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Thyroid

Goitre
Causes, investigation and management
Kiernan Hughes
Creswell Eastman

Background Goitre refers to an enlarged thyroid gland. Causes of goitre


Goitre refers to an enlarged thyroid. Common causes of goitre include autoimmune disease, the formation of one or more
include autoimmune disease, thyroid nodules and iodine thyroid nodules and iodine deficiency (Table 1). Goitre
deficiency. occurs when there is reduced thyroid hormone synthesis
Objective secondary to biosynthetic defects and/or iodine deficiency,
This article outlines the causes, investigation and leading to increased thyroid stimulating hormone (TSH).
management of goitre in the Australian general practice This stimulates thyroid growth as a compensatory
setting. mechanism to overcome the decreased hormone synthesis.
Elevated TSH is also thought to contribute to an enlarged
Discussion
Patients with goitre may be asymptomatic, or may present thyroid in the goitrous form of Hashimoto thyroiditis, in
with compressive symptoms such as cough or dysphagia. combination with fibrosis secondary to the autoimmune
Goitre may also present with symptoms due to associated process in this condition. In Graves disease, the goitre
hypothyroidism or hyperthyroidism. Thyroid stimulating results mainly from stimulation by the TSH receptor
hormone is the appropriate first test for all patients with goitre; antibody (Figure 1).
if this hormone is low a radionuclide scan is helpful. Thyroid
ultrasound has become an extension of physical examination When diffuse enlargement of the thyroid occurs in the absence of
and should be performed in all patients with goitre. Ultrasound nodules and hyperthyroidism, it is referred to as a diffuse nontoxic
can determine what nodules should be biopsied. Treatment goitre. This is sometimes called ‘simple goitre’ because of the
options for goitre depend on the cause and the clinical
absence of nodules, or ‘colloid goitre’ because of the presence of
picture and may include observation, iodine supplementation,
uniform follicles that are filled with colloid. Worldwide, diffuse goitre
thyroxine suppression, thionamide medication (carbimazole or
is most commonly caused by iodine deficiency and is termed ‘endemic
propylthiouracil), radioactive iodine ablation and surgery.
goitre’ when it affects >5% of the population in a given geographic
Keywords area (Figure 2).
goitre; thyroid diseases The prevalence of goitre, diffuse and nodular, is dependent on
the status of iodine intake of the population. In general, in iodine
sufficient countries the prevalence of clinically palpable goitre is
less than 4%. In countries with a previous deficiency corrected by
universal salt iodination, elderly subjects may have a prevalence of
approximately 10%. This can be attributed to lack of nutritional iodine
in early adult life, as longstanding endemic goitres usually do not
regress with iodine supplementation.1
Smoking is also known to be goitrogenic, with cigarette smoke
containing goitrogens including thiocyanates. Smoking may also
exacerbate autoimmune thyroid disease (and possibly autoimmunity
in general). The goitrogenic effect of smoking is most pronounced in
people with intercurrent iodine or selenium deficiency.2 Certain raw
foods, such as soybeans, cassava and cruciferous vegetables, are
lightly goitrogenic but their typical impact is only modest.3

Iodine deficiency
Iodine deficiency has re-emerged in Australia over recent decades.4
Urinary iodine concentration (UIC) is an excellent proxy marker

572 Reprinted from Australian Family Physician Vol. 41, No. 8, august 2012
Table 1. Common causes of goitre
• Hashimoto thyroiditis
• Graves disease
• Familial or sporadic multinodular goitre
• Iodine deficiency
• Follicular adenoma
• Colloid nodule or cyst
• Thyroid cancer

