Autoimmune Thyroid Disease and Pregnancy



Thyroid disorders are the second most common endocrinologic disorders found in pregnancy. Overt hypothyroidism is estimated to occur in 0.3-0.5% of pregnancies. Subclinical hypothyroidism appears to occur in 2-3%, and hyperthyroidism is present in 0.1-0.4%.[1]

Autoimmune thyroid dysfunctions remain a common cause of both hyperthyroidism and hypothyroidism in pregnant women. Graves disease accounts for more than 85% of all cases of hyperthyroid, whereas Hashimoto thyroiditis is the most common cause of hypothyroidism.

Postpartum thyroiditis (PPT) reportedly affects 4-10% of women. PPT is an autoimmune thyroid disease that occurs during the first year after delivery. Women with PPT present with transient thyrotoxicosis, hypothyroidism, or transient thyrotoxicosis followed by hypothyroidism. This presentation may be unrecognized, but is important because it predisposes the woman to develop permanent hypothyroidism.[2]

Women with a past history of treated Graves disease or a thyrotoxic phase in early pregnancy are at increased risk of developing (Graves) hyperthyroidism postpartum.[3]

Of interest, symptoms of autoimmune thyroid diseases tend to improve during pregnancy. A postpartum exacerbation is not uncommon and perhaps occurs because of an alteration in the maternal immune system during pregnancy. The improvement in thyroid autoimmune diseases is thought to be due to the altered immune status in pregnancy.


The defect that predisposes an individual to develop autoimmune thyroid disease is still unknown. Proposed mechanisms include a tissue-specific defect in suppressor T-cell activity, a genetically programmed presentation of a thyroid-specific antigen, and an idiotype/anti-idiotype reaction. Regardless of the cause, the common outcome is the production of 1 or more types of autoantibodies, which affect thyroid function positively or negatively.

Graves disease

Adams and colleagues described the concept of Graves disease as an autoimmune dysfunction of the thyroid gland. These investigators noted that the sera of patients with Graves disease contained a factor that stimulated the murine thyroid gland. This factor had a longer duration of action than that of thyrotropin (ie, thyroid-stimulating hormone [TSH]), the long-acting thyroid stimulator.[4, 5, 6, 7]

Further studies revealed that these long-acting thyroid stimulators are autoantibodies directed against the TSH receptor. The activating versions of the TSH receptor are the thyroid-stimulating autoantibodies, which activate adenylate cyclase and which stimulate thyroid function.

In terms of histologic features, the thyroid glands of patients with Graves disease show follicular hypertrophy and hyperplasia (see Histologic Findings).

Hashimoto thyroiditis

Hashimoto thyroiditis is also known as goitrous chronic thyroiditis. Almost all patients with this disease have positive test results for the thyroid peroxidase antibody (anti-TPO), an autoantibody against thyroid peroxidase enzyme. Of these patients, 50-70% also have positive results for antithyroglobulin antibodies.

Classic histologic findings of Hashimoto thyroiditis are extensive lymphocytic infiltration, follicular rupture, eosinophilia, various degrees of hyperplasia, and fibrosis (see Histologic Findings).

Atrophic chronic thyroiditis

Atrophic chronic thyroiditis is a rare autoimmune cause of hypothyroidism. This condition is characterized by the presence of blocking autoantibodies to the TSH receptors.

Postpartum thyroiditis

PPT is a variant of chronic autoimmune thyroiditis (Hashimoto thyroiditis). PTT is characterized by the presence of antimicrosomal antibodies. Histologic examination of PTT-affected thyroid glands affected reveals destructive lymphocytic thyroiditis (see Histologic Findings).



United States

Hyperthyroidism affects 0.1-0.4% of pregnancies. Graves disease accounts for 85% of these cases. Hypothyroidism affects up to 2.2% of pregnant women and Hashimoto thyroiditis is the most common cause. Atrophic thyroiditis is less common. Postpartum thyroiditis has a prevalence ranging from 3.3-8.8% in the United States.

The most common cause of thyrotoxicosis in the postpartum period is postpartum thyroiditis. Specifically, the prevalence of postpartum thyrotoxicosis has been shown to be 4.1% vs 0.2% for thyrotoxicosis related to Graves disease.


The reported range for the frequency of PPT is wide. In Thailand, as few as 2 in 100 postpartum women are affected. By comparison, some Canadian studies revealed a frequency of 2 per 10 postpartum women. These differences may be due to variations in diagnostic criteria, in genetic factors, and in iodine consumption.[8]


Fetal and maternal outcomes improve when thyroid function returns to normal.


Uncontrolled hyperthyroidism, especially in the second half of pregnancy, can lead to numerous complications. Maternal complications include miscarriage, infection, preeclampsia, preterm delivery, congestive heart failure (CHF), thyroid storm, and placental abruption.

