Endocrinology: Thyroid disease (Complete)

• Basics: What Is Thyroid Disease? | Thyroid Physiology | Thyroid Function Tests | Interpreting TFT Patterns | History and Examination | Antibodies and Imaging
• Hypothyroidism: Hypothyroidism: Causes | Hashimoto's Thyroiditis | Hypothyroidism: Clinical Features | Levothyroxine Treatment | Subclinical Hypothyroidism | Central (Secondary) Hypothyroidism | Myxoedema Coma
• Hyperthyroidism: Hyperthyroidism: Causes | Hyperthyroidism: Clinical Features | Graves' Disease | Thyroid Eye Disease | Toxic Multinodular Goitre | Toxic Adenoma | Antithyroid Drugs | Radioiodine | Thyroidectomy | Subclinical Hyperthyroidism | Thyroid Storm
• Thyroiditis: Subacute (de Quervain's) Thyroiditis | Postpartum Thyroiditis | Painless (Silent) Thyroiditis | Riedel's Thyroiditis
• Drug-induced: Amiodarone | Lithium | Immunotherapy and Other Drugs
• Goitre, nodules and cancer: Goitre | Thyroid Nodules | Papillary Carcinoma | Follicular Carcinoma | Medullary Carcinoma | Anaplastic Carcinoma | Thyroid Lymphoma
• Special situations: Thyroid Disease in Pregnancy | Congenital Hypothyroidism | Older Adults | Non-thyroidal Illness | Unusual TFT Patterns
• Revision: Drug Reference Table | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🦋 Thyroid disease is one of the commonest endocrine problems. About 1 in 30 people in the UK take levothyroxine, and women are affected 5–10 times more often than men. The thyroid can be underactive (hypothyroidism), overactive (hyperthyroidism), inflamed (thyroiditis), or enlarged and nodular (goitre, nodules, cancer).
Your four questions for every patient: What do the TFTs show - is the problem in the thyroid or the pituitary? What is the cause? Is it an emergency (storm, myxoedema coma, airway compression)? Is there a lump that could be cancer?

What Is Thyroid Disease?

The thyroid makes hormones that set the body's metabolic rate. Too little hormone slows everything down; too much speeds everything up. Thyroid disease falls into four groups:

• Hypothyroidism: Too little hormone. In the UK it is usually caused by autoimmune Hashimoto's thyroiditis; worldwide, iodine deficiency is the commonest cause.
• Hyperthyroidism (thyrotoxicosis): Too much hormone. The commonest cause is Graves' disease, followed by toxic nodular disease and thyroiditis.
• Thyroiditis: Inflammation that releases stored hormone (a temporary toxic phase), often followed by a hypothyroid phase.
• Structural disease: Goitre, nodules and cancer. These may occur with normal hormone levels.

Terminology:

• Thyrotoxicosis: The clinical state of excess thyroid hormone from any cause.
• Hyperthyroidism: Thyrotoxicosis caused specifically by the gland overproducing hormone.

The distinction matters: thyroiditis causes thyrotoxicosis without hyperthyroidism, so antithyroid drugs do not help.

💡 Clinical Pearl: Thyroid symptoms are vague and common (tiredness, weight change, low mood). The diagnosis rests on blood tests, not on symptoms alone.

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Thyroid Physiology

The control loop (hypothalamic–pituitary–thyroid axis):

• The hypothalamus releases TRH.
• TRH stimulates the pituitary to release TSH.
• TSH stimulates the thyroid to make T4 (thyroxine) and a smaller amount of T3 (triiodothyronine).
• T4 and T3 feed back to switch off TRH and TSH. This negative feedback is the key to interpreting TFTs.

How hormone is made:

• The thyroid traps iodine from the blood.
• The enzyme thyroid peroxidase (TPO) attaches iodine to the protein thyroglobulin, forming T4 and T3.
• Hormone is stored in the gland as colloid and released as needed. The gland holds several weeks' supply.

T4 and T3:

• T4 is a prohormone. Deiodinase enzymes in the tissues convert it to active T3.
• Over 99% of both hormones in the blood is bound to proteins. Only the free fraction is active, which is why labs measure free T4 (FT4) and free T3 (FT3).
• T4 has a half-life of about 7 days. After any change in levothyroxine dose, it takes about 6 weeks to reach a new steady state. This is why TFTs are rechecked 6–8 weeks after a dose change.

