Thyroid enlargement

The normal thyroid gland is impalpable. The term goitre (Latin, guttur = the throat) is used to describe generalised enlargement of the thyroid gland. A discrete swelling (nodule) in one lobe with no palpable abnormality elsewhere is termed an isolated (or solitary) swelling. Discrete swellings with evidence of abnormality elsewhere in the gland are termed dominant.

A scheme for categorising thyroid enlargement is given in Table 44.3.

Simple goitre

Aetiology

Simple goitre may develop as a result of stimulation of the thyroid gland by TSH, either as a result of inappropriate secretion from a microadenoma in the anterior pituitary (which is rare), or in response to a chronically low level of circulating thyroid hormones. The most important factor in endemic goitre is dietary deficiency of iodine (see below) but defective hormone synthesis probably accounts for many sporadic goitres (see below). TSH is not the only stimulus to thyroid follicular cell proliferation and other growth factors including immunoglobulins exert an influence. The heterogeneous structural and functional response in the thyroid resulting in characteristic nodularity may be due to the presence of clones of cells particularly sensitive to growth stimulation.

Iodine deficiency

The daily requirement of iodine is about 0.1—0.15 mg. In nearly all districts where simple goitre is endemic, there is a very low iodide content in the water and food. Endemic areas are in the mountainous ranges, such as the Rocky Mountains, the Alps, the Andes and the Himalayas. In Great Britain endemic goitre is found in the Mendips, Chilterns, Cotswolds and the Pennine chain of Derbyshire and Yorkshire. Endemic goitre is also found in lowland areas where the soil lacks iodide or the water supply comes from far away mountain ranges, e.g. the Great Lakes of North America, the Plains of Lombardy, the Struma valley3, the Nile valley and the Congo.

Calcium is also goitrogenic and goitre is common in low-iodine areas on chalk or limestone, e.g. Derbyshire and Southern Ireland. Although iodides in food and water may be adequate, failure of intestinal absorption may produce iodine deficiency (McCarrison).

Defective hormone synthesis

Enzyme deficiency/dyshormonogenesis. It is probable that enzyme deficiencies of varying severity are responsible for many sporadic goitres, i.e. in nonendemic areas. There is often a family history suggesting a genetic defect. Environmental factors may compensate in areas of high iodine intake, for example goitre is almost unknown in Iceland where the fish diet is rich in iodine. Similarly a low intake of iodine encourages goitre formation in those with a metabolic predisposition.

Goitrogens. Well-known goitrogens are the vegetables of the brassica family (cabbage, kale and rape) which contain thiocyanate, drugs such as para-aminosalicylic acid (PAS) and, of course, the antithyroid drugs. Thiocyanates and perchlorates interfere with iodide trapping; carbimazole and thiouracil compounds interfere with the oxidation of iodide and the binding of iodine to tyrosine.

Surprisingly enough, iodides in large quantities are goitrogenic because they inhibit the organic binding of iodine and produce an iodide goitre.

The natural history of simple goitre

Stages in goitre formation are:

persistent growth stimulation causes diffuse hyperplasia; all lobules are composed of active follicles and iodine uptake is uniform. This is a diffuse hyperplastic goitre, which may persist for a long time but is reversible if stimulation ceases;

later, as a result of fluctuating stimulation, a mixed pattern develops with areas of active lobules and areas of inactive lobules;

active lobules become more vascular and hyperplastic until haemorrhage occurs, causing central necrosis and leaving only a surrounding rind of active follicles;

necrotic lobules coalesce to form nodules filled with either iodine-free colloid or a mass of new but inactive follicles;

continual repetition of this process results in a nodular goitre. Most nodules are inactive and active follicles are present only in the internodular tissue.

  Diffuse hyperplastic goitre

Diffuse hyperplasia corresponds to the first stages of the natural history. The goitre appears in childhood in endemic areas but, in sporadic cases, it usually occurs at puberty when metabolic demands are high puberty goitre (Fig. 44.12). If TSH stimulation ceases, the goitre may regress, but tends to recur later at times of stress such as pregnancy. The goitre is soft, diffuse and may become large enough to cause discomfort. A colloid goitre is a late stage of diffuse hyperplasia when TSH stimulation has fallen off and when many follicles are inactive and full of colloid (Fig. 44.13).

Nodular goitre

Nodules are usually multiple, forming a multinodular goitre. Occasionally, only one macroscopic nodule is found, but microscopic changes will be present throughout the gland:

this is one form of a clinically solitary nodule. Nodules may be colloid or cellular, and cystic degeneration and haemorrhage are common, as is subsequent calcification. Nodules appear early in endemic goitre and later (between 20 and 30 years) in sporadic goitre, although the patient may be unaware of the goitre until the late 40s or 50s. All types of simple goitre are far more common in the female than in the male and the presence of oestrogen receptors in normal thyroid tissue and in nodular goitre is relevant.