Fetal and neonatal complications include prematurity, small size for gestational age, intrauterine fetal death, fetal or neonatal goiter, and/or thyrotoxicosis. Overtreatment may cause iatrogenic fetal hypothyroidism. When maternal thyroid antibody titers are greater than 300% of the normal upper limit, the fetus is at risk of fetal hyperthyroidism and should be evaluated by ultrasound for evidence of hyper- or hypothyroidism. Fetal hyperthyroidism can include tachycardia, accelerated maturation of bone, goiter, growth restriction, and congestive heart failure.[9]


Maternal complications of untreated hypothyroidism include microcytic anemia, preeclampsia, placental abruption, postpartum hemorrhage, cardiac dysfunction, and miscarriage. Fetal or neonatal complications include prematurity, low birth weight, congenital anomalies, stillbirth, and poor neuropsychological development. Abalovich et al showed about 60% risk of fetal loss with inadequate treatment or detection of hypothyroidism.[10] Leung et al noted a 22% risk of gestational hypertension in pregnancy associated with hypothyroidism, compared to controls.[11] Allan et al demonstrated an increased risk of fetal death with hypothyroidism.[12]

In particular, overt maternal hypothyroidism is associated with neonatal neurologic developmental delay because of the transplacental transfer of thyroid hormone in early pregnancy is inadequate. This process is required for brain development. The fetal thyroid does not begin to concentrate iodine until 10-12 weeks of gestation. Therefore, before this time, the mother must provide for all of the fetus' thyroxine (T4) requirements. Thus, the conclusion of all available evidence demonstrates that hypothyroidism is associated with significant adverse maternal and fetal sequelae.

Subclinical hypothyroidism may be associated with an increased risk of adverse pregnancy complications such as spontaneous abortions, fetal loss, and preterm labor. A study by Wilson et al found that women diagnosed with subclinical hypothyroidism during their pregnancy have an increased risk for severe preeclampsia.[13] An association between maternal subclinical hypothyroidism and adverse fetal neurocognitive development is biologically plausible though not clearly demonstrated.

Approximately 10-15% of the population have thyroid antibodies, a number which may be even higher in the obstetric population[14] . These antibodies have been linked to an increased risk of spontaneous abortion.

It is debated whether isolated hypothyroxinemia causes any adverse effects on the developing fetus; reports of decreased IQ in offspring have been criticized for methodological processes and the plausibility of the conclusion.

Postpartum thyroiditis

Complications associated with postpartum thyroiditis (PPT) are maternal, and depression is common. Permanent hypothyroidism occurs in as many as 20-40% of women.[15] These patients are also at high risk for recurrent PPT with subsequent pregnancies.


Autoimmune thyroid diseases occur more often in women than in men. The female-to-male ratio is 5-10:1.[16]


Autoimmune thyroid dysfunction most often affects women of reproductive age.


Symptoms of hyperthyroid can be easily confused with symptoms of the hypermetabolic state of pregnancy. Mild hypothyroid symptoms can be difficult to distinguish from the common aches and pains of pregnancy. Obtaining a careful patient history is essential in the evaluation of women thought to have thyroid dysfunction.



Postpartum thyroiditis

Subclinical hypothyroidism



Fetal thyroid dysfunction


Postpartum thyroiditis


The defect that predisposes an individual to develop autoimmune thyroid disease is still unknown. Proposed mechanisms include a tissue-specific defect in suppressor T-cell activity, a genetically programmed presentation of a thyroid-specific antigen, and an idiotype/anti-idiotype reaction. Regardless of the cause, the common outcome is the production of 1 or more types of autoantibodies.

Laboratory Studies



Postpartum thyroiditis

Generally, TSI is negative in PPT in the majority of cases, while it is positive with postpartum Graves disease. An elevated T4:T3 ratio suggests the presence of PPT. The radioiodine uptake is elevated or normal in Graves disease and low in PPT.

Imaging Studies

Imaging modalities currently available for the evaluation of thyroid disease are ultrasonography, CT scanning, MRI, and radioactive iodine uptake testing. Radioactive iodine uptake testing is contraindicated in pregnancy. Ultrasonography is considered a safe test in pregnancy, and sonographic findings can help in differentiating a cystic nodule from a solid nodule. Spectral Doppler ultrasound may be a useful adjunct to distinguish hyperthyroid and hypothyroid postpartum thyroiditis.[22]


Thyroid biopsy is rarely necessary for diagnosing autoimmune thyroid disease in pregnant women.

The workup of a thyroid nodule should not be delayed in pregnancy. Fine-needle aspiration biopsy can provide valuable cytologic information.

Histologic Findings

The essential histologic findings of Graves disease are glandular hyperplasia and hypertrophy characterized by increased height of the follicular cells and redundancy of the follicular wall. Lymphocytic infiltration reflects the immune aspect of this disease.

Ophthalmopathy of Graves disease is characterized by lymphocytic infiltration of the orbital contents with lymphocytes, mast cells, and plasma cells. Likewise, lymphocytic infiltration is readily observed in association with the dermal thickening seen in the dermopathy found in patients with Graves disease.

