Graves disease in the first trimester of pregnancy
The case
A 28-year-old woman who is 8 weeks pregnant by her last menstrual period presents with 3 weeks of progressive palpitations, heat intolerance, tremor and 4 kg of weight loss. She has no past medical history. She is anxious, with a pulse of 120/min, blood pressure 110/70 mmHg, fine hand tremor and a diffusely enlarged, non-tender thyroid with a bruit. There is no eye disease. She is a non-smoker on no medication. TSH is below 0.01 mU/L (0.4–4.0), free T4 42 pmol/L (9–19) and free T3 12 pmol/L (3.5–6.5). Thyroid peroxidase antibody is negative and TSH receptor antibody (TRAb) is strongly positive. She wishes to continue the pregnancy. What is the most appropriate initial management?
Options
- APropylthiouracil and a beta-blocker
- BPropranolol alone as a temporising measure
- CCarbimazole with fetal monitoring
- DUrgent total thyroidectomy
- ERadioactive iodine
Think it through before you read on. Which single option is best, and why are the other four wrong?
Show the answer and explanation
Answer
A. Propylthiouracil and a beta-blocker
Why this is the right answer
This is overt Graves disease: suppressed TSH, high free T4 and T3, a diffuse goitre with a bruit, and positive TSH receptor antibodies. The diagnosis is clear, and treatment cannot wait. Untreated thyrotoxicosis in pregnancy increases the risk of miscarriage, pre-eclampsia, preterm birth, growth restriction and maternal heart failure.
The choice of antithyroid drug depends on the trimester. Carbimazole (and its active form methimazole) is linked to a specific pattern of birth defects when used in weeks 6 to 10 of pregnancy: aplasia cutis, choanal atresia, oesophageal atresia and abdominal wall defects. Propylthiouracil (PTU) has a much lower risk of these defects, so it is the preferred drug in the first trimester. Therapeutic Guidelines (Endocrinology) and the American Thyroid Association guideline follow this approach [VERIFY].
PTU carries a small risk of severe liver injury, so after the first trimester (around 16 weeks) most guidelines advise switching to carbimazole for the rest of the pregnancy.
A beta-blocker such as propranolol controls palpitations and tremor while the antithyroid drug takes effect over several weeks. It is used short-term only.
The lowest dose that keeps free T4 at the upper end of normal is used, because antithyroid drugs cross the placenta and can cause fetal hypothyroidism. TRAb levels should be checked again in the third trimester because they predict neonatal Graves disease.
Why the other options are wrong
- B
Propranolol treats symptoms only; it does not lower thyroid hormone production.
- C
Carbimazole in the first trimester is associated with aplasia cutis and choanal and oesophageal atresia.
- D
Surgery is for drug intolerance or failure, and is done in the second trimester if needed.
- E
Radioiodine crosses the placenta and destroys the fetal thyroid; it is absolutely contraindicated in pregnancy.
High-yield takeaway
Graves in pregnancy: propylthiouracil in the first trimester, switch to carbimazole after 16 weeks, and never give radioiodine.
Reference: Therapeutic Guidelines: Endocrinology, Hyperthyroidism in pregnancy (and ATA Guidelines for Thyroid Disease in Pregnancy 2017) (2022)
Common questions
Why not carbimazole in the first trimester?
It is linked to aplasia cutis, choanal atresia and oesophageal atresia when used in weeks 6 to 10. Propylthiouracil carries a much lower risk of these defects.
When is the switch from PTU to carbimazole made?
At around 16 weeks, after organ formation is complete, because PTU carries a small risk of severe liver injury.
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