Extra iodine has two important effects:

• Wolff–Chaikoff effect: A large iodine load temporarily switches off hormone production. This is used therapeutically before surgery and in thyroid storm.
• Jod–Basedow effect: In a gland with autonomous nodules, an iodine load (e.g. CT contrast, amiodarone) triggers excess hormone production.

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Thyroid Function Tests

• TSH: The best single screening test for primary thyroid disease. The pituitary is very sensitive to small changes in thyroid hormone, so TSH changes before FT4 goes out of range. Typical reference range: about 0.4–4.0 mU/L (laboratory-dependent).
• Free T4: Measure it when TSH is abnormal, when pituitary disease is suspected, or to monitor treatment of hyperthyroidism. Typical range: about 10–22 pmol/L (laboratory-dependent).
• Free T3: Useful when TSH is suppressed but FT4 is normal (T3 toxicosis), and in assessing hyperthyroidism.
• When TSH misleads: TSH alone is unreliable in:
  • Pituitary disease.
  • The first months of treating hyperthyroidism (TSH can stay suppressed for months after FT4 normalises).
  • Acute illness.
  • Pregnancy.
  In these situations, use FT4 (and FT3).
• Biotin interference: High-dose biotin supplements (hair, skin and nail products) interfere with many immunoassays, producing a falsely low TSH and falsely high FT4 that mimic hyperthyroidism. Ask about supplements and repeat the test after stopping biotin for at least 2 days.

💡 Clinical Pearl: Do not check TFTs in acutely unwell patients unless thyroid disease is genuinely suspected. Illness and drugs (steroids, dopamine) distort the results; recheck after recovery.

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Interpreting TFT Patterns

Use the feedback loop: if the thyroid is the problem, TSH moves in the opposite direction to FT4. If TSH and FT4 move in the same direction, think of the pituitary, an assay problem or a rare cause.

💡 MRCP Pearl: A patient who takes their levothyroxine only in the days before a blood test can have a high FT4 and a high TSH at the same time. The FT4 reflects recent tablets; the TSH reflects weeks of under-treatment.

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History and Examination

History:

• Symptoms of under- or over-activity (see the clinical features sections).
• Neck swelling, pain or compressive symptoms: difficulty swallowing, breathing or noisy breathing (stridor), hoarse voice.
• Eye symptoms: gritty eyes, double vision, bulging eyes, reduced vision.
• Recent pregnancy, viral illness or iodine exposure (CT contrast).
• Drugs: amiodarone, lithium, immunotherapy, biotin.
• Previous neck irradiation.
• Personal or family history of thyroid or other autoimmune disease.

Examining the thyroid:

• Inspection from the front: Ask the patient to swallow (a goitre or nodule moves up) and to stick out their tongue (a thyroglossal cyst moves up).
• Palpation from behind: Size, consistency, tenderness, single nodule versus multinodular, and lymph nodes.
• Retrosternal extension: Percuss over the sternum. Pemberton's sign: raising both arms causes facial congestion and breathlessness.
• Auscultation: A bruit over a diffuse goitre suggests Graves' disease (increased blood flow).

Thyroid status:

• Pulse (rate and rhythm - AF).
• Hands: tremor, sweating, palmar erythema, onycholysis, thyroid acropachy (clubbing in Graves').
• Reflexes (slow-relaxing in hypothyroidism).
• Proximal muscle weakness.
• Skin and hair.
• Eyes: lid lag, lid retraction, proptosis, eye movements.
• Shins: pretibial myxoedema (Graves').

💡 Clinical Pearl: Lid lag and lid retraction occur in any cause of thyrotoxicosis (adrenaline-like effect on the eyelid muscle). Proptosis, chemosis and restricted eye movements are specific to Graves' disease.

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Antibodies and Imaging

Antibodies:

• TPO antibodies (anti-thyroid peroxidase): Present in over 90% of Hashimoto's and in many patients with Graves'. In subclinical hypothyroidism, positive TPO antibodies predict progression to overt disease.
• TSH receptor antibodies (TRAb): Highly sensitive and specific for Graves' disease. NICE recommends measuring them when the cause of hyperthyroidism is unclear. In pregnancy, they cross the placenta and can make the baby thyrotoxic.
• Thyroglobulin antibodies: Less useful diagnostically. They matter in thyroid cancer follow-up because they interfere with thyroglobulin measurement.