Hashimoto thyroiditis is characterized by extensive diffuse lymphocytic infiltration. Other classic findings are follicular rupture, eosinophilia, various degrees of hyperplasia, and fibrosis.

PPT is characterized by destructive lymphocytic infiltration of the thyroid gland.

See also Pathophysiology.

Medical Care


Prenatal counseling and management of Graves disease:

Women with hyperthyroidism should be treated either with ablative therapy (iodine radiation or surgery) or medical therapy and become euthyroid before attempting pregnancy. For ablative therapy, TSI titers tend to increase and remain elevated for many months. A pregnancy test should be performed 48 hours before the iodine radiation ablation to avoid radiation exposure to the fetus. Conception should be delayed for 6 months postablation to allow time for the dose of T4 to be adjusted to obtain target values for pregnancy (serum TSH between 0.3 and 2.5 mIU/L).

If the patient chooses thioamide drugs (ATD therapy), propylthiouracil (PTU) should be used in the first trimester of pregnancy, because of the risk of methimazole (MMI) embryopathy; and consideration should be given to discontinuing PTU after the first trimester and switching to MMI in order to decrease the incidence of liver disease. Contraception should be used until normal thyroid function is achieved.[3, 17]

Pregnancy management:

The goal of treatment is to maintain clinical euthyroidism, with the mother's FT4 level in the high-normal range. In order to prevent overtreatment and possible neonatal hypothyroidism, the lowest dose possible should be used to keep maternal free T4 and free T3 in upper limit of the normal range.[23]

Thioamide drugs (ie, ATDs) are the first-line treatment in pregnancy. PTU, methimazole (MMI), and carbimazole (CMI) are the ATDs available in the United States. These drugs inhibit iodination of thyroglobulin and thyroglobulin synthesis by competing with iodine for the enzyme peroxidase. PTU, MMI, and CMI are equally effective.

A controversial association exists between MMI and fetal scalp defects, aplasia cutis, and choanal and/or esophageal atresia. Some studies have reported a positive association between the two and others reported no association, which may be due to the fact that the studies showing no association were underpowered or did not assess outcomes at the optimal ages.[24] Additionally, PTU has recently been shown to increase the risk of malformations, usually milder than those with MMI, but a change from one to the other has not been shown to protect against birth defects.[25]

Because of the potential for worse malformations with MMI, PTU tends to be the first choice in this class of drugs.[25]  However, PTU confers a higher risk of maternal agranulocytosis and liver failure. Although in a recent Danish population-based study there were only 41 and 11 cases, respectively, per 5 million inhabitants over a 10-year period. By contrast, ATD-associated birth defects occurred in 3.4% of exposed neonates (44 cases per 5 million over 10 years).[26]

A 1:20 dosage ratio of MMI to PTU is recommended when transitioning from one drug to the other.[17]

The US Food and Drug Administration (FDA) had added a boxed warning, the strongest warning issued by the FDA, to the prescribing information for propylthiouracil. The boxed warning emphasizes the risk for severe liver injury and acute liver failure, some of which have been fatal. The boxed warning also states that propylthiouracil should be reserved for use in those who cannot tolerate other treatments such as methimazole, radioactive iodine, or surgery.

The decision to include a boxed warning was based on the FDA's review of postmarketing safety reports and meetings held with the American Thyroid Association, the National Institute of Child Health and Human Development, and the pediatric endocrine clinical community.

The FDA has identified 32 cases (22 adult and 10 pediatric) of serious liver injury associated with propylthiouracil (PTU). Of the adults, 12 deaths and 5 liver transplants occurred, and among the pediatric patients, 1 death and 6 liver transplants occurred. PTU is indicated for hyperthyroidism due to Graves disease.[27]

These reports suggest an increased risk for liver toxicity with PTU compared with methimazole. Serious liver injury has been identified with methimazole in 5 cases (3 resulting in death). PTU is considered as a second-line drug therapy, except in patients who are allergic or intolerant to methimazole, or for women who are in the first trimester of pregnancy. Rare cases of embryopathy, including aplasia cutis, have been reported with methimazole during pregnancy.

The FDA recommends the following criteria be considered for prescribing PTU. For more information, see the FDA Safety Alert.

Free T4 and TSH should be measured approximately every 2-4 weeks at initiation of therapy and every 4-6 weeks after achieving the target value.

Doses of ATDs should be maintained at the lowest dose needed to keep the mother's FT4 level in the high-normal range. Weight gain, pulse rate, FT4 results, and TSH levels should be monitored monthly.

Beta-blockers (eg, atenolol, nadolol, propranolol) are valuable adjuncts to ATDs. These drugs effectively alleviate symptoms of hypermetabolic states. With prolonged use, beta-blockers are associated with fetal morbidity. Therefore, these drugs should be used for only a short period (ie, 2 wk) while one waits for the ATDs to take effect.

