Thyroid disorders: hypothyroidism, hyperthyroidism, goitre and tumours

The thyroid is a commanded gland: it obeys the pituitary, and it does not command it. The sequence begins in the hypothalamus, a small region at the base of the brain, which releases thyrotropin-releasing hormone, TRH, into the tiny portal vessels that drain toward the anterior pituitary. The pituitary answers by secreting thyrotropin, better known as TSH, into the bloodstream. TSH then reaches the gland and stimulates every stage of hormone production: the uptake of iodine, the building of thyroglobulin, the protein scaffold the gland assembles its hormone on, the coupling of iodine onto the amino acid tyrosine, and the discharge of finished hormone into the blood.

Two negative-feedback arms close the loop: rising T4 and T3 switch off TSH secretion at the pituitary and also reduce TRH release from the hypothalamus. This is why TSH is the most sensitive single test of thyroid function. When the gland fails, the pituitary senses the shortfall and pushes TSH upward, so a high TSH with a low free T4 is the classic signature of primary hypothyroidism, meaning disease in the gland itself. When the pituitary fails instead, it cannot push TSH up at all, so TSH and free T4 are both low; this is secondary, or central, hypothyroidism, and it is the one pattern in which a low TSH does not mean an overactive gland.

Most T3 in the blood is not made by the thyroid. The gland secretes mainly T4, and an enzyme called deiodinase removes one iodine atom from T4 in the liver, the kidneys and other tissues, producing the far more potent T3; roughly eighty per cent of circulating T3 comes from this peripheral conversion. Thyroid hormone then enters the cell nucleus and binds to receptors that switch genes for energy metabolism on or off, which is why its effects appear in every tissue and why they take weeks rather than minutes to develop or to fade.

Two practical rules follow. First, a change of replacement dose is judged only after six to eight weeks, because that is how long the blood level takes to reach a new steady state. Second, a patient whose gland has been removed or destroyed cannot produce any T4 and depends entirely on the daily tablet.

Graves’ disease is the commonest cause of an overactive thyroid, and its mechanism explains its strangest sign. The immune system makes an antibody that binds to the TSH receptor on thyroid cells and switches it on, exactly as TSH would, but with no brake from the pituitary. Because the antibody does not stop when the hormone level rises, the feedback loop is overridden and the gland pours out T4 and T3 continuously. The same antibody attack targets the tissue behind the eye: lymphocytes infiltrate the orbit, the muscles and fat swell, and the eyeballs are pushed forward. This is the exophthalmos, or ophthalmopathy, that accompanies Graves’ disease and not the other forms of hyperthyroidism, and it can also thicken the skin over the shins.

Left uncontrolled, the excess hormone sensitises the heart and blood vessels to catecholamines, so the patient develops a resting tachycardia, a bounding pulse, atrial fibrillation and, in older people, heart failure instead of the textbook picture. The most feared complication is thyroid storm: an abrupt exaggeration of every feature with fever above 38.5 °C, delirium, vomiting, profuse sweating, tachyarrhythmia and cardiovascular collapse. It is usually triggered by an event that adds stress — infection, surgery, trauma, childbirth, or stopping antithyroid treatment — and it is a medical emergency with a substantial mortality when untreated.

Treatment is layered rather than single. Thionamide drugs — propylthiouracil, methimazole and its prodrug carbimazole — block the enzyme that attaches iodine to thyroglobulin, so no new hormone can be made, but they do nothing to the hormone already stored in the gland. That is why iodine, given as Lugol’s solution or potassium iodide, is added about an hour later: a large iodine load shuts down both the release of stored hormone and its synthesis, the Wolff–Chaikoff effect. Propranolol is given not only to slow the pulse but also to block the peripheral conversion of T4 to T3 and to control tremor and anxiety. Radioactive iodine is swallowed and concentrated by the gland, where its radiation destroys overactive tissue over several weeks, and surgery is reserved for a gland so large that it compresses the trachea, or for a patient who cannot tolerate the other options.

Every choice carries a cost the nurse must know. Thionamides can cause agranulocytosis, so a sore throat or fever in a patient taking them is reported at once and a full blood count obtained. Radioactive iodine almost always leaves the patient hypothyroid within a year, which is accepted and treated with a daily tablet. Surgery risks bleeding into the neck, damage to the recurrent laryngeal nerve with persistent hoarseness, and removal of the parathyroid glands with it, which causes hypocalcaemia and tingling in the hands and fingers.

Severe, long-standing hypothyroidism changes the tissues themselves. The body deposits glycosaminoglycans, long sugar chains, in the skin and in the tissues around the heart; because these molecules hold water, the face becomes puffy, the tongue thickens, the voice deepens and the skin feels firm and does not pit under pressure. This is myxoedema, and it is quite different from the pitting oedema of heart failure.

When the condition becomes extreme, myxoedema coma can develop: the patient is hypothermic, unconscious or drowsy, breathes shallowly, has a slow pulse and low blood pressure, and may have a low blood glucose and a low sodium. It is a medical emergency, usually triggered by cold, infection, sedatives or years of untreated disease. This is why this section insists that hypnotics and sedatives are given with caution: a hypothyroid patient clears these drugs slowly and can be pushed into respiratory failure.

At the other end of life, congenital hypothyroidism is present from birth. The infant brain depends on thyroid hormone during the first months, so untreated disease causes irreversible intellectual disability and stunted growth. The word cretinism used by older texts is now avoided — it is a stigmatising label — and the condition is simply called congenital hypothyroidism. The great change since those texts were written is newborn screening: a drop of blood from the heel is tested a few days after birth, and an affected baby starts levothyroxine within the first two weeks, which preserves normal development.

Replacement therapy looks simple and is not. Levothyroxine is taken once daily in the morning on an empty stomach, at least half an hour before food, because food, calcium, iron and antacids bind it in the gut and reduce its absorption. It interacts with warfarin, so the anticoagulant dose may need to fall as the thyroid state is corrected, and it makes the heart work harder, so it is started at a low dose and increased slowly in older people or those with ischaemic heart disease. Desiccated animal thyroid and liothyronine, the synthetic T3, are still sold but are seldom first choice, because their hormone content varies and their blood levels swing. Over-replacement is not harmless: a suppressed TSH, atrial fibrillation and accelerated bone loss are the price of a dose that is too high, which is why the level is rechecked after six to eight weeks and then at least yearly, and why the nurse asks about palpitations, sweating and weight loss at every review.