Treatment. Thyrotoxicosis during pregnancy can nearly always be controlled by thionamide drugs. Propylthiouracil (PTU) has been historically preferred because it partially inhibits the conversion of T4 to T3 and crosses the placenta less readily than methimazole. he latter has also been associated with a rare methimazole embryopathy, characterized by esophageal or choanal atresia as well as aplasia cutis, a congenital skin defect. yoshihara and associates (2012, 2015) analyzed outcomes in Japanese women with irst-trimester hyperthyroidism and found a twofold increased risk of major fetal malformations in pregnancies exposed to methimazole compared with either PTU or potassium iodide. Speciically, seven of nine cases with aplasia cutis and the only case of esophageal atresia were in the group of methimazole-exposed fetuses. here have also been reports of a PTU-associated embryopathy (Andersen, 2014).
In 2009, the Food and Drug Administration issued a safety alert on PTU-associated hepatotoxicity. his warning prompted the American Thyroid Association and the American Association of Clinical Endocrinologists (201r1) to recommend PTU therapy during the first trimester followed by methimazole beginning in the second trimester. he obvious disadvantage is that this might lead to poorly controlled thyroid function. Accordingly, at Parkland Hospital, we continue to prescribe PTU treatment throughout pregnancy.
Transient leukopenia can be documented in up to 10 percent of women taing antithyroid drugs, but this does not require therapy cessation (American College of Obstetricians and Gynecologists, 2017). In approximately 0.3 percent, however, agranuloytosis develops suddenly and mandates drug discontinuance (Thomas, 2013). It is not dose related, and because of its acute onset, serial leukocyte counts during therapy are not helpul.
Thus, fever or sore throat develops, women are instructed to discontinue medication immediatey and report or a complete blood count.
herapy may have other side efects. First, as noted, hepatotoxicity is a possibility and develops in approximately 0.1 percent of treated women. Serial measurement of hepatic enzyme levels does not prevent fulminant PTU-related hepatotoxicity. Second, approximately 20 percent of patients treated with PTU develop antineutrophil cytoplasmic antibodies NC). Despite this, only a small percentage of these subsequently develops serious vasculitis (Kimura, 2013). Finally, although thionamides have the potential to cause fetal complications, these are uncommon. In some cases, thionamides may even be therapeutic for the fetus, because TSH-receptor antibodies cross the placenta and can stimulate the fetal thyroid gland to cause thyrotoxicosis and goiter.
The initial thionamide dose is empirical. For nonpregnant patients, the American hyroid Association recommends that methimazole be used at an initial higher daily dose of 10 to 20 mg orally followed by a lower maintenance dose of 5 to 10 mg. If PTU is selected, a dose of 50 to 150 mg orally three times daily may be initiated depending on clinical severity (Bahn, 2011). At Parkland Hospital, we usually initially give 300 or 450 mg of PTU daily in three divided doses for pregnant women. Occasionally, daily doses of 600 mg or higher are necessary. As discussed, we generally do not transition women to methimazole during the second trimester. he goal is treatment with the lowest possible thionamide dose to maintain thyroid hormone levels slightly above or in the high normal range, while TSH levels remains suppressed (Bahn, 2011). Serum free T 4 concentrations are measured every 4 to 6 weeks.