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).
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 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
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
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.
The
importance of discrete swellings lies in the risk of neoplasia compared with
other thyroid swellings. Some 15
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 ultra
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.
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