A 32-year-old G1P0 woman at 12 weeks gestation presents to her obstetrician for a follow-up appointment. She first presented 4 weeks ago with bilateral hand tremors. At that time, she was found to have a thyroid-stimulating hormone (TSH) concentration <0.01 mU/L and an elevated free T4. She was started on propranolol and propylthiouracil. The dosage of both medications has been titrated to the maximum dose. She reports mild improvement in her symptoms but continues to experience sweating and palpitations. She has a past medical history of polycystic ovary syndrome. Her family history is notable for hypothyroidism in her mother. She does not smoke cigarettes, stopped drinking alcohol prior to pregnancy, and does not use drugs. Her temperature is 97.6°F (36.4°C), blood pressure is 113/70 mmHg, pulse is 126/min, and respirations are 18/min. On physical exam, she appears anxious, mildly diaphoretic and has a non-tender prominence on her neck which is shown in Figure A. Which of the following is the most appropriate next step in management?
Oral iodinated contrast
Thyroidectomy in the 2nd trimester
Methimazole
Continue routine prenatal care only
Thyroidectomy in the 2nd trimester
This patient who initially presented with tremors, a suppressed TSH, and elevated T4 has Graves disease which was appropriately treated with propranolol and propylthiouracil. However, she has persistent symptoms (diaphoresis, palpitations, tachycardia, nontender goiter) despite maximum doses of these medications, which should then be treated with surgical thyroidectomy which can be performed safely in the 2nd trimester of pregnancy.

Graves disease is caused by TSH receptor antibodies that activate the TSH receptor to synthesize thyroid hormone, leading to hyperthyroidism with suppressed TSH levels. The initial treatment for Graves disease is symptom control with a beta-blocker (e.g., propranolol) and inhibition of thyroid hormone synthesis with a thionamide (e.g., propylthiouracil or methimazole). In the 1st trimester of pregnancy, propylthiouracil is preferred to methimazole. In the 2nd and 3rd trimesters, methimazole is the preferred thionamide. The treatment of choice in pregnancy for Graves disease that is refractory to propranolol and a thionamide is thyroidectomy, which can safely be performed in the 2nd trimester. This is reserved only for more severe cases refractory to medical treatment. In nonpregnant patients, radioiodine ablation is the preferred treatment for refractory Graves disease but is contraindicated during pregnancy due to the risk of ablating the fetal thyroid.

Davies et al. reviewed the pathogenesis, diagnosis, and treatment of Graves disease. They found that Graves disease is caused by autoantibodies to the TSH receptor, resulting in overactive thyroid hormone secretion. They recommend that Graves's disease be treated with antithyroid drugs, radioiodine ablation, or surgery depending on clinical characteristics.

Figure A demonstrates goiter, a common finding in Graves disease that reflects thyroid growth in response to activation by TSH receptor antibodies.

Incorrect Answers:
Answer A: Continuing routine prenatal care does not address the symptoms of the patient's hyperthyroidism. Poorly-controlled hyperthyroidism can lead to spontaneous abortion, premature labor, low birth weight, heart failure, and preeclampsia in pregnant individuals. Therefore, Graves disease should be treated in pregnant individuals.

Answer B: Methimazole is a thionamide that is an alternative to propylthiouracil in nonpregnant individuals. It is more potent than propylthiouracil. Methimazole is contraindicated during the 1st trimester of pregnancy due to its teratogenic effects on the fetus during organogenesis.

Answer C: Oral iodinated contrast agents inhibit the peripheral conversion of T4 to T3 and may be used in thyroid storm in nonpregnant patients outside of the United States. Patients with thyroid storm present with tachycardia, arrhythmias, heart failure, and hyperpyrexia.

Answer D: Radioiodine ablation is the preferred definitive treatment for Graves disease in nonpregnant individuals. It is contraindicated in pregnancy as fetal thyroid tissue has developed by 10-12 weeks of gestation and may be ablated alongside the maternal tissue.

Bullet Summary:
Initial treatment of Graves disease in pregnancy is propranolol and propylthiouracil, whereas severe symptoms that are refractory to medical management should be treated with thyroidectomy.