other autoimmune disorders
• History of head/neck radiation
• Family history of thyroid dysfunction
• Morbid obesity(body mass index> 40kg/m2)
• Use of amiodarone or lithium, or recent administration of iodinated
radiologic contrast
• Unexplained fertility
• Residing in an area of known moderate to severe iodine sufficiency
Komplikasi
• Maternal: infertility,
Preeklampsia(44%) abruption (19%)
Misscarriage
Hipertensi gestational
Perdarahan post partum
• Fetal
• Abrupsio plasenta
• Prematurity
• Low birth weight (31%)
• Stillbirth/fetal death (12%)
• Gawat Janin
• Congenital malformations,
• Impaired mental and somatic development
• Differential diagnosis
• Hashimoto thyroiditis(i.e., chronic lymphocytic
Thiroiditis), an autoimmune diseasecommon
cause hypothyroid, 8% to 10% of women of
reproductive age.
I therapy, ablation for grave disease, and
thyroidectomy (e.g for thyroid cancer) 10
% to 20% are hypothyroid within the first 6 months
and 2% to 4% become hypothyroid each year
thereafter
• Drugs that inhibit the syntesis of thyroid
hormones : thionamide, iodides,lithium.
• Carbamazepine, phenytoin and rifampicin can
increase thyroid hormone clereance
• Aluminium hydroxide, cholestyramine, and
most importantly, ferrous sulfate and
sucralfate can interfere with the intestinal
absorption of thyroxine, and they should not
be overlooked
• Pituitary disease, pituitary tumours after
pituitary surgery or irradiation, and in
Sheehan syndrome and lymphocytic
hypophysitis, an autoimmune disease.
• Management
Prevention
• Seleniumselenoproteins act as antioxidants
and decrease thyroid inflamation in
autoimmune thyroiditis by reducing TPO
antibody titers.
Up to 30 % of women with TPO antibodies
develop permanent hypothyroidism following
postpartum thyroid dysfunction
• Preconception
• Treatment
• In newly diagnosed pregnant women: initial dose
of 100 mcg of L-thyroxine  2 to 2,4 mcg/kg
perday)
• In nonpregnant patients (1,7 to 2 mcg/kg perday0
• Severe hypothyroidism(delay in the normalization
of the serum TSH, normal FT4 or FT4I values
first 2 weeks of therapy if sufficient L-thyroxine is
administered. Maintenance dose required
between 75 and 250 mcg of L-thyroxine per day
• Women planning their pregnancies should have a
serum TSH below 2,5 Miu/l,ideally closer to 1
mIU/L, ideally closer to 1 Miu/L, serum TSH
should be repeted every 2 to 6 weeks during the
first 20 weeks gestation and at 24 to 28 weeks
and at well as serum FT4 or FT4I within normal
trimester spesific reference ranges
• Immediately after delivery, patient should return
to their pregnancy dose,and TSH levels shouldbe
measured six to eight weeks postpartum, with
follow up with medical doctor/endocrinologist
• Armour Thyroid at 30 mg/day initial dose,
then increased incrementally by 15 mg every
tow to three weeks until maintenance dose of
60 to 120 mg/day, is an alternative if
levothyroxine is unavailable.
• Iodine supplementation  250 ug of iodine is
recommended during pregnancy and breast-
feeding
Goal of levothyroxine treatment in pregnancy is
maternal serum TSH 0,5 to 2,0 u U/ml, and FT4
in upper third of normal range.
TSH and FT4 levels should be checked
preconceptionally, at first prenatal visit in first
trimester, 4 weeks after altering the
dose,(therefore, every 4 weeks until TSH is
normal, especially in the first 20 weeks), and at
least every trimester in pregnancy
Poros hipothalamus hipofise organ target
kelenjar tiroid
BIOSINTESIS HORMON TIROID
 Didalam sirkulasi jumlah T4 yang berikatan
dengan globulin (TBG) di hepar lebih banyak
dibandingkan T3
 T3 bentuk yang paling aktif
 T4TBG → T3
 T3 dan T4 yang bekerja pada sel organ target
 Pada kehamilan dengan gemelli peningkatan
HCG dapat semakin tinggi → Hipertiroid
 Studi pada 63 women with hCG concentrations
>200,000 IU/L, TSH (0.2 mIU/L) dan 67% dari
100% jika konsentrasi hCG >400,000 IU/L
 Faktor pencetus hipertiroid
dalam kehamilan
 Hipertiroid dalam kehamilan pada umumnya
disebabkan oleh penyakit autoimun Grave.
Penyebab yang lainnya, adalah struma
multinodular, adenoma toksik, tiroiditis
 Grave’ disease → proses autoimun →
antibody tiroid → menempel dan
mengaktivasi reseptorTSH →hiper fungsi
dari kelenjar tiroid