Imaging:

• Ultrasound: The key test for nodules and goitre. It is graded with the British Thyroid Association U1–U5 classification and guides FNA. It is not needed for uncomplicated hypo- or hyperthyroidism.
• Isotope uptake scan (technetium or iodine): Shows whether the gland is overproducing:
  • Graves': Diffuse high uptake.
  • Toxic multinodular goitre: Patchy uptake, with hot and cold areas.
  • Toxic adenoma: A single "hot" nodule; the rest of the gland is suppressed.
  • Thyroiditis or excess thyroxine intake: Low or absent uptake.
• CT or MRI neck and chest: For retrosternal goitre, airway compression and cancer staging. Iodinated CT contrast can precipitate thyrotoxicosis in nodular glands and delays radioiodine treatment.
• Fine-needle aspiration (FNA): Cytology of suspicious nodules, reported as Thy1–Thy5.

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Hypothyroidism: Causes

• Primary (thyroid failure, 95%):
  • Hashimoto's thyroiditis - the commonest cause in the UK.
  • Atrophic autoimmune thyroiditis.
  • After treatment for hyperthyroidism: Radioiodine or thyroidectomy.
  • Drugs: Amiodarone, lithium, immune checkpoint inhibitors, tyrosine kinase inhibitors, interferon, over-treatment with carbimazole.
  • Thyroiditis: The hypothyroid phase of subacute, postpartum or silent thyroiditis - often temporary.
  • Iodine deficiency: The commonest cause worldwide.
  • Neck irradiation.
  • Congenital hypothyroidism.
  • Riedel's thyroiditis.
• Central (secondary or tertiary, rare): Pituitary or hypothalamic disease - tumour, surgery, radiotherapy, Sheehan's syndrome, hypophysitis.

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Hashimoto's Thyroiditis

Mechanism: An autoimmune disease in which T cells and antibodies (especially TPO antibodies) gradually destroy the thyroid. Lymphocytes infiltrate the gland and it slowly fails over years. It is most common in middle-aged women.

Clinical pattern: Gradual onset of hypothyroidism, often with a small, firm, painless goitre. Occasionally there is a brief early thyrotoxic phase ("Hashitoxicosis").

Diagnosis: Raised TSH, low or normal FT4, and positive TPO antibodies.

Associations - other autoimmune diseases:

• Type 1 diabetes.
• Addison's disease.
• Pernicious anaemia.
• Coeliac disease.
• Vitiligo.
• Premature ovarian insufficiency.
• Autoimmune polyglandular syndromes.

Management: Lifelong levothyroxine.

💡 Clinical Pearl: A rapidly enlarging goitre in a woman with long-standing Hashimoto's is thyroid lymphoma until proven otherwise - Hashimoto's increases the risk of lymphoma substantially.

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Hypothyroidism: Clinical Features

Low thyroid hormone slows the metabolic rate. Mucopolysaccharides also build up in the tissues (myxoedema), causing non-pitting swelling. Features develop gradually and are easily attributed to ageing or depression.

Symptoms:

• Tiredness, lethargy, slowed thinking.
• Low mood.
• Weight gain with poor appetite.
• Cold intolerance.
• Constipation.
• Dry skin and hair, hair loss (including the outer third of the eyebrows).
• Hoarse voice.
• Menorrhagia and infertility.
• Muscle aches and cramps.
• Carpal tunnel syndrome.

Signs:

• Bradycardia.
• Slow-relaxing reflexes (best seen at the ankle).
• Cool, dry, pale skin.
• Puffy face and periorbital oedema.
• Goitre (in Hashimoto's).
• Pericardial or pleural effusions.
• Ataxia (rare).

Blood clues:

• Raised cholesterol.
• Hyponatraemia.
• Raised CK.
• Macrocytosis, or normocytic anaemia.
• Raised prolactin.

💡 Clinical Pearl: Check TFTs in unexplained hyponatraemia, a raised CK, hypercholesterolaemia before starting a statin (hypothyroidism increases the risk of statin myopathy), and in new dementia or depression.

