Key Facts

Hypothyroidism results from insufficient thyroid hormone production. It is one of the most common chronic conditions managed in primary care. Primary hypothyroidism (thyroid gland failure) accounts for >95% of cases.

Epidemiology

• Prevalence: 2-5% of the UK adult population
• More common in women (10:1 ratio) and increases with age
• Subclinical hypothyroidism: prevalence 5-10%, particularly in elderly women
• Hashimoto thyroiditis prevalence: approximately 2% of women

Aetiology

• Autoimmune (Hashimoto thyroiditis): most common cause in UK; associated with anti-TPO antibodies in >90%
• Iatrogenic: post-thyroidectomy, post-radioiodine therapy, post-external radiotherapy to neck
• Drugs: amiodarone (can cause hypo- or hyperthyroidism), lithium, carbimazole, interferon-alpha, immune checkpoint inhibitors
• Iodine deficiency: most common cause worldwide (uncommon in UK)
• Secondary (central): pituitary failure (low TSH, low fT4) — rare
• Congenital hypothyroidism: detected by newborn screening (Guthrie test)

Pathophysiology

• In Hashimoto thyroiditis, autoimmune destruction of thyroid follicular cells by anti-TPO and anti-thyroglobulin antibodies leads to progressive thyroid failure
• Reduced T4 and T3 production causes loss of negative feedback on the hypothalamus and pituitary, resulting in elevated TSH
• Thyroid hormones regulate metabolic rate, thermogenesis, growth, and development
• Deficiency leads to widespread metabolic slowing affecting cardiovascular, neurological, GI, and musculoskeletal systems

Common Symptoms

• Fatigue and lethargy
• Weight gain (modest, typically 2-5 kg)
• Cold intolerance
• Constipation
• Dry skin and hair
• Hair loss (diffuse)
• Menorrhagia or oligomenorrhoea
• Depression and cognitive slowing
• Myalgia and arthralgia
• Hoarse voice

Clinical Signs

• Bradycardia
• Non-pitting oedema (myxoedema)
• Goitre (in Hashimoto thyroiditis)
• Delayed relaxation of deep tendon reflexes
• Periorbital oedema
• Dry, coarse skin
• Carpal tunnel syndrome

Red Flags

• Myxoedema coma: hypothermia, altered consciousness, bradycardia, hypotension — medical emergency
• Severe untreated hypothyroidism in pregnancy — risk of neurodevelopmental impairment in offspring
• Rapidly enlarging goitre or compressive symptoms — exclude thyroid lymphoma (especially in Hashimoto) or anaplastic carcinoma
• Pituitary symptoms (headache, visual field defects) — consider secondary hypothyroidism

Bedside

• Weight, BMI
• Heart rate and blood pressure
• Thyroid examination (goitre, nodules)
• Deep tendon reflexes (delayed relaxation phase)

Bloods

• TSH: primary screening test; elevated in primary hypothyroidism
• Free T4: low in overt hypothyroidism; normal in subclinical
• Anti-TPO antibodies: positive in Hashimoto thyroiditis (>90%); helps confirm autoimmune aetiology and predicts progression of subclinical hypothyroidism
• FBC: macrocytic anaemia may be present
• Lipid profile: hypercholesterolaemia common in hypothyroidism
• U&Es: hyponatraemia may occur
• Cortisol/Short Synacthen test: if secondary hypothyroidism suspected (must exclude adrenal insufficiency before starting levothyroxine)

Imaging

• Thyroid ultrasound: if nodule detected on examination or asymmetric goitre
• Not routinely required for diagnosis of hypothyroidism

Special Tests

• Fine needle aspiration: if suspicious thyroid nodule on USS
• Pituitary function tests and MRI pituitary: if secondary hypothyroidism suspected (low/normal TSH with low fT4)

Non-pharmacological

• Patient education about lifelong nature of treatment
• Take levothyroxine consistently, preferably 30-60 minutes before breakfast on empty stomach
• Awareness of symptoms of over- and under-replacement
• Inform about drug interactions affecting absorption

Pharmacological

• Levothyroxine (T4): treatment of choice
  • Standard starting dose: 50-100mcg OD in young, fit adults
  • Lower starting dose: 25mcg OD in elderly, cardiac disease, or severe/prolonged hypothyroidism
  • Titrate by 25mcg increments every 6-8 weeks based on TSH
  • Target: TSH within reference range (0.4-4.0 mU/L); some patients feel best at lower end
  • Average maintenance dose: 100-150mcg OD (approximately 1.6mcg/kg/day)
• Pregnancy: levothyroxine dose usually needs to increase by 25-50% from first trimester; aim TSH <2.5 mU/L in first trimester
• Myxoedema coma: IV liothyronine (T3) 5-20mcg + IV hydrocortisone 100mg (before levothyroxine, to cover possible coexistent adrenal insufficiency)
• Subclinical hypothyroidism:
  • TSH >10 mU/L: treat with levothyroxine
  • TSH 4-10 mU/L: consider treatment if symptomatic, positive anti-TPO antibodies, or planning pregnancy; otherwise monitor 6-monthly
• Drug interactions: iron, calcium, PPI (separate by ≥4 hours); oestrogen (may increase levothyroxine requirement); carbamazepine, phenytoin (increase clearance)

Surgical

• Thyroidectomy: not for hypothyroidism itself; may be needed for compressive goitre or concurrent thyroid malignancy

Referral Criteria

• Suspected secondary hypothyroidism (low/normal TSH, low fT4): endocrinology referral
• Hypothyroidism in pregnancy: shared care with endocrinology
• Persistent symptoms despite optimised TSH: endocrinology review to consider T3/T4 combination therapy
• Thyroid nodule with suspicious features: 2-week-wait referral
• Children with hypothyroidism: paediatric endocrinology

• With appropriate levothyroxine replacement, life expectancy is normal
• Symptoms typically improve within 3-6 months of treatment initiation
• Subclinical hypothyroidism progresses to overt hypothyroidism at 2-5% per year (higher if anti-TPO positive)
• Myxoedema coma mortality: 30-60% even with treatment
• Cardiovascular risk: untreated hypothyroidism associated with hypercholesterolaemia, accelerated atherosclerosis, and heart failure
• Hashimoto thyroiditis carries a small increased risk of thyroid lymphoma (rare)

Levothyroxine Dose Adjustment Guide

Causes of Persistently Elevated TSH on Levothyroxine