A goitre is an enlargement of the thyroid gland which is visible as a swelling at the base of the neck.A goitre can range in size from a barely noticeable lump to a large swelling, depending on the cause.

Causes

The thyroid gland may enlarge (without any disturbance of its function) at puberty, during pregnancy, or in women taking oral contraceptives. In many parts of the world the main cause of a goitre is a dietary deficiency of iodine, an element that the thyroid needs in order to produce thyroid hormone. This form of the condition is called endemic goitre. A condition called toxic goitre develops as a result of thyrotoxicosis in Graves’ disease and in certain other forms of hyperthyroidism (overactivity of the thyroid gland). A goitre is also a feature of different types of thyroiditis (inflammation of the thyroid gland), including Hashimoto’s thyroiditis and De Quervain’s thyroiditis. Other causes include a tumour or nodule in the gland and, in rare cases, thyroid cancer. There are also various types of familial goitre. This kind of goitre is caused by an inherited thyroid disorder; it appears during childhood and is often associated with signs of hypothyroidism, such as learning difficulties.

Symptoms

A goitre can range in size from a barely noticeable lump to a large swelling, depending on the cause. Large goitres may press on the oesophagus or the trachea and therefore make swallowing or breathing difficult.

Diagnosis and Treatment

Diagnosis may involve various thyroid-function tests, including blood tests and radionuclide scanning, to determine the activity of the thyroid gland. A goitre that is not due to disease may eventually disappear of its own accord. Goitre due to iodine deficiency can be treated by iodine-rich foods. When a goitre is the result of disease, treatment is for the underlying disorder. Large goitres can be surgically removed (see thyroidectomy).

Goitre - non-technical article

Goitre in detail - technical

Essentials

Endemic goitre—which is particularly common in the Himalayas, the Andes, and parts of Africa—is mainly due to iodine deficiency, can cause massive thyroid enlargement, but rarely leads to compressive symptoms. Its main impact on health is the association with endemic cretinism, which can be prevented by iodine supplementation, achievable by iodization of salt or bread, intramuscular or oral iodized oil as a single annual dose, or iodination of drinking water.

Sporadic goitre—cause unknown; presentation is with neck swelling or sensation of pressure or discomfort; most patients are euthyroid and do not require treatment.

Introduction

The distribution of thyroid size in any population forms a continuous, positively skewed curve, whose shape depends on the age, sex, and country of residence of the individuals assessed. Hence a precise definition of goitre is impossible. Ultrasound is the most accurate method to assess thyroid size, and estimates of goitre prevalence based on inspection and palpation underestimate the true frequency. However, simple schemes, such as that shown in Bullet list 1, are useful in field studies of goitre prevalence.

Of the many causes of goitre (Bullet list 2), those associated with disturbances of thyroid function are considered later. The remainder can be classified broadly as endemic and sporadic nontoxic goitres.

Endemic goitre

Prevalence

Goitre is said to be endemic when the prevalence exceeds 10% in children aged 6 to 12 years, although this figure is arbitrary and it has recently been suggested that a prevalence of more than 5% should be used. Over 200 million people are affected worldwide, especially in the Himalayas, Andes, and parts of Africa, although Eastern and Southern Europe are also involved.

Aetiology

The main cause is iodine deficiency, with goitre prevalence exceeding 30% in areas with very low iodine intakes (<30 µg/day). However, endemic goitre is not exclusively related to iodine deficiency. Naturally occurring goitrogens, such as those in vegetables of the cabbage family and in cassava, exaggerate the effects of iodine deficiency by the action of thiocyanates and cyanoglucosides, respectively, on iodine transport. Where selenium and iodine deficiency coincide, thyroid cell destruction and gland fibrosis minimize goitre formation. In Japan, endemic goitre actually results from iodine excess, as well as goitrogens in seaweed, and in Kentucky, chemically polluted water is goitrogenic.

Bullet list 1 WHO/UNICEF grading of goitre

Bullet list 2 Causes of goitre

Clinical presentation

Diffuse goitre is more frequent in girls, and gradually becomes nodular with age and increasing iodine deficiency. Endemic goitres can be massive but give few compressive symptoms. In areas of marginal iodine deficiency, such as Belgium, a modest goitre only appears when demands on thyroidal iodide metabolism are increased during puberty or in pregnancy.

The major impact of endemic goitre and iodine deficiency on health is the association with endemic cretinism. Two forms of cretinism can be delineated in separate geographical areas, but there is considerable overlap. First, when maternal iodine intake is severely reduced causing hypothyroidism there is reduced placental transfer of T₄ to the fetus, resulting in a profound neurological deficit in the infant, with mental deficiency, deafness, speech defects, and spastic gait. Second, hypothyroidism in the infant after birth produces the typical features of cretinism, in particular stunted growth. The thyroid in such patients may be enlarged or atrophic and it is clear from field studies that iodine deficiency alone cannot account for the multiple forms of endemic cretinism.

Management

Iodine supplementation is perhaps the simplest and cheapest of all remedies and it prevents a condition that has devastating consequences; it is sobering that iodine deficiency still persists. There are few complications from iodine supplementation, although thyrotoxicosis may result in a variable proportion of individuals (the Jod–Basedow phenomenon) some of whom have avoided this previously through lack of sufficient iodine. Political, social, and economic inertia are at the heart of continuing iodine deficiency. Effective programmes are best targeted at children and women intending pregnancy. Iodization of salt or bread is widely used in developed countries, but intramuscular or oral iodized oil, as a single annual dose, or iodination of drinking water is preferable in areas where distribution of iodized foodstuffs is a problem.

