Thyrotoxicosis and Hyperthyroidism

⚠️ Definitions

• Hyperthyroidism 🔥 = excess production and release of thyroid hormones (T3/T4) from the thyroid.
• Thyrotoxicosis ☢️ = clinical syndrome of thyroid hormone excess, from any source (thyroidal or extrathyroidal).

📊 Prevalence

• 🇪🇺 Europe: ~0.8% of population.
• 🇺🇸 USA: 1–3% prevalence.
• ♀️ More common in women (5–10x higher).

🔎 Causes of Hyperthyroidism / Thyrotoxicosis

• Graves’ disease 🌸 – Commonest cause (esp. women 30–50). – Diffuse goitre, ↑ RAI uptake, ophthalmopathy, pretibial myxoedema. – Autoantibodies: TSH receptor (TRAb). – Smoking 🚬 ↑ risk of eye disease.
• Toxic multinodular goitre 🪢 – Common in older adults, iodine-deficient areas. – Patchy uptake on RAI scan.
• Toxic adenoma (“hot nodule”) 🔥 – Solitary nodule, focal ↑ uptake on scan. – Causes classical thyrotoxicosis.
• Thyroiditis 🦠 – Often post-viral (subacute, painful). – Release of pre-formed hormone (NOT ↑ synthesis). – Features: tender thyroid, ↑ ESR/CRP, ↓ uptake on RAI. – Rx: NSAIDs/β-blockers; steroids if severe.
• TSH-secreting pituitary adenoma 🎯 – Rare. Raised TSH + T4. – Features: thyrotoxicosis + bitemporal hemianopia.
• Hashimoto’s “Hashitoxicosis” 🌀 – Transient thyrotoxic phase in autoimmune thyroiditis. – Antibodies: anti-TPO, anti-TG.
• Jod-Basedow effect 💊 – Thyrotoxicosis after excess iodine (contrast, amiodarone).
• hCG-mediated 🤰 – Hydatidiform mole, choriocarcinoma.
• McCune-Albright syndrome 🧬 – Triad: fibrous dysplasia of bone, café-au-lait spots, endocrine hyperfunction (incl. thyroid).

📊 Comparison Table – Common Causes of Thyrotoxicosis

🩺 Clinical Features

• Weight loss ⚖️ despite ↑ appetite.
• Heat intolerance ☀️, sweating.
• Palpitations ❤️ (AF, tachycardia common).
• Neuro: anxiety, tremor, irritability.
• GI: diarrhoea, ↑ bowel frequency.
• Muscle: proximal myopathy 💪.
• Graves’ specific: Ophthalmopathy 👁️, pretibial myxoedema, thyroid acropachy.

🔬 Investigations

• ↑ Free T3/T4, ↓ TSH (except pituitary adenoma).
• TRAb positive → Graves.
• Other antibodies: anti-TPO, anti-TG (autoimmune thyroiditis).
• RAI uptake scan: diffuse (Graves) vs patchy (multinodular) vs focal (adenoma) vs ↓ uptake (thyroiditis).
• ECG: AF common → ↑ stroke risk 🧠.
• Other: mild ↑ Ca, ↑ ALP, ↓ K⁺ (periodic paralysis, esp. SE Asians).

💊 Management

• Symptomatic: – Propranolol 20–40 mg TDS (also ↓ T4→T3 conversion). – Useful for tremor, palpitations, anxiety.
• Antithyroid drugs 💊 – Carbimazole (1st line UK): start 20–40 mg OD → titrate to euthyroid (usual maintenance 5–15 mg). – Propylthiouracil (PTU): preferred in 1st trimester pregnancy; also blocks T4→T3 conversion. – Regimens: titration vs “block & replace” (carbimazole + thyroxine). – Duration: ~12–18 months, then trial withdrawal. ⚠️ Major adverse effect: agranulocytosis (0.5%) → fever/sore throat = urgent FBC + stop drug.
• Radioactive Iodine (I-131) ☢️ – Single dose effective in most. – Contraindicated in pregnancy & breastfeeding. – May worsen eye disease → avoid in active Graves’ orbitopathy (esp. smokers). – Hypothyroidism common post-treatment → lifelong thyroxine.
• Surgery 🔪 – Indications: large obstructive goitre, suspicious nodules, relapse after drugs/RAI, or pregnancy contraindicating RAI. – Risks: recurrent laryngeal nerve injury, hypocalcaemia (parathyroid removal).

🤰 Hyperthyroidism in Pregnancy

• Specialist endocrine + obstetric care required 👩‍⚕️.
• 1st trimester: PTU (less teratogenic).
• 2nd–3rd trimester: Carbimazole (preferred to avoid PTU hepatotoxicity).
• Surgery: 2nd trimester safest if needed.
• Uncontrolled thyrotoxicosis ↑ risk: miscarriage, pre-eclampsia, IUGR, stillbirth.

🚨 Thyroid Storm (Medical Emergency)

• Severe thyrotoxicosis with fever 🌡️, tachyarrhythmias ❤️, delirium 🧠, multi-organ failure.
• Precipitated by infection, surgery, trauma.
• Rx: – IV propranolol/esmolol (rate control). – PTU high dose (600–1000 mg load, then 200–300 mg q6h). – Lugol’s iodine after PTU (blocks release). – IV hydrocortisone (stress dose). – Supportive (fluids, cooling, ICU).

📚 References

• NICE CKS: Hyperthyroidism
• De Leo, Lee & Braverman. Hyperthyroidism. N Engl J Med 2016.