Diagnosis is usually straightforward. The patient is euthyroid: the nodules are palpable and often visible; they are smooth, usually firm and not hard, and the goitre is painless and moves freely on swallowing. Hardness and irregularity, due to calcification, may simulate carcinoma. A painful nodule, sudden appearance or rapid enlargement of a nodule raises suspicion of carcinoma but is usually due to haemorrhage into a simple nodule. Differential diagnosis from autoimmune thyroiditis may be difficult.

Investigations. Tests of thyroid function are necessary to exclude mild hyperthyroidism, and the estimation of titres of thyroid antibodies to differentiate from autoimmune thyroiditis. Plain radiographs of the chest and thoracic inlet may show calcification and tracheal deviation or compression.

Complications. Tracheal obstruction is due to gross lateral displacement, or compression in a lateral or anteroposterior plane by retrosternal extension of the goitre (Fig. 44.14). Acute respiratory obstruction may follow haemorrhage into a nodule impacted in the thoracic inlet.

Secondary thyrotoxicosis. Many patients with nodular goitres experience transient episodes of mild hyperthyroidism. The incidence is difficult to estimate, but figures as high as 30 per cent have been suggested.

Carcinoma, which is usually of follicular pattern. It is uncommon but an increased incidence has been reported from endemic areas.

Prevention and treatment of simple goitre

In endemic areas, e.g. Switzerland, parts of the USA and Argentina, the incidence of goitre has been strikingly reduced by the introduction of iodised salt.

In the early stages a hyperplastic goitre may regress if thyroxine is given in a dose of 0.15—0.2 mg daily for a few months.

The nodular stage of simple goitre is irreversible. Most patients with multinodular goitre are asymptomatic and do not require operation. Operation may be indicated on cos­metic grounds if the goitre is unsightly. Retrosternal extension with actual or incipient tracheal compression is an indication for operation, as is the presence of a dominant area of enlargement which may be neoplastic.

There is a choice of surgical treatment: (a) total thyroidectomy with immediate and life-long replacement of thyroxine; or (b) some form of partial resection to conserve sufficient functioning thyroid tissue to subserve normal function whilst eliminating the risk of hypoparathyroidism which accom­panies total thyroidectomy. Partial resection aims to remove the bulk of the gland, leaving up to 8 g of relatively normal tissue in each remnant. The technique is essentially the same as described for toxic goitre, as are the postoperative complications. More often, however, the multinodular change is asymmetrically distributed, with one lobe more significantly involved than the other. Under these circumstances total lobectomy on the more affected side is the appropriate management with either subtotal resection or no intervention on the less affected side. In many cases the causative factors persist and recurrence is likely. Reoperation for recurrent nodular goitre is more difficult and hazardous and for this reason many thyroid surgeons favour total thyroidectomy in younger patients. When a unilateral lobectomy alone has been performed for asymmetric goitre, reoperation is straight­forward should it become necessary on the remaining lobe.

After subtotal resection it has been customary to give thyroxine to suppress TSH secretion with the aim of preventing recurrence. Whether this is either necessary or effective is uncertain, although the evidence of benefit in endemic areas is better than elsewhere. There is some evidence that recur­rence after surgery may reduce in size after treatment with radioactive iodine.

Clinically discrete swellings

Discrete thyroid swellings (thyroid nodules) are common and are present in 3—4 per cent of the adult population in the UK and USA. They are three to four times more frequent in women than men.

Diagnosis

A discrete swelling in an otherwise impalpable gland is termed isolated or solitary, whereas the preferred term for a similar swelling in a gland with clinical evidence of gener­alised abnormality in the form of a palpable contralateral lobe or generalised mild nodularity is dominant. About 70 per cent of discrete thyroid swellings are clinically isolated and about 30 per cent dominant. The true incidence of isolated swellings is somewhat less than the clinical estimate. Clinical classification is inevitably subjective and overesti­mates the frequency of truly isolated swellings. When such a gland is exposed at operation or examined by ultrasonography, computed tomography (CT) or magnetic resonance imaging (MRI), clinically impalpable nodules are often detected. The true frequency of thyroid nodularity compared with the clinical detection rate by palpation is shown in (Fig. 44.15).Establishing the presence of such minor abnormality is unnecessary because the management of discrete swellings, be they isolated or dominant, is similar.

The importance of discrete swellings lies in the risk of neoplasia compared with other thyroid swellings. Some 15 per cent of isolated swellings prove to be malignant, and an additional 30—40 per cent are follicular adenomas. The remainder are non-neoplastic largely consisting of areas of colloid degeneration, thyroiditis or cysts. Although the inci­dence of malignancy or follicular adenoma in clinically domi­nant swellings is approximately half that of truly isolated swellings, it is substantial and cannot be ignored.