Iodide decreases serum T4 and T3 levels by 30-50% in 10 days. Iodide is used in combination with ATDs and beta-blockers during the preoperative treatment of patients with hyperthyroidism. Iodide can also be used in the medical treatment of patients with thyroid storm. Fetal hypothyroidism resulting from placental passage is reported with prolonged use of iodide products; therefore, iodide use should be limited to less than 2 weeks.

Use of radioactive iodine is contraindicated in pregnancy.

The prevalence of fetal and neonatal hyperthyroidism is 1-5% in women with active or past history of Graves hyperthyroidism. Fetal and neonatal morbidity and mortality are increased if unrecognized and untreated.

A determination of serum TSI antibodies by 24–28 weeks' gestation is helpful in detecting pregnancies at risk for fetal and neonatal hyperthyroidism. Testing in the first trimester may also be helpful.

Fetal surveillance with serial ultrasounds should be performed in women who have uncontrolled hyperthyroidism and/or women with high TSI antibodies (levels greater than 3 times the upper limit of normal) or those that develop preeclampsia. Signs of potential fetal hyperthyroidism that may be detected by ultrasonography include intrauterine growth restriction, presence of fetal goiter, accelerated bone maturation, and fetal hydrops. A consultation with an experienced obstetrician or maternal–fetal medicine specialist is optimal.[3]

Gestational thyrotoxicosis is a transient, non-autoimmune form of the disease associated with hyperemesis gravidarum. It does not require treatment with ATDs, only supportive care, as it resolves spontaneously once human chorionic gonadotropin levels fall after the first trimester.

Postpartum hyperthyroidism:

MMI in doses up to 20–30 mg/d is safe for lactating mothers and their infants. PTU at doses up to 300 mg/d is a second-line agent due to concerns about severe hepatotoxicity. ATDs should be administered following a feeding and in divided doses. Breast-feeding infants of mothers taking ATDs should be screened with thyroid function tests.


The goal of treatment is to normalize maternal TSH levels. It should be remembered that iodine deficiency is an important cause of neonatal neurologic damage worldwide. The recommended mean intake of iodine during pregnancy and lactation is approximately 250 mcg/d.

Thyroid hormone replacement using synthetic thyroxine (T4) is the treatment for patients with hypothyroidism, which should be corrected before pregnancy occurs. A full replacement dosage of 1.6-2.0 mcg/kg/day should be started at the time of diagnosis. Preconception thyroid medication should be adjusted to achieve a TSH level of less than 2.5 mU/mL before pregnancy. Other thyroid preparations, such as T3 or desiccated thyroid, are strongly discouraged.

The goal of thyroid hormone treatment is to normalize maternal serum TSH values within the trimester-specific pregnancy reference range (first trimester, 0.1-2.5 mIU/L; second trimester, 0.2-3.0 mIU/L; third trimester, 0.3-3.0 mIU/L).

The dosage of thyroid hormone should be increased at 4-6 weeks of gestation; an increase of 25-30% may be required. This is because the increased requirement for thyroid hormone (endogenous or exogenous thyroxine) occurs as early as 4–6 weeks of pregnancy and gradually increases through 16–20 weeks of pregnancy, and thereafter plateaus until time of delivery. However, unlike healthy women, those with preexisting hypothyroidism or subclinical hypothyroidism are unable to increase thyroid hormone production. Hypothyroid women who are newly pregnant should preemptively increase their thyroid hormone dose by approximately 30% and notify their clinician promptly. This can be achieved by increasing the dosing from once daily to a total of nine doses per week (double the daily dose two days each week).

Thyroid hormone adjustments may be made as shown in the Table below.

Table. Mean Increases in Dosages of Thyroid Hormone According to Serum TSH levels

View Table

See Table

If hypothyroidism is diagnosed during pregnancy, the thyroid medication should be titrated rapidly to achieve TSH levels of less than 2.5 mcg. During pregnancy, the full replacement dosage of T4 is approximately 2.0-2.4 mcg/kg/d.

Results of thyroid function tests (TFTs) should be checked within 30 days after the dosage is changed. TFTs should be repeated until the results return to normal. In general, TSH should be measured every 4 weeks during the first half of pregnancy because dose adjustments are often required. TSH cam be monitored less often (at least once each trimester) in the latter half of pregnancy, as long as the dose is unchanged.

There are conflicting reports regarding whether it is beneficial to treat women who have been diagnosed with subclinical hypothyroidism during pregnancy.[28, 29]  Similarly, professional societies differ in their recommendations with the Endocrine Society favoring universal treatment, the American Thyroid Association preferring treatment only of women who are also positive for TPO antibodies, and the American College of Obstetricians and Gynecologists opting against treatment over a lack of data showing a benefit.[3, 17, 20, 30]

Patients with TPO antibodies alone or with subclinical hypothyroidism are at increased risk of preterm birth, but there is not currently enough evidence to recommend TSH and TPO antibody screening in low-risk women.[31] However, patients with subclinical hypothyroidism who are positive for TPO antibodies in pregnancy should be treated to normalize maternal TSH levels, but evidence is insufficient to recommend or discourage universal thyroid hormone treatment in those with subclinical hypothyroidism who are negative for thyroid antibodies. Additionally, elevated IL-6 levels in the first trimester, irrespective of thyroid autoimmunity or subclinical hypothyroidism, are a risk factor for adverse pregnancy outcomes.[32]

Women with subclinical hypothyroidism who are not initially treated should be monitored for progression to hypothyroidism with a serum TSH and FT4 approximately every 4 weeks until 16-20 weeks gestation and at least once between 26 and 32 weeks gestation.

Women with thyroid antibodies in pregnancy who are euthyroid should be monitored with TFTs because of their high risk of developing hypothyroidism. Serum TSH should be evaluated every 4 weeks during the first half of pregnancy and at least once between 26 and 32 weeks gestation.

After delivery, the dosage of thyroid medication should be reduced to the preconception dose. Additional TSH testing should be performed at approximately 6 weeks postpartum.

Isolated hypothyroxinemia should not be treated in pregnancy. There is theoretical concern for impaired fetal neurodevelopment in the setting of decreased availability of T4, but to date no study has demonstrated any benefit to treating women with isolated hypothyroxinemia during pregnancy.[3, 20, 21]


All pregnant and lactating women should ingest a minimum of 250 mg iodine daily.[33, 34] To achieve a total of 250 mg iodine ingestion daily in North America, all women who are planning to be pregnant or are pregnant or breastfeeding should supplement their diet with a daily oral supplement that contains 150 mg of iodine.[35] Potassium iodide is the favored source because kelp and other forms of seaweed do not provide a consistent delivery of daily iodide. Strategies for ensuring adequate iodine intake during preconception, pregnancy, and lactation should vary according to regional dietary patterns and availability of iodized salt.

Sustained iodine intake from diet and dietary supplements exceeding 500–1100 mg daily should be avoided due to concerns about the potential for fetal hypothyroidism. Pharmacologic doses of iodine exposure during pregnancy should be avoided, except in preparation for thyroid surgery for Graves disease. Clinicians should carefully weigh the risks and benefits when ordering medications such as amiodarone, some local anesthetics, anti-asthmatic medications and expectorants, or diagnostic tests that will result in high iodine exposure.

Interestingly, potassium iodide has been used in Japan as an alternative to using traditional ATDs during the first trimester to better balance the risks of maternal and neonatal harm. In a retrospective cohort study, women with Graves disease, all living in an iodine-sufficient area, who were treated with potassium iodide had a lower incidence of major fetal anomalies than those treated with MMI (1.53% [4/260)] versus 4.14% [47/1134]). In the potassium iodide group, 2 (0.8%) infants had malformations consistent with MMI embryopathy compared to 18 (1.6%) in the MMI group.[36]


Surgical Care


Subtotal thyroidectomy induces remission in most patients with Graves disease. Surgery should be used as the second line of treatment in pregnant women.

Surgery is reserved for patients who meet 1 of the following criteria:

When surgery is needed, it should be performed during the second trimester.


No surgical care is recommended.


Consultation with perinatologists and endocrinologists is recommended.

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.


Clinical Context:  Derivative of thiourea that inhibits organification of iodine by thyroid gland. Blocks oxidation of iodine in thyroid gland, inhibiting thyroid hormone synthesis. Inhibits T4-to-T3 conversion (advantage over other agents). DOC in patients with hyperthyroidism during pregnancy because of reports of fetal aplasia cutis (reversible scalp defect) in association with MMI or CMI. Taper gradually to minimum dosage required to maintain clinical euthyroid and to avoid fetal hypothyroidism.

Methimazole, MMI (Tapazole)

Clinical Context:  Inhibits thyroid hormone by blocking oxidation of iodine in thyroid gland, but not known to inhibit peripheral conversion of thyroid hormone. Taper gradually to minimum dosage required to maintain clinical euthyroid and to avoid fetal hypothyroidism. Cases of fetal aplasia cutis reported.

Class Summary

ATDs are effective, reversible treatments for hyperthyroidism. The consensus among experts is that ATDs should be first-line treatments for pregnant women with hyperthyroidism. ATDs inhibit iodination of thyroid thyroglobulin and thyroglobulin synthesis by competing with iodine for peroxidase. PTU and MMI are available in the United States. PTU and MMI are equally effective.

Both PTU and MMI cross the placenta and can cause fetal hypothyroidism and goiter. In addition, both PTU and MMI are excreted in small amounts in breast milk. MMI is not bound to plasma protein as much as PTU; therefore, it is excreted into the breast milk in slightly higher concentrations than PTU is.

