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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Thyrotoxicosis = clinical syndrome of excess thyroid hormones. Hyperthyroidism = thyroid gland overproduction
- Graves' disease (60–80% of cases): autoimmune, diffuse goitre, thyroid eye disease, pretibial myxoedema. TRAb positive
- Toxic multinodular goitre and toxic adenoma are other common causes. Thyroiditis causes transient thyrotoxicosis without hyperthyroidism
- Diagnosis: suppressed TSH + raised fT4 (±fT3). TRAb confirms Graves'. Technetium scan if TRAb negative
- Treatment: carbimazole (titration or block-and-replace) first while awaiting definitive treatment. Radioactive iodine is first-line definitive for Graves' (NICE NG145)
- Thyroid storm: medical emergency — propranolol, propylthiouracil, hydrocortisone, Lugol's iodine, cooling, ITU
Overview
Hyperthyroidism is a condition in which the thyroid gland produces excess thyroid hormones (T4 and T3), resulting in the clinical syndrome of thyrotoxicosis. Graves' disease is the commonest cause (60–80%), caused by TSH-receptor stimulating antibodies (TRAb) that activate the TSH receptor on thyroid follicular cells. Other causes include toxic multinodular goitre (Plummer disease), toxic adenoma (single hot nodule), and drug-induced (amiodarone, lithium). Thyroiditis (subacute/de Quervain, postpartum, silent) causes transient thyrotoxicosis from pre-formed hormone release rather than new synthesis. Graves' disease has a triad of manifestations: thyrotoxicosis, ophthalmopathy (thyroid eye disease), and dermopathy (pretibial myxoedema).
Epidemiology
Thyrotoxicosis affects approximately 2% of women and 0.2% of men in the UK. Graves' disease accounts for 60–80% of all cases and has a female:male ratio of approximately 5–10:1. Peak incidence is 30–50 years. Toxic multinodular goitre is more common in older adults and in iodine-deficient regions. Risk factors for Graves' include family history of autoimmune thyroid disease, other autoimmune conditions (T1DM, Addison, vitiligo), female sex, smoking (particularly for thyroid eye disease), and recent psychological stress.
Clinical Features
Symptoms
Weight loss despite increased appetite (hypermetabolic state)
Heat intolerance, excessive sweating
Palpitations — may indicate AF or sinus tachycardia
Tremor (fine resting tremor of outstretched hands)
Anxiety, irritability, emotional lability, insomnia
Diarrhoea or increased bowel frequency
Oligomenorrhoea or amenorrhoea
Eye symptoms (Graves'): grittiness, excessive tearing, double vision, proptosis, visual loss
Signs
Tachycardia (often resting >90 bpm), atrial fibrillation (10–25% of older patients)
Fine tremor of outstretched hands
Warm, moist skin; palmar erythema
Diffuse non-tender goitre (Graves') — may have thyroid bruit
Lid retraction and lid lag (any cause of thyrotoxicosis)
Graves' ophthalmopathy: proptosis (exophthalmos), periorbital oedema, chemosis, ophthalmoplegia
Pretibial myxoedema (Graves'-specific): waxy, indurated plaques on anterior shins
Thyroid acropachy (rare Graves'-specific): clubbing + periosteal new bone formation
Thyroid storm: hyperpyrexia >40°C, tachycardia >140, confusion, seizures, jaundice, cardiac failure
Investigations
First-line
TSHSuppressed (<0.1 mU/L) in primary thyrotoxicosis — most sensitive first-line test
Free T4Elevated in overt hyperthyroidism. If normal with suppressed TSH, check free T3 (T3 thyrotoxicosis)
Free T3Elevated — particularly important in T3 thyrotoxicosis (fT4 may be normal)
Second-line
TSH receptor antibodies (TRAb)Positive in >95% of Graves' disease — the key differentiating test (NICE NG145)
Technetium-99m thyroid uptake scanIf TRAb negative — differentiates diffuse (Graves'), nodular (toxic MNG/adenoma), or low uptake (thyroiditis, exogenous thyroxine)
FBC and LFTsBaseline before starting antithyroid drugs — carbimazole can cause agranulocytosis and hepatotoxicity
Specialist
Thyroid USSIf palpable nodule — assess for malignancy. Not routinely needed for Graves'