Figure 2. Woman from Northern


Thailand with endemic goitre secondary
to iodine deficiency

Figure 1. Macroscopic appearance of a


thyroid gland removed from a patient is stretched taut across the surface of an expanding goitre, but
with diffuse goitre secondary to Graves this event is rare. Symptoms suggesting obstruction of the trachea
disease
may occur. These include cough, stridor and shortness of breath.
Occasionally tenderness and a sudden increase in goitre size arise
for current iodine intake and is a useful screening tool for iodine due to haemorrhage into a nodule. Symptoms of hyperthyroidism or
deficiency at a population level.5,6 However, day-to-day variations hypothyroidism may be evident at presentation.
in UIC preclude the use of UIC as a diagnostic tool to assess the
iodine nutritional status of an individual, unless multiple samples are
Thyroid examination
collected over a period of weeks to derive an average level.7 As this The thyroid gland is located superficially and, while usually not visible,
is neither practical nor a prudent use of resources, the public health is easily palpated. A careful examination should record the size, shape
response has instead focused on supplementation. Since October and consistency of the gland. The number, dimensions and consistency
2009, all bread produced in Australia and New Zealand (with the of any nodules should also be recorded. Importantly, in patients
exception of organic bread) must contain added iodine from iodised with long, thin necks, a prominent but normal thyroid gland may be
salt.8 Consequently, adults and children who eat bread regularly perceived by an examiner as abnormal and in patients with short, fat
should receive sufficient quantities of iodine. However, the iodised necks, nodules may be extremely difficult to detect. The accuracy of
salt in bread alone does not meet the increased daily requirements thyroid palpation depends greatly on the experience of the examiner.
of the majority of pregnant and breastfeeding women. The National Substernal goitre may obstruct the thoracic inlet. Pemberton sign
Health and Medical Research Council recommends that all women refers to faintness with evidence of facial congestion and cyanosis due
who are pregnant, breastfeeding or considering pregnancy, take an to external jugular venous obstruction when the arms are raised above
iodine supplement of 150 micrograms each day.9 Women with pre- the head, a manoeuvre that draws the thyroid into the thoracic inlet.
existing thyroid conditions should seek advice from their medical
practitioner before commencing a supplement.
Laboratory investigations
Patients with goitre or thyroid nodules should have a serum thyroid
Clinical presentation stimulating hormone (TSH) to determine the current functional status
Nodular goitre is most often detected simply as a mass in the of the thyroid. If the TSH is abnormal, a free T4 and free T3 should
neck, but an enlarging gland may also produce pressure symptoms also be checked. Checking for antibodies against thyroperoxidase
on the trachea and the oesophagus. As well as discomfort, there (anti-TPO) and thyroglobulin (anti-TG) is recommended as thyroid
may be difficulty in breathing, dysphagia, cough and hoarseness. autoimmunity may coexist with goitre. If the patient is hyperthyroid, a
Paralysis of the recurrent laryngeal nerve may occur when the nerve thyroid receptor antibody (TRAb) can help to confirm Graves disease.

Reprinted from Australian Family Physician Vol. 41, No. 8, august 2012 573
FOCUS Goitre – causes, investigation and management

Imaging There has been a move toward greater uniformity in thyroid FNA
Due to the limitations of the physical examination, ultrasound has cytology reporting to help provide more clinically useful results.15
become an invaluable tool and an extension of clinical examination in Any patient who doesn’t have benign cytology should be referred for
specialist endocrinology practice. An ultrasound performed at the time specialist opinion – this includes referring patients with results of
of the initial clinical assessment is not only useful for diagnosis, but undetermined significance on histology. It is recommended that all
also as a baseline for monitoring the progress of thyroid volume or the benign thyroid nodules be followed with serial ultrasound examination
size of nodules. Thyroid ultrasound should be performed in all patients 6–18 months after the initial FNA to assess for interval change. If
with known or suspected thyroid nodules.10 the nodule has grown significantly (>20% in two dimensions with a
A radionuclide thyroid scan is indicated in patients with a minimal increase of 2 mm), the FNA should be repeated.
subnormal TSH to determine the functional status of any nodules
within the thyroid and the underlying cause of clinical or subclinical Treatment of goitre
hyperthyroidism. Since hyperfunctioning (‘hot’) nodules rarely harbour Potential treatment options for goitre will depend on the cause and the
malignancy, if one is found that corresponds to the nodule in question clinical picture. Options include observation, iodine supplementation,
no cytological evaluation is necessary.10 

 thyroxine suppression, thionamides (carbimazole or propylthiouracil),
A computed tomography (CT) scan of the neck is not a routine radioactive iodine (I131) ablation and surgery. Patients with an
part of the investigation of a thyroid nodule, but may be performed asymptomatic euthyroid goitre can usually be observed without
in patients with significant compressive symptoms, or to evaluate specific treatment. Growth preventing intervention is usually
the degree of retrosternal extension or tracheal compression. In unnecessary, as benign nodules usually grow quite slowly.16
the presence of a nodule or goitre, CT scans should be ordered as Iodine supplementation will usually reduce thyroid volume in
‘noncontrast’ due to risk of contrast induced hyperthyroidism or children and adolescents living in iodine deficient environments.17
hypothyroidism in patients with nodular thyroid disease. Contrast However, for the general population and nonpregnant, nonlactating
should also be routinely avoided when imaging other regions in the women in Australia, iodine supplementation over what is obtained
presence of goitre unless essential for medical care. from iodine fortified bread is not necessary. Iodine supplementation
is unlikely to be beneficial for other forms of goitre.17 High dose
Thyroid nodules
The normal thyroid gland is a fairly homogenous
structure, but nodules often form within its substance. Patient with
These nodules may be the result of growth and fusion thyroid nodule
of localised colloid filled follicles, or discrete adenomas
or cysts. Thyroid carcinoma also typically presents as a
nodule. Between 4% and 7% of the general population TSH
have a palpable thyroid nodule.11 Around 30–50% of
adults have a thyroid nodule visible on ultrasound.12
TSH N or ↑ TSH ↓
The major challenge for the clinician and patient is
determining which of these nodules are clinically
important; a structured diagnostic approach is required
Ultrasound to assess Radioisotope scan
(Figure 3). need for FNA and ultrasound
Ultrasound enables characterisation of nodules and
detection of other clinically significant nodules that are
not palpable (Figure 4). Importantly, the risk of malignancy Cold nodule Hot nodule
is the same for incidental impalpable lesions as for
nodules of the same size that are palpable.13
Ultrasound is essential to determine those nodules, if Doesn’t meet Meets Consider
any, which should be subjected to fine needle aspiration criteria* criteria* radioactive
iodine ablation,
(FNA) cytology (Table 2 ).
thionamide
Increasingly, thyroid ultrasound is being performed by medication or
endocrinologists and endocrine surgeons at the time of Monitor FNA surgery
their initial assessment. For patients who require a biopsy,
ultrasound is useful to guide the biopsy and essential when Figure 3. Diagnostic approach to a patient with a thyroid nodule
* Criteria refers to clinical and ultrasound features associated with an
the nodule is not readily palpable, as ultrasound increases
increased risk of malignancy and therefore warrant FNA (see Table 2)
the likelihood of obtaining a diagnostic sample.14

