Overview
Graves' Disease
1. Overview
Graves' Disease is an autoimmune condition causing Hyperthyroidism (Thyrotoxicosis). It is the most common cause of overactive thyroid (75% of cases).
It is unique because it causes:
- Thyroid Eye Disease (Graves' Ophthalmopathy).
- Pretibial Myxedema (Skin changes).
- Diffuse Goitre.
Pathophysiology
- Production of TSH Receptor Antibodies (TRAb).
- These antibodies mimic TSH and stimulate the thyroid receptor continuously.
- Result: Excessive T3/T4 production and Gland growth (Goitre).
2. Epidemiology
- Gender: Female > Male (10:1).
- Age: 20-40 years peak.
- Genetics: Strong familial link (HLA-DR3).
- Trigger: Stress, Smoking (Huge risk for Eye Disease), Post-partum.
3. Clinical Features
General Thyrotoxicosis Symptoms
- Weight loss despite increased appetite.
- Heat intolerance / Sweating.
- Palpitations (Sinus Tachycardia / AF).
- Tremor / Anxiety / Irritability.
- Diarrhea.
- Oligomenorrhea.
Graves' Specific Features
- Eye Disease (50%):
- Proptosis/Exophthalmos: Bulging eyes (retro-orbital inflammation).
- Lid Retraction: Staring look.
- Lid Lag: Upper lid lags behind eye on downgaze.
- Diplopia: Limitation of eye movement (Inferior rectus tethering).
- Pretibial Myxedema: Thickened, waxy, orange-peel skin on shins.
- Thyroid Acropachy: Clubbing/swelling of fingers (Rare).
- Goitre: Diffuse, smooth, loud Bruit (increased blood flow).
4. Diagnosis
- Thyroid Function Tests (TFTs):
- Disseminated: Low TSH (<0.01). High T3/T4.
- (If T3 is high but T4 is normal = T3 Toxicosis).
- Antibodies:
- TRAb (TSH Receptor Ab): Positive in 95%. Pathognomonic.
- TPO Ab: Also positive (non-specific, seen in Hashimoto's too).
- Ultrasound/Scintigraphy:
- Scan: Diffuse high uptake ("Hot Gland").
- Differentiation: Toxic Nodule has "Hot Nodule". Thyroiditis has "Low Uptake".
5. Management Algorithm
Three modalities: Drugs, Radioiodine, Surgery.
┌─────────────────────────────────────────────────────────────────────────────┐
│ GRAVES' DISEASE MANAGEMENT │
├─────────────────────────────────────────────────────────────────────────────┤
│ SYMPTOM CONTROL (First Line) │
│ • **Beta Blockers** (Propranolol 40mg TDS). │
│ • Relieves tremor, palpitations, anxiety immediately. │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ 1. ANTITHYROID DRUGS (ATD) - The 18 Month Plan │
│ • **Carbimazole** (Methimazole in US). │
│ • Regimen A: **Titration**: Start 20-40mg, reduce as TFTs normalize. │
│ • Regimen B: **Block and Replace**: High dose Carbimazole (40mg) + │
│ Levothyroxine added back. (Prevents hypothyroidism, more stable). │
│ • **Duration**: 12-18 months. │
│ • **Remission**: 50% chance of permanent cure. 50% relapse. │
│ • **Warning**: WARN ABOUT SORE THROAT (Agranulocytosis). │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ 2. RADIOIODINE (RAI - I-131) │
│ • Indication: Relapse after drugs, or first line in older patients. │
│ • Capsule swallowed. Destroys gland over months. │
│ • **Contraindications**: │
│ - Pregnancy / Breastfeeding (Avoid pregnancy for 6 months). │
│ - Active Eye Disease (Can worsen ophthalmopathy). │
│ - Young Children. │
│ • Result: Leads to Hypothyroidism (Lifelong Thyroxine). │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ 3. SURGERY (Thyroidectomy) │
│ • Indication: Large compressive goitre, Severe eye disease (where RAI │
│ unsafe), Patient preference. │
│ • Risks: Recurrent Laryngeal Nerve damage (Hoarse voice), │
│ Hypoparathyroidism (Low Calcium). │
│ └─────────────────────────────────────────────────────────────────────┘
6. Complications
- Thyroid Storm: Life-threatening exacerbation (fever, agitation, heart failure). Mortality 10%.
- Atrial Fibrillation: Stroke risk.
- Osteoporosis: Long term catabolic effect of T3.
- Malignant Exophthalmos: Optic nerve compression -> Blindness.
7. Pregnancy
- Carbimazole: Teratogenic (Aplasia Cutis) in 1st trimester.
- Propylthiouracil (PTU): Drug of choice in 1st trimester. Switch to Carbimazole in 2nd/3rd.
- TRAb: Can cross placenta and cause Neonatal Thyrotoxicosis.
8. Special Considerations
Agranulocytosis
- Rare (0.5%) but fatal side effect of Antithyroid Drugs.
- Bone marrow stops making neutrophils.
- Patient Education: "If you get a sore throat, fever, or mouth ulcers, STOP drug and get FBC immediately."
Smoking & Eyes
- Smoking significantly worsens Thyroid Eye Disease.
- RAI worsens Eye Disease (Give prophylactic steroids if mild eye disease).
9. Key Clinical Pearls
Exam-Focused Points
- Lid Lag: A sign of Hyperthyroidism (Sympathetic overactivity).
- Proptosis: A sign of GRAVES' specifically (Autoimmune retro-orbital fat).
- Bruit: Heard over Graves' goitre (Hypervascular). Not heard in Hashimoto's.
- Agranulocytosis: The classic emergency scenario for Carbimazole.
- Block and Replace: Cannot be used in Pregnancy (Levothyroxine doesn't cross placenta well, but Carbimazole does -> Hypothyroid Fetus).
Common Exam Scenarios
- Patient on Carbimazole has sore throat. Action? (Urgent blood count).
- Pregnant woman with Graves'. Drug? (PTU in first trimester).
- Patient wants Radioiodine but has bulging eyes. (Caution/Contraindicated - high risk of worsening eyes).
10. Patient Explanation
What is it?
"Your immune system is producing an antibody that is accidentally switching your thyroid gland to 'MAXIMUM POWER'. It is like a car with the accelerator stuck down."
Will it get better?
"We can control it with medication. We usually treat for 18 months to try and 'reset' the immune system. In half of people, it goes away forever. In the other half, it comes back, and we might need to permanently disable the gland with radiation or surgery."
11. Evidence & Guidelines
Key Guidelines
| Guideline | Organization | Year | Key Points |
|---|---|---|---|
| Thyrotoxicosis | NICE (NG145) | 2019 | Management pathways. |
| Thyroid Eye Dis | EUGOGO | 2021 | Selenium and Steroids for eyes. |
Evidence-Based Recommendations
| Recommendation | Evidence Level |
|---|---|
| Antithyroid Drugs for 12-18m | High |
| Radioiodine for Relapse | High |
| Stop Smoking | High (For Eye Disease) |
13. References
- NICE Guideline [NG145]. Thyroid disease: assessment and management. 2019.
- Kahaly GJ, et al. 2021 European Group on Graves' Orbitopathy (EUGOGO) Clinical Practice Guidelines. Eur J Endocrinol. 2021.