Key Facts

Hypothyroidism is common and easily treated with levothyroxine. Autoimmune thyroiditis is the commonest cause in iodine-sufficient countries. Dose adjustments require 6-8 weeks before rechecking TSH.

Epidemiology

Prevalence ~2-5%. F:M 5-10:1. Incidence increases with age. Subclinical hypothyroidism: ~5-10% of women >60 years.

Aetiology

Primary (most common): Hashimoto thyroiditis (autoimmune — anti-TPO +), post-radioiodine treatment, post-thyroidectomy, iodine deficiency (developing world), drugs (amiodarone, lithium, checkpoint inhibitors), infiltrative (amyloid, haemochromatosis). Secondary (central): pituitary tumour, surgery, radiation, Sheehan syndrome, infiltrative (sarcoidosis).

Pathophysiology

Primary: thyroid gland failure → low T4/T3 → loss of negative feedback → raised TSH. Hashimoto: CD4+ T cell and antibody-mediated destruction of thyroid follicular cells; lymphocytic infiltration; anti-TPO and anti-thyroglobulin antibodies. Results in generalised reduction in metabolic rate affecting all organ systems.

Symptoms

• Fatigue, lethargy, somnolence
• Weight gain (modest — due to fluid retention more than fat)
• Cold intolerance
• Constipation
• Dry skin, brittle hair, hair loss (diffuse alopecia; lateral third of eyebrows — madarosis)
• Menorrhagia (early), oligomenorrhoea/amenorrhoea (severe)
• Depression, impaired concentration, memory problems
• Hoarse voice

Signs

• Bradycardia
• Periorbital/facial puffiness (myxoedema)
• Goitre (Hashimoto — initially; may atrophy late)
• Delayed relaxation of deep tendon reflexes
• Dry, cool, pale skin
• Non-pitting oedema (myxoedema — glycosaminoglycan deposition)
• Carpal tunnel syndrome
• Hyperlipidaemia, anaemia (normocytic or macrocytic)

Red Flags

• Severe hypothyroidism with altered consciousness → myxoedema coma (see separate topic)
• Hypothyroidism in pregnancy → urgent treatment (risk of fetal neurodevelopmental impairment)
• Rapid thyroid enlargement in Hashimoto → exclude thyroid lymphoma

TFTs

• TSH: raised in primary hypothyroidism (>4.5 mU/L); low/normal in central
• Free T4: low
• Free T3: usually low (but may be maintained initially)

Autoantibodies

• Anti-TPO (thyroid peroxidase): positive in ~95% of Hashimoto
• Anti-thyroglobulin: positive in ~60-80%

Additional Bloods

• FBC: normocytic or macrocytic anaemia
• Lipid profile: hyperlipidaemia (raised LDL)
• U&Es: hyponatraemia (dilutional — impaired free water excretion)
• CK: mildly raised (myopathy)
• Cortisol: check before starting levothyroxine if secondary hypothyroidism suspected (risk of adrenal crisis if coexistent hypoadrenalism)

Levothyroxine Replacement

• Standard dose: 1.6 μg/kg/day (typically 50-150 μg OD)
• Starting dose: 50-100 μg OD in young, healthy adults
• Elderly/cardiac disease: start 25 μg OD; increase by 25 μg every 4-6 weeks (rapid replacement may precipitate angina/MI/AF)
• Take on empty stomach, 30-60 minutes before breakfast (consistent timing)
• Target TSH: within reference range (0.4-4.5 mU/L); check 6-8 weeks after dose change
• Once stable: annual TFT

Drug Interactions

• Absorption reduced by: calcium, iron, PPIs, cholestyramine (take ≥4 hours apart)
• Increased requirement: pregnancy (increase by ~25-50%), oestrogen (OCP, HRT)

Subclinical Hypothyroidism

• TSH >10 mU/L: treat with levothyroxine
• TSH 4.5-10: treat if symptomatic, positive anti-TPO, or planning pregnancy; otherwise monitor

Pregnancy

• Increased levothyroxine requirement (~25-50% increase); check TFTs every 4 weeks in first half
• TSH target: <2.5 mU/L in first trimester (some guidelines)

Referral Criteria

• Endocrinology: suspected central hypothyroidism, difficulty achieving target TSH, pregnancy with complex thyroid disease
• Suspected thyroid lymphoma (rapid goitre growth in Hashimoto)

Excellent with levothyroxine replacement. Normal life expectancy when adequately treated. Over-replacement (suppressed TSH): risk of AF, osteoporosis (especially in postmenopausal women). Under-replacement: persistent symptoms, cardiovascular risk (hyperlipidaemia). Subclinical hypothyroidism: ~2-5% per year progress to overt hypothyroidism (higher if anti-TPO positive).

Causes of Hypothyroidism

Levothyroxine Dose Adjustment Guide