Hyperthyroidism In Pregnancy - StatPearls - NCBI Bookshelf 05/07/22 00.

17

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.

Hyperthyroidism In Pregnancy
Kevin Sorah; Thomas L. Alderson.
Author Information
Last Update: May 8, 2022.

Continuing Education Activity

Hyperthyroidism is an uncommon condition that complicates approximately 0.1% to 0.4% of
pregnancies. The condition is marked by increased levels of circulating thyroid hormones, T4
and T3, as well as a decreased level of thyroid-stimulating hormone (TSH), also known as
thyrotropin. Though relatively rare, identification and treatment of overt hyperthyroidism are
important to mitigate maternal and fetal complications. This activity reviews the evaluation and
management of hyperthyroidism in pregnancy and explains the role of the interprofessional team
in managing patients with this condition.

Objectives:

Identify the etiology of hyperthyroidism in pregnancy.

Describe the appropriate evaluation of hyperthyroidism in pregnancy.

Review the management options for hyperthyroidism in pregnancy.

Describe the importance of improving care coordination among the interprofessional team
to improve outcomes for patients affected by hyperthyroidism in pregnancy.

Access free multiple choice questions on this topic.

Introduction
Hyperthyroidism is an uncommon condition that complicates approximately 0.1% to 0.4% of
pregnancies.[1] The condition is marked by increased levels of circulating thyroid hormones, T4
and T3, as well as a decreased level of thyroid-stimulating hormone (TSH), also known as
thyrotropin. Though relatively rare, identification and treatment of overt hyperthyroidism are
important to mitigate maternal and fetal complications.[2] Ideally, hyperthyroidism is diagnosed
before conception, and treatment is started to achieve euthyroid status. However, up to half of all
pregnancies in the United States are unplanned, making an early diagnosis of thyroid dysfunction
imperative.[3] This review addresses the etiology, epidemiology, pathophysiology, and initial
evaluation of hyperthyroidism in pregnancy, followed by a discussion of treatment, management,
and complications.

Etiology
Hyperthyroidism in pregnancy requiring treatment is most often caused by Grave disease, which
is estimated to account for 85% to 95% of clinically significant cases of hyperthyroidism.[1][2]
[3][4][5] This autoimmune condition is marked by the presence of thyrotropin (TSH)-receptor
antibodies (TRAb), which can bind to thyroid receptors and cause their activation, leading to
increased production of thyroid hormones.[5]

https://www.ncbi.nlm.nih.gov/books/NBK559203/ Halaman 1 dari 10

Hyperthyroidism In Pregnancy - StatPearls - NCBI Bookshelf 05/07/22 00.17

Epidemiology
The overall prevalence of Grave disease is 0.5%.[6] The incidence of hyperthyroidism in
pregnancy is 0.1% to 0.2%.[7] The Grave disease most often occurs in women between the ages
of 20 and 40, with the incidence increasing with age.[1] Clinically significant
hyperthyroidism from other causes is much less common. For example, hyperthyroidism due to
thyroid nodules is much less likely in women under the age of 40, with an incidence of less than
0.001% to 0.002%.[8] In areas with known iodine deficiency, the prevalence of hyperthyroidism
can be higher due to the development of functional thyroid nodules.[4]

Pathophysiology
Throughout pregnancy, multiple physiologic changes contribute to fluctuating levels of thyroid
hormones. Due to increased circulating estrogens, pregnancy brings a 50% increase in thyroxine-
binding globulin (TBG), which binds circulating T4, causing a decrease in free T4 levels. To
compensate, the thyroid grows in size and increases the production of T4 and T3 by 50%.[2][7]
[8][9] Due to TSH's homology with human chorionic gonadotropin (hCG), rising hCG levels in
the first trimester lead to stimulation of the thyroid, in turn causing a further elevation in free T4.
[4][6][8][10] The hCG levels peak between 8 to 12 weeks of gestation and gradually decrease
thereafter.[3][10]

Conversely, the developing placenta contains deiodinase type 3 (DIO3), which deactivates T4
and T3. Excessive function by this enzyme can lead to hypothyroidism. Typically, this effect is
outweighed by increased hCG production in early pregnancy, leading to a net increase in free T4
with a decreased median TSH and reference range.[8][11] This transient increase in free T4
usually resolves by mid-pregnancy as hCG levels plateau and decline.