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Levothyroxine Treatment

Levothyroxine (synthetic T4) replaces the missing hormone. NICE NG145 guidance:

Starting dose:

• Adults under 65 without heart disease: Start at the full replacement dose, about 1.6 micrograms/kg/day (often 100–125 micrograms daily).
• Age 65 or over, or with cardiovascular disease: Start 25–50 micrograms daily and increase gradually.
• Severe ischaemic heart disease: Start lower still (12.5–25 micrograms) - a sudden rise in metabolic rate can precipitate angina or MI.

Adjusting the dose:

• Change by 25 microgram steps.
• Recheck TFTs 6–8 weeks after each change (the time to reach a new steady state).
• Aim for a TSH within the reference range and resolution of symptoms.
• Once stable, check TFTs annually.

How to take it:

• Once daily on an empty stomach, 30–60 minutes before breakfast or caffeine.
• Separate by about 4 hours from iron, calcium, antacids and some other drugs, which reduce absorption.
• PPIs, coeliac disease and atrophic gastritis also reduce absorption.

Pitfalls:

• Over-replacement (suppressed TSH) increases the risk of AF and osteoporosis, especially in older women.
• Persistently high TSH despite a high dose: Think about poor adherence, malabsorption (coeliac disease), interacting drugs and pregnancy.
• Liothyronine (T3): Not recommended routinely by NICE; specialist use only.
• Changes in need: Pregnancy, weight change and new drugs (e.g. oestrogen, enzyme inducers) alter the dose required.

💡 Clinical Pearl: Persisting tiredness despite a normal TSH on levothyroxine is common. Look for other causes (anaemia, B12, coeliac disease, depression, sleep apnoea) rather than pushing the dose up until the TSH is suppressed.

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Subclinical Hypothyroidism

Definition: A raised TSH with a normal FT4. Repeat the test after 3 months before acting, because many cases resolve - especially after illness. In older people, TSH naturally drifts upwards with age.

Natural history: About 2–5% a year progress to overt hypothyroidism. The risk is higher with positive TPO antibodies and with a TSH above 10.

When to treat (NICE NG145):

• Consider levothyroxine if the TSH is 10 mU/L or more on two tests 3 months apart.
• TSH above the range but below 10, with symptoms, in adults under 65: Consider a 6-month trial of levothyroxine; stop it if the symptoms do not improve.
• Older adults (especially over 70–80): Generally observe. The TRUST trial showed no benefit from treating mild subclinical hypothyroidism in people over 65.
• Pregnancy or planning pregnancy: Treat (see Pregnancy).

If not treating: Recheck TFTs periodically, typically every 6–12 months, or sooner if symptoms develop.

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Central (Secondary) Hypothyroidism

Mechanism: The thyroid is normal but receives too little TSH because of pituitary or hypothalamic disease.

TFTs: Low FT4 with a low or inappropriately "normal" TSH. Because the TSH looks normal, this pattern is easily missed.

Causes:

• Pituitary adenoma, surgery or radiotherapy.
• Sheehan's syndrome (pituitary infarction after postpartum haemorrhage).
• Hypophysitis (including from immunotherapy).
• Head injury, infiltration.

Investigations: Assess other pituitary hormones - cortisol, gonadotrophins, prolactin - and arrange a pituitary MRI.

Management:

• Levothyroxine, monitored by FT4 (aim for the mid-upper reference range). TSH is useless for monitoring.
• Always check and replace cortisol first. Giving thyroxine to someone with untreated adrenal insufficiency speeds up cortisol breakdown and can precipitate an adrenal crisis.

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Myxoedema Coma

Mechanism: The most severe form of hypothyroidism - decompensation of long-standing untreated hypothyroidism, usually triggered by a stressor. It is rare, with a mortality of up to 25–50%.

Triggers:

• Infection.
• Cold weather.
• Sedatives and opioids.
• Surgery, stroke, MI.
• Stopping levothyroxine.

Clinical pattern: Typically an older woman in winter, with:

• Reduced consciousness or confusion.
• Hypothermia.
• Bradycardia and hypotension.
• Hypoventilation with CO₂ retention.
• Hyponatraemia.
• Hypoglycaemia.
• Pericardial effusion.
• Puffy face and non-pitting oedema.

