Thyroid Function — MRCS Part B Applied surgical science and critical care

An applied sciences station on the thyroid: what it makes, how the hormones travel, and the two clinical pictures a surgeon has to recognise before operating on a neck.

The hormones

The follicular cells trap iodide, oxidise it with thyroid peroxidase and attach it to tyrosine residues on thyroglobulin in the colloid, coupling the iodotyrosines into thyroxine (T4, four iodines) and, in smaller amounts, tri-iodothyronine (T3, three). T4 is the main product, and about 80% of the T3 in the blood is made from it in the liver, kidney and muscle by deiodinases; T3 is several times more active and acts within hours, T4 over days. The parafollicular C cells, of neural crest origin, make calcitonin, which lowers calcium a little and matters mainly as the tumour marker of medullary carcinoma.

Histology

Spherical follicles of cuboidal epithelium around a store of colloid, in a rich capillary bed, with the C cells scattered between the follicles and a fibrous capsule sending septa into the gland. The follicles are flat and full of colloid when the gland is resting, tall and scalloped at the edge of the colloid when it is stimulated.

Transport and control

More than 99% of the circulating hormone is bound to thyroxine-binding globulin, transthyretin and albumin; only the free fraction is active, which is why pregnancy and the pill, which raise the binding globulin, raise the total without changing the free level. The hypothalamus releases TRH, the pituitary releases TSH, and TSH drives every step of synthesis and release; T3 and T4 feed back on both, so a suppressed TSH with a raised free T4 is primary hyperthyroidism and a raised TSH with a low free T4 is primary hypothyroidism.

Hyperthyroidism

Causes: Graves' disease (antibodies against the TSH receptor, the commonest cause, with eye signs and pretibial myxoedema), a toxic multinodular goitre, a toxic adenoma, thyroiditis releasing stored hormone, excess thyroxine or iodine (including amiodarone), and rarely a TSH-secreting pituitary tumour. Symptoms and signs: weight loss with a good appetite, heat intolerance and sweating, tremor, palpitations and atrial fibrillation, anxiety, diarrhoea, oligomenorrhoea, proximal weakness, a goitre with a bruit, warm moist hands, tachycardia and lid lag; exophthalmos and ophthalmoplegia belong to Graves' disease alone. Investigations: TSH and free T4 and T3, TSH-receptor and peroxidase antibodies, a radioisotope uptake scan to distinguish a diffuse, a nodular and a cold pattern, and ultrasound of any nodule. Management: a beta-blocker for the symptoms at once; carbimazole (or propylthiouracil in early pregnancy) for a year or so, watching for agranulocytosis; radioiodine for relapse, nodular disease or an adenoma; and thyroidectomy for a large goitre, compression, severe eye disease or patient choice, always with the patient made euthyroid first, because an operation on a toxic gland can precipitate a thyroid storm.

Hypothyroidism

Causes: autoimmune (Hashimoto's) thyroiditis, the commonest in the UK; iodine deficiency, the commonest worldwide; treatment of hyperthyroidism by radioiodine or surgery; drugs such as amiodarone and lithium; congenital absence or dyshormonogenesis; pituitary failure; and the hypothyroid phase of a thyroiditis. The picture is the mirror image: weight gain, cold intolerance, tiredness, constipation, dry skin and hair, bradycardia, slow-relaxing reflexes and a hoarse voice, and in the surgical patient slow recovery from anaesthesia and a risk of myxoedema coma. Treatment is levothyroxine, titrated to the TSH.