There is also an increased dietary iodine requirement, from 150 micrograms to 250 micrograms
daily, due to increased thyroid hormone synthesis during pregnancy. There is also an appreciable
loss of iodine in urine due to the increased glomerular filtration rate in pregnancy.[8]

Grave disease involves TRAbs that bind the TSH receptor and impact the production of thyroid
hormones. These antibodies can be stimulatory or inhibitory. In Grave disease, the net effect of
TRAbs is stimulatory, causing a pathologic increase in free T4 that usually requires medical
management.[2][3][4][8]

Pregnancy results in a period of immunosuppression to avoid rejection of the developing fetus.

[2] Antibody titers, including TRAbs, decrease as the pregnancy progresses, especially in the
second and third trimesters. In the postpartum period, the immune system returns to the pre-
pregnancy state, and antibody titers increase. This increases the risk of relapse in Grave disease
or another condition known as postpartum thyroiditis.[2][9]

History and Physical

Many signs and symptoms of hyperthyroidism mirror normal physiologic processes of
pregnancy, including tachycardia and dyspnea.[4][8] Other symptoms of hyperthyroidism
include diaphoresis, heat intolerance, palpitations, insomnia, frequent bowel movements,
nervousness, increased appetite, pruritus, anxiety, and tremors. Physical exam findings may
include goiter and hypertension. In those affected by Grave disease, exophthalmos or proptosis is
present approximately 50% of the time, and pretibial myxedema less than 10% of the time.[1][3]
[8]

https://www.ncbi.nlm.nih.gov/books/NBK559203/ Halaman 2 dari 10

Hyperthyroidism In Pregnancy - StatPearls - NCBI Bookshelf 05/07/22 00.17

Identifying a history of Grave disease is important even if surgery or radioiodine ablation was
performed, since TRAbs may persist and cause fetal hyperthyroidism.[4][10]

Evaluation
When new-onset hyperthyroidism is suspected in pregnancy, laboratory evaluation is similar to
the non-gravid patient.[8] Evaluation starts with a TSH level, which is often decreased in
pregnancy due to the stimulation of the thyroid by hCG, causing negative feedback on TSH
production. If the TSH level is lower than the reference range, thyroid hormone levels should be
checked to help differentiate overt hyperthyroidism from normal physiologic changes in
pregnancy. Most commonly, free T4 levels are evaluated. Total levels of T4 and T3, free T4
index, or TBG may be clinically useful if available.[2][4][8][10][11][12]

The interpretation of these laboratory studies is different in the pregnant patient, as the normal
values vary between trimesters and the non-gravid state due to increasing levels of TBG.[8][10]
[12] Reference ranges for TSH are trimester-specific. TSH ranges from 0.1 to 2.5 mIU/L, 0.2 to
3.0 mIU/L, and 0.3 to 3.5 mIU/L in the first, second, and third trimesters, respectively.[6] If non-
pregnant reference ranges are applied in error, misclassification of thyroid status can occur.[6]
Free T4 reference ranges need to be established by individual laboratories.[12]

A definitive diagnosis of hyperthyroidism may be difficult due to normally fluctuating levels of

thyroid hormone in pregnancy. If the diagnosis is uncertain, it is appropriate to observe the
thyroid level trends with further laboratory testing rather than immediately starting antithyroid
drug therapy.[11] Adverse outcomes have not been demonstrated with subclinical
hyperthyroidism.[1][2][4][6][7][9][10][11][12] TRAbs are usually measurable in Grave disease
and can be used to confirm the diagnosis and differentiate from gestational transient
thyrotoxicosis.[1][2][4][8][10][11][12] It is important to note that the most frequently used
assays do not differentiate between stimulatory and inhibitory TRAbs. If there is uncertainty
about the diagnosis, more sensitive assays for stimulatory TRAbs can be used.[8] TRAbs should
also be measured in any woman with a history of Grave disease or history of positive TRAbs,
who has had a neonate affected by Grave disease or has had recent radioiodine ablation or
thyroidectomy. This screening is recommended by the American Thyroid Association and the
Endocrine Society between 20 to 24 weeks of gestation.[2][3][4][8][12]

