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Goitre and thyroid nodules
Thyroid cancer
Goitre and thyroid nodules
A goitre is an enlarged thyroid gland and may be
diffuse or nodular (consisting of a solitary or
multiple nodules).
When diffuse enlargement of the thyroid occurs in the
absence of nodules and hyperthyroidism, it is referred to
as a diffuse nontoxic goiter. This is sometimes called
simple goiter, because of the absence of nodules, or
colloid goiter, because of the presence of uniform follicles
that are filled with colloid.
Worldwide, diffuse goiter is most commonly caused by
iodine deficiency and is termed endemic goiter when it
affects >5% of the population. In nonendemic regions,
sporadic goiter occurs, and the cause is usually unknown.
Thyroid enlargement in teenagers is sometimes referred
to as juvenile goiter.
Differential diagnosis of goitre
Thyrotoxic patients
• Graves’ disease
• Multinodular goitre
• Solitary adenoma
• Thyroiditis (subacute or painless)
Hypothyroid patients
• Hashimoto’s thyroiditis
Euthyroid patients
• Simple goitre (non - toxic)
• Malignancy: thyroid carcinoma, lymphoma
• Riedel’s thyroiditis
Clinical presentations
A mass in the neck noticed by the physician, the patient or relatives
may be the only presenting complaint.
Features in the history and examination that raise the suspicion of
malignancy include:
● age < 20 or > 60 years
● recent rapid enlargement of a thyroid nodule
● local compressive symptoms: dysphagia, dyspnoea, hoarseness,
● family history of thyroid cancer or multiple endocrine neoplasia
● history of exposure to radiation
● lymphadenopathy.
Thyroid examination
Thyroid examination should include the following steps:
• Inspection : ask the patient to swallow (the goitre moves upward).
• Palpation : examine the goitre with the patient swallowing — the
goitre moves upward. This may be lost in anaplastic carcinoma and
Riedel ’ s thyroiditis (a rare chronic inflammatory disease of the
thyroid gland characterized by a dense fibrosis replacing normal
thyroid parenchyma, which results in a ‘woody’ goitre). Determine
the size, whether the goitre is nodular or diffusely enlarged, soft or
hard, or tender (e.g. in subacute thyroiditis or bleeding into a cyst)
and the presence of lymph nodes.
• Percussion of the upper mediastinum (dull in retrosternal goitre).
• Auscultation : for a bruit (in hyperthyroidism) and inspiratory stridor
(in cases of tracheal compression).
• Determination of thyroid status (look for features of hypothyroidism
or thyrotoxicosis).
Thyroid function tests
1. TSH and free T4 (to exclude thyrotoxicosis and
2. Serum thyroglobulin levels are increased in both benign
and malignant nodules, and can only be used in the follow
- up of patients with treated differentiated (papillary and
follicular) cancers.
3. Calcitonin should be measured when medullary cell
carcinoma is suspected (usually after fine needle
aspiration cytology results)
4. Respiratory flow-volume loop studies (to exclude
tracheal obstruction)
The cytologist’s report may be one of the following:
• Non – diagnostic
• Non - neoplastic (abundant colloid, features compatible
with multinodular goitre or thyroiditis)
• Follicular lesions: adenoma or carcinoma
• Suspicious of malignancy
• Diagnostic for malignancy.
Ultrasound - guided fine needle aspiration should be
performed where there is high suspicion of malignancy,
suspicious ultrasound features, presence of cervical lymph
Ultrasound of thyroid gland (There are no ultrasonographic findings that
are specifi c for thyroid carcinoma. However, features that raise suspicion
of malignancy include hypoechogenicity, irregular border,
microcalcifications and increased colour Doppler flow).
2. Radioisotope uptake scan (should be performed in all patients with
suppressed TSH)
Malignant nodules are more likely to be cold (i.e. not to take up radioisotope).
However, most (80%) cold nodules are benign (e.g. colloid nodules,
haemorrhage, cysts or inflammatory lesions such as Hashimoto’s thyroiditis).
Hot nodules are associated with a low incidence of thyroid cancer. However,
the presence of hot nodules does not exclude malignancy.
3. Computed tomography (CT) or magnetic resonance imaging (MRI) of
the neck and thoracic inlet (in cases of Clinical suspicion of a retrosternal
goitre causing tracheal compression)
Treatment of non-toxic goitre and
thyroid nodules
Following fine needle aspiration of thyroid nodules and
cytological examination, all patients should be discussed at a
specialist thyroid multidisciplinary meeting.
• Patients with non - diagnostic cytology need repeat
ultrasound - guided fine needle aspiration immediately.
• Patients with suspicious or malignant cytology should be
offered surgery.
• Patients with benign cytology should be followed up
clinically with palpation (and with ultrasound if a nodule is
not easily palpable). Some guidelines recommend repeat
fine needle aspiration after 6 months to reduce falsenegative rates. Surgery may also be offered in the presence
of symptoms caused by local compression or significant
cosmetic disfigurement.
Thyroid cancer
Thyroid cancer is the most common endocrine malignancy.
Classification of thyroid carcinoma:
• Papillary (70 – 80%)
• Follicular (15%)
• Anaplastic (5%)
• Medullary (5 – 10%)
• Lymphoma (5 – 10%)
Main aetiology factors are:
• Exposure to ionizing radiation
• Genetic factors (genetic mutation)
• Family history of thyroid cancer
Papillary thyroid cancer
Papillary thyroid cancer is the most common thyroid cancer. It is often
multifocal. About 15 – 20% show local extra - thyroidal invasion.
Papillary carcinomas metastasize via the lymphatics to the regional
lymph nodes (clinically evident in about one third of patients at
presentation) and distantly, for example to the lungs and bones (2 –
10% at diagnosis).
Papillary carcinomas are typically unencapsulated. They are
characterized by papillae consisting of one or two layers of tumour
cells surrounding a fibrovascular core. The cells and nuclei are large,
and their cytoplasm has a