Management (ICU, endocrinology input):

• Send bloods first, then treat without waiting for results: TFTs and a random cortisol.
• Hydrocortisone 100 mg IV (then 6–8 hourly) before or with thyroid hormone, in case of coexisting adrenal insufficiency.
• Thyroid hormone: IV liothyronine (T3), e.g. 5–20 micrograms slowly, repeated every 4–12 hours, or IV/oral levothyroxine according to local protocol. Use cautious doses in older people and those with heart disease.
• Supportive care:
  • Ventilatory support.
  • Passive rewarming (active rewarming can cause vasodilatation and collapse).
  • IV glucose.
  • Careful correction of sodium.
  • Treat the trigger (e.g. antibiotics).
  • Avoid sedatives.

⚠️ Safety Pearl: In any hypothermic, drowsy older patient with hyponatraemia, think myxoedema coma. Give hydrocortisone before or with thyroid hormone.

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Hyperthyroidism: Causes

Gland overproducing hormone (high uptake on isotope scan):

• Graves' disease - about 75% of cases in the UK.
• Toxic multinodular goitre - common in older people and iodine-deficient areas.
• Toxic adenoma - a single "hot" nodule.
• Iodine-induced: Amiodarone type 1, CT contrast in a nodular gland.
• Rare:
  • TSH-secreting pituitary adenoma.
  • hCG-driven: hyperemesis gravidarum, molar pregnancy, choriocarcinoma (hCG resembles TSH).
  • Struma ovarii.

Release of stored hormone or external hormone (low uptake on isotope scan):

• Thyroiditis: Subacute (de Quervain's), postpartum, painless, amiodarone type 2, immune checkpoint inhibitors.
• Excess levothyroxine: Over-replacement or deliberate (factitious) - low serum thyroglobulin.

💡 Clinical Pearl: Before starting carbimazole, make sure the gland is actually overproducing. Antithyroid drugs are useless in thyroiditis - the problem is leakage of stored hormone, not overproduction.

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Hyperthyroidism: Clinical Features

Excess thyroid hormone raises the metabolic rate and increases sensitivity to adrenaline, producing a "revved-up" state.

Symptoms:

• Weight loss despite increased appetite.
• Heat intolerance and sweating.
• Palpitations.
• Anxiety, irritability and insomnia.
• Tremor.
• Frequent loose stools.
• Oligomenorrhoea.
• Muscle weakness (difficulty climbing stairs).
• Breathlessness.
• Pruritus.

Signs:

• Tachycardia or AF.
• Fine tremor.
• Warm, sweaty skin.
• Hyperreflexia.
• Proximal myopathy.
• Lid lag and lid retraction.
• Goitre.
• Systolic hypertension with a wide pulse pressure.
• High-output heart failure.

Specific to Graves': Eye disease, pretibial myxoedema, thyroid acropachy, a diffuse goitre with a bruit.

Complications:

• AF and stroke.
• Heart failure.
• Osteoporosis.
• Thyrotoxic periodic paralysis: Sudden weakness with hypokalaemia, classically in young men of East Asian origin after carbohydrate-rich meals or exercise.

Older adults: Often present atypically ("apathetic thyrotoxicosis") with weight loss, AF, heart failure, low mood or confusion, and few adrenergic features.

💡 Clinical Pearl: Check TFTs in every patient with new AF. Hyperthyroidism is a treatable cause, and rate control is difficult until it is corrected.

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Graves' Disease

Mechanism: An autoimmune disease in which TSH receptor antibodies (TRAb) bind to and stimulate the TSH receptor, mimicking TSH. The gland grows (a diffuse goitre) and overproduces hormone regardless of the body's needs. The same immune process affects the tissues behind the eyes (thyroid eye disease) and the skin.

Who gets it: Women aged 20–50 most often. Risk factors include a family history, smoking (especially for eye disease), other autoimmune disease, the postpartum period, and alemtuzumab treatment.

Clinical pattern: Thyrotoxicosis plus features specific to Graves':

• A diffuse, smooth goitre, often with a bruit.
• Thyroid eye disease (in about a third of patients clinically).
• Pretibial myxoedema: Raised, thickened, orange-peel plaques on the shins.
• Thyroid acropachy: Clubbing and swollen fingers.

Diagnosis: Suppressed TSH, raised FT4 and/or FT3, and positive TRAb. An isotope scan (diffuse high uptake) is used if the cause is unclear.