Treatment / Management
Hyperthyroidism in pregnancy is treated with medications that inhibit excessive thyroid hormone
synthesis. The antithyroid drugs (ATD) most commonly used in the U.S. are thioamides,
propylthiouracil (PTU), and methimazole (MMI). Carbimazole is a prodrug of methimazole that
is commonly used outside of North America, with similar efficacy and side effect profile.[3][8]
[12] All ATDs can cross the placenta and affect the fetus.[2][4][5][7]

Historically, PTU was commonly used for hyperthyroidism in all patients. However, it is
associated with hepatoxicity that can lead to liver failure and subsequent need for transplantation.
Therefore, methimazole is more commonly used now if tolerated. An exception to this is during
early pregnancy due to methimazole and carbimazole's association with a rare embryopathy,
which includes aplasia cutis, abdominal wall defects, esophageal atresia, choanal atresia, eye
abnormalities, urinary tract abnormalities, and circulatory defects.[1][2][4][5][7][8][11]
[12] After the first trimester, when the majority of organogenesis is complete, patients are then
transitioned to methimazole. This transition is necessary to decrease the likelihood of

https://www.ncbi.nlm.nih.gov/books/NBK559203/ Halaman 3 dari 10

Hyperthyroidism In Pregnancy - StatPearls - NCBI Bookshelf 05/07/22 00.17

hepatotoxicity.[2][4][8][10][12] PTU is associated with less severe birth defects that may not be
discovered until years after birth. Some congenital defects noted at birth include unilateral
kidney dysgenesis or agenesis, situs inversus, and cardiac outflow tract defects. These defects
typically occur in isolation as opposed to methimazole embryopathy, which is linked to a
constellation of defects.[6][10][11] Due to the detrimental maternal health effects and the risk of
fetal loss with untreated overt hyperthyroidism, treatment with antithyroid drugs is usually
necessary, despite potential teratogenicity.[6][11] If a patient does not tolerate PTU, treatment
with methimazole is preferred to no treatment at all, even in the first trimester.[13] ATDs cross
the placenta and can correct fetal hyperthyroidism caused by maternal TRAbs. However, ATDs
can overcorrect fetal hyperthyroidism even if the mother is euthyroid, causing fetal
hypothyroidism. Thus, the goal of treatment is to use the lowest dose of antithyroid medication
possible, with a TSH target slightly lower than the reference range and a maternal free T4 at the
high-end of normal.[1][2][3][4][6][8][10][11][12] If the TSH becomes normal, it likely means
that the fetus is receiving too much ATD.[8]

When treatment is initiated, dose-adjusted, or transitioned between drugs, thyroid function tests
should be obtained to confirm a euthyroid state. Testing can be performed every two to four
weeks as indicated to ensure the maintenance of euthyroid status.[3][10][12] PTU and
methimazole are both effective antithyroid drugs but require different doses due to different
pharmacokinetics. When switching, a 1 to 20 ratio of methimazole/PTU can be used as the initial
conversion factor.[4] PTU is given 100 to 300 mg daily between three doses due to a shorter
half-life than methimazole, which is dosed 5 to 15 mg once daily.[8] Thus, switching between
the drugs may result in a period of hyperthyroidism until the dose can be appropriately adjusted.
[6]

Due to the natural immunosuppression during pregnancy, TRAb titers often decrease during the
second half of pregnancy.[2][4][6][8] Titers can be remeasured in the third trimester, and if levels
are low or undetectable, the provider can consider tapering and discontinuing the antithyroid
medication.[2][3][8][10]

Side effects of thioamide therapy occur in up to 15% of women.[1] The most common side
effects are rash and pruritus.[3] Other side effects include joint pain, fever, nausea, and taste
alterations. More serious side effects like agranulocytosis, vasculitis, sepsis, and hepatotoxicity
are rarer.[1][8]