574 Reprinted from Australian Family Physician Vol. 41, No. 8, august 2012
Goitre – causes, investigation and management FOCUS

iodine is another option and reduces goitre size by about 50% in the
majority of patients over 6–12 months.20 However, the required dose
<< mass is usually high and may need to be fractionated to ensure radiation
safety. In patients with toxic adenoma, goitre is rarely a significant
problem in its own right, but radioactive iodine can be helpful to treat
RIGHT LEFT the hyperthyroidism and could also shrink the adenoma. Radioactive
THYROID iodine carries a significant risk of causing hypothyroidism over
time, and so patients require annual TSH follow up. Occasionally,
hyperthyroidism can also occur with radioactive iodine treatment.
Surgery is appropriate in patients who have troubling compressive
Esophagus symptoms and/or fail to respond to medical therapy. Thyroid surgery
requires meticulous care to avoid damage to surrounding structures but
Figure 4. Thyroid ultrasound of a patient with an is now a low risk procedure in experienced hands.21
impalpable nodule incidentally discovered on
ultrasound. Fine needle aspiration cytology of the lesion Key points
revealed a papillary carcinoma
• Goitre is common and is usually due to autoimmune disease, thyroid
nodules or iodine deficiency.
Table 2. Which thyroid nodules to biopsy
• Thyroid stimulating hormone is the appropriate first test to assess
• High risk history* >5 mm the functional status of the thyroid.
• Abnormal cervical lymph node All nodules† • Patients who have a subnormal TSH should have a radionuclide
• Microcalcification >1 cm thyroid scan and specialist advice should be sought on the most
• Solid nodule >1 cm appropriate treatment.
• Mixed cystic – solid >1.5–2 cm • Thyroid ultrasound is an essential part of the evaluation of patients
• Spongiform >2 cm with goitre and will help determine the need for a FNA biopsy in
• Purely cystic FNA not indicated patients with thyroid nodules.
* High risk history includes head and neck irradiation, • Patients with euthyroid goitre or benign nodules can generally
thyroid cancer in a first degree relative, radiotherapy be observed clinically with repeat ultrasound in 6–18 months. In
or radiation exposure as a child, uptake on F–18 some cases patients may be offered a therapeutic trial of thyroxine
fluorodeoxyglucose positron emission tomography, suppressive therapy. Other treatment options include thionamides
multiple endocrine neoplasia type 2, elevated
(carbimazole or propylthiouracil), radioactive iodine ablation and
calcitonin
surgery.
† In the case of cervical lymphadenopathy the cervical
node itself is usually biopsied and, if thyroid cancer • Patients with suspicious nodules or atypical cytology should be
is present, a total thyroidectomy performed with the referred for specialist evaluation.
entire specimen subjected to histological examination
Authors
Kiernan Hughes MBBS(Hons), MSc, CCPU, FRACP, is Consultant
iodine supplements, such as kelp, should be avoided as they have the Endocrinologist, Sydney Thyroid Clinic, New South Wales. kiernan-
potential to trigger hypothyroidism or hyperthyroidism. [email protected]
Controlled trials have shown a beneficial effect of thyroxine Creswell Eastman AM MBBS, MD, FRACP, FRCPA, FAFPHM, is
treatment for both diffuse goitres and thyroid nodules. A goitre Principal, Sydney Thyroid Clinic and Clinical Professor of Medicine,
reduction of 20–40% can be achieved, but results are variable and Sydney Medical School, New South Wales.
potential long term harms of TSH suppression warrant consideration.18
Conflict of interest: none declared.
The most difficult challenge for the clinician is to obtain suppression
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