Sporadic goitre

Prevalence

Goitre occurs in around 5% of the iodine-sufficient population and is 4 times more common in women. However, the prevalence varies with area and generally declines with age; over 60% of goitres found in adolescents regress over the next 20 years. The character also changes over time, from a diffuse (sometimes called simple) goitre to a multinodular goitre. 

Aetiology

The aetiology of sporadic goitre is largely unknown. Unidentified goitrogens may be responsible in a few patients, and in others mild iodine deficiency in infancy may initiate goitrogenesis which persists despite a subsequently normal iodine intake. A large proportion are probably the result of mild defects in hormone synthesis; compensatory growth ensures normal thyroid function and current tests cannot identify the nature of the defect. Familial clustering of sporadic goitre supports this idea. Although TSH is the most obvious thyroid growth factor, TSH levels by definition are normal in sporadic goitre, which may therefore be the result of other autocrine and paracrine growth factors (e.g. insulin-like growth factor-1, epidermal growth factor, fibroblast growth factor).

Progression to a multinodular goitre occurs when unencapsulated nodules form in a long-standing diffuse goitre. These nodules contain colloid-rich polyclonal follicles and are usually distinct from adenomas, which are encapsulated and derived from a single thyroid follicular cell with a somatic mutation conferring growth advantage. However, some goitres contain both nodules and adenomas, suggesting a spectrum of pathological changes. Because thyroid follicular cells are heterogeneous, nodules generally develop with varying degrees of function, giving rise to ‘hot’and ‘cold’ areas on scintiscanning with radio-iodine. Some nodules develop autonomy and may eventually cause hyperthyroidism, completing the evolution from nontoxic to toxic multinodular goitre (see below). Other nodules undergo degeneration with haemorrhage, fibrosis, and cyst formation.

Clinical presentation

Patients usually seek attention because of the appearance of the neck or a sensation of pressure or discomfort. Equally, they may be unaware of a long-standing small goitre which is noticed on examination. Careful palpation is sufficient to distinguish true goitre, which moves on swallowing, from a prominent pad of fat over the front of the neck. Very large goitres can cause dysphagia or even stridor when the trachea is compressed, but these symptoms are uncommon. Venous compression at the thoracic inlet is even rarer; this sign is exacerbated by asking the patient to raise his/her arms (Pemberton’s sign). Pain in the thyroid, which radiates to the jaw, is uncommon and suggests either destructive thyroiditis (see below) or haemorrhage into a cyst in a multinodular goitre. In the latter, the pain is usually unilateral, acute, and associated with a rapid change in thyroid size; symptoms resolve spontaneously in a few days.

Investigations

Thyroid function should be assessed by checking TSH levels, and then free T₃ and T₄ levels if the TSH is abnormal to rule out goitre associated with thyroid dysfunction. The presence of thyroid peroxidase antibodies is also useful as a marker of an underlying autoimmune thyroiditis, which occurs in 10 to 20% of multinodular goitres. The use of imaging varies between centres. Ultrasound is useful in determining thyroid size and nodularity accurately and may reassure an anxious patient that the thyroid is not enlarging. Thyroidal uptake of radioisotopes (especially ⁹⁹Tcm pertechnetate) is indicated if destructive thyroiditis is suspected as a cause of goitre. Otherwise, the major role for imaging is to ensure there is no tracheal compression or intrathoracic/retrosternal component in a patient with suggestive symptoms, and a CT scan is then the preferred investigation.

Treatment

Most patients with euthyroid sporadic goitre do not require treatment. Neck discomfort or cosmetic concerns may prompt intervention but it is necessary to take a careful history to ensure that discomfort or difficulty swallowing is indeed caused by the goitre. T₄, given at doses to maintain slightly suppressed TSH levels (0.1–0.3 mU/litre), leads to a reduction in goitre size in up to 60% of patients but is unlikely to have any effect on a very nodular goitre or when the TSH level is already low (so-called subclinical hyperthyroidism, discussed below). This treatment is now less used than previously as there are concerns about the long-term effects of suppressive doses of T₄ on the heart and skeleton, and treatment must be continued long-term to maintain any improvement.

Radio-iodine, by contrast, is increasingly being given to reduce goitre size. Doses of ¹³¹I range from 600 to 3400 MBq (hospitalization is required for doses>800 MBq). Recent trials suggest that recombinant TSH administration may allow lower ¹³¹I doses to be given, increasing the potential for outpatient treatment. Goitre size is usually reduced by more than 50% at 2 years, and most of the improvement occurs within 2 to 3 months. Long-term follow-up data are not yet available, although hypothyroidism certainly occurs in 20 to 40% by 5 years. Tracheal compression by a goitre can be treated with ¹³¹I despite theoretical concerns over acute worsening due to a radiation thyroiditis.

Surgery is used in other centres and is particularly indicated for severe tracheal compression or retrosternal goitres and if there is any suspicion of malignancy. Thyroidectomy is the most effective treatment available for goitre, but there may be a recurrence in around 20% of patients within 10 years and is not avoidable by giving T₄ replacement. Complications, including recurrent laryngeal nerve damage, hypoparathyroidism, and hypothyroidism, are more likely with the biggest goitres, near total thyroidectomy, and reoperation.