hyperthyroidism

hyperthyroidism The classic picture of excessive thyroid activity is that of a patient with Graves' disease — a form of thyrotoxicosis. Robert Graves was a renowned Dublin physician, whose bicentenary was celebrated in 1996. In addition to promoting a radical innovation in medical education — ward rounds with bedside teaching — he wrote in 1835 the first clear description of this disease. In a short paper titled ‘Palpitation of the heart with enlargement of the thyroid gland’, he recognized the defining significance of a ‘triad’ of symptoms: goitre, protruding eyes, and palpitations.

In the UK about 2% of women will suffer from thyroid overactivity (hyperthyroidism). It is ten times less likely among men. The hyperthyroidism of at least 50% of the patients is due to Graves' disease — now known to be an autoimmune condition.

Normally, thyroid activity is subject to positive regulation by thyroid stimulating hormone (TSH), which is secreted from the pituitary and stimulates thyroid growth and function. Very rarely, thyrotoxicosis is caused by excessive production of TSH. Hyperthyroidism of non-autoimmune origin is usually due to either a toxic nodular goitre (‘Plummer's disease’, after a physician at the Mayo Clinic in the 1920s) or a toxic adenoma — a benign tumour in which the cells retain the follicular arrangement characteristic of the thyroid gland. In complete contrast, the overactivity encountered in Graves' disease is due to the aberrant production of autoantibodies, known as thyroid stimulating antibodies. These mimic TSH and persistently stimulate the thyroid follicular cells. These antibodies are unique in having a stimulating as opposed to a blocking action. They were first described in a classic series of studies conducted in the 1950–60s by Adams and Purves in the University of Otago.

Thyroid overactivity results in the secretion of excessive amounts of thyroid hormones into the bloodstream. As a consequence, the clinical symptoms are the exaggerated effects of thyroid hormones on peripheral tissues. The basal metabolic rate increases and the effects of some other hormones — notably adrenaline — are potentiated. The symptoms include persistent weight loss despite a healthy appetite, sweating, hand tremor, and often a goitre. The patient is agitated, fatigues easily, and is intolerant of heat. Adrenaline potentiation is most seriously manifested by atrial fibrillation (a fast, irregular heartbeat). Some symptoms are additionally indicative of an autoimmune origin of the hyperthyroidism — Graves' disease. These include eye signs, which range from protruding eyes (exophthalmos) to — in very rare cases — optic nerve compression with loss of vision. There can also be a characteristic thickening of the skin over the lower legs and on the tops of the feet or big toes. If there is a goitre, it is a diffuse enlargement and an isotope scan shows that the entire gland is uniformly overactive.

A hyperthyroid patient may be rendered euthyroid (hormone levels within normal limits) with antithyroid drugs, for example carbimazole, which inhibit the biosynthesis of thyroid hormones. After treatment for 12–18 months, spontaneous remissions occur in about half the patients with Graves' disease, so that if the antithyroid drugs are withdrawn the symptoms do not recur. This is typical of the ‘waxing and waning’ of some autoimmune conditions, and remissions were described without specific treatment in the early nineteenth-century reports. By contrast, spontaneous remission will not occur in patients suffering from hyperthyroidism of non-autoimmune origin. If remission is not achieved, long-term treatment usually requires partial or total elimination of the thyroid. This is achieved either by the use of radioiodine or by surgical removal (thyroidectomy).

N. J. Marshall

See also goitre; hormones; hypothyroidism; thyroid.