Management:

• Symptom control: A beta blocker (e.g. propranolol) while waiting for definitive control.
• Three treatment options: Antithyroid drugs, radioiodine and surgery - see their sections.
• NICE NG145: Offer radioiodine as first-line definitive treatment, unless antithyroid drugs are likely to achieve remission or radioiodine is unsuitable. In practice, many UK patients start with a course of carbimazole, aiming for remission.
• Smoking: Stop - it worsens eye disease and reduces the chance of remission.

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Thyroid Eye Disease

Mechanism: An autoimmune inflammation of the fat and muscles behind the eye, driven by the same antibodies as Graves' disease. The tissue swells, pushing the eye forwards (proptosis) and restricting eye movements. It can occur when the patient is hyperthyroid, euthyroid or hypothyroid. Smoking is the biggest modifiable risk factor.

Features:

• Gritty, watery eyes and photophobia.
• Proptosis (exophthalmos).
• Lid retraction.
• Periorbital swelling.
• Chemosis (conjunctival oedema).
• Diplopia, especially on looking up (inferior rectus involvement).
• Exposure keratitis.

Sight-threatening - emergency referral to ophthalmology:

• Dysthyroid optic neuropathy: Reduced visual acuity, reduced colour vision (red desaturation), a relative afferent pupillary defect.
• Corneal ulceration from inability to close the eyes.

Management:

• All patients:
  • Stop smoking.
  • Restore and keep thyroid function normal, avoiding swings into hypothyroidism.
  • Lubricating drops.
  • Head-up sleeping; sunglasses.
• Mild disease: Selenium supplementation for 6 months.
• Moderate to severe active disease: Specialist thyroid eye clinic.
  • IV methylprednisolone (e.g. 500 mg weekly for 6 weeks, then 250 mg weekly for 6 weeks).
  • Second-line options: mycophenolate, other immunosuppressants or biologics, orbital radiotherapy.
• Optic neuropathy: Urgent high-dose IV steroids, and orbital decompression surgery if there is no response.
• Burnt-out (inactive) disease: Rehabilitative surgery - orbital decompression, then squint surgery, then eyelid surgery.
• Radioiodine can worsen active eye disease. Avoid it in active moderate–severe disease, and give oral steroid cover in mild disease or in smokers.

⚠️ Safety Pearl: Ask every Graves' patient about blurred vision and colour vision. A loss of red colour vision means optic nerve compression - same-day ophthalmology.

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Toxic Multinodular Goitre

Mechanism: Over many years, a nodular goitre develops several nodules that function autonomously - independent of TSH. It is the second commonest cause of hyperthyroidism, mainly in older people and in iodine-deficient regions.

Clinical pattern:

• A nodular goitre, which may cause compressive symptoms.
• Often mild or subclinical hyperthyroidism, frequently presenting as AF, weight loss or osteoporosis.
• No eye disease.
• An iodine load (CT contrast, amiodarone) can trigger overt thyrotoxicosis.

Diagnosis: Suppressed TSH; isotope scan shows patchy uptake, with multiple hot and cold areas; TRAb negative.

Management:

• Radioiodine: The usual choice.
• Surgery: For large or compressive goitres.
• Antithyroid drugs: Control the hormone levels but rarely produce remission, because the nodules remain autonomous. Long-term low-dose carbimazole is an option in frail patients.

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Toxic Adenoma

Mechanism: A single benign nodule that produces hormone autonomously, usually because of a somatic mutation in the TSH receptor. The excess hormone suppresses TSH, so the rest of the gland switches off.

Clinical pattern: A single palpable nodule, usually over 2.5–3 cm, with hyperthyroidism (often mild) and no eye disease.

Diagnosis: Isotope scan shows a single "hot" nodule with suppressed uptake elsewhere. Hot nodules are almost never malignant.

Management: Radioiodine (the suppressed normal tissue is spared, so hypothyroidism afterwards is less common), or hemithyroidectomy.

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Antithyroid Drugs

How they work: Thionamides - carbimazole and propylthiouracil (PTU) - block TPO and so stop new hormone synthesis. Stored hormone is still released, so it takes 4–6 weeks to see an effect. PTU also reduces conversion of T4 to T3.

