Hypothyroidism

Pathophysiology:

Underactivity of the thyroid gland may be:

• Primary (due to disease of the thyroid)
• Secondary (due to hypothalamic-pituitary disease)

Is one of the commonest endocrine disorders in the UK:

• 1.4% of women
• < 0.1% of men

Causes of primary hypothyroidism:

Congenital:

• Agenesis
• Ectopic thyroid remnants

Autoimmune:

• Atrophic thyroiditis
• Hashimoto’s thyroiditis

Defects of hormone synthesis:

• Iodine deficiency
• Dyshormonogenesis
• Antithyroid drugs
• Other drugs (e.g. lithium, amiodarone, interferon)

Infective:

• Post-subacute thyroiditis

Post-irradiation:

• Radioactive iodine therapy
• External neck irradiation

Infiltration:

• Tumour

Causes of secondary hypothyroidism:

• Isolated TSH deficiency

Symptoms:

• Tiredness/malaise
• Weight gain (despite reduced appetite)
• Cold intolerance
• Depression
• Reduced libido
• Constipation
• Deepening of voice
• Dry, brittle, unmanageable hair
• Poor memory
• Goitre
• Deafness
• Myalgia

Signs:

• Bradycardia
• Psychosis/dementia
• Ataxia
• Poverty of movement
• Hypertension
• Hypothermia
• Oedema
• Dry skin
• Anaemia
• Proximal myopathy
• Large tongue

Investigation of primary hypothyroidism:

Serum TSH:

• Ix of choice
• A high TSH confirms primary hypothyroidism

A low total/free T₄ level confirms the hypothyroid state and is especially important if there is any evidence of HP-axis disease, when TSH may be low or normal.

Thyroid (and other organ-specific) autoantibodies may be present. Other abnormalities include the following:

• Anaemia (usually normochromic and normocytic, but may be macrocytic or microcytic)
• Increased AST levels (from muscle and/or liver)
• Increased creatine kinase levels
• Hypercholesterolaemia
• Hyponatraemia (due to an increase in ADH and impaired free water clearance)

Treatment:

Replacement therapy with T₄ is given for life:

• In the young and fit - 100μg daily
• In the small, old or frail – 50μg daily
• Patients with severe IHD - 25μg daily to begin with, including serial ECGs. The dose would then be increased at 3-4 week intervals if angina does not occur/worsen and the ECG does not deteriorate.

Adequacy of replacement should be assessed clinically and by thyroid function tests (TSH and, possibly, T₄₎ after at least 6 weeks on a steady dose – the aim being to restore TSH to well within the normal range.

If TSH remains high, the dose of T₄ should be increased in 25-50μg increments and the tests repeated six weeks later.

Clinical improvement on T₄ may not begin for two weeks or more and full resolution of symptoms may take up to six weeks.

During pregnancy, about a 50μg increase in T₄ dosage is often needed to maintain normal TSH levels (probably because of the increased TBG levels).