Hyperthyroidism
Excess thyroid hormone production causing a hypermetabolic state. Commonest cause is Graves disease (~75%). Presents with weight loss, heat intolerance, palpitations, tremor, and anxiety. Treated with antithyroid drugs, radioiodine, or surgery.
Key Facts
Graves disease (~75%): autoimmune; TSH receptor stimulating antibodies (TRAb); diffuse goitre, orbitopathy, pretibial myxoedema Other causes: toxic multinodular goitre (~15%), toxic adenoma (~5%), thyroiditis (subacute/de Quervain, postpartum), drugs (amiodarone), exogenous thyroxine Clinical features: weight loss, heat intolerance, palpitations (AF in ~10-15%), tremor, anxiety, sweating, diarrhoea, proximal myopathy, goitre, lid lag, lid retraction Diagnosis: suppressed TSH (<0.1 mU/L) + raised free T4 ± free T3; TRAb positive in Graves Treatment (NICE CKS): carbimazole 20-40mg/day (titration or block-and-replace regimen) for 12-18 months; radioiodine (¹³¹I) for relapse/definitive; thyroidectomy for large goitre/compression Agranulocytosis: rare but life-threatening side effect of carbimazole/PTU (~0.2-0.5%); warn patients — sore throat/fever → urgent FBC
Overview
Key Facts
Graves disease is the commonest cause of hyperthyroidism. First-line treatment is antithyroid drugs for 12-18 months. Relapse rate after ATD is ~50%. Radioiodine is the definitive treatment. Agranulocytosis requires immediate ATD cessation.
Epidemiology
Prevalence ~0.5-2%. F:M 5-10:1. Graves: peak age 30-50 years. Toxic MNG: older patients. Thyrotoxicosis factitia: intentional/accidental thyroxine ingestion.
Aetiology
Graves disease: TSH receptor stimulating antibodies (TRAb/TSI) → thyroid gland stimulation → excess T4/T3. HLA-DR3 associated. Environmental triggers: stress, smoking (especially for orbitopathy), infection, iodine excess. Toxic multinodular goitre: autonomous nodules; often elderly; gradual onset. Toxic adenoma: single autonomous nodule.
Pathophysiology
Excess thyroid hormone increases basal metabolic rate, oxygen consumption, heat production, and sympathetic activity. Effects: cardiac — tachycardia, AF, high-output cardiac failure; musculoskeletal — myopathy, osteoporosis; GI — increased motility; CNS — anxiety, tremor, hyperreflexia.
Clinical Presentation
Symptoms
- Weight loss (despite increased appetite)
- Heat intolerance, sweating
- Palpitations (sinus tachycardia, AF)
- Tremor (fine), anxiety, irritability, insomnia
- Diarrhoea/increased stool frequency
- Proximal muscle weakness
- Menstrual irregularity (oligomenorrhoea)
Signs
- Tachycardia, AF
- Fine tremor, warm moist palms
- Goitre (diffuse in Graves; nodular in MNG)
- Lid lag, lid retraction (any cause of thyrotoxicosis)
- Hyperreflexia
Graves-Specific Features
- Graves orbitopathy: proptosis (exophthalmos), periorbital oedema, conjunctival injection, diplopia (EOM restriction), optic neuropathy (sight-threatening)
- Pretibial myxoedema: waxy plaques on shins
- Thyroid acropachy: digital clubbing (rare)
Red Flags
- AF with thyrotoxicosis → rate control + anticoagulation
- Thyroid storm (see separate topic)
- Graves orbitopathy with visual loss → urgent ophthalmology
- Agranulocytosis on ATDs: sore throat/fever → STOP ATD, urgent FBC
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Graves disease | Diffuse goitre, TRAb+, orbitopathy | TRAb, uptake scan |
| Toxic MNG | Nodular goitre, elderly | Uptake scan, USS |
| Toxic adenoma | Single hot nodule | Uptake scan |
| Subacute thyroiditis | Painful thyroid, preceded by viral illness, self-limiting | ESR (raised), low uptake scan |
| Amiodarone thyrotoxicosis | Type 1 (excess iodine) or type 2 (destructive) | Drug history, USS Doppler |
| Thyrotoxicosis factitia | Low thyroglobulin, no goitre | Thyroglobulin (low), uptake (suppressed) |
Diagnosis / Investigation
TFTs
- TSH: suppressed (<0.1 mU/L)
- Free T4: raised; free T3: raised (T3 thyrotoxicosis if T4 normal)
Autoantibodies
- TRAb (TSH receptor antibodies): positive in >95% of Graves; highly specific
- Anti-TPO: positive in ~75% of Graves (less specific)
Imaging
- Thyroid uptake scan (technetium-99m/¹²³I): diffuse increased uptake = Graves; patchy = MNG; single hot nodule = toxic adenoma; low/absent uptake = thyroiditis, factitia
- USS thyroid: nodule assessment; Doppler for vascularity
Bloods
- FBC: baseline before ATDs
- LFTs: baseline (ATDs can cause hepatotoxicity)
- ESR: raised in subacute thyroiditis
Other
- ECG: AF, tachycardia
- DEXA: if osteoporosis suspected (prolonged thyrotoxicosis)
Management
Antithyroid Drugs (First-Line — NICE CKS)
- Carbimazole 20-40mg/day initially; two approaches:
- Titration: start high, reduce to maintenance (5-15mg/day) based on TFTs
- Block-and-replace: high-dose carbimazole (40mg/day) + levothyroxine 100-150μg/day
- Duration: 12-18 months then withdraw; remission in ~50% (Graves)
- Propylthiouracil (PTU) 200-400mg/day: reserved for first trimester pregnancy (carbimazole teratogenic — aplasia cutis) or carbimazole intolerance
- Side effects: rash (~5%), arthralgia, GI; agranulocytosis (~0.2-0.5%) — warn patient: sore throat/fever → STOP drug, urgent FBC
Beta-Blockers (Symptom Control)
- Propranolol 40-80mg TDS: controls palpitations, tremor, anxiety while ATDs take effect (2-6 weeks for ATD onset); also inhibits T4→T3 conversion
Radioiodine (¹³¹I)
- Definitive treatment; commonly used for relapse after ATDs, toxic MNG
- Contraindicated: pregnancy/breastfeeding, active moderate-severe Graves orbitopathy
- Most become hypothyroid → lifelong levothyroxine
- Avoid close contact with children/pregnant women for ~3 weeks after treatment
Thyroidectomy
- Total thyroidectomy: large goitre with compressive symptoms, suspected malignancy, severe Graves orbitopathy (radioiodine may worsen), patient preference
- Risks: recurrent laryngeal nerve injury (hoarseness ~1%), hypoparathyroidism (~1-2%), hypothyroidism (expected after total)
- Render euthyroid with ATDs pre-operatively + Lugol iodine (10 days pre-op to reduce thyroid vascularity)
Graves Orbitopathy
- Mild: lubricants, selenium 100μg BD (EUGOGO trial)
- Moderate-severe: IV methylprednisolone pulses, orbital radiotherapy
- Sight-threatening (optic neuropathy): urgent IV steroids ± surgical decompression
- Teprotumumab (anti-IGF-1R): emerging therapy
Referral Criteria
- Endocrinology: all new thyrotoxicosis for diagnosis and management
- Ophthalmology: Graves orbitopathy
- Surgery: large goitre, compression, malignancy suspected
Prognosis
Graves: ~50% remission after 12-18 months ATDs; ~50% relapse. Radioiodine: >90% cure but most become hypothyroid. Surgery: >95% cure; hypothyroidism expected. Toxic MNG/adenoma: rarely remit spontaneously; radioiodine or surgery usually needed. Untreated thyrotoxicosis: risk of AF, heart failure, osteoporosis, thyroid storm. Graves orbitopathy: ~5% develop sight-threatening disease.
Other Relevant Information
Causes of Thyrotoxicosis
| Cause | Goitre | Uptake Scan | TRAb |
|---|---|---|---|
| Graves | Diffuse | Diffuse high | Positive |
| Toxic MNG | Multinodular | Patchy | Negative |
| Toxic adenoma | Single nodule | Hot nodule | Negative |
| Subacute thyroiditis | Tender | LOW | Negative |
| Factitia | Absent | LOW | Negative |
Block-and-Replace vs Titration
| Feature | Block-and-Replace | Titration |
|---|---|---|
| ATD dose | High fixed + levothyroxine | Variable, tapered |
| TFT checks | Less frequent | More frequent |
| Side effects | Higher dose → more SE | Lower maintenance dose |
| Duration | 6-12 months | 12-18 months |