New Graves Disease at 10 Weeks of Pregnancy
A 29-year-old woman, 10 weeks pregnant in her second pregnancy (the first ended in miscarriage at 8 weeks), presents with 6 weeks of palpitations, heat intolerance, 4 kg weight loss and tremor. Pulse 118 bpm, BP 128/68 mmHg, BMI 20, smooth diffuse goitre, no ophthalmopathy and no pretibial myxoedema. TSH <0.01 mIU/L, free T4 46 pmol/L (reference 12–22), free T3 12.8 pmol/L (reference 3.1–6.8), TSH-receptor antibody 9.2 IU/L (positive). Full blood count normal, ALT 28 U/L, bilirubin normal. She takes no regular medication and no iodine supplements. She has read that radioiodine 'fixed' her sister's thyroid and asks why she cannot have it now; she is also frightened that any drug will harm the baby.
1. Which drug do you start, at what dose, and what is the treatment target? Explain why radioiodine and surgery are not options now.
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This is untreated Graves disease complicating early pregnancy, and treatment should start now.
Drug choice: propylthiouracil (PTU). Methimazole and carbimazole are associated with a rare embryopathy (aplasia cutis, choanal atresia, oesophageal atresia) with the highest risk of exposure between about 6 and 10 weeks of gestation, which is precisely when she is now. PTU is therefore preferred in the first trimester.
Dose: PTU 100 mg three times daily (range 50–150 mg three times daily) is a typical starting dose for free T4 roughly twice the upper limit of normal. A beta-blocker (propranolol 10–20 mg three times daily) can be added short term for symptoms and tachycardia.
Target: the lowest dose that keeps free T4 at, or just above, the upper limit of the pregnancy-specific reference range. Do not aim for a normal TSH - over-treatment causes fetal hypothyroidism and goitre.
Radioiodine is absolutely contraindicated in pregnancy: the fetal thyroid begins trapping iodine at around 10–12 weeks, and ablation causes fetal hypothyroidism and cretinism. Surgery is reserved for severe drug intolerance, refractory disease or a very large goitre compressing the airway, and is best performed in the second trimester; it is not first-line here.
2. Describe the monitoring plan, the adverse effects you warn her about, and whether the drug should be switched later.
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Monitoring: thyroid function tests every 2–4 weeks until stable, then every 4–6 weeks; weight, pulse and blood pressure at each visit. Graves disease often flares in the first trimester and improves in the second and third as immune tolerance develops, so doses frequently need reducing - review even if she feels well.
Adverse effects to counsel explicitly:
- Agranulocytosis (about 0.3–0.6%): stop the drug and seek an urgent full blood count for fever or sore throat; do not wait for the next appointment.
- Hepatotoxicity: baseline liver function is normal; stop and check liver enzymes if jaundice, dark urine, right upper quadrant pain or malaise. PTU can cause fatal hepatic necrosis, which is why it is not continued indefinitely.
- ANCA-associated vasculitis with PTU: rash, arthralgia, haematuria.
- Pruritus and minor rash.
Switching: after the first trimester, most clinicians switch to carbimazole/methimazole (or methimazole) to reduce cumulative PTU hepatic risk, at an equivalent dose (PTU 100 mg ≈ carbimazole 10 mg approximately), with thyroid function checked 2–4 weeks later. Keeping PTU throughout is an acceptable alternative if she is stable, since switching itself can destabilise control.
3. What are the fetal and neonatal risks of her TSH-receptor antibody, and what is the postpartum plan?
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TSH-receptor antibodies are IgG and cross the placenta, so they can stimulate the fetal thyroid regardless of the mother's treatment or free T4. Her titre of 9.2 IU/L is positive.
Fetal risks: miscarriage, growth restriction, fetal tachycardia, fetal goitre, craniosynostosis in severe cases, and fetal thyrotoxicosis. Measure TRAb again around 20–24 weeks; if still high, arrange serial growth scans and fetal heart-rate assessment, and involve fetal medicine.
Neonatal risks: neonatal Graves disease, which may appear in the first days to 2 weeks of life (delayed if she is on antithyroid drugs, which cross the placenta and partially treat the fetus). Cord blood and neonatal thyroid function testing, plus clinical surveillance for at least 1–2 weeks, are needed; the neonatology team should be told antenatally.
Postpartum plan:
- Graves disease commonly relapses after delivery; check thyroid function at about 6–8 weeks and sooner if symptomatic.
- Both PTU and methimazole are compatible with breastfeeding, though methimazole is generally preferred for lactation; monitor the infant's growth and thyroid status if doses are high.
- Radioiodine can be offered once breastfeeding has finished if definitive treatment is wanted; discuss contraception and defer pregnancy for at least 6 months after radioiodine.
Her previous miscarriage should prompt early booking and reassurance that treated maternal disease improves outcomes.