Potassium iodide (KI) is another medication that can be used to treat mild hyperthyroidism.
However, there have been limited studies in pregnancy. Most use in pregnancy has been in Japan,
which has shown effectiveness in treating mild hyperthyroidism with minimal adverse effects. Of
note, Japan has a higher iodine intake than most of the world, so the effectiveness of KI cannot
be extrapolated to other countries. Nevertheless, KI can be considered in women with mild
hyperthyroidism who do not tolerate ATDs.[2][8][11]

Surgery is optimally performed outside of pregnancy. In women who do not attain adequate
control of hyperthyroidism with high doses of ATDs, who have an allergy to ATDs, or are poorly
compliant with therapy, surgery can be considered. Surgery is also an option in patients who
have a large goiter causing compression issues. Total or subtotal thyroidectomy can be performed
in pregnancy, preferably in the second trimester, when the risk of fetal loss and complications is
lowest.[1][2][3][4][7][8][10][12]

If Grave disease has been previously treated outside of pregnancy with thyroidectomy or ablative

https://www.ncbi.nlm.nih.gov/books/NBK559203/ Halaman 4 dari 10

Hyperthyroidism In Pregnancy - StatPearls - NCBI Bookshelf 05/07/22 00.17

therapy, there may be TRAbs that persist. These antibodies are IgG proteins and can cross the
placenta and cause fetal hyperthyroidism.[1][8][11] In this special scenario, treatment with a
block-and-replace strategy may be warranted. This entails treating the fetal hyperthyroidism with
antithyroid drug therapy while simultaneously maintaining maternal euthyroid status via
levothyroxine, which does not cross the placenta as easily as ATDs.[4][8][11]

Radioiodine ablation (RAI) is a procedure that can be used to destroy active thyroid tissue.
However, RAI is absolutely contraindicated in pregnancy due to the ability of radioiodine to
cross the placenta and subsequently ablate the fetal thyroid, leading to congenital
hypothyroidism.[1][3][4][7][12] Before fetal thyroid development, RAI carries a risk for
spontaneous abortion or fetal malformations. Women who elect to undergo RAI outside of
pregnancy are advised to avoid conception for at least six months.[3][4][7][12] This ensures
clearance of radioiodine and allows adequate timing to achieve a stable euthyroid state with
levothyroxine.[12]

Beta-blockers such as propranolol can be used in pregnancy for symptomatic control until a
euthyroid state is maintained.[1][2][4] Once the euthyroid status is stable, beta-blockers should
be discontinued due to the risk of intrauterine growth restriction, fetal bradycardia, and neonatal
hypoglycemia with continued use.[2][3][13][8]

Fetal Surveillance

In women with Grave disease, the fetal anatomy ultrasound provides an opportunity to screen for
evidence of fetal thyroid anatomy and function. This survey should be completed between 18 to
22 weeks of gestation. Findings that may indicate thyroid dysfunction are an enlarged thyroid,
intrauterine growth restriction, hydrops, advanced bone maturity, fetal tachycardia, goiter,
oligohydramnios, or cardiac failure.[3][8][10][12]

TRAb should be remeasured between 18 to 22 weeks and 30 to 34 weeks to evaluate the risk of
fetal and neonatal hyperthyroidism, respectively.[2][4] While there is no consensus in
professional societies, further monitoring may be used if TRAb levels are greater than three
times the upper limit of normal or if there is a history of a newborn affected by a thyroid
disorder.[3] Further monitoring may include serial growth ultrasounds, amniotic fluid index,
evaluation of the fetal heart rate, and fetal thyroid ultrasound to check for goiter.[3][4][10]

Differential Diagnosis
While Grave disease is the most common cause of clinically significant hyperthyroidism in
pregnancy, other causes must be considered to determine if treatment is necessary.[8]

Gestational transient thyrotoxicosis (GTT), also known as transient gestational

hyperthyroidism (TGH), is the most common cause of transient hyperthyroidism in
pregnancy. It affects 1% to 3% of pregnancies and thus is encountered more frequently
than Grave disease in pregnancy.[2][4][6][10] The transient hyperthyroidism is due to
homology between the beta subunit of hCG and TSH. Increasing hCG levels in the first
trimester cause weak stimulation of the thyroid and subsequently causes rises in the free
T4, total T4, and total T3 levels, as well as a decrease in the TSH level. This transient rise
in thyroid hormone levels typically resolves by 14-20 weeks’ gestation as hCG levels
decline, and does not require treatment with antithyroid medication.[2][3][4][6][8] GTT is
often associated with nausea and vomiting that can be as severe as hyperemesis
gravidarum. Up to 50% to 70% of women with hyperemesis gravidarum present with

