Write a short note on thyrotoxicosis, Graves' disease and thyroid storm.

Definition

Thyrotoxicosis is the clinical state resulting from excess circulating thyroid hormone. Hyperthyroidism strictly means excess hormone *production* by the gland — an important distinction, since thyroiditis and exogenous hormone cause thyrotoxicosis without hyperthyroidism.

Causes

Graves' Disease

An autoimmune disorder in which TSH receptor-stimulating antibodies (TRAb/TSI) bind and activate the TSH receptor, causing diffuse gland hyperplasia and unregulated hormone production. It affects women 5–10 times more often, peaks at 20–50 years, and is associated with HLA-DR3 and with other autoimmune diseases.

Features unique to Graves' (not seen in other causes of thyrotoxicosis):

• Diffuse, smooth goitre with a bruit (from increased vascularity)
• Graves' ophthalmopathy — proptosis (exophthalmos), lid retraction and lid lag, periorbital oedema, chemosis, diplopia from extraocular muscle involvement, and in severe cases optic nerve compression with visual loss. Caused by retro-orbital glycosaminoglycan deposition and fibroblast activation; worsened by smoking and by radioiodine therapy
• Pretibial myxoedema — non-pitting, indurated plaques over the shins
• Thyroid acropachy — clubbing with periostitis (rare)

Clinical Features of Thyrotoxicosis

• General: heat intolerance, excessive sweating, weight loss despite increased appetite, fatigue.
• Cardiovascular: palpitations, sinus tachycardia, atrial fibrillation (in 10–20%, especially the elderly), wide pulse pressure, high-output cardiac failure.
• Neuromuscular: fine tremor, anxiety, irritability, emotional lability, insomnia, proximal myopathy, brisk reflexes, hypokalaemic periodic paralysis (notably in Asian men).
• Gastrointestinal: increased bowel frequency, diarrhoea.
• Reproductive: oligomenorrhoea, infertility, gynaecomastia.
• Elderly — "apathetic thyrotoxicosis": weight loss, atrial fibrillation, heart failure and depression without the classic hyperadrenergic features; easily missed.

Investigations

• TSH — the single best initial test: suppressed in primary thyrotoxicosis. Free T4 and free T3 raised (T3-toxicosis has raised T3 with normal T4).
• TSH receptor antibodies (TRAb) — confirm Graves' disease; also predict fetal risk in pregnancy.
• Anti-TPO antibodies — positive in autoimmune thyroid disease generally.
• Radioiodine uptake scan — diffuse increased uptake in Graves', focal ("hot") nodule in toxic adenoma, patchy in multinodular goitre, and low uptake in thyroiditis and factitious thyrotoxicosis — the key discriminator when the cause is unclear. Contraindicated in pregnancy and lactation.
• ECG for atrial fibrillation; CBC (may show mild neutropenia before treatment — important baseline); LFT (baseline before antithyroid drugs).

Management

• Beta-blockers (propranolol) — rapid symptomatic control of tremor, palpitations, anxiety and heat intolerance; propranolol additionally inhibits peripheral T4 to T3 conversion.
• Antithyroid drugs (thionamides): carbimazole/methimazole (first-line) and propylthiouracil (PTU). They inhibit thyroid peroxidase; PTU also blocks peripheral conversion. Used as a titration regimen or "block and replace" for 12–18 months in Graves'. PTU is preferred in the first trimester of pregnancy and in thyroid storm; carbimazole is preferred otherwise because PTU carries a risk of severe hepatotoxicity.
• Radioiodine (I-131) — definitive, simple and effective; the commonest definitive treatment in many centres. Contraindicated in pregnancy, lactation and active ophthalmopathy (which it may worsen). Hypothyroidism is an expected consequence requiring lifelong thyroxine.
• Surgery (subtotal or total thyroidectomy) — for large compressive goitre, suspicion of malignancy, failure of or intolerance to drugs, or patient preference. Requires preoperative rendering euthyroid plus iodine (Lugol's) to reduce vascularity. Complications: hypoparathyroidism, recurrent laryngeal nerve injury, hypothyroidism.
• Ophthalmopathy: smoking cessation (the strongest modifiable factor), lubricants, head elevation, selenium in mild disease; corticosteroids, orbital radiotherapy, teprotumumab or decompression in severe disease; specialist ophthalmology input.

Thyroid Storm (thyrotoxic Crisis)

A decompensated, life-threatening exacerbation of thyrotoxicosis, with mortality of 10–30% even with treatment.

Precipitants: infection, surgery (especially thyroid surgery in an unprepared patient), trauma, childbirth, diabetic ketoacidosis, radioiodine therapy, iodinated contrast, and abrupt withdrawal of antithyroid drugs.

Features:

• hyperpyrexia (often > 40 °C), marked tachycardia and atrial fibrillation with heart failure, agitation, delirium, seizures and coma, vomiting, diarrhoea, jaundice and abdominal pain, and dehydration with shock. The Burch–Wartofsky score aids recognition
• the diagnosis is clinical, since hormone levels are no higher than in uncomplicated thyrotoxicosis.

Management — treat immediately, in intensive care:

1. Beta-blockade — propranolol intravenously or orally for adrenergic control.

2. Propylthiouracil — preferred over carbimazole here because it also blocks peripheral T4→T3 conversion.

3. Iodine (Lugol's solution or potassium iodide) — given at least 1 hour AFTER the thionamide, to block hormone release (Wolff–Chaikoff effect). Giving iodine first provides substrate for further hormone synthesis.

4. Corticosteroids (hydrocortisone) — block peripheral conversion and treat relative adrenal insufficiency.

5. Supportive: cooling with paracetamol (avoid aspirin, which displaces thyroid hormone from binding proteins), intravenous fluids, correction of electrolytes, treatment of heart failure and arrhythmia.

6. Identify and treat the precipitant — particularly infection.