Thyroid Disease

The thyroid gland produces thyroxine (T4) and triiodothyronine (T3), regulated by hypothalamic TRH → pituitary TSH → thyroid negative feedback. T4 is the main secretory product but is converted peripherally to the more active T3. Thyroid function is assessed by TSH (most sensitive), free T4, and free T3.

Hypothyroidism is characterised by fatigue, cold intolerance, weight gain, constipation, bradycardia, dry skin, hair loss, and myxoedema (non-pitting oedema). The most common cause in iodine-sufficient countries is Hashimoto's thyroiditis (autoimmune: anti-TPO and anti-thyroglobulin antibodies, lymphocytic infiltration). TSH is elevated; free T4 is low (or low-normal in subclinical hypothyroidism where TSH is elevated but FT4 is normal). Treatment: levothyroxine (L-T4) oral replacement; dose titrated to normalise TSH. Subclinical hypothyroidism (elevated TSH, normal FT4) requires treatment if TSH > 10 mU/L, symptoms are present, or the patient is pregnant.

Hyperthyroidism presents with heat intolerance, sweating, weight loss, palpitations (AF risk), tremor, anxiety, diarrhoea, and proptosis (in Graves' disease). Graves' disease — the most common cause — is an autoimmune condition driven by TSH-receptor stimulating antibodies (TRAb/TSI), which mimic TSH action. Distinctive features include diffuse goitre and ophthalmopathy (Graves' orbitopathy: exophthalmos, lid lag, ophthalmoplegia). Toxic nodular goitre (Plummer's disease) or solitary toxic adenoma may also cause hyperthyroidism. TSH is suppressed; free T4 and/or T3 are elevated.

Thyroiditis (painful subacute de Quervain's, or painless lymphocytic) causes transient hyperthyroidism as follicles are disrupted, followed by transient hypothyroidism before recovery. TRAb is negative. Treatment: beta-blockers for symptoms, NSAIDs for pain.

Thyroid storm is a life-threatening crisis of severe hyperthyroidism. Precipitants include surgery, infection, or iodine load. Treatment: PTU (blocks new hormone synthesis AND peripheral T4 → T3 conversion), propylthiouracil or carbimazole, beta-blockers, Lugol's iodine (blocks thyroid hormone release — given after PTU), corticosteroids, and supportive care.

Thyroid cancer: papillary thyroid cancer is the most common (> 80%), associated with RET/PTC rearrangements, generally excellent prognosis. Treatment: total thyroidectomy ± radioactive iodine (RAI) ablation, followed by thyroglobulin surveillance. Medullary thyroid cancer is associated with MEN2 (RET mutations) and calcitonin secretion. Anaplastic thyroid cancer has very poor prognosis.

In pregnancy, thyroid hormone requirements increase by ~30–50%. Hypothyroidism must be treated aggressively (TSH target < 2.5 mU/L in first trimester) as untreated maternal hypothyroidism causes fetal neurocognitive impairment. Graves' disease in pregnancy carries risks of neonatal thyrotoxicosis (TRAb crosses the placenta).