https://www.ncbi.nlm.nih.gov/books/NBK559203/ Halaman 5 dari 10

Hyperthyroidism In Pregnancy - StatPearls - NCBI Bookshelf 05/07/22 00.17

hyperthyroidism.[1][3][6] GTT can be differentiated from Grave-induced hyperthyroidism

by a lack of TRAbs. Those with GTT also lack goiter and ophthalmopathy on physical
exam, and thyroid texture will appear normal on ultrasound.[2][6] The incidence of GTT
increases with increasing hCG levels. Higher hCG levels are more likely to occur in
multifetal gestations and molar pregnancies.[2][4] In GTT, hCG levels are usually higher
than 200,000 IU/L.[6]

Hydatidiform molar pregnancies are a type of gestational trophoblastic disease. Complete

molar pregnancies are usually accompanied by incredibly high hCG levels and thus can
have increased activation of TSH receptors.[8] Complete removal of the molar pregnancy
by dilation and suction curettage is required for treatment.[7]

Single toxic adenoma and toxic multinodular goiter involve autonomous nodules that
produce thyroid hormones. These autonomous nodules are usually found in women who
are at least 40 years old.[2][6] Thyroid hormone production by these nodules is usually
less than in someone with Grave disease. Thus, antithyroid drugs may not be necessary. If
antithyroid drugs are used, there is a greater risk of fetal hypothyroidism than in Grave
disease since there are no competing stimulatory TRAbs to activate the fetal thyroid.[4]
Ultrasound can aid in the differential diagnosis, but a definitive diagnosis is made by
thyroid scintigraphy. This procedure is absolutely contraindicated in pregnancy.[4]

Subacute thyroiditis, also known as DeQuervain subacute thyroiditis, is a rare cause of

thyroid inflammation precipitated by a viral infection, which can cause the release of
thyroid hormones.[8]

There can be mutations in the thyroid hormone receptor that cause resistance to thyroid
hormone. This leads to increased TSH levels and a further increase in circulating thyroid
hormone and increases fetal exposure to thyroid hormone. Pregnant women with thyroid
hormone resistance have an increased risk of spontaneous abortion.[8] There is also the
possibility of TSH receptor mutations that cause hyperresponsiveness to hCG leading to
hyperthyroidism, similar to gestational transient thyrotoxicosis.[2][3][8]

There are a few rare neoplastic causes of hyperthyroidism in pregnancy. Struma ovarii is a
type of ovarian teratoma that contains functional thyroid tissue. This can be a rare cause of
hyperthyroidism in pregnancy.[1][8] A TSH-producing pituitary adenoma is a rare benign
tumor of the pituitary gland that is capable of producing TSH.[8] In a patient with thyroid
cancer, metastatic lesions may have some functionality and produce TSH.[8]

Hyperthyroidism can also be caused by excessive intake of levothyroxine used to treat

hypothyroidism.[10]

Prognosis
With treatment and close laboratory observation, pregnancy outcomes are improved, and adverse
outcomes are decreased.[3][8][9][10] Women are at the highest risk of complications if their
overall control of hyperthyroidism is poor. If untreated, 10% of women can experience
congestive heart failure.[1] A thyroid storm is life-threatening and complicates about 1% to 2%
of pregnancies affected by hyperthyroidism.[3]

Many pregnant women experience remission of Grave disease towards the end of pregnancy due
to the immunosuppressive effects of pregnancy and associated decrease in TRAb titers.

https://www.ncbi.nlm.nih.gov/books/NBK559203/ Halaman 6 dari 10

Hyperthyroidism In Pregnancy - StatPearls - NCBI Bookshelf 05/07/22 00.17

[11] There is also the possibility that TRAbs may switch from stimulating to inhibitory activity.
[13]

There is an increased risk of exacerbation or relapse in the 3 to 18 months after delivery due to
the rebounding immune system, with the highest risk seven to nine months postpartum.[4][10]
[11] Most women who are in remission from Grave disease before pregnancy will relapse
postpartum or experience thyroiditis.[1]