Regimens for Graves' disease (12–18 months):

• Titration regimen: Carbimazole 20–40 mg daily initially, reduced gradually to a maintenance dose (typically 5–15 mg) as FT4 normalises. Check TFTs every 4–6 weeks.
• Block-and-replace: Carbimazole 40 mg daily plus levothyroxine, usually for about 6 months. It gives more stable levels but higher drug exposure. Not used in pregnancy.
• Monitoring: Use FT4 and FT3 - TSH may stay suppressed for months.

Outcome: About 50% of Graves' patients achieve lasting remission. Remission is less likely with:

• A large goitre.
• A very high TRAb.
• Smoking.
• Severe disease at presentation.
• Male sex.

Relapse is treated with radioiodine or surgery, or long-term low-dose antithyroid drugs.

Side effects:

• Agranulocytosis (about 0.1–0.5%, usually in the first 3 months). Patients must be told to stop the drug and have an urgent FBC if they develop a sore throat, mouth ulcers, fever or other signs of infection (MHRA advice).
• Rash and itch - common. May allow a switch to the other drug.
• Hepatotoxicity - PTU can cause severe liver failure.
• Acute pancreatitis with carbimazole (MHRA) - stop permanently.
• Teratogenicity: Carbimazole can cause malformations (e.g. aplasia cutis) if taken in the first trimester. Women of child-bearing potential need effective contraception.

When PTU is preferred:

• The first trimester of pregnancy.
• Thyroid storm.
• Intolerance of carbimazole.

PTU dose: 200–400 mg daily in divided doses, then a lower maintenance dose.

⚠️ Safety Pearl: Sore throat or fever on carbimazole or PTU = stop the drug and check the neutrophil count the same day.

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Radioiodine

How it works: Radioactive iodine-131 is given as a single oral capsule. The thyroid takes it up like normal iodine, and the radiation destroys thyroid cells over weeks to months. It is effective, safe and widely used in the UK.

Indications:

• First-line definitive treatment for Graves' disease (NICE).
• Relapse after antithyroid drugs.
• Toxic multinodular goitre and toxic adenoma.

Contraindications and precautions:

• Pregnancy and breastfeeding: Contraindicated.
• Avoiding conception: Women must avoid pregnancy for 6 months; men should avoid fathering a child for 4 months.
• Active moderate–severe thyroid eye disease: Radioiodine can worsen it; give steroid cover in milder cases.
• Radiation protection: Patients must be able to follow radiation safety advice, such as limiting close contact with young children and pregnant women for a period.
• Before treatment: Stop carbimazole about 1 week before.

Outcome: Most Graves' patients become hypothyroid within months and need lifelong levothyroxine. This is an expected, not unwanted, result. Check TFTs every 4–6 weeks for the first 6 months.

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Thyroidectomy

Indications:

• Large goitre or compressive symptoms.
• Suspected or confirmed cancer.
• Moderate to severe thyroid eye disease (avoids the risk of radioiodine).
• Pregnancy planned soon.
• Failure of, or intolerance to, other treatments.
• Patient preference.

Preparation: The patient must be made euthyroid with antithyroid drugs first to prevent thyroid storm. Potassium iodide is sometimes used briefly before surgery to reduce gland vascularity.

Complications:

• Haemorrhage causing neck haematoma and airway compromise - an emergency. Open the wound (cut the sutures or clips) at the bedside and call senior help.
• Hypocalcaemia: From parathyroid damage or removal. Check calcium after surgery; watch for tingling, Chvostek's and Trousseau's signs. May be temporary or permanent.
• Recurrent laryngeal nerve injury: Hoarse voice (unilateral); stridor and airway obstruction (bilateral).
• Hypothyroidism: Inevitable after total thyroidectomy - needs lifelong levothyroxine.
• Thyroid storm: If operated on while thyrotoxic.

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Subclinical Hyperthyroidism

Definition: A low TSH with normal FT4 and FT3. Repeat the test before acting, because non-thyroidal illness, steroids and early pregnancy also lower TSH.

Causes: Over-replacement with levothyroxine (commonest), early Graves', toxic nodules, thyroiditis.

Risks - especially when the TSH is below 0.1 mU/L in people over 65:

• AF.
• Osteoporosis and fractures.
• Possibly heart failure and dementia.

