Graves' Disease
Summary
Graves' Disease is an autoimmune disorder where TSH Receptor Antibodies (TRAb) stimulate the thyroid gland to produce excessive thyroid hormone. It is the most common cause of hyperthyroidism (60-80%). It is characterized by the triad of Hyperthyroidism, Ophthalmopathy (TED), and Dermopathy (Pretibial Myxoedema). [1,2]
Clinical Pearls
Agranulocytosis: Every patient started on Carbimazole MUST be warned: "If you get a sore throat or fever, stop the drug and get a blood count immediately." Neutropenia occurs in 0.3% but is fatal if missed.
Smoking & Eyes: Smoking is the single biggest risk factor for the development and worsening of Thyroid Eye Disease. Radioiodine treatment can also worsen eye disease in smokers - always cover with prophylactic steroids in this group.
The "Bruit": A Graves' goitre is extremely vascular. Placing a stethoscope over the gland often reveals a loud continuous bruit (the "Thyroid Inferno" on ultrasound).
Demographics
- Prevalence: 1-2% of women.
- Gender: Female:Male = 10:1.
- Age: Peak 30-50 years.
- Genetics: Strong association with HLA-DR3 and other autoimmune diseases (T1DM, Addison's, Pernicious Anaemia).
Mechanism
- Autoantibodies: B-cells produce Thyroid Stimulating Immunoglobulins (TSI/TRAb).
- Mimicry: These antibodies bind to the TSH receptor on thyroid follicular cells and mimic TSH.
- Unregulated Growth: Unlike TSH, TRAb secretion is not suppressed by high T3/T4 (no negative feedback). This drives continuous hormone production and gland growth (Goitre).
- Eye Disease: TSH receptors are also expressed on orbital fibroblasts. TRAb binding here causes inflammation, fat expansion, and muscle swelling -> Proptosis.
| Condition | Features | Uptake Scan (Technetium) |
|---|---|---|
| Graves' Disease | Ophthalmopathy, Bruit, Goitre. | Diffusely Increased |
| Toxic Multinodular Goitre | Elderly, Lumpy gland. | Patchy "Hot" Nodules |
| Toxic Adenoma | Single lump. | Single "Hot" Spot |
| Thyroiditis (Viral/Postpartum) | Tender (Viral). Transient. | Low/Absent Uptake |
| Exogenous Thyroxine | History of taking T4. | Low Uptake |
Thyrotoxicosis Symptoms
Graves' Specific Signs
Biochemistry
- TSH: Suppressed (less than 0.05).
- Free T4/T3: Elevated.
- TRAb Antibodies: Positive in >95% (Diagnostic).
- TPO Antibodies: Positive in 75% (non-specific, also in Hashimoto's).
Imaging
- Ultrasound: Diffusely enlarged, hypoechoic, hypervascular ("Inferno").
- Technetium Uptake Scan: Differentiates Graves' (High diffuse) from Thyroiditis (Low).
Management Algorithm
GRAVES' DISEASE CONFIRMED
(Low TSH + High T3/T4 + TRAb Positive)
↓
SYMPTOM CONTROL
Beta-Blockers (Propranolol)
(Until euthyroid state reached)
↓
DEFINITIVE THERAPY
┌──────────────┼──────────────┐
MEDICAL RADIOIODINE SURGERY
(1st Line) (Relapse/Old) (Large Goitre)
↓ ↓ ↓
Carbimazole I-131 Pill Total Thyroidectomy
(12-18 months) (Avoid in eye (Risks: Voice/Ca)
disease/kids)
1. Antithyroid Drugs (ATD)
- Carbimazole: First line. 20-40mg daily. Taper down as thyroid levels drop ("Titration") OR keep high dose and add Thyroxine ("Block and Replace").
- PTU (Propylthiouracil): Second line. Use in Pregnancy (1st Trimester) or Thyroid Storm. Risk of hepatotoxicity.
- Duration: Treat for 12-18 months then stop. 50% relapse rate.
2. Radioiodine (RAI)
- Patient swallows I-131 capsule. Radiation destroys gland over weeks.
- Contraindications: Pregnancy (teratogenic), Active Eye Disease (worsens it), Children.
- Outcome: Permanent Hypothyroidism (needs lifelong Thyroxine).
3. Surgery
- Total Thyroidectomy.
- Indications: Large obstructive goitre, severe eye disease (cannot have RAI), pregnancy (if drugs fail).
- Risks: Recurrent Laryngeal Nerve palsy (Hoarse voice), Hypoparathyroidism (Low Calcium).
- Thyroid Storm: Life-threatening hypermetabolic state. High fever, confusion, tachycardia >140. Mortality 10-20%. Treat with Beta-blockers, PTU, Steroids, and Potassium Iodide.
- Atrial Fibrillation: Risk of stroke.
- Osteoporosis: Accelerated bone turnover.
- Medical therapy cures ~50%. The rest relapse and need RAI/Surgery.
- Eye disease runs a separate course to the thyroid disease (can get worse even after thyroid is removed).
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Thyroid Disease | NICE NG145 (2019) | Carbimazole 1st line. TRAb testing standard. |
| Thyroid Eye Disease | EUGOGO | Selenium + Steroids for active eye disease. |
Landmark Evidence
1. Iodine in Pregnancy
- Studies confirm that Carbimazole is associated with Aplasia Cutis (scalp defects) and Choanal Atresia in the fetus. PTU is preferred in the first trimester.
What is Graves' Disease?
It is a condition where your immune system mistakenly attacks your thyroid gland. Instead of destroying it, it switches it "ON", making it produce far too much hormone.
Why do I feel so wired?
Thyroid hormone is the body's accelerator pedal. Having too much is like having a brick on the accelerator. Your heart races, you feel hot, shaky, and anxious, and you burn fuel (weight) rapidly.
What about my eyes?
The same antibody that attacks the thyroid can attack the muscles behind the eye, causing them to swell. This pushes the eyes forward. Smoking makes this much, much worse, so you must stop smoking.
Is it curable?
Yes. We usually start with tablets for 18 months to reset the system. If it comes back, we can use a radioactive iodine pill or surgery to permanently remove the thyroid (you would then take a hormone replacement tablet daily).
Primary Sources
- NICE. Thyroid disease: assessment and management (NG145). 2019.
- Ross DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism. Thyroid. 2016.
- Bartalena L, et al. The 2021 European Group on Graves' Orbitopathy (EUGOGO) clinical practice guidelines. Eur J Endocrinol. 2021.
Common Exam Questions
- Diagnosis: "Positive TRAb?"
- Answer: Graves' Disease.
- Pharmacology: "S/E of Carbimazole?"
- Answer: Agranulocytosis (Sore throat).
- Pregnancy: "Drug of choice?"
- Answer: PTU (1st Trimester), Carbimazole (2nd/3rd).
- Eye Disease: "Effect of Radioiodine?"
- Answer: Can worsen eye disease (use steroids).
Viva Points
- Block and Replace: Explain the regimen. High dose Carbimazole (40mg) to completely switch off the gland, plus Levothyroxine to replace physiological needs. Smoother control but higher drug side effects. Not for pregnancy.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.