Clinical hyperthyroidism, or thyrotoxicosis, complicates about 1 in 1000 to 2000 pregnancies. When mild, thyrotoxicosis may be difficult to diagnose during pregnancy; helpful signs are shown in Table 74-1. The diagnosis is confirmed when an abnormally low (suppressed) thyroid-stimulating hormone (TSH) level is accompanied by abnormally elevated serum free T4 level. Rarely, hyperthyroidism is caused by abnormally high serum triiodothyronine (T3) levels—so-called T3—toxicosis. The major cause of hyperthyroidism in pregnancy is Graves disease, an organ-specific autoimmune process usually associated with thyroid-stimulating antibodies. In many women, thyroid-stimulating antibody activity declines during pregnancy, associated with chemical remission.
TABLE 74-1. Signs of Thyrotoxicosis in Pregnancy
Pregnancy outcomes depend upon whether metabolic control is achieved. Women who remain hyperthyroid despite therapy, and in those whose disease is untreated, there is a higher incidence of preeclampsia, heart failure, and adverse perinatal outcomes. Thyroid storm is encountered only rarely in untreated women with Graves disease. Heart failure is more common than thyroid storm and is caused by the profound myocardial effects of thyroxine, which result in a high-output state. Pulmonary edema is precipitated by intercurrent preeclampsia, anemia, or sepsis.
Thyrotoxicosis during pregnancy can nearly always be controlled with thionamide drugs. Both propylthiouracil (PTU) and methimazole (Tapazole) are effective and safe. Transient leucopenia manifests in about 10 percent, but this does not require cessation of therapy. In about 0.3 percent, agranulocytosis develops suddenly and mandates discontinuing the drug. Thus, if fever or sore throat develops, women are instructed to discontinue medication immediately and report for a complete blood count. Some clinicians prefer PTU because it partially inhibits the conversion of T4 to T3 and it crosses the placenta less readily than methimazole. It is also not associated with embryopathy characterized by esophageal/choanal atresia or aplasia cutis, which has been attributed to methimazole. The dose of PTU is empirical, usually starting at 300 to 450 mg daily. The median time to normalization of free T4 has been reported to be 7 to 8 weeks. Other therapy includes thyroidectomy after thyrotoxicosis is medically controlled, though this is seldom done during pregnancy. Management guidelines for thyroid storm or heart failure are listed in Table 74-2. Ablation with therapeutic radioactive iodine is contraindicated.
TABLE 74-2. Suggested Treatment of Thyroid Storm in Pregnancy
Subclinical hyperthyroidism is defined as an abnormally low serum TSH level along with normal serum thyroid hormone levels in an asymptomatic woman. It occurs in about 1 to 2 percent of pregnancies, in some cases the result of exogenous thyroxine ingestion. Subclinical hyperthyroidism has not been associated with any adverse pregnancy outcomes. About half of these women eventually develop normal TSH concentrations. Long-term effects are less clear, and it seems reasonable to periodically monitor for overt disease.
EFFECTS OF MATERNAL THYROTOXICOSIS ON THE FETUS AND INFANT
The neonate may manifest transient thyrotoxicosis, which sometimes requires antithyroid drug treatment. Fetal or neonatal thyrotoxicosis can result from the transplacental passage of maternal thyroid stimulating antibodies and occurs in approximately 1 percent of neonates born to women with Graves disease. Such fetal thyrotoxicosis usually responds to maternal thionamide therapy, but fetal demise has been reported. Conversely, longstanding in-utero exposure to thionamides may cause neonatal hypothyroidism. In either case, the fetus may develop a goiter. Earlier estimates of adverse fetal effects induced by thionamide drugs were exaggerated, and their use in pregnancy carries an extremely small risk. Long-term studies evaluating intellectual and physical development of children born to thyrotoxic mothers treated with these drugs during pregnancy have found no adverse effects on subsequent growth and development.
For further reading in Williams Obstetrics, 23rd ed.,
see Chapter 53, “Thyroid and Other Endocrine Disorders.”