Investigation

Thyroid function. The thyroid functional status should be established by estimation of serum thyroid hormones and TSH. If hyperthyroidism associated with a discrete swelling is confirmed biochemically, it indicates either a ‘toxic adenoma’ or a manifestation of toxic multinodular goitre. The combination of toxicity and nodularity is important and constitutes the only indication for isotope scanning to localise the area(s) of hyperfunction.

Autoantibody titres. The autoantibody status is important in determining which swellings may be a manifestation of chronic lymphocytic thyroiditis.

Isotope scan. Isotope scanning used to be the mainstay of investigation of discrete thyroid swellings to determine the functional activity relative to the surrounding gland according to isotope uptake.

On scanning, swellings are categorised as ‘hot’ (over­active), ‘warm’ (active) or ‘cold’ (underactive). A hot nodule is one that takes up isotope, while the surrounding thyroid tissue does not. Here the surrounding thyroid tissue is inactive because the nodule is producing such high levels of thyroid hormones that TSH secretion is suppressed. A warm nodule takes up isotope and so does normal thyroid tissue about it. A cold nodule takes up no isotope (Fig. 44.7).

About 80 per cent of discrete swellings are cold but only 15 per cent prove to be malignant and the use of this criterion as an indication for operation lacks discrimination. Routine isotope scanning has been abandoned except when toxicity is associated with nodularity.

Ultrasonography was formerly widely used as a noninva­sive supplement to clinical examination in determining the physical characteristics of thyroid swellings. Although ultrasonography can demonstrate subclinical nodularity and cyst formation, the former is clinically irrelevant and the latter apparent at aspiration, which should be routine in all discrete swellings.

Fine-needle aspiration cytology (FNAC). FNAC has become established as the investigation of choice in discrete thyroid swellings. FNAC has excellent patient compliance, is simple and quick to perform in the out-patient department and is readily repeated. This technique, developed in Scandinavia some 30 years ago, has become popular in the rest of Europe and North America in the last 20 years.

Thyroid conditions that may be diagnosed by FNAC include colloid nodules (Fig. 44.16), thyroiditis, papillary carcinoma (Fig. 44.17), medullary carcinoma, anaplastic carcinoma and lymphoma. FNAC cannot distinguish between a benign follicular adenoma (Fig. 44.18) and follicular carcinoma as this distinction is dependent not on cytology but on histological criteria, which include capsular and vascular invasion.

Although FNAC has been reported as highly accurate by Lowhagen and his colleagues at the Karolinska Hospital, who were its pioneers, and by other authors, high accuracy has not always been reproducible, especially when results are analysed critically. There are very few false positives with respect to malignancy but there is a definite false-negative rate with respect to both benign and malignant neoplasia.

FNAC is less reliable in cystic than in solid swellings, often yielding only cyst fluid with macrophages and degenerate cells. After aspiration a further sample should be taken from the cyst wall, for cytology. Relatively few cysts are permanently abolished by one or more aspirations and, because of the risk of malignancy, recurrent cysts should be removed.

Radiology. Chest and thoracic inlet radiographs are only necessary when there is clinical evidence of tracheal deviation or compression or retrosternal extension.

Other scans. CT and MRI scans give excellent anatomical detail of thyroid swellings but have no role in the first line of investigation. They are occasionally useful in assessing recurrent and retrosternal swellings. The increased use of these imaging modalities in other head and neck swellings has created a new clinical conundrum which has been termed the ‘Thyroid Incidentaloma’. These are clinically unsuspected and impalpable thyroid swellings which with few exceptions require no further investigation or surgery.

Indirect laryngoscopy to determine the mobility of the vocal cords is widely used preoperatively, although usually for medicolegal rather than clinical reasons.

Large-bore needle (Trucut) biopsy. Trucut biopsy has a high diagnostic accuracy but has poor patient compliance and may be associated with complications such as pain, bleeding, tracheal and recurrent laryngeal nerve damage. It has little application in routine assessment except in locally advanced, surgically unresectable malignancy (either anaplastic carci­noma or lymphoma) when Trucut biopsy may avoid operation.

  The main indication for operation is the risk of neoplasia which includes follicular adenoma as well as malignant swellings. The reason for advocating the removal of all follicular neoplasms is that it is seldom possible to distinguish between a follicular adenoma and carcinoma cytologically. The distinction usually depends on histological evidence of capsular or vascular invasion and FNAC cannot make this distinction, although on occasion cellular nuclear features may be so abnormal as to suggest malignant change. On this basis, some 50 per cent of isolated and 25 per cent of dominant swellings should be removed on the grounds of neoplasia. Even when the cytology is negative, the age and sex of the patient and the size of the swelling may be relative indications for surgery, especially when a large swelling is responsible for symptoms. Some patients are happier to have a swelling removed even when cytology is negative.

