Graves Disease and Thyroid Eye Disease
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Direct answer
Graves disease is autoimmune hyperthyroidism in which thyroid-stimulating antibodies activate the TSH receptor, producing diffuse goitre, suppressed TSH and raised free thyroxine. Thyroid eye disease is the orbital inflammation that can accompany it, causing proptosis, lid retraction and diplopia, and smoking worsens its course. Antithyroid drugs, radioiodine or surgery control the gland, while orbitopathy needs its own treatment, often with steroids.
What you must remember
- Antibodies: TSH receptor-stimulating antibodies cause the thyrotoxicosis and drive diffuse, high radioiodine uptake.
- Antithyroid drugs: carbimazole or methimazole; propylthiouracil is usually preferred in the first trimester of pregnancy.
- Radioiodine: contraindicated in pregnancy and breastfeeding; it can worsen orbitopathy and cause hypothyroidism.
- Surgery: indicated for large goitre, compressive symptoms, suspicious nodules or patient preference, and is often done in the second trimester of pregnancy.
- Eye signs: proptosis, lid retraction, lid lag, chemosis and extraocular muscle enlargement.
- Active orbitopathy: intravenous methylprednisolone for moderate to severe disease; teprotumumab is a biologic option.
- Optic neuropathy: a sight-threatening emergency that needs urgent steroids and orbital decompression.
A 34-year-old with palpitations and proptosis
A 34-year-old woman has three weeks of palpitations, weight loss, heat intolerance and tremor. Examination reveals a diffuse goitre with a bruit, fine tremor and exophthalmos.
- Confirm thyrotoxicosis: Free thyroxine is high, TSH is undetectable, TSH receptor antibodies are strongly positive and radioiodine uptake is diffusely raised.
- Start medical control: Carbimazole controls the thyrotoxicosis and a beta-blocker treats her symptoms.
- Choose definitive treatment: Six months later the disease relapses, and she prefers a definitive option. Radioiodine is chosen after contraception is discussed, because pregnancy must be avoided for some months afterwards.
- Treat the orbits: Two months after treatment she develops worsening proptosis and diplopia. Her clinical activity score is raised, so intravenous methylprednisolone is started.
- Stop smoking: Smoking cessation is advised, because smoking worsens orbitopathy and reduces the response to steroids.
- Monitor long term: Thyroid function is checked regularly, since radioiodine often leads to hypothyroidism and lifelong levothyroxine. Ophthalmology follow-up continues, and she is warned that eye changes can lag behind thyroid results by months.
Where the examiner tests the eyes and pregnancy
Graves disease questions often test pregnancy rules and eye signs.
- Trap: radioiodine in pregnancy or breastfeeding. Correct: radioiodine is contraindicated in both, and propylthiouracil is preferred in the first trimester.
- Trap: assuming eye signs track thyroid hormone levels. Correct: orbitopathy can appear even if the thyroid is normal or after radioiodine, and it does not follow thyroid hormone levels.
- Trap: missing lid signs in the eye examination. Correct: lid lag and lid retraction are part of the classic eye findings and should be recognised at the bedside.
- Trap: a wait-and-see approach to optic neuropathy. Correct: it is a sight-threatening emergency that needs urgent steroids and orbital decompression if steroids fail.
Radioiodine can also worsen orbitopathy, so steroid cover is considered in those with active disease.
Frequently asked questions
What antibodies cause hyperthyroidism in Graves disease?
TSH receptor-stimulating antibodies cause hyperthyroidism in Graves disease by binding and activating the TSH receptor on thyroid follicular cells. This drives hormone production and diffusely increased radioiodine uptake. TSH receptor antibody levels also help predict relapse after antithyroid drug treatment.
Why should radioiodine be avoided in pregnancy and breastfeeding?
Radioiodine is avoided in pregnancy because it crosses the placenta and can destroy the fetal thyroid. It is avoided in breastfeeding because iodine is secreted into breast milk. Contraception and a waiting period are needed before conception after treatment.
Which antithyroid drug is preferred in the first trimester of pregnancy?
Propylthiouracil is usually preferred in the first trimester of pregnancy for Graves disease because carbimazole has been linked to rare congenital abnormalities. Treatment is kept at the lowest effective dose. Thyroid function is monitored closely throughout pregnancy.
How is active moderate-to-severe thyroid eye disease treated?
Active moderate-to-severe thyroid eye disease is treated with intravenous methylprednisolone, and biologic therapy such as teprotumumab is an option in selected patients. Smoking cessation is important and improves outcomes. Orbital decompression or strabismus surgery is considered later for persistent problems.
Why does smoking worsen thyroid eye disease?
Smoking worsens thyroid eye disease by increasing orbital inflammation and reducing the response to steroid treatment. It is one of the strongest modifiable risk factors for severe disease. Patients should be strongly advised to stop smoking.