AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

goitrous chronic thyroiditis, postpartum thyroiditis, PPT, atrophic thyroiditis, chronic autoimmune thyroiditis, subacute thyroiditis, thyroiditis, subacute, autoimmune thyroid dysfunction, endocrinopathy, excess thyroid hormone, TH, thyroid gland, thyroid peroxidase antibody, anti-TPO

miscarriage, pregnancy loss, preeclampsia, preterm delivery, maternal infection, maternal congestive heart failure, maternal CHF, placental abruption, prematurity, small size for gestational age, fetal growth restriction, intrauterine fetal death

fetal goiter, neonatal goiter, fetal thyrotoxicosis, neonatal thyrotoxicosis, iatrogenic fetal hypothyroidism, maternal microcytic anemia, postpartum hemorrhage, maternal cardiac dysfunction, prematurity, low birth weight, congenital anomalies, stillbirth, poor neuropsychological development, thyroid function test, TFT

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

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.

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.

Pathophysiology

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.

Graves disease

Adams and Purves 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.^{2, 3, 4, 5}

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).

Frequency

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.¹

International

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.

Mortality/Morbidity

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

Hyperthyroidism

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, and fetal or neonatal goiter and/or thyrotoxicosis. Overtreatment may cause iatrogenic fetal hypothyroidism.

Hypothyroidism

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.

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.

Approximately 10-15% of the population has thyroid antibodies. These antibodies have been linked to an increased risk of spontaneous abortion.

Subclinical hypothyroidism also has been associated with spontaneous abortion and with preterm labor.

Postpartum thyroiditis

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

Sex

Autoimmune thyroid diseases occur more often in women than in men. The female-to-male ratio is 5-10:1.⁶

Age

Autoimmune thyroid dysfunction most often affects women of reproductive age.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

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.

Hyperthyroidism

• Patients with hyperthyroidism usually report loss of concentration, nervousness, and emotional lability.
• Tremor, heat intolerance, excessive sweating, palpitations, and hyperdefecation are also common findings.
• Patients may report having difficulty with climbing stairs; this is a sign of proximal muscle weakness.
• Some patients may report that their neck is getting bigger than it was before. This change is caused by the enlarged thyroid gland.

Hypothyroidism

• Untreated patients with moderate-to-severe hypothyroidism have impaired fertility. As a result, women with this disease are rarely pregnant at the time of presentation.
• Symptoms of mild hypothyroidism can mimic those of normal pregnancy, making diagnosis difficult.
• Lethargy, weight increase, and constipation are commonly reported.
• Patients frequently report having cold intolerance, stiffness, muscle cramping, carpal tunnel syndrome, dry hair and skin, and a deepened voice.

Postpartum thyroiditis

• PPT has 3 phases:
• 1. Hyperthyroid phase, when thyroid hormones are being released because of thyroid destruction
  2. Hypothyroid phase
  3. Resolution, or euthyroid, phase
• The most common time for women present with PPT is 1-8 months after delivery, with a peak incidence at 6 months. This timing is important because the process may overlap with the next pregnancy in women who have short pregnancy intervals.
• Depending on the stage of disease at the time of presentation, patients may have symptoms of hyperthyroid or hypothyroid, as outlined above.

Subclinical hypothyroidism

• Subclinical hypothyroidism affects 2-3% of women in pregnancy.
• The symptoms of subclinical hypothyroidism are vague and nonspecific.
• The diagnosis is based on a normal level of free thyroxine (FT4) and an elevated TSH level.

Physical

Hyperthyroidism

• General appearance: In general, patients with hyperthyroidism are restless, anxious, and fidgety.
• Skin and hair: The patient's skin is warm and moist, with a velvety texture, and their hair is fine and silky.
• Eyes
• • The eyes usually have a characteristic stare, with a widened palpebral fissure.
  • Lid lag and failure to wrinkle the brow during the upward gaze are common findings.
  • With careful observation, infrequent blinking is noted.
  • With the infiltrating ophthalmopathy of Graves’ disease, potential findings include proptosis, ophthalmoplegia, chemosis, conjunctivitis, periorbital swelling, corneal ulceration, optic neuritis, and optic dystrophy.
• Thyroid
• • A goiter is present in almost every pregnant patient with Graves’ disease.
  • The gland is diffusely enlarged, usually 2-4 times normal.
  • The gland can be soft or firm, and it is seldom tender to palpation.
  • A thrill or bruit may be present.
  • Thoroughly examine the thyroid gland for nodules. The presence of a nodule requires further workup during pregnancy to rule out malignancy.
• Heart
• • Findings on cardiac examination include a wide pulse pressure due to increased systolic pressure and decreased diastolic pressure.
  • Sinus tachycardia is common. A resting tachycardia greater than 100 bpm that does not change with Valsalva is helpful in distinguishing hyperthyroid tachycardia from that of pregnancy.
  • Atrial arrhythmias can also be found on examination. These usually occur in the form of atrial fibrillation.
  • Other findings are systolic murmurs, an increased intensity of the apical first sound, cardiac enlargement, and cardiac failure.
• Nails
• • Separation of the nail from the distal nail bed, known as onycholysis or Plummer nail, can often be found when the extremities are examined. The ring fingers are most commonly affected.
  • Fine tremor of the fingers and hyperreflexia can also be noted.

Fetal thyroid dysfunction

• Suggestive findings
• • Fetal tachycardia (fetal heart rate >160 bpm)
  • Intrauterine growth restriction
  • Fetal goiter
  • Hydrops
• Causes
• • The risk of fetal or neonatal thyrotoxicosis is related to the mother's level of thyroid receptor–stimulating antibodies because the antibodies freely cross the placenta.
  • Fetal or neonatal hypothyroidism may also be due to maternal use of antithyroid drugs (ATDs), as these cross the placenta.
• Diagnosis and screening
• • Fetal diagnosis requires umbilical cord sampling to differentiate hyperthyroidism from hypothyroidism.
  • In women with a past or current history of autoimmune thyroid disease, thyroid antibody values should be checked at the end of the first pregnancy. For those with positive results for thyroid receptor–stimulating antibodies or those taking ATDs, fetal ultrasonography should be performed at least monthly after 20 weeks of gestation.
• Treatment
• • Fetal thyroid dysfunction is treated with adjustment of maternal ATD therapy.
  • Fetal hypothyroidism may require intra-amniotic administration of T4.

Hypothyroidism

• Motor function and cognition: Patients with hypothyroidism appear to have slowing of speech and movement. They can also be forgetful and exhibit difficulty with concentration.
• Skin: The skin is usually dry, pale, and yellowish.
• Hair: Hair is thin, brittle, and sparse.
• Head, eyes, ears, nose, and throat
• • Auditory acuity may be decreased.
  • Eye examination may reveal periorbital puffiness.
  • A large tongue and an expressionless face can be observed in patients with severe disease.
• Thyroid gland
• • A goiter associated with Hashimoto thyroiditis is firm, diffusely enlarged, and usually painless to palpation.
  • In patients with atrophic chronic thyroiditis, the thyroid gland may be normal or not palpable.
• Heart
• • A low-normal heart rate is common.
  • The heart can be enlarged if it is dilated.
  • Pericardial effusion is present in severe cases.
• GI tract
• • Bowel sounds may be decreased or absent.
  • Paralytic ileus has been reported in severe cases of hypothyroidism.
• Extremities: Examination of the extremities may reveal nonpitting edema and hyporeflexia, with prolongation of the relaxation phase of the reflex response.
• Fetus: Fetal examination usually reveals normal findings in mild cases.

Postpartum thyroiditis

• Presenting findings: Patients with PPT can present with symptoms of hyperthyroidism or hypothyroidism, depending on the stage of disease.
• Phases of disease: As many as one third of women with PPT present with hyperthyroidism at 1-4 months after birth. This period is followed by a hypothyroid phase lasting as long as 2 months. Recovery then ensues.

Causes

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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Hyperthyroidism

Disorders associated with thyroid hyperfunction include these:

• Excessive production of TSH
• Abnormal thyroid stimulation (eg, due to Graves disease, trophoblastic tumors)
• Intrinsic thyroid autonomy (eg, hyperfunctioning adenoma, toxic multinodular goiter, thyroid malignancy)

About 30-60% of women with hyperemesis gravidarum have gestational hyperthyroidism. This condition is characterized by elevated FT4 values, suppressed TSH levels, minimal thyroid enlargement, variable evidence of clinical hyperthyroidism, and absent thyroid antibodies. Gestational hyperthyroidism is due to the thyroid-stimulation effects of human chorionic gonadotropin (hCG) and is most likely to arise in the setting of elevated hCG concentrations (eg, molar or multiple pregnancies). Treatment is usually not needed because spontaneous recovery occurs after the first trimester.

Disorders not associated with thyroid hyperfunction include these:

• Disorders of hormone storage (eg, subacute thyroiditis, thyrotoxicosis phase of chronic thyroiditis)
• Disorders associated with an extrathyroidal source of hormone (eg, thyrotoxicosis factitia, ectopic thyroid tissue [struma ovarii, functioning follicular carcinoma])

Hypothyroidism

Thyroid-related conditions include the following:

• Thyroprivic conditions (eg, primary idiopathic, postablative, postradiation)
• Goitrous conditions (eg, iodine deficiency, drug-elicited disorders, chronic thyroiditis [Hashimoto thyroiditis])

Other thyroid conditions are related to the following entities:

• Suprathyroid conditions
• Pituitary conditions (eg, Sheehan syndrome)
• Hypothalamic conditions (eg, inadequate thyroid-releasing hormone)
• Self-limited conditions (eg, withdrawal of suppressive thyroid therapy, PPT)

Effects of commonly used drugs

Creasy and Resnik described effects of commonly used drugs on the results of tests for thyroid hormone. The following is an adapted list of effects and examples of drugs that cause them:

• Inhibition of thyroid function - Iodine, lithium, and sulfonylureas
• Inhibition of T4 and triiodothyronine (T3) conversion - Glucocorticoids, propranolol, amiodarone, and propylthiouracil (PTU)
• Increase in TSH levels - Iodine, lithium, dopamine antagonists, and cimetidine
• Decrease in TSH levels - Glucocorticoids, dopamine agonists, and somatostatin
• Inhibition of the binding of T4 and T3 to transport proteins - Phenytoin, sulfonylureas, diazepam, furosemide, and salicylates
• Inhibition of GI absorption of thyroid hormones - Cholestyramine, ferrous sulfate, aluminum hydroxide, and sucralfate

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

Hyperthyroidism

• T3, T4, FT3, FT4, and TSH tests
• • Total T3 and total T4 levels are increased due to a rise in the amount of thyroid-binding globulin. Free T3 (FT3) and FT4 levels are high-normal in the first trimester and return to normal by the second trimester.
  • Total T4 values are not useful in pregnant women because they rise in response to the estrogen-induced increase in the amount of thyroid-binding globulin.
  • FT3 values should be measured when the TSH value is suppressed but the FT4 level is normal. An elevated T3 level confirms T3 toxicosis.
  • TSH concentrations fall during pregnancy, especially in the first trimester, because hCG cross-reacts with TSH receptors on the thyroid gland.
  • • In a prospective study of 666 women in Belgium, suppressed TSH levels were noted in 15%, 10%, and 5% in first-, second-, and third-trimester pregnancies.⁷
    • Trimester-specific TSH normograms have been described. TSH levels are significantly lower and FT4 levels are significantly higher in the first trimester than levels in the second or third trimesters.
  • TSH levels alone should not be used to diagnose hyperthyroidism in pregnancy.
  • The FT4 index is slightly low or normal.
  • Among patients in a hyperthyroid state, the TSH level is low, whereas the FT4 or FT4 index value is elevated.
• Resin T3 update test: Resin T3 uptake is reduced because the number of unsaturated binding sites increases.
• Test for thyroid-stimulating immunoglobulins
• • Patients with Graves disease almost always have positive results for thyroid-stimulating immunoglobulins (TSIs).
  • Measurement of TSI concentrations should be part of the workup for patients with hyperthyroidism.
• CBC, liver function test, and determination of calcium and magnesium levels
• • These laboratory tests should be ordered after hyperthyroidism is diagnosed.
  • Findings or conditions that can occur with hyperthyroidism include normochromic normocytic anemia, mild neutropenia, elevated liver enzyme levels, mild hypercalcemia, and hypomagnesemia.
• Antimicrosomal antibody test: Women who have positive results for antimicrosomal antibodies early in pregnancy or shortly after delivery are at risk for developing PPT.

Hypothyroidism

• FT4 and TSH tests
• • In primary hypothyroidism, TSH levels are elevated and the FT4 value or FT4 index should be low.
  • With suprathyroid hypothyroidism, the TSH level may be normal or low, and the FT4 level or FT4 index is low.
  • In subclinical hypothyroidism, the FT4 value is normal, and the TSH level is elevated.
• Tests for anti-TPO and antithyroglobulin antibodies
• • levels of anti-TPO and antithyroglobulin antibodies should be measured in pregnant women with possible hypothyroidism to determine if Hashimoto thyroiditis is the cause.
  • Measurement of anti-TPO antibody concentrations is often sufficient because the results are almost always positive in patients with Hashimoto thyroiditis.
• CBC and liver function tests
• • Consider ordering a CBC and liver function tests after hypothyroidism is diagnosed.
  • Anemia is observed in as many as 30-40% of patients because erythropoiesis is decreased.
  • Concomitant vitamin B-12 or folic acid deficiency should be considered if the anemia is macrocytic.
  • Leukocyte and platelet counts are usually normal.

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.

Procedures

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.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Hyperthyroidism

The goal of treatment is to maintain clinical euthyroidism, with the mother's FT4 level in the high-normal range.

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, aplastic cutis, and choanal and/or esophageal atresia. Therefore, PTU tends to be the first choice in this class of drugs.

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.

Hypothyroidism

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 is the treatment for patients with hypothyroidism, which should be corrected before pregnancy occurs. A full replacement dosage of 1.7-2.0 mcg/kg/d 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.

The dosage of thyroid hormone should be increased at 4-6 weeks of gestation; an increase of 30-50% may be required. In general, adjustments are made as shown in the Table below.

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

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. Afterward, levels may be checked 6-8 weeks.

Patients with subclinical hypothyroidism should be treated to normalize maternal TSH levels. Women with thyroid antibodies in pregnancy who are euthyroid should be monitored with TFTs because of their high risk of developing hypothyroidism.

After delivery, the dosage of thyroid medication usually needs to be decreased over 4 weeks.

Surgical Care

Hyperthyroidism

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:

• High doses of ATDs (PTU > 300 mg, MMI > 20 mg) are required.
• Clinical hyperthyroidism cannot be controlled.
• Fetal hypothyroidism occurs at the dosage needed for maternal control.
• The patient cannot tolerate ATDs.
• The patient is noncompliant.
• Malignancy is suspected.

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

Hypothyroidism

No surgical care is recommended.

Consultations

Consultation with perinatologists and endocrinologists is recommended.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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

Drug Category: Antithyroid drugs

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.

Drug Name	Methimazole, MMI (Tapazole)
Description	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.
Adult Dose	20-40 mg/d PO
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Has anti–vitamin K activity; may potentiate activity of oral anticoagulants
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Monitor PT during therapy; may cause hypoprothrombinemia and bleeding; once symptoms of hyperthyroidism resolve, elevated serum TSH levels indicate need to lower maintenance dosage

Drug Category: Iodides

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.

Drug Category: Thyroid hormones

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.

Drug Category: Beta-adrenergic blocker

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.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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:

• Fever
• Tremors
• Agitation
• Altered mental status (eg, coma)
• Pronounced cardiovascular symptoms (eg, heart failure, tachyarrhythmias including atrial fibrillation)
• Nausea, vomiting, and/or diarrhea

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. Propanolol provides beta-blockade and controls the patient's heart rate.

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

Further Outpatient Care

Hyperthyroidism

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.

Hypothyroidism

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.

Deterrence/Prevention

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:

• Personal history of thyroid disease
• Family history of thyroid disease
• Goiter
• Positive thyroid antibodies
• Symptoms or clinical signs suggestive of thyroid disease (eg, anemia, elevated cholesterol level, hyponatremia)
• Pregestational diabetes
• Other autoimmune disorders
• Infertility
• Previous head and neck irradiation
• History of miscarriage or preterm birth

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.

Complications

Hyperthyroidism

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

Maternal complications

• Miscarriage
• Infection
• Preeclampsia
• Preterm delivery
• Congestive heart failure
• Thyroid storm
• Placental abruption

Fetal and neonatal complications

• Prematurity
• Small size for gestational age
• Intrauterine fetal death
• Toxemia
• Fetal or neonatal thyrotoxicosis, including accelerated bone maturation, goiter, and hydrops

Hypothyroidism

Maternal complications of untreated hypothyroidism

• Microcytic anemia
• Preeclampsia
• Placental abruption
• Postpartum hemorrhage
• Cardiac dysfunction
• Miscarriage

Fetal or neonatal complications

• Prematurity
• Stillbirth
• Delayed bone maturation
• Goiter
• Hydrops
• Poor neurologic development

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.

Prognosis

• 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 eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

General

In pregnant women, thyroid dysfunction can easily be diagnosed by obtaining TSH and/or FT4 levels. TSH and FT4 tests are relatively inexpensive given the potential medical and legal pitfalls that can occur if a diagnosis is missed.

The thyroid gland should be examined in every pregnant patient. At present, no conclusive evidence supports universal screening of pregnant women for thyroid dysfunction. However, high-risk patients should be tested.

Hyperthyroidism

Hyperthyroidism affects approximately 1 in 2000 pregnant women. Because the signs and symptoms of hyperthyroidism are similar to the normal changes of pregnancy, careful history taking and detailed physical examination are important in every pregnant patient.

The outcome of pregnancy in the setting of hyperthyroidism largely depends on the degree of metabolic control. Adverse perinatal outcomes, an increased risk of preeclampsia, and CHF are some potential complications in patients with a poorly controlled state.

Pregnant women with positive TSI results or those taking an ATD should be monitored for fetal thyroid dysfunction.

Hypothyroidism

Maternal hypothyroidism in early pregnancy is associated with fetal or neonatal neurologic deficiency.

Most of the available data indicates that adequate replacement of thyroid hormone greatly improves the outcome of the pregnancy.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Mar 17, 2008