Graves Disease (Thyrotoxicosis) ✅

⚠️ Smokers with Graves' Disease have a significantly higher risk of developing thyroid eye disease (TED). Smoking cessation is essential to reduce complications and improve outcomes. 💨

📖 About

• Autoimmune disease: Graves’ disease is the most common cause of hyperthyroidism (60–80% of cases).
• Leading cause of thyrotoxicosis in the UK and worldwide.
• Immune-mediated stimulation of TSH receptors drives thyroid hormone overproduction.

🔎 Risk Factors

• Gender: Women >> Men (~10:1).
• Age: Typically 30–50 years.
• Postpartum: Increased risk in first 6–12 months.
• Smoking: Major modifiable risk factor for TED; worsens severity and prognosis.
• Family history: Genetic predisposition via HLA-B8, DR3.

🧬 Pathophysiology & Aetiology

• TSH receptor antibodies (TRAb): Stimulate follicular hyperplasia, ↑ T3/T4 production; cross placenta → neonatal thyrotoxicosis.
• Thyroid peroxidase antibodies (TPOAb): Present in ~80%.
• Orbital fibroblast activation: Glycosaminoglycan deposition → proptosis, diplopia, orbital oedema.
• Autoimmunity can be triggered by infections, stress, or iodine exposure.

🩺 Clinical Presentation

• Symptoms: Weight loss, heat intolerance, palpitations, anxiety, tremor, diarrhoea.
• Elderly: May present with apathetic thyrotoxicosis – fatigue, anorexia, atrial fibrillation.
• Examination: Diffuse, smooth goitre with bruit/thrill, tremor, warm moist skin, tachycardia, hyperreflexia.

🌟 Specific Signs

• Thyroid Eye Disease (TED): Lid lag, lid retraction, proptosis, diplopia, corneal ulceration (~40% of patients).
• Pretibial myxoedema: Non-pitting, pink-orange plaques (~5%).
• Thyroid acropachy: Rare clubbing with onycholysis.

🔬 Investigations (NICE & ATA Guidelines)

• Thyroid function tests: ↑Free T4/T3, suppressed TSH (<0.05 mIU/L).
• TRAb: Confirms autoimmune aetiology; predicts risk of TED.
• Radionuclide uptake scan: Diffuse uptake in Graves’, distinguishes from toxic adenoma/multinodular goitre.
• Thyroid ultrasound: Optional; evaluates nodularity.
• Ophthalmology assessment: Baseline visual acuity, colour vision, intraocular pressure, exophthalmometry for TED severity.

🧾 Differentials

• Toxic multinodular goitre
• Toxic adenoma
• Exogenous thyroxine excess
• Subacute thyroiditis (painful, self-limiting)

⚕️ Management (NICE & ATA/ETA Guidance)

• Symptom control: Beta-blockers (propranolol 20–40 mg QDS) for palpitations, tremor, anxiety.
• Antithyroid drugs (ATDs): Carbimazole first-line (20–40 mg daily titrated), propylthiouracil reserved for pregnancy or intolerance.
• Radioiodine therapy: Avoid in active TED, particularly smokers; may worsen ophthalmopathy.
• Surgery: Subtotal or total thyroidectomy for severe, compressive, or refractory disease.
• Atrial fibrillation: Consider anticoagulation per CHA₂DS₂-VASc; monitor for hyperthyroid-related cardiomyopathy.

👁️ Thyroid Eye Disease (TED) Management

• Initial muscle involved: Inferior rectus → restricted upgaze.
• Smoking cessation: Most important modifiable factor.
• Ophthalmology referral: Monitor acuity, optic nerve function, intraocular pressure.
• Conservative: Lubricants, eyelid taping, head elevation, selenium supplementation if mild.
• Medical therapy: IV/oral glucocorticoids (prednisolone 60 mg), immunomodulators (ciclosporin, rituximab, teprotumumab where available).
• Advanced: Orbital radiotherapy or surgical decompression in sight-threatening disease.

💡 Exam Tips

• Hyperthyroid patient who smokes → always ask about eye symptoms; early TED referral improves prognosis.
• TRAb positive → confirms Graves’ and risk stratification for TED.
• Active TED = contraindication to radioiodine therapy.
• Diffuse goitre with bruit → hallmark on palpation.
• Pretibial myxoedema or acropachy → pathognomonic but rare.

📚 References

• NICE NG145: Thyroid disease – assessment and management
• ATA Guidelines: 2016 Hyperthyroidism Management
• ETA/Endocrine Society: Thyroid Eye Disease Guidelines
• Ross DS, et al. 2016. American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 26(10):1343–1421.