Goitre is defined as an enlargement of the thyroid gland which can be seen as a swelling in the front of the neck. There are several types of goitre which are features of different thyroid disorders.
Endemic goitre
On a worldwide basis, this is the most notable class of goitre. It arises because of insufficient iodine in the diet. This occurs in regions of the world where the iodine content of the normal diet or drinking water falls below the minimum requirement of about 25 mg/day. At least 1 billion people worldwide are at risk of iodine deficiency. Whereas most of these live in mountainous areas of developing countries, even in Europe 50-100 million people (15-30%) inhabit areas of at least moderate deficiency. In Britain the best recognized region is the Peak District and this is the reason why this goitrous condition is known colloquially as ‘Derbyshire neck’: but iodination of table salt has now made it rare.
The thyroid is unique in its ability to extract iodine from the blood and utilize it for the biosynthesis of hormones. The thyroid gland itself is positively regulated by a hormone from the pituitary gland named ‘thyroid stimulating hormone’, (TSH). The relationship between the pituitary and the thyroid is a classic example of negative feedback: the secretion of thyroid hormones influences TSH secretion from the pituitary; excessive secretion from the thyroid gland raises the concentration of thyroid hormones in the blood, which switches off TSH secretion by the pituitary. Conversely, if the rate of thyroid hormone secretion is inappropriately low, TSH from the pituitary increases.
It is this negative feedback regulation which results in the endemic goitres found in iodine-deficient regions. Iodine is an essential component of both thyroid hormones (T3 and T4). When there is insufficient iodine in the diet the thyroid is unable to synthesize and secrete sufficient quantities of T4 or, in the most restrictive conditions, of T3. As a consequence, pituitary secretion of TSH increases. This ‘trophic’ hormone stimulates both the function and the growth of the thyroid gland, so that it enlarges, eventually forming a goitre. In stimulating growth, TSH acts in conjunction with other growth factors, produced locally within the thyroid gland itself. Endemic goitres are however limited in size, and it is now thought that one of the local growth factors acts as a negative regulator.
Iodine deficiency is prevented by its addition to staple foods such as household salt, bread, and cheese. Iodine can also be effective when given by injection as an intramuscular depot of a slowly resorbable iodized oil. On a long-term basis this leads to the disappearance of goitres, but a more rapid resolution may be obtained surgically.
The correct level of iodine supplementation for household salt was first determined in the 1930s by Purves, in the University of Otago, New Zealand. He showed that when the salt was appropriately supplemented, the levels of iodine excreted in the urine of nurse volunteers in the city of Dunedin increased to equate with those excreted by a control group selected from the inhabitants of an iodine-replete Pacific island. When the suitably iodized salt was subsequently used prophylactically throughout Otago, there was a dramatic decline in the incidence of goitre in the populace of this province.
Goitres in iodine-abundant environments
A variety of goitrous conditions occur which are not due to iodine deficiency in the diet. These range from non-toxic, so-called ‘sporadic’, goitres to those associated with autoimmune hyper- and hypothyroidism. In addition there are rare inborn errors of thyroid hormone biosynthesis which usually cause congenital hypothyroidism, high TSH, and a goitre. Thus a goitre per se does not reveal the thyroid status of the person, as it may be associated with either under- or overactivity of the gland or may be present in a ‘euthyroid’ individual — one with normal hormone levels.
There is a range of techniques for investigating the nature of a goitre, from manual examination by a skilled thyroidologist (needle aspiration biopsy), to imaging techniques such as radiology, ultrasound, radionuclide scanning, computed tomography, and, more recently, magnetic resonance imaging. These are useful both in discriminating the goitre type and also in observing changes such as shrinking of thyroid volume following treatment. Conventional radiology provides information on the effects of goitre growth on surrounding tissues; for example it identifies goitres which are pressing on the windpipe, causing breathing difficulties, and require prompt surgical intervention.
A large proportion of patients who have either an over- or an underactive thyroid suffer from autoimmune conditions and their thyroids exhibit varying degrees of infiltration by lymphocytes. In the hyperthyroidism of Grave's disease we have a unique example of antibodies (known as thyroid stimulating antibodies) which mimic the action of a pituitary trophic hormone, namely TSH. This leads to persistent and unregulated stimulation of the thyroid. A diffuse and symmetrical goitre is often present. Conversely in the hypothyroidism of Hashimoto's disease there is autoimmune destruction of thyroid follicular cells, leading to underproduction of the hormones and eventually to thyroid failure. Large multinodular goitres are characteristic of this condition; there is extensive lymphocytic infiltration and with the passage of time mere remnants of thyroid follicles.
Aberrant growth within the thyroid may produce solitary nodules. These can be ‘hot’, when they avidly accumulate orally administered radioactive isotopes of iodine and usually suppress the activity of the surrounding thyroid tissue. Alternatively they may be non-functional — ‘cold’ — when iodine uptake is abnormally low. About 10% of these ‘cold’ nodules are malignant; however the overall incidence of thyroid cancer is very low, with only about 750 newly diagnosed cases reported annually in all of England and Wales.
Thus goitres occur in several different forms, due to a variety of widely differing causes, some of which are at present only poorly understood. It is likely that advances in our knowledge of local regulators of thyroid growth, including some subtle effects of iodine which have recently come to light, will lead to improved understanding and management.
Goitres are long-recognized clinical and cosmetic problems: they influenced even male fashions in the Regency period when high collars were adopted to alleviate the embarrassment of the Prince Regent who suffered from an unsightly goitre. Indeed his search for a cure, by daily drinking several pints of sea water, presumably influenced his choice of Brighton for the location of his Pavilion. Conversely, small goitres, particularly in women, have been considered marks of beauty. Examples are seen in some of Lely's portraits of ladies of the seventeenth century Dutch court.
— N. J. Marshall
See also hormones; hyperthyroidism; hypothyroidism; thyroid.