Complications
Treatment of overt hyperthyroidism in pregnancy is essential to decrease the risk of maternal and
fetal complications. Maternal complications include an increased risk of pregnancy loss,
gestational hypertension, preeclampsia, placental abruption, and preterm labor. When
thyrotoxicosis progresses to a thyroid storm, there is an increased risk of congestive heart failure,
admission to intensive care, and maternal death.[2][3][4][5][6][7][8][10] Appropriate levels of
thyroid hormones are important for fetal development. Thyroid hormones are known to impact
brain morphology by regulating migration, growth, and differentiation of fetal neuronal cells.[3]
Fetal complications of hyperthyroidism include prematurity, low birth weight, goiter,
tachycardia, fetal hydrops, cardiac failure, early bone maturation, intrauterine growth restriction,
and neurodevelopmental abnormalities. Fetal effects can be either due to the transplacental
passage of excess thyroid hormone or TRAbs that subsequently activate the fetal thyroid.[2][3]
[4][6][7][8][12] The risk of fetal effects increases with increasing maternal TRAb
concentrations.[2]

Overtreatment with antithyroid drugs in pregnancy can cause fetal hypothyroidism. Conversely,
women who receive adequate antithyroid treatment during pregnancy usually give birth to a
euthyroid neonate. However, TRAbs that previously crossed the placenta will still be present.
Antithyroid drugs are metabolized by the newborn within two to three days of birth. TRAbs can
then cause neonatal hyperthyroidism, affecting 1.5 to 2% of neonates in mothers with Grave
disease. This may resolve within a few weeks or persist for four to six months.[1][2][3][4][8]
[10] If neonatal hyperthyroidism persists, it is associated with 27% morbidity and 1.2%
mortality.[10] Possible sequelae include heart failure, hepatic dysfunction, microcephaly,
craniostenosis, pulmonary hypertension, coagulopathy, and intellectual disability.[10]

Thyroid Storm

A thyroid storm is a life-threatening complication that can occur when hyperthyroidism is

uncontrolled and is a manifestation of the most decompensated state of disease. In addition to
uncontrolled hyperthyroidism, there is usually a precipitating event before a thyroid storm. These
events can include labor, cesarean section, preeclampsia, trauma, or an infection.[2][3]
[8] Patients may present with severe tachycardia, tachyarrhythmias, mental status changes, heat
intolerance, fever, nausea and vomiting, diarrhea, congestive heart failure, and multi-organ
failure. In addition to antithyroid drugs, thyroid storm requires intensive care admission,
electrolyte replacement, fluid resuscitation, cooling, and oxygen. PTU or methimazole can be
used to stop thyroid hormone synthesis. At least one hour after ATD therapy, potassium iodide or
Lugol solution can be given to block further hormone release from the thyroid. If given before or
too soon after ATDs, KI can worsen the thyroid storm. Beta-blockers can be used to improve
tachycardia and tachyarrhythmias. High-dose glucocorticoids can also be given to decrease the
peripheral conversion of T4 to T3. If heart failure is present, digoxin can be used to increase
cardiac output. It is also important to address the precipitating event of thyroid storm, such as

https://www.ncbi.nlm.nih.gov/books/NBK559203/ Halaman 7 dari 10

Hyperthyroidism In Pregnancy - StatPearls - NCBI Bookshelf 05/07/22 00.17

antibiotics, for an underlying infection. If the patient is febrile, acetaminophen should be used
rather than aspirin, since aspirin can increase circulating thyroid hormones.[3][8]

On initial presentation, fetal distress may be noted. As the mother receives treatment, the fetal
status may improve. Delivery should be avoided if possible since both labor or cesarean section
can worsen thyroid storm.[3]