Management:

• Over-replacement: Reduce the levothyroxine dose (unless deliberate TSH suppression for thyroid cancer).
• Endogenous cause: Refer to endocrinology if the TSH is below 0.1 on two occasions 3 months apart (NICE). Treat the cause, especially in older patients or those with AF or osteoporosis.

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Thyroid Storm

Mechanism: A life-threatening decompensation of thyrotoxicosis, with mortality of 10–30%. It is usually triggered in someone with untreated or partially treated hyperthyroidism.

Triggers:

• Infection.
• Surgery (especially thyroidectomy in a thyrotoxic patient).
• Radioiodine.
• Stopping antithyroid drugs.
• Iodine contrast.
• Trauma, childbirth, DKA.

Clinical pattern:

• Fever (often above 40 °C).
• Marked tachycardia or fast AF.
• Heart failure.
• Agitation, delirium, seizures or coma.
• Vomiting, diarrhoea and jaundice.

The Burch–Wartofsky score helps judge the likelihood of storm. TFT levels do not distinguish storm from uncomplicated thyrotoxicosis - the diagnosis is clinical.

Management (ICU, endocrinology): Act on every step of hormone production and action:

• Block the adrenergic effects: Propranolol (e.g. 60–80 mg orally 4-hourly, or IV in small increments). Also reduces T4-to-T3 conversion. Use caution, or short-acting esmolol, in heart failure.
• Stop new hormone synthesis: PTU (preferred: e.g. 500–1000 mg loading, then 250 mg 4-hourly) or high-dose carbimazole.
• Stop hormone release: Iodine (Lugol's iodine or potassium iodide), given at least 1 hour after the thionamide. Otherwise the iodine becomes fuel for more hormone.
• Reduce T4-to-T3 conversion and treat relative adrenal insufficiency: Hydrocortisone 100 mg IV 6–8 hourly.
• Supportive care:
  • Cooling and paracetamol. Avoid aspirin - it displaces thyroid hormone from binding proteins.
  • IV fluids, oxygen.
  • Treat AF and heart failure.
  • Treat the trigger.
• Refractory storm: Plasma exchange or emergency thyroidectomy.

⚠️ Safety Pearl: In thyroid storm the order matters: thionamide first, iodine an hour later. Use paracetamol for fever, not aspirin.

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Subacute (de Quervain's) Thyroiditis

Mechanism: A self-limiting inflammation of the thyroid, thought to follow a viral infection (often an upper respiratory tract infection a few weeks before). Inflamed follicles release their stored hormone, causing temporary thyrotoxicosis. It is also called granulomatous thyroiditis.

Clinical pattern:

• Painful, tender goitre, with pain radiating to the jaw or ear.
• Fever and malaise.
• Thyrotoxic symptoms.
• Most common in women aged 30–50.

The typical course has three phases over several months:

• 1. Thyrotoxic phase (weeks): Stored hormone leaks out.
• 2. Hypothyroid phase: The store is empty.
• 3. Recovery: Most return to normal; about 5–15% remain permanently hypothyroid.

Investigations:

• Raised FT4 and suppressed TSH.
• Markedly raised ESR and CRP.
• Low or absent uptake on isotope scan.
• TRAb negative.

Management:

• NSAIDs for pain.
• Prednisolone for severe pain (e.g. 20–40 mg daily, tapered over weeks). The response is dramatic.
• Beta blocker for thyrotoxic symptoms.
• No antithyroid drugs - the gland is not overproducing.
• Levothyroxine only if the hypothyroid phase is symptomatic or prolonged.

💡 Clinical Pearl: Painful tender thyroid + thyrotoxicosis + high ESR + low uptake = de Quervain's thyroiditis. Do not give carbimazole.

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Postpartum Thyroiditis

Mechanism: Autoimmune thyroiditis occurring within 12 months of delivery (or miscarriage). The immune system rebounds after the suppression of pregnancy. It affects about 5–10% of women, especially those with positive TPO antibodies or type 1 diabetes.

Clinical pattern: A painless thyroiditis, with a thyrotoxic phase (typically 1–4 months postpartum) followed by a hypothyroid phase (4–8 months). Symptoms are easily mistaken for postnatal tiredness or depression.

Distinguishing it from postpartum Graves' disease: Graves' has positive TRAb, a bruit, eye signs, and high isotope uptake. An isotope scan is avoided while breastfeeding, or used only with a suitable isotope and advice on interrupting feeding.

Management: