Hyperthyroidism
Description
- Hyperthyroidism = gland overproducing. Thyrotoxicosis = excess hormone from any source
- Not interchangeable - thionamides only work if the gland is synthesising
Patterns
| Uptake | Tg | Course | |
|---|---|---|---|
| Graves | High, diffuse | inc | Relapsing |
| Toxic MNG / adenoma | High, focal | inc | Progressive, no remission |
| Destructive thyroiditis | Absent/low | inc | Hyper -> eu -> hypo -> recovery |
| Exogenous T4 | Absent | dec | Resolves on cessation |
- Graves = organ-specific autoimmunity with extrathyroidal disease
- Orbitopathy 30-50%, dermopathy ~0.5%, acropachy 0.1-1%
- Eye and skin disease run independently of thyroid function - controlling TFTs does not treat them
Epidemiology
- Overt thyrotoxicosis ~0.5-1%; subclinical 1-2%
- F>M 8:1, peak 30-50y
- Graves 50-80% of all thyrotoxicosis
- Toxic MNG dominates age >65 and in iodine-deficient regions
- Australia iodine-replete since mandatory bread fortification (2009)
- Jod-Basedow now mostly iatrogenic - contrast, amiodarone, kelp
Aetiopathogenesis
Graves
- Stimulating TRAb -> TSH-receptor -> unregulated cAMP -> synthesis + gland growth
- TPO/Tg antibodies commonly present but not pathogenic
- Genetic: CTLA4, CD25, CD40, TSHR, Tg. Concordance MZ ~30%
- Triggers: iodine load, smoking, post-partum, alemtuzumab (immune reconstitution, often late)
- Orbitopathy: TSH-R and IGF-1R co-expressed on orbital fibroblasts
- -> GAG deposition + adipogenesis -> inc orbital volume in a fixed bony box -> proptosis, optic nerve compression
- This is why IGF-1R blockade works
Amiodarone
- 37% iodine by weight, t1/2 ~100 days - disease persists months after cessation
| Type 1 | Type 2 | |
|---|---|---|
| Mechanism | Iodine load on nodular/latent Graves gland | Destructive thyroiditis |
| Gland | Abnormal | Normal |
| Doppler flow | Normal/inc | dec |
| Treatment | Thionamide (+/- perchlorate) | Glucocorticoid |
- Scintigraphy useless - body iodine-loaded. Mixed forms common -> treat both
Diagnosis
Biochemistry
- dec TSH + inc fT4/fT3
- T3-toxicosis (inc T3, normal T4) - early Graves, toxic adenoma
- Non-suppressed TSH with inc fT4 -> TSHoma or thyroid hormone resistance, not primary
- Biotin causes spurious inc fT4 / dec TSH - stop 48h before
Establish the cause
- TRAb first - sens/spec ~97%. Positive -> Graves, no scan needed
- Radionuclide uptake scan if TRAb negative - separates high- from low-uptake
- US + Doppler if scan unavailable, iodine-loaded, or pregnant
- Thyroglobulin: low = exogenous/factitious; high in everything else
Subclinical
- dec TSH, normal fT3/fT4, confirmed on repeat 3-6 months
- Risk concentrates at TSH <0.1 mU/L: AF, osteoporosis, dementia, mortality
Thyroid storm
- Clinical diagnosis - hormone levels no higher than uncomplicated thyrotoxicosis
- Fever, delirium, AF/HF, GI failure + precipitant (surgery, infection, iodine, DKA, labour)
- Burch-Wartofsky >=45 suggestive
Management
All symptomatic patients
- Propranolol 10-40 mg qid - also dec T4->T3 conversion
- Metoprolol/atenolol if selectivity needed; atenolol avoided in pregnancy
- Smoking cessation - the single biggest modifiable determinant of eye outcome
Graves - three definitive options
- Carbimazole (AU: methimazole not marketed; carbimazole is its prodrug)
- 15-45 mg/day, taper to 5-15 mg maintenance; titration preferred to block-replace
- Stop at 12-18 months if TRAb negative
- TRAb still positive -> relapse 80-100%; TRAb negative -> 20-30%
- Agranulocytosis 0.2-0.5% - sore throat/fever = FBE same day, stop drug
- Routine FBE monitoring does NOT prevent it - written warning does
- Hepatotoxicity: carbimazole cholestatic, PTU hepatocellular/fulminant
- Radioiodine - definitive, hypothyroidism in most
- Contraindicated: pregnancy, breastfeeding, active orbitopathy
- Steroid cover 6-12 weeks if smoker or mild eye disease
- Euthyroid outcome far more likely for a toxic nodule - suppressed surrounding tissue is spared
- Total thyroidectomy - large goitre, compression, suspected malignancy, planning pregnancy soon
- Render euthyroid first +/- Lugol's iodine
Toxic adenoma / toxic MNG
- Definitive therapy (RAI or surgery) - autonomy does not remit
- Thionamide is a bridge only - near-universal relapse on cessation
Destructive thyroiditis
- Self-limiting - no thionamide (nothing is being synthesised)
- Beta blocker; NSAID/aspirin, prednisolone if severe pain (subacute)
- Thyroxine in hypothyroid phase; ~20% permanently hypothyroid
Subclinical
- Treat if TSH <0.1 AND (age >65, OR AF/HF/CVD, OR osteoporosis, OR cognitive impairment)
- TSH 0.1-lower limit: treat only with osteoporosis or cardiac risk
Orbitopathy
- Mild: selenium, lubricants, euthyroidism, cease smoking
- Moderate-severe active: teprotumumab (anti-IGF-1R) first-line (ATA/ETA)
- EUGOGO retains IV methylprednisolone (cumulative <=8 g) +/- MMF - access, not efficacy
- Australian access restricted
- Sight-threatening (dysthyroid optic neuropathy): high-dose IV steroid then urgent decompression
- Inactive: rehabilitative surgery in sequence - decompression -> squint -> lids
Pregnancy
- PTU in first trimester (carbimazole -> aplasia cutis, choanal/oesophageal atresia), switch back after
- Lowest dose to keep fT4 at upper limit of normal - maternal overtreatment causes fetal hypothyroidism
- TRAb at 18-22 weeks: high titre -> fetal/neonatal Graves risk
Storm
- ICU. PTU (blocks conversion) -> then iodine >=1h later, glucocorticoid, propranolol, cooling, treat precipitant
- Iodine before thionamide fuels synthesis
Associations
- Other autoimmunity - T1DM, coeliac, Addison, vitiligo, pernicious anaemia, myasthenia
- AF - ~10-15% of overt thyrotoxicosis, rises with age
- Osteoporosis, thyrotoxic periodic paralysis (Asian males, hypokalaemic)
- Hypercalcaemia, inc ALP, abnormal LFTs
- Smoking - orbitopathy and dermopathy only
Natural history & complications
- Graves: relapsing-remitting. ~50% relapse after a thionamide course
- Predictors of relapse: young, large goitre, high T3, persistent TRAb, smoking
- Toxic nodular disease: never remits
- Adolescent thyrotoxicosis -> accelerated growth, normal final height (contrast hypothyroidism)
Complications
- AF, cardiomyopathy, high-output failure
- Osteoporosis, fracture
- Thyroid storm - mortality 10-30% even treated
- Post-treatment hypothyroidism - near-universal after RAI/surgery, lifelong TFT follow-up
- Sight loss from dysthyroid optic neuropathy
🔒
6 more sections, plus exam facts
Premium unlocks every note across every specialty, and the full exam fact library behind it.
Get premium access