There are useful clinical criteria to assist in selection for operation according to the risk of neoplasia and malignancy. Hard texture alone is not reliable since tense cystic swellings may be suspiciously hard but a hard, irregular swelling with any apparent fixity, which is unusual, is highly suspicious. Evidence of recurrent laryngeal nerve paralysis, suggested by hoarseness and a nonocclusive cough, and confirmed by indirect laryngoscopy, is almost pathognomonic. Deep cervical lymphadenopathy along the internal jugular vein in association with a clinically suspicious swelling is almost diagnostic of papillary carcinoma. In most patients, however, such features are absent but there are risk factors associated with sex and age. The incidence of thyroid carcinoma in women is about three times that in men, but a discrete swelling in a male is much more likely to be malignant than in a female and it is seldom justifiable to avoid removing such a swelling in a man. The risk of carcinoma is increased at either end of the age range and a discrete swelling in a teenager of either sex must be provisionally diagnosed as carcinoma. The risk increases as age advances beyond 50 years, and more so in males.

Thyroid cysts

Routine FNAC (or ultrasonography) shows that over 30 per cent of clinically isolated swellings contain fluid and are cystic or partly cystic. Tense cysts may be hard and mimic carcinoma. Bleeding into a cyst often presents with a history of sudden painful swelling which resolves to a variable extent over a period of weeks if untreated. Aspiration yields altered blood but      re accumulation is frequent. About 50 per cent of cystic swellings are the result of colloid degeneration, or of uncertain aetiology, because of an absence of epithelial cells in the lining. Although most of the remainder are the result of involution in follicular adenomas (Fig. 44.19) some 10—15 per cent of cystic follicular swellings are histo­logically malignant (30 per cent in males and 10 per cent in females). Papillary carcinoma is often associated with cyst formation (Fig. 44.20).

Most patients with discrete swellings, however, are females aged 20—40 years in whom the risk of malignancy, although significant, is low and the indications for operation are not clear cut. FNAC is the most appropriate investigation to aid selection.

The indications for operation in isolated or dominant thyroid swellings are listed in Table 44.4.

Retrosternal goitre

Very few retrosternal goitres arise from ectopic thyroid tissue; most arise from the lower pole of a nodular goitre. If the neck is short and the pretracheal muscles are strong, as in men, the negative intrathoracic pressure tends to draw these nodules into the superior mediastinum.

Clinical features

A retrosternal goitre is often symptomless and is discovered on a routine chest radiograph. There may, however, be severe symptoms:

dyspnoea, particularly at night, cough and stridor (harsh sound on inspiration). Many of these patients may attend a chest clinic with a diagnosis of asthma before the true nature of the problem is discovered;

  dysphagia;

   •  engorgement of neck veins and superficial veins on the chest wall. In severe cases there may be obstruction of the superior vena cava (Fig. 44.21);

   •  recurrent nerve paralysis is rare. The goitre may also be malignant or toxic.

Radiographs show a soft-tissue shadow in the superior mediastinum sometimes with calcification and often causing deviation and compression of the trachea (Fig. 44.14). Radio-graphs of the thoracic inlet give better definition than a chest radiograph. Significant tracheal compression and obstruction may be demonstrated objectively by a flow—volume loop pulmonary function test in which the rate of flow is plotted against the volume of air inspired and then expired. Deterioration in flow due to increase in tracheal compression either acutely or in the long term may be used to monitor progression of the disease and indicate the need for surgery. The changes are reversed by operation (Fig. 44.22).

Treatment

If obstructive symptoms are present in association with thyrotoxicosis it is unwise to treat a retrosternal goitre with antithyroid drugs or radioiodine as these may enlarge the goitre. Resection can almost always be carried out from the neck and a midline sternotomy is hardly ever necessary. The cervical part of the goitre should first be mobilised by ligation and division of the superior thyroid vessels, and by ligature and division of the middle thyroid veins and the inferior thyroid artery. The retrosternal goitre can then be delivered by traction and finger mobilisation. Haemorrhage   is rarely a problem because the goitre takes its blood supply with it from the neck. The recurrent laryngeal nerve should be identified if possible before delivering the retrosternal goitre, as it may be abnormally displaced and is particularly vulnerable to injury from traction or tearing. If a large multinodular goitre cannot be delivered intact from the retrosternal position it may be broken with the fingers and delivered piecemeal, but this should never he done if the lesion is solitary and there is the possibility of carcinoma.