JOURNAL READING

Pharmacologic Treatment of Hyperthyroidism

during Pregnancy
Matteo Cassina,* Marta Dona, Elena Di Gianantonio, and Maurizio Clementi
Teratology Information Service, Clinical Genetics Unit, Department of Womens and Childrens
Health,
University of Padova, Padova, Italy

PRESENTED BY :
Neneng Wulandari I11110049

LECTURER :
dr. Iqbal Lahmadi, Sp.PD

Department of Internal Medicine

Kartika Husada Hospital
Faculty of Medicine Tanjungpura University
 ABSTRACT
Clinical hyperthyroidism has been associated with an increased risk of
maternal, fetal, and neonatal complications.

The available antithyroid drugs

methimazole/ carbimazole propylthiouracil

exposure during the first trimester of

pregnancy is associated with an propylthiouracil-induced
increased risk of congenital hepatotoxicity
malformations

Until now, there has been no evidence that children prenatally exposed to
methimazole/carbimazole or propylthiouracil have an increased risk of
neurodevelopmental delay.
 INTRODUCTION
Clinical hyperthyroidism is not uncommon in childbearing
age, with an estimated prevalence during pregnancy
ranging between 0.1 and 1%

Maintaining a maternal euthyroid state during pregnancy is

essential for a normal embryo-fetal development, and
maternal and fetal hyperthyroidism have been associated
with an increased risk of complications.

Complications are related to duration and severity of

thyrotoxicosis
Hyperthyroidism Etiology in Pregnancy

Hyperthyroidism Etiology in Pregnancy

Graves disease > 85%

presence of
antibodies Toxic
Usually Improves adenoma -
stimulating the
exacerbate during 2nd
thyroid-
d during 1st and 3rd - < 5%
stimulating
trimester trimester
hormone (TSH)
receptor
 Hyperthyroidism Treatment Options

Treatment
hyperthyroidism

Pharmacologic Surgery Radiotherapy

Thionamide Thyridectomy 131 I

Methimazole (MMI) - Only if high dose of drugs Always

are persistenly needed to contraindicated
Carbimazole (CMZ) control the disease in pregnant
- Severe adverse effects
woman
Propylthiouracil (PTU) ocur
- Patient are not compliant
- The goiter constrict the
airway
 Maternal Adverse effect of Antithyroid Drugs

Adverse effect

Minor adverse effect Mayor adverse effect

Skin reaction Agranulocytosis

0,3%
Arthralgia
Hepatotoxicity
Gastrointestinal 0,1-0,2%
effect
Vasculitis
Table 1. Recurrent Birth Defects Reported in Children
Exposed to Methimazole/Carbimazole During Pregnancy
(72 Case Reports)
Birth defects N
Ectodermal anomalies 54
Choanal atresia 19
Gastroitestinal anomalies 16
Abdominal wall defects 6
- Omphalocele 3
- Gastroschisis 1
- Non spesified 2
Other birth defect 9
Case Reports Methimazole / Carbimazole And
Congenital Malformations

Retrospective Uncontrolled Studies

McCarroll et al. (1976) Wing et al. (1994)

25 children whose mothers were
treated with CMZ 30 mg (1st
trimester) and 10-20 mg (3rd
trimester) during pregnancy 2
children with congenital adactyly and
congenital cataracts
36 pregnant hyperthyroid women
treated with MMI. The rate of
major congenital malformations
was 2.7%, and no cases with
congenital scalp defects were
observed.

Bowman and Vaidya (2011)

Between July 1963 and September
2010, 57 cases of congenital defects
were reported following in utero
exposure to CMZ.
Case Reports Methimazole / Carbimazole And
Congenital Malformations
Retrospective and Prospective
Controlled Studies
Momotani et al. (1984) Chen et al. (2011)
infants exposure to MMI The rate of 73 case hyperthyroid women were
malformation in the nontreated exposed to MMI during pregnancy (65
hyperthyroid group (6.0%), in the during the first trimester) none of
nontreated euthyroid group (0.3%). them delivered a baby with major
congenital malformations.