Iodide (SSKI, Pima)

Clinical Context:  DOC. Rapidly inhibits release of thyroid hormones by directly affecting thyroid gland. Inhibits synthesis of thyroid hormones. Also appears to attenuate cyclic adenosine monophosphate (cAMP)–mediated effects of TSH.

Class Summary

Iodides inhibit the release of stored thyroid hormones. They decrease serum T4 and T3 concentrations by 30-50% by the 10th day of treatment. Iodides are reserved for the treatment of severe thyrotoxicosis or for preoperative treatment in combination with ATDs and beta-blockers. These agents readily cross the placenta by the 12th week of gestation and are readily taken up by the fetal thyroid gland. Long-term use of iodides can lead to fetal hypothyroidism and goiter. In pregnant women, these drugs should generally be used for no longer than 2 weeks.

Levothyroxine (Synthroid)

Clinical Context:  Levo isomer of T4. Once absorbed, T4 deiodinated to T3 in extrathyroidal tissues. First choice in treatment of hypothyroidism during pregnancy because it mimics physiologic state. Measure TSH levels q4wk, and adjust dosage.

Class Summary

Several forms of thyroid hormones are commercially available. They include levothyroxine, liothyronine, and liotrix. Levothyroxine is the DOC for treating pregnant women with hypothyroidism. No conclusive evidence supports the use of levothyroxine to prevent perinatal hypothyroidism.

Propranolol (Inderal)

Clinical Context:  DOC in treating cardiac arrhythmias resulting from hyperthyroidism. Controls cardiac and psychomotor manifestations in minutes.

Class Summary

Beta-blockers are valuable adjunct to ATDs. These drugs are effective for alleviating symptoms of hypermetabolic state (eg, palpitation, sweating, nervousness, tremor). They are safe during pregnancy to achieve immediate control of symptomatic thyrotoxicosis. The goal of beta-blockage is to reduce the mother's heart rate to less than 100 bpm. Prolonged use of beta-blockers has been associated with intrauterine growth restriction, fetal bradycardia, hypoglycemia, and an abnormal response to stress; therefore, long-term use not recommended during pregnancy.

Further Outpatient Care


Pregnant women with hyperthyroidism should be monitored monthly. Important parameters include vital signs (specifically the pulse rate), weight, FT4 and TSH concentrations, and measures of fetal well-being. The woman's pulse should be maintained below 100 bpm. Maternal weight gain should be appropriate for the mother's prepregnancy weight. TSH levels can be maintained near the low limit of normal as long as the patient is clinically euthyroid. FT4 values should be maintained at the upper limit of normal to ensure that the fetus' requirements are adequately met.

Fetal monitoring during pregnancy is essential. Fetal thyrotoxicosis is suggested when the fetal heart rate is faster than 160 bpm. Ultrasonography may reveal intrauterine growth retardation, advanced bone age, and craniosynostosis. Thyroid-stimulating autoantibodies can cross the placenta and activate the fetal thyroid gland.

In all pregnant women with Graves disease, TSI levels should be measured in the third trimester. A high TSI value is most likely to be associated with fetal thyrotoxicosis. Neonates born to mothers with Graves disease should be evaluated for hyperthyroidism. Approximately 1% of these babies have hyperthyroidism. If left untreated, their mortality rate can be as high as 30%.

All patients' TSH and FT4 levels should be evaluated after delivery. Women can continue taking ATDs while breastfeeding.


Patients with newly diagnosed hypothyroidism should receive TSH testing every 4 weeks, and their dosage of T4 should be adjusted as needed. The T4 replacement dosage increases by 30% by the 10th week of gestation and by 48% by the 20th week.

In all pregnant women with preexisting hypothyroidism, TSH levels should be measured at 6-8 weeks' gestation. Subsequent TSH measurements may be obtained at 16-20 and 28-32 weeks' gestation. After delivery, the dosage of T4 should be reduced to the prepregnancy amount.

Antenatal fetal surveillance may be beneficial. Delivery should be considered at term. In general, women should go past dates.

Long-term follow-up care of patients with hypothyroidism is mandatory.

Postpartum thyroiditis

Patients with PPT should receive long-term follow-up care because PTT frequently recurs with subsequent pregnancies.

Patients with significantly elevated levels antimicrosomal antibodies, a family history of hypothyroidism, or a prominent goiter are at the greatest risk for developing permanent hypothyroidism.

TSH levels should be measured at least once a year.

Further Inpatient Care

Treatment of maternal or fetal complications

Patients with clinically significant maternal or fetal complications from hyperthyroidism or hypothyroidism should be admitted to the hospital.

Management of thyroid storm

Patients with thyroid storm should be admitted to an intensive care unit. Thyroid storm is a life-threatening condition due to the acute exacerbation of symptoms of hyperthyroidism, such as the following:

Thyroid storm can be triggered by stress, such as preeclampsia or induction of labor, especially in patients with poorly controlled hyperthyroidism.