Postpartum Thyroiditis

Postpartum thyroiditis (PPT) is a condition that typically occurs within six weeks of delivery but
may happen up to one year postpartum due to immune rebound after normal immunosuppression
of pregnancy.[7][8] Antithyroid peroxidase antibodies are present, and TRAbs are typically
absent.[7] Often, there is a period of transient hyperthyroidism caused by autoimmune
destruction of thyroid tissue and subsequent release of thyroid hormone stores.[7][8] This is then
followed by a period marked by hypothyroidism, which may persist.[7][8] It is important to
differentiate PPT from new-onset Grave disease. PPT does not require treatment with ATDs, as
hyperthyroidism is transient. However, beta-blockers can be used for symptomatic control during
this period.[7][8] The overall incidence of PPT is 5.4%. Women with type 1 diabetes mellitus are
at 3 to 4 times higher risk.[7]

Deterrence and Patient Education

Women who are planning to get pregnant often seek pre-conceptual counseling. In women with
Grave disease, this is an opportune time to discuss treatment options before pregnancy.[2][4][7]
Some women may opt to undergo surgery or radioiodine ablation (RAI) to cure their Grave
hyperthyroidism, especially in women with high TRAb titer or a history of fetal thyroid issues in
a previous pregnancy.[10] Surgery may be preferred to RAI in women with especially high titers,
as RAI can initially increase TRAb titers.[2][7] This route potentially mitigates the need for
antithyroid drugs and avoids the adverse maternal side effects and potential teratogenicity from
PTU and methimazole, but requires thyroid hormone replacement for life. Thyroid hormone
levels need to be optimized with levothyroxine before pregnancy.[7] In some cases, TRAbs
persist and can cross the placenta and cause fetal hyperthyroidism, necessitating a block-and-
replace strategy as detailed above.[4][8][11]

Most non-pregnant women with Grave disease use methimazole due to a lower risk of
hepatotoxicity than PTU.[8] Some women may prefer to switch to PTU before becoming
pregnant. If a patient chooses to remain on methimazole until after becoming pregnant, it is
important to counsel the patient on the risk of methimazole embryopathy if she is not changed to
PTU before organogenesis.[3][4][7][11] When compared to the risk of methimazole
embryopathy, the risk of PTU-induced hepatotoxicity is lower.[10]

Pearls and Other Issues

Subclinical hyperthyroidism is typically not associated with adverse effects and does not require
treatment.[1][2][4][6][7][9][10][11][12] Treatment could lead to fetal hypothyroidism and
adverse outcomes.[12] Using the correct trimester-specific reference ranges and interpreting
them appropriately aids in avoiding unnecessary treatment while also avoiding adverse outcomes
of undertreatment.[6]

Breastfeeding is not contraindicated while on ATDs as long as the dose is low. Women should
take their ATD right after breastfeeding to allow some metabolism before their next lactation. If

https://www.ncbi.nlm.nih.gov/books/NBK559203/ Halaman 8 dari 10

Hyperthyroidism In Pregnancy - StatPearls - NCBI Bookshelf 05/07/22 00.17

ATD doses are high, monitoring of neonatal free T4 is warranted.[4] PTU passes into breast milk
to a lesser degree than methimazole, but methimazole is preferred since PTU can cause maternal
hepatotoxicity.[7][8][10] Radioiodine ablation of the maternal thyroid is absolutely
contraindicated when breastfeeding due to I-131 passage into breastmilk and its concentration in
maternal breast tissue.[4][7][8]

Enhancing Healthcare Team Outcomes

The concept of universal screening for thyroid disease in pregnancy has been a point of
controversy. While professional obstetric societies recommend targeted screening for thyroid
disease in those who are at high risk for thyroid dysfunction, there are some arguments for
universal screening. Thyroid function tests are relatively low cost. If all pregnant women are
screened for thyroid disease at the initial prenatal visit, many cases of both overt
hyperthyroidism and hypothyroidism can be diagnosed earlier. This allows for earlier
intervention to optimize thyroid hormone levels to decrease maternal and fetal risks.[6][9]

Without universal screening, all members of the health care team should be aware of the
symptoms of hyperthyroidism in pregnancy to know when to screen for thyroid disease.
Providers, provider's assistants, nurse practitioners, nurses, and medical assistants should all
know how to take a history that includes previously diagnosed thyroid disease, including any
thyroid procedures.[12]

Primary care providers and endocrinologists should inquire whether a patient with Grave disease
is planning future pregnancies. This allows the patient to optimize their thyroid hormone levels
with appropriate medication and to get adequate counseling during the preconception period, as
it is recommended to postpone conceptions until the patient is euthyroid and stable.[2][11] Any
changes to an antithyroid medication regimen should be made by five weeks gestation to
minimize exposure to inappropriate medication and to optimize thyroid hormone levels early in
the pregnancy.[11]

Neonatology should be made aware of following neonates born to women with Grave disease for
signs and symptoms of transient hyperthyroidism or neonatal Grave disease due to TRAbs that
crossed the placenta before birth.[3][10]

Review Questions

Access free multiple choice questions on this topic.

