Hypothyroidism

Hypothyroidism is a common endocrine disorder, affecting approximately 2% of the UK population, with a 10:1 female-to-male ratio. Primary hypothyroidism (99% of cases) results from failure of the thyroid gland itself. The most common cause in iodine-sufficient regions like the UK is Hashimoto's thyroiditis, an autoimmune condition involving anti-TPO (thyroid peroxidase) and anti-thyroglobulin antibodies. Internationally, iodine deficiency remains the leading cause. Other causes include iatrogenic (post-thyroidectomy or radioactive iodine), medications (amiodarone, lithium), or subacute thyroiditis (the 'hypothyroid phase'). Secondary hypothyroidism (rare) is due to pituitary or hypothalamic failure (e.g., Pituitary adenoma, Sheehan's Syndrome). Subclinical hypothyroidism is defined as a high TSH with a normal free T4; management of this depends on the TSH level, age, and symptoms. Untreated severe hypothyroidism can progress to myxoedema coma, a life-threatening emergency presenting with hypothermia, bradycardia, and altered mental status. Levothyroxine is the standard of care, with the dose titrated to normalise the TSH.

In primary hypothyroidism, the thyroid gland fails to produce sufficient T4 and T3. This removes the negative feedback on the anterior pituitary and hypothalamus, leading to increased secretion of TSH and TRH. In Hashimoto's thyroiditis, there is a lymphocytic infiltration of the thyroid gland, leading to terminal fibrosis and atrophy. This is a Type IV cell-mediated response and a Type II antibody-mediated response where anti-TPO antibodies interfere with the enzyme responsible for iodine organification. Thyroid hormones are essential for regulating the basal metabolic rate; their absence leads to a general slowing of physical and mental processes. Mucopolysaccharides accumulate in the dermis, causing the characteristic non-pitting 'myxoedema' (puffiness). Secondary causes involve a lack of TSH, which leads to thyroid atrophy.

The onset is often insidious. Patients report fatigue, lethargy, cold intolerance (feeling the cold more than others), weight gain despite poor appetite, constipation, and heavy periods (menorrhagia). Mental features include 'brain fog', poor memory, and depression. Physical signs include bradycardia, cool/pale/dry skin, brittle hair, loss of the outer third of the eyebrows (Queen Anne's sign), a hoarse voice, and a characteristic delay in the relaxation phase of the deep tendon reflexes (pathognomonic). There may be a goitre in Hashimoto's. Complications include hyperlipidaemia (T4 is needed for LDL receptor expression), carpal tunnel syndrome, and in the elderly, heart failure. Myxoedema coma is the extreme presentation.

Primary screen: Serum TSH. If TSH is abnormal, measure Free T4. Findings: 1. Primary: High TSH, Low T4. 2. Secondary: Low TSH, Low T4. 3. Subclinical: High TSH (usually <10), Normal T4. Antibodies: Anti-TPO (positive in 90% of Hashimoto's). Bloods: Check for associated anaemia (macroblastic due to hypothyroidism itself or co-existing Pernicious Anaemia) and hyperlipidaemia. ECG: Bradycardia, low voltage complexes.

First-line: Oral Levothyroxine (synthetic T4). Normal starting dose: 50-100mcg once daily. In the elderly or those with ischaemic heart disease, start lower (25mcg) as rapid replacement can precipitate MI. Monitoring: Check TSH every 6-12 weeks after a dose change. Once stable, check annually. Target: Normalisation of TSH (usually 0.5 - 4.0 mU/L). Subclinical Hypothyroidism: Treat if TSH >10 mU/L, or if TSH <10 but the patient is symptomatic, has positive antibodies, or has CVD risk. Pregnancy: Increase dose as soon as pregnancy is confirmed; maintain TSH in the lower half of the reference range.