The Committee on Practice Bulletins–Obstetrics of the American College of Obstetricians and Gynecologists (ACOG) has developed a practice guideline on thyroid disease in pregnancy. ACOG Practice Bulletin No. 32 appears in the November 2001 issue of Obstetrics and Gynecology.
The ACOG guideline discusses changes in thyroid function during pregnancy, hyperthyroidism, hypothyroidism, and clinical considerations; and provides recommendations. The following information is a summary of the ACOG practice bulletin.
Thyroid Function During Pregnancy
Normal pregnancy, hyperthyroidism, and hypothyroidism affect thyroid function test results (see accompanying table). In pregnancy, the values influenced by the serum thyroid binding hormone level (i.e., total thyroxine, total triiodothyronine, and resin triiodothyronine uptake) change significantly.
Plasma iodide levels decrease as a result of fetal iodide use and increased maternal renal clearance. In about 15 percent of pregnant women, these lower iodide levels are associated with a noticeable increase in thyroid gland size.
Thyrotoxicosis is a clinical and biochemical state resulting from excess production of and exposure to thyroid hormone because of any etiology. Hyperthyroidism, which occurs in 0.2 percent of pregnancies, is thyrotoxicosis resulting from hyperfunction of the thyroid gland. The many signs and symptoms of hyperthyroidism include tremors, nervousness, insomnia, excessive sweating, heat intolerance, tachycardia, hypertension, and goiter.
Graves' disease is responsible for 95 percent of hyperthyroidism cases in pregnancy. Distinctive ophthalmic signs include eyelid lag or retraction; dermal signs include localized and pretibial myxedema. The diagnosis of this disease is generally based on an elevated free thyroxine (FT4) level or free thyroxine index (FTI), with suppression of thyroid-stimulating hormone (TSH) in the absence of thyroid mass or nodular goiter.
Thyroid storm, a rare condition affecting 1 percent of pregnant women with hyperthyroidism, is characterized by severe, acute exacerbation of the signs and symptoms of hyperthyroidism. Thyroid storm is a medical emergency.
Unless hyperthyroidism is treated adequately, pregnant women are at increased risk for severe preeclampsia, preterm delivery, heart failure, and, possibly, miscarriage. Low birth weight in neonates also can occur.
Graves' disease and its treatment (thioamides) increase fetal and neonatal risks. Fetal thyrotoxicosis needs to be considered in women who have a history of Graves' disease; if this condition is diagnosed, appropriate consultation should be sought. Because of antibodies that cross the placenta, the possibility of neonatal immune-mediated hypothyroidism or hyperthyroidism is an additional concern.
Hypothyroidism is usually caused by a primary thyroid abnormality, although a few cases are caused by hypothalamic dysfunction. In pregnant or postpartum women, the most common causes are chronic thyroiditis or chronic autoimmune thyroiditis (Hashimoto's disease), subacute thyroiditis, radioactive iodine therapy, thyroidectomy, and iodine deficiency. Hashimoto's disease is the most frequent cause in industrialized nations; worldwide, iodine deficiency is the most common cause.
Signs and symptoms of hypothyroidism include fatigue, muscle cramps, constipation, cold intolerance, hair loss, and others. With progression of the disorder, voice changes, weight gain, intellectual slowness, and insomnia can occur. Untreated hypothyroidism progresses to myxedema and myxedema coma. Presentation of advanced hypothyroidism in pregnancy is unusual. Subclinical hypothyroidism is identified by an elevated TSH level in a pregnant woman without symptoms.
Untreated maternal hypothyroidism increases the risk of preeclampsia. Whether subclinical hypothyroidism increases this risk is uncertain. Inadequate treatment of hypothyroidism is associated with low birth weight in neonates. Maternal hypothyroidism from iron deficiency increases the risk of congenital cretinism (growth failure, mental retardation, other neuropsychologic defects). Iodine therapy in the first and second trimesters significantly reduces neurologic abnormalities associated with this disorder.
Cretinism also occurs with untreated congenital hypothyroidism. Newborn screening for congenital hypothyroidism is offered throughout the United States. Treatment in the first several weeks of life can result in nearly normal intelligence and growth.
Clinical Considerations and ACOG Recommendations
What laboratory tests for thyroid disease are used in pregnant women? TSH testing (now performed using monoclonal antibodies) is the recommended initial test for screening and evaluating patients with symptomatic disease. TSH and FT4 or FTI testing should be performed in pregnant women with suspected hyperthyroidism or hypothyroidism. The thyrotropin-releasing hormone level is another test of thyroid function. The clinical usefulness of various antibody tests depends on the individual situation.
What medications are used to treat hyperthyroidism and hypothyroidism in pregnancy? Hyperthyroidism in pregnant women is treated with a thioamide (propylthiouracil or methimazole). Recent studies have found no significant differences between propylthiouracil and methimazole in mean FT4 or TSH levels in newborn cord-blood samples, as well as no cases of aplasia cutis and similar rates of fetal anomalies for both agents. Women treated with propylthiouracil or methimazole can breastfeed safely.