Comment on this article.

References
1. Earl R, Crowther CA, Middleton P. Interventions for hyperthyroidism pre-pregnancy and
during pregnancy. Cochrane Database Syst Rev. 2013 Nov 19;(11):CD008633. [PubMed:
24249524]
2. Moleti M, Di Mauro M, Sturniolo G, Russo M, Vermiglio F. Hyperthyroidism in the pregnant
woman: Maternal and fetal aspects. J Clin Transl Endocrinol. 2019 Jun;16:100190. [PMC
free article: PMC6484219] [PubMed: 31049292]
3. King JR, Lachica R, Lee RH, Montoro M, Mestman J. Diagnosis and Management of
Hyperthyroidism in Pregnancy: A Review. Obstet Gynecol Surv. 2016 Nov;71(11):675-685.
[PubMed: 27901552]

https://www.ncbi.nlm.nih.gov/books/NBK559203/ Halaman 9 dari 10

Hyperthyroidism In Pregnancy - StatPearls - NCBI Bookshelf 05/07/22 00.17

4. Kobaly K, Mandel SJ. Hyperthyroidism and Pregnancy. Endocrinol Metab Clin North Am. 2019
Sep;48(3):533-545. [PubMed: 31345521]
5. Hackmon R, Blichowski M, Koren G. The safety of methimazole and propylthiouracil in
pregnancy: a systematic review. J Obstet Gynaecol Can. 2012 Nov;34(11):1077-1086.
[PubMed: 23231846]
6. Negro R, Stagnaro-Green A. Clinical aspects of hyperthyroidism, hypothyroidism, and
thyroid screening in pregnancy. Endocr Pract. 2014 Jun;20(6):597-607. [PubMed: 24449669]
7. Sarkar S, Bischoff LA. Management of Hyperthyroidism during the Preconception Phase,
Pregnancy, and the Postpartum Period. Semin Reprod Med. 2016 Nov;34(6):317-322.
[PubMed: 27741549]
8. Cooper DS, Laurberg P. Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol. 2013
Nov;1(3):238-49. [PubMed: 24622372]
9. Stagnaro-Green A, Dong A, Stephenson MD. Universal screening for thyroid disease during
pregnancy should be performed. Best Pract Res Clin Endocrinol Metab. 2020
Jul;34(4):101320. [PubMed: 31530447]
10. Illouz F, Luton D, Polak M, Besançon A, Bournaud C. Graves' disease and pregnancy. Ann
Endocrinol (Paris). 2018 Dec;79(6):636-646. [PubMed: 30224035]
11. Laurberg P, Andersen SL. ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the
incidence, diagnosing and therapy of Graves' disease. Eur J Endocrinol. 2016
Nov;175(5):R219-30. [PubMed: 27280373]
12. De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, Eastman CJ,
Lazarus JH, Luton D, Mandel SJ, Mestman J, Rovet J, Sullivan S. Management of thyroid
dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice
guideline. J Clin Endocrinol Metab. 2012 Aug;97(8):2543-65. [PubMed: 22869843]
13. Lazarus JH. Management of hyperthyroidism in pregnancy. Endocrine. 2014
Mar;45(2):190-4. [PubMed: 24174179]
14. Lazarus JH. Management of hyperthyroidism in pregnancy. Endocrine. 2014
Mar;45(2):190-4. [PubMed: 24174179]

Copyright © 2022, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution, and reproduction in
any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is provided to the
Creative Commons license, and any changes made are indicated.

Bookshelf ID: NBK559203 PMID: 32644629

https://www.ncbi.nlm.nih.gov/books/NBK559203/ Halaman 10 dari 10