Episode kekambuhan → riwayat hipertiroid
 Transien hipertiroidisme didiagnosis pada sekitar
3-5 % dari kehamilan dan termasuk wanita dengan
hiperemesis gravidarum , kehamilan kembar dan
mola hidatidosa

 B HCG meningkat pada trimester pertama

puncaknya pada minggu 10-12 kehamilan

 TSH menurun dan FT4 normal

 DIAGNOSIS
 Pada kasus yang jelas diagnosis klinis kehamilan dengan
hipertiroid mudah ditegakkan
 Sebaliknya pada kasus yang ringan secara klinis maupun
laboratorium sulit untuk membuat diagnosis
 Diagnosis hipertiroidisme harus selalu dikonfirmasi oleh
pengukuran FT 4 danTSH
 TSH < 2.5 mIU/L (trimester pertama) setelah < 3.0 mIU/L
 Hipertiroidisme ,TSH< 0,1 mIU/L
 PRINSIP PENATALAKSANAAN
Implementasi bertujuan memberikan perawatan
terbaik untuk ibu hamil dan mencegah efek buruk
pada ibu , janin dan neonatus

1.Observasi

2.Obat anti tiroid

3.β Blocker

4.Operatif
(Tiroidektomi)
2015
100 evidence-based
recommendations
KONSEKUENSI PENGGUNAAN
OBAT ANTI TIROID

EFEK SAMPING OAT

EFEKTERATOGENIK OAT

RESIKO HIPOTIROID BAYI

 Dosis obat tergantung pada keadaan hipertiroid dan minggu
gestasi
 Pada awal kehamilan sebelum terbentuknya plasenta,
diberikan dengan dosis 3 sampai 4 kali 100 mg sehari,
sedangkan MMI 3 kali 10 mg sehari
 Setelah keadaan eutiroid tercapai maka dosis dapat
diturunkan
 Target TSH 0,1 -2,5 trimester pertama dan 0,3-3,0 trimester
kedua dan tiga
 fT4 serum (rujukan 10-26 pmol/l), fT3 (rujukan 3 – 7 pmol/l)
 Kasus Graves disease pengobatan sampai 1-2 tahun. ( TSH,
T3,T4 N 6 bulan prognosis baik)
 Pada umumnya dengan dosis PTU 100-200 mg/hari dan MMI
10-15 mg/hari selama hamil tidak akan memberikan efek
hipotiroid pada anak
 Pertimbangan pemberian
Beta-blocker dalam kehamilan

Mengontrol gejala
hypermatabolik
( takikardi, tremor dsb)

Dosis aman digunakan

40 mg selama 3 minggu
tidak berbahaya terhadap
bayi
Rekomendasi tingkat A
1 Rekomendasi pertama (tidak melakukan screening
universal untuk penyakit tiroid pada kehamilan).
2.TSH adalah tes skrining lini pertama untuk menilai
status tiroid pada kehamilan.
3.TSH dan FT4 harus diukur untuk mendiagnosis
penyakit tiroid pada kehamilan.
4. Wanita hamil dengan hiportiroidisme yang jelas
harus ditangani dengan thioamide untuk
meminimalkan hasil yang merugikan risiko.
5. FT4 harus dipantau pada wanita hamil dengan
hipertiroidisme dan thioamide dosis disesuaikan.
• Monitoring
• Mengukur kadar TSH pada usia 6-8
minggu,16-20 minggu dan pada 28-32 minggu
 Mempertahankan euthyroidism di pasien ini
adalah sangat penting.
 beberapa studi telah menunjukkan bahwa
penatalaksanaan maksimal pasien
hipothyroid dalam kehamilan akan
meningkatkan .ibu dan anak
• Treatment
ATA and AACE: Levothyroxine 1 to 2 ug/kg/day
or approximately 100 ug daily  surveillance is
with TSH levels measured 4 to 6 week intervals
Thyroxine dose is adjusted by 25 to 50 ug
increments until TSH value become normal