The precipitating condition should be identified and treated. General management includes the intravenous administration of fluids, cardiovascular monitoring, and implementation of cooling measures. PTU is the ATD of choice because it blocks peripheral conversion of T4 to T3. Iodide is given 1-3 hours after the ATD to inhibit the release of thyroid hormones. Dexamethasone is also given to block peripheral conversion of T4 to T3 and to prevent adrenal insufficiency. Propranolol provides beta-blockade and controls the patient's heart rate.

Aggressive thyroid hormone replacement and supportive care are the cornerstones of managing myxedema.


The benefits of universal screening for thyroid disease in pregnancy has not been justified. However, women with the following indicators of high risk should be screened:

Screening for PPT is recommended for postpartum women with type 1 diabetes and for those with positive anti-TPO results. Screening should occur at 3 and 6 months after delivery.



Uncontrolled hyperthyroidism, especially in the second half of pregnancy, can lead to numerous complications.

Maternal complications

Fetal and neonatal complications


Maternal complications of untreated hypothyroidism

Fetal or neonatal complications

Postpartum thyroiditis

Complications associated with PPT are maternal, and depression is common. Permanent hypothyroidism may occur in as many as 30% of patients. These women are also at high risk for recurrent PPT after subsequent pregnancies.


The outcome of pregnancies affected by autoimmune thyroid disease depends on the degree of metabolic control. Women with euthyroid disease can expect satisfactory outcomes of their pregnancy. With close follow-up postpartum, medical therapy can be adjusted to ensure a euthyroid state. This helps ensure a good prognosis.

Patient Education

The importance of compliance with medical therapy should be stressed. The need for frequent laboratory assessment should be discussed. The adverse effects of medical therapy, including the fetal risks, should be outlined.

For excellent patient education resources, visit eMedicineHealth's Thyroid and Metabolism Center. Also, see eMedicineHealth's patient education article Thyroid Problems.


Dotun A Ogunyemi, MD, Vice Chair of Patient Safety and Quality, William Beaumont Hospital; Professor, Oakland University, William Beaumont School of Medicine; Clinical Services Professor of Obstetrics and Gynecology, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Carl V Smith, MD, The Distinguished Chris J and Marie A Olson Chair of Obstetrics and Gynecology, Professor, Department of Obstetrics and Gynecology, Senior Associate Dean for Clinical Affairs, University of Nebraska Medical Center

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor Emeritus of Medicine, St Louis University School of Medicine

Disclosure: Nothing to disclose.


