Graves Disease in Pregnancy

Graves disease in pregnancy is autoimmune hyperthyroidism caused by antibodies that stimulate the TSH receptor. It may be new, relapsed or controlled. Antibodies cross the placenta and can cause fetal or neonatal thyrotoxicosis. It matters because poor control causes miscarriage, preeclampsia, preterm birth, growth restriction and thyroid storm, and antithyroid drugs carry fetal risk.

• Disease often improves in the second half of pregnancy and relapses after delivery.
• Women treated before pregnancy still pass antibodies after thyroidectomy or radioiodine.
• Carbimazole in early pregnancy can cause fetal malformations.

Women have weight loss, tremor, palpitations, heat intolerance, goitre, eye signs (exophthalmos, lid lag) and sometimes pretibial myxoedema. Pulse is usually above 100 per minute.

• Diffuse goitre with a bruit.
• Eye signs are specific for Graves disease.
• Differential diagnosis: gestational transient thyrotoxicosis, toxic nodule, thyroiditis, anxiety, normal pregnancy.
• Complications: thyroid storm, heart failure, atrial fibrillation, miscarriage, preeclampsia, preterm birth, fetal growth restriction, fetal goitre and tachycardia, neonatal thyrotoxicosis, agranulocytosis from drugs.

The approach is thyroid function, antibody levels and fetal surveillance.

• TSH, free T4 and free T3; TSH below 0.1 mIU/L with raised free T4 confirms disease.
• TSH receptor antibodies at booking and at 18 to 22 weeks; above 3 times the upper limit means high risk to the fetus.
• Full blood count and liver enzymes before and during antithyroid drugs.
• Fetal ultrasound every 4 weeks from 20 weeks if antibodies are high: fetal heart above 170 per minute, goitre, growth restriction, hydrops.

The principle is the lowest effective antithyroid drug dose, with a switch of drug by trimester and fetal surveillance when antibodies are high.

• Supportive: preconception counselling; stop smoking; admit for storm; teach to report sore throat, fever or jaundice at once.
• Pharmacological: propylthiouracil 100 mg oral 8-hourly in the first trimester up to 16 weeks, then carbimazole 10 to 20 mg oral once daily, adjusted by free T4 every 2 to 4 weeks to keep free T4 at the upper limit of normal; maximum propylthiouracil 600 mg daily and carbimazole 40 mg daily; propranolol 10 to 40 mg oral 8-hourly for symptoms for no more than 2 to 4 weeks; if the fetus is thyrotoxic with antibodies high, continue the drug and add levothyroxine 25 to 50 micrograms oral daily if the mother becomes hypothyroid; thyroid storm: propylthiouracil 600 to 1000 mg oral then 250 mg 4-hourly, hydrocortisone 100 mg IV 8-hourly, propranolol 1 to 2 mg IV slowly, potassium iodide 5 drops oral 8-hourly started 1 hour after the first propylthiouracil dose, paracetamol 1 g oral 6-hourly, cooling.
• Procedures: subtotal thyroidectomy in the second trimester for severe drug reaction, agranulocytosis or non adherence; no radioactive iodine.
• Special groups: women with agranulocytosis (neutrophils below 1 x 10^9/L) stop the drug and give broad-spectrum antibiotics; breastfeeding is compatible with carbimazole up to 20 mg or propylthiouracil up to 300 mg daily in divided doses after feeds; neonates have thyroid tests at days 3 to 5 and 10 to 14 and heart rate checks.
• Red flags: heart rate above 120 per minute, temperature above 38 degrees Celsius, sore throat, jaundice, fetal heart above 170 per minute.
• Follow-up: free T4 every 2 to 4 weeks; growth scans every 4 weeks from 28 weeks; postnatal thyroid tests at 6 weeks and then every 3 months for a year.