A 26-year-old pregnant woman at 16 weeks gestation comes to the office for prenatal follow-up. The patient has a 2-year history of mild hyperthyroidism due to Graves disease and started taking propylthiouracil when she decided to attempt pregnancy. The patient has had no tremulousness, palpitations, diarrhea, or heat intolerance. She has no other medical problems and no drug allergies. She takes a prenatal vitamin. The patient does not use tobacco, alcohol, or illicit drugs. Temperature is 36.7 C (98 F), blood pressure is 110/60 mm Hg, and pulse is 88/min. Physical examination reveals no lid lag, exophthalmos, or hand tremors. The thyroid gland is normal to palpation. Fetal heart rate is normal. Thyroid hormone levels are within the laboratory's reference ranges. During this visit, her thyroid treatment is changed from propylthiouracil to methimazole. Switching the patient's therapy at this time is aimed at decreasing which of the following complications?
Thionamide antithyroid drugs (eg, propylthiouracil [PTU], methimazole) are used to decrease thyroid hormone production. In Graves disease, they can be used to induce a euthyroid state in preparation for definitive treatment with radioiodine or surgery and can sometimes achieve remission in patients with mild disease.
Methimazole is preferred for most patients due the hepatotoxicity of PTU; PTU often causes transient elevations in hepatic transaminases and occasionally can cause severe idiosyncratic liver injury with acute liver failure. However, methimazole has potential teratogenic effects (eg, aplasia cutis [Choice A], esophageal atresia, facial anomalies), so PTU is preferred in the first trimester of pregnancy. Thereafter, the patient should be returned to methimazole therapy.
(Choice B) Thyroid dysgenesis (abnormal development of the thyroid gland) can manifest as absence (agenesis), ectopic location, or hypoplasia of the thyroid gland. The thyroid gland is normally fully developed by week 12; therefore, switching from PTU to methimazole at 16 weeks gestation is unlikely to cause thyroid dysgnesis. Thionamide antithyroid drugs can cause hypothyroidism with goiter (rather than dysgenesis) in newborns, but the effects are typically transient as the drugs are cleared within days.
(Choice D) Graves ophthalmopathy is due to the activation of TSH receptors on orbital fibroblasts by thyrotropin receptor autoantibodies, which leads to the expansion of the ground substance of retro-orbital tissues and edema of the extraocular muscles. Radioiodine therapy for Graves disease can acutely worsen ophthalmopathy, but this is less of a concern with antithyroid drugs.
(Choice E) Risk factors for thyroid cancer include exposure to ionizing radiation, iodine-deficient diet, and certain familial cancer syndromes (eg, familial adenomatous polyposis). Antithyroid drugs do not increase the risk for thyroid cancer.
Educational objective:
Thionamide antithyroid drugs (eg, propylthiouracil [PTU], methimazole) are used to decrease thyroid hormone production. Methimazole is preferred for most patients due to the hepatotoxicity of PTU. However, methimazole has potential teratogenic effects, so PTU is preferred in the first trimester of pregnancy.