The goal is to maintain FT4 or FTI in the high-normal range using the lowest possible thioamide dosage. Measuring the FT4 or FTI every two to four weeks can be helpful. Until thioamide therapy reduces thyroid hormone levels, a beta blocker (e.g., propranolol) can be used to reduce symptoms.
Agranulocytosis, a side effect of thioamides, usually presents with sore throat and fever. If these symptoms develop, a complete blood cell count should be obtained, and the thioamide should be discontinued. Other side effects include hepatitis, vasculitis, and thrombocytopenia.
Although suppression of fetal and neonatal thyroid function can occur with thioamide therapy for Graves' disease, it is usually transient, and treatment is rarely required. Fetuses of women with Graves' disease should be monitored for normal heart rate and appropriate growth; unless problems are detected, ultrasound screening for fetal goiter is not necessary. The newborn's physician needs to be aware that the mother has Graves' disease because of the associated risk of neonatal thyroid dysfunction.
Thyroidectomy should be reserved for women who do not respond to thioamide therapy. Treatment with iodine 131 (I-131) is contraindicated in pregnant women. Fetal thyroid is unlikely to have been ablated if inadvertent exposure to this agent occurred before 10 weeks of gestation. If exposure occurred after this time, the woman needs to consider the risk of induced congenital hypothyroidism and whether pregnancy should be continued. Women should not breastfeed for four months after treatment with I-131.
Hypothyroidism in pregnant women is treated with levothyroxine in a sufficient dosage to return the TSH level to normal. The dosage should be adjusted every four weeks until the TSH level is stable. Checking the TSH level every trimester is advised.
What thyroid function changes occur with hyperemesis gravidarum? Nausea and vomiting of pregnancy is associated with biochemical hyperthyroidism (undetectable TSH level, elevated FTI, or both). The condition is rarely associated with clinical hyperthyroidism, and no treatment is usually required. Routine thyroid testing is not recommended unless other signs of hyperthyroidism are present.
How is thyroid storm diagnosed and treated in pregnancy? This extreme hypermetabolic state is associated with a high risk of maternal heart failure. Diagnosis is based on a combination of signs and symptoms: fever, tachycardia out of proportion to the fever, altered mental status (nervousness, restlessness, confusion, seizures), vomiting, diarrhea, and cardiac arrhythmia. An inciting event (e.g., surgery, infection, labor, delivery) may be identified. Untreated thyroid storm can result in shock, stupor, and coma. Serum-free triiodothyronine (FT3), FT4, and TSH levels help confirm the diagnosis, but treatment should not be delayed for test results.
A standard series of drugs is used to treat thyroid storm: propylthiouracil or methimazole; saturated solution of potassium iodide or sodium iodide (alternatives: Lugol's solution, lithium); dexamethasone (and with a history of severe bronchospasm: reserpine, guanethidine, diltiazem); and phenobarbital. General supportive measures, such as oxygen, antipyretics, and appropriate monitoring, are also important. The perceived underlying cause of thyroid storm should be treated.
Depending on gestational age, fetal status should be evaluated with ultrasound examination, nonstress testing, or a biophysical profile. Unless deemed necessary, delivery during thyroid storm should be avoided.
How should thyroid cancer be managed during pregnancy? All thyroid nodules should be evaluated; up to 40 percent are found to be malignant. Thyroid cancer is treated with thyroidectomy and radiation (i.e., I-131). Thyroidectomy can be performed, preferably during the second trimester, but radiation therapy should not be administered until after the pregnancy. Management options for thyroid cancer are termination of the pregnancy followed by full treatment, treatment during pregnancy, and preterm or term delivery followed by full treatment. Gestational age and tumor characteristics affect the management choice. Women should not breastfeed for four months after I-131 treatment.
How is postpartum thyroiditis diagnosed and treated? Postpartum thyroiditis is diagnosed by new onset of an abnormal TSH level, abnormal FT4 level, or both. Antibody testing may be useful in confirming the diagnosis. Whether postpartum thyroiditis requires treatment is less clear.
TSH and FT4 levels should be evaluated in women who develop a goiter during pregnancy or after delivery. Evaluation may also be appropriate for women who develop post-partum symptoms of hyperthyroidism or hypothyroidism. Evaluation depends on the physician's judgment, as some of these symptoms are common in the postpartum period. Whether treatment is needed depends on the severity of the abnormality and symptoms. The risk of permanent hypothyroidism is greatest in women with the highest levels of TSH and antithyroid peroxidase antibodies.
Which pregnant women should be screened for thyroid dysfunction? Screening is appropriate in pregnant women with symptoms of thyroid disease or a history of thyroid disease. Thyroid nodules or goiter should be evaluated.
Available data support a possible association between maternal hypothyroidism and decrements in some neuropsychologic tests in their children. However, further testing is needed to document validity and provide evidence of treatment efficacy. According to ACOG, it is premature to recommend universal hypothyroidism screening in pregnant women.