The authors concluded that maternal
uncontrolled hyperthyroidism during
the sensitive period of organogenesis
may cause congenital malformations
and that the beneficial role of MMI
treatment outweighs its teratogenic
effect.
There was no increased risk of low
birth weight (LBW), preterm birth,
small for gestational age infants, and
congenital anomalies among babies of
women receiving MMI compared with
women with untreated
hyperthyroidism.
Case Reports Propylthiouracil And
Congenital Malformations
Retrospective and Prospective
Controlled Studies

Chen et al. (2011)

Women receiving PTU treatment had a
higher risk of giving birth to LBW
infants than did untreated women

High doses of PTU (>150 mg/day)

and PTU use in the second
trimester were independently
associated with increased LBW risk.
Antithyroid Drugs And Fetal And Neonatal Thyroid
Dysfunction

Thionamides inhibit the fetal thyroid function after

the 10th week of pregnancy and may cause fetal
hypothyroidism and goiter.
Most studies have shown that PTU and MMI have
equal potential to induce these complications.
Nevertheless, neonatal hypothyroidism and goiter are
usually transient and spontaneously resolve within a
few months.
Cognitive Development After Antithyroid Drugs
Exposure In Utero

Methimazole and Carbimazole Propylthiouracil

Exposure to MMI or PTU during None of them detected an

pregnancy in doses sufficient to
control maternal hyperthyroidism
does not pose any threat to
intellectual capacity of the
offspring.
increased risk of
neurodevelopmental delay
after exposure to both
MMI/CMZ and PTU.
 Management Of Hyperthyroid Pregnant Women
Hypertyroid in Pregnancy

Diagnose Monitoring Theraphy

Diagnosed Thyroid function should 1st trimester drug of

before be regularly checked choice PTU
conception throughout gestation 2nd and 3rd trimester low
New diagnoses every 4 weeks. dose MMI avoid PTU
are rare during Free T4 levels should be induced hepatotoxicity
pregnancy. maintained in the upper MMI/CMZ should be
normal range, using the considered a viable
lowest possible dose of second choice if :
drugs. the patient is intolerant
to PTU
has an allergic reaction
to PTU
fails to become
euthyroid on PTU
Management Of Hyperthyroid Pregnant Women

The American Thyroid Association recommends that equivalent

doses of PTU to MMI are 10:1 to 15:1 (100 mg PTU=7.5 to 10 mg
MMI) and those of CMZ to MMI are 10:8.
PTU therapy might be maintained during the second
and third trimesters, but hepatic enzymes should be
measured every 4 week.
TSH receptor antibody levels may be persistently elevated, even
in euthyroid women with a previous history of GD treated with
radioiodine or surgery.
Serial ultrasound scans are recommended.
It is recommended that delivery occur in a medical center with a
neonatal intensive care unit.
Management Of Hyperthyroid Pregnant Women

Thyroid function of newborn infants should be carefully

monitored in case of maternal GD that has been adequately
treated with antithyroid drugs.
The plasma levels of T4, T3, and TSH should be measured at
birth in any infants exposed to antithyroid drugs during
pregnancy.
Thyroid function should be checked 3 to 7 days later or when
clinical signs suggestive of hyperthyroidism appear in infants
delivered by women with a history of GD.
Once neonatal hyperthyroidism is confirmed, the levels of TSH
receptor-stimulating antibodies should be measured.
Teratologic Counseling

Serial ultrasound
Fetal heart rate
Doppler examination of the fetal thyroid gland
MMI/CMZ are the first choice of drugs for the treatment of
hyperthyroidism during the second and third trimesters.
In case of PTU treatment during the second and third trimesters,
hepatic enzymes should be measured every 4 weeks.
Clinical Endocrinologists have recently suggested that PTU
should be avoided during breastfeeding.
Thank You