ECGAssess for AF, particularly in patients >60 years with thyrotoxicosis
CT/MRI orbitsIf thyroid eye disease with proptosis, ophthalmoplegia, or optic nerve compression — assess extraocular muscle enlargement
1
Initial treatment (all causes)
- Beta-blocker: propranolol 40 mg TDS (non-selective — also inhibits peripheral T4→T3 conversion) for symptom control
- Antithyroid drug: start carbimazole while awaiting specialist assessment
- Check FBC and LFTs BEFORE starting carbimazole
- Warn patient: sore throat + fever → urgent FBC to exclude agranulocytosis (occurs in ~0.5%)
2
Definitive treatment — Graves' disease
- Radioactive iodine (RAI) is first-line definitive treatment (NICE NG145) unless: active thyroid eye disease, pregnancy planned within 4–6 months, suspected compression/malignancy
- Antithyroid drugs (carbimazole) as first-line definitive if remission likely: mild disease, small goitre, low TRAb — titration regimen for 12–18 months
- Block-and-replace regimen: carbimazole 40 mg daily + levothyroxine (used for ~6 months, avoids dose titration but more side effects)
- Surgery (total thyroidectomy): if RAI unsuitable, compression symptoms, suspected malignancy, or patient preference
- ~50% relapse rate after first course of antithyroid drugs — consider RAI or surgery for persistent/relapsed disease
3
Definitive treatment — toxic nodular disease
- Toxic multinodular goitre: RAI first-line. Surgery if compression or suspected malignancy
- Toxic adenoma: RAI or hemithyroidectomy. Lifelong antithyroid drugs if surgery/RAI unsuitable
4
Thyroid eye disease
- Smoking cessation (single most important modifiable factor)
- Selenium supplementation 100 mcg BD for 6 months (mild/moderate disease)
- Artificial tears, sunglasses, head-of-bed elevation
- Severe/active: IV methylprednisolone pulses. Specialist ophthalmology referral
- Sight-threatening (optic nerve compression): urgent orbital decompression
- Avoid RAI in active thyroid eye disease (risk of exacerbation)
5
Thyroid storm (emergency)
- Medical emergency — ITU admission
- IV propranolol (or oral if tolerated) — control tachycardia
- Propylthiouracil (PTU) preferred over carbimazole (also blocks peripheral T4→T3 conversion)
- IV hydrocortisone 100 mg QDS (blocks T4→T3 conversion and treats possible adrenal insufficiency)
- Lugol's iodine (potassium iodide) — 1 hour AFTER PTU (blocks further hormone release)
- Active cooling, IV fluids, treat precipitant (infection, surgery, iodine load, DKA)
Complications
- Atrial fibrillation: Occurs in 10–25% — more common in older patients. Anticoagulate per CHA₂DS₂-VASc
- Heart failure: High-output cardiac failure from prolonged thyrotoxicosis
- Osteoporosis: Excess thyroid hormones increase bone resorption. DEXA indicated
- Thyroid storm: Mortality 20–30% even with treatment. Triggered by infection, surgery, trauma, iodine load
- Graves' ophthalmopathy: Sight-threatening in ~5%. Optic neuropathy requires emergency decompression
- Agranulocytosis: Carbimazole/PTU side effect (~0.5%) — sore throat + fever = urgent FBC
- Post-treatment hypothyroidism: Almost inevitable after RAI or thyroidectomy — lifelong levothyroxine
UKMLA Exam Tips
- 1Suppressed TSH + raised fT4/fT3 = thyrotoxicosis. If both suppressed (low TSH + low fT4) → think secondary hypothyroidism, not thyrotoxicosis
- 2TRAb differentiates Graves' from other causes. Technetium scan if TRAb negative
- 3Graves'-specific features: thyroid eye disease, pretibial myxoedema, thyroid acropachy. These do NOT occur in other causes
- 4Lid retraction and lid lag are non-specific — any cause of thyrotoxicosis. Proptosis/exophthalmos = Graves' only
- 5Carbimazole: warn about agranulocytosis (sore throat → urgent FBC). Block-and-replace vs titration — know both
- 6In thyroid storm: PTU preferred over carbimazole (extra T4→T3 conversion block). Give hydrocortisone BEFORE iodine
- 7Amiodarone thyrotoxicosis: type 1 = excess synthesis (give carbimazole); type 2 = destructive thyroiditis (give steroids)
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