  1. Neale DM, Cootauco AC, Burrow G. Thyroid disease in pregnancy. Clin Perinatol. 2007 Dec. 34 (4):543-57, v-vi. [View Abstract]
  2. Roti E, Uberti Ed. Post-partum thyroiditis--a clinical update. Eur J Endocrinol. 2002 Mar. 146 (3):275-9. [View Abstract]
  3. [Guideline] Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011 Oct. 21 (10):1081-125. [View Abstract]
  5. ADAMS DD, KENNEDY TH, PURVES HD, SIRET NE. Failure of TSH antisera to neutralize long-acting thyroid stimulator. Endocrinology. 1962 Jun. 70:801-5. [View Abstract]
  6. ADAMS DD. The presence of an abnormal thyroid-stimulating hormone in the serum of some thyrotoxic patients. J Clin Endocrinol Metab. 1958 Jul. 18 (7):699-712. [View Abstract]
  7. Adams DD. The pathogenesis of thyrotoxicosis the discovery of LATS. N Z Med J. 1975 Jan 8. 81 (531):15-7. [View Abstract]
  8. Gerstein HC. How common is postpartum thyroiditis? A methodologic overview of the literature. Arch Intern Med. 1990 Jul. 150 (7):1397-400. [View Abstract]
  9. Luton D, Le Gac I, Vuillard E, Castanet M, Guibourdenche J, Noel M, et al. Management of Graves' disease during pregnancy: the key role of fetal thyroid gland monitoring. J Clin Endocrinol Metab. 2005 Nov. 90 (11):6093-8. [View Abstract]
  10. Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid. 2002 Jan. 12 (1):63-8. [View Abstract]
  11. Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JH. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol. 1993 Mar. 81 (3):349-53. [View Abstract]
  12. Allan WC, Haddow JE, Palomaki GE, Williams JR, Mitchell ML, Hermos RJ, et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen. 2000. 7 (3):127-30. [View Abstract]
  13. Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol. 2012 Feb. 119 (2 Pt 1):315-20. [View Abstract]
  14. Blumenthal NJ, Byth K, Eastman CJ. Prevalence of thyroid dysfunction and thyroid antibodies in a private obstetrical practice in Sydney. Aust N Z J Obstet Gynaecol. 2016 Jun. 56 (3):307-11. [View Abstract]
  15. Stagnaro-Green A. Approach to the patient with postpartum thyroiditis. J Clin Endocrinol Metab. 2012 Feb. 97 (2):334-42. [View Abstract]
  16. Friedrich N, Schwarz S, Thonack J, John U, Wallaschofski H, Völzke H. Association between parity and autoimmune thyroiditis in a general female population. Autoimmunity. 2008 Mar. 41 (2):174-80. [View Abstract]
  17. [Guideline] Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and other causes of Thyrotoxicosis. Thyroid. 2016 Aug 12. [View Abstract]
  18. Brent GA. Maternal thyroid function: interpretation of thyroid function tests in pregnancy. Clin Obstet Gynecol. 1997 Mar. 40 (1):3-15. [View Abstract]
  19. Medici M, Korevaar TI, Visser WE, Visser TJ, Peeters RP. Thyroid function in pregnancy: what is normal?. Clin Chem. 2015 May. 61 (5):704-13. [View Abstract]
  20. [Guideline] De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012 Aug. 97 (8):2543-65. [View Abstract]
  21. Furnica RM, Lazarus JH, Gruson D, Daumerie C. Update on a new controversy in endocrinology: isolated maternal hypothyroxinemia. J Endocrinol Invest. 2015 Feb. 38 (2):117-23. [View Abstract]
  22. Gaberšček S, Osolnik J, Zaletel K, Pirnat E, Hojker S. An Advantageous Role of Spectral Doppler Sonography in the Evaluation of Thyroid Dysfunction During the Postpartum Period. J Ultrasound Med. 2016 Jul. 35 (7):1429-36. [View Abstract]
  23. Gianetti E, Russo L, Orlandi F, Chiovato L, Giusti M, Benvenga S, et al. Pregnancy outcome in women treated with methimazole or propylthiouracil during pregnancy. J Endocrinol Invest. 2015 Sep. 38 (9):977-85. [View Abstract]
  24. Laurberg P, Andersen SL. Antithyroid Drug Use in Pregnancy and Birth Defects: Why Some Studies Find Clear Associations, and Some Studies Report None. Thyroid. 2015 Nov. 25 (11):1185-90. [View Abstract]
  25. Li X, Liu GY, Ma JL, Zhou L. Risk of congenital anomalies associated with antithyroid treatment during pregnancy: a meta-analysis. Clinics (Sao Paulo). 2015 Jun. 70 (6):453-9. [View Abstract]
  26. Andersen SL, Olsen J, Laurberg P. Antithyroid Drug Side Effects in the Population and in Pregnancy. J Clin Endocrinol Metab. 2016 Apr. 101 (4):1606-14. [View Abstract]
  27. US Food and Drug Administration. FDA MedWatch Safety Alerts for Human Medical Products. Propylthiouracil (PTU). Available at Accessed: June 3, 2009.
  28. Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J Clin Endocrinol Metab. 2010 Apr. 95 (4):1699-707. [View Abstract]
  29. Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012 Feb 9. 366 (6):493-501. [View Abstract]
  30. [Guideline] American College of Obstetricians and Gynecologists. Practice Bulletin No. 148: Thyroid disease in pregnancy. Obstet Gynecol. 2015 Apr. 125 (4):996-1005. [View Abstract]
  31. Kumru P, Erdogdu E, Arisoy R, Demirci O, Ozkoral A, Ardic C, et al. Effect of thyroid dysfunction and autoimmunity on pregnancy outcomes in low risk population. Arch Gynecol Obstet. 2015 May. 291 (5):1047-54. [View Abstract]
  32. Oztas E, Erkenekli K, Ozler S, Aktas A, Buyukkagnıcı U, Uygur D, et al. First trimester interleukin-6 levels help to predict adverse pregnancy outcomes in both thyroid autoantibody positive and negative patients. J Obstet Gynaecol Res. 2015 Nov. 41 (11):1700-7. [View Abstract]
  33. WHO Secretariat, Andersson M, de Benoist B, Delange F, Zupan J. Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: conclusions and recommendations of the Technical Consultation. Public Health Nutr. 2007 Dec. 10 (12A):1606-11. [View Abstract]
  34. Institute of Medicine, Food and Nutrition Board. Iodine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press; 2001.
  35. Caldwell KL, Pan Y, Mortensen ME, Makhmudov A, Merrill L, Moye J. Iodine status in pregnant women in the National Children's Study and in U.S. women (15-44 years), National Health and Nutrition Examination Survey 2005-2010. Thyroid. 2013 Aug. 23 (8):927-37. [View Abstract]
  36. Yoshihara A, Noh JY, Watanabe N, Mukasa K, Ohye H, Suzuki M, et al. Substituting Potassium Iodide for Methimazole as the Treatment for Graves' Disease During the First Trimester May Reduce the Incidence of Congenital Anomalies: A Retrospective Study at a Single Medical Institution in Japan. Thyroid. 2015 Oct. 25 (10):1155-61. [View Abstract]
Serum TSH level,

mIU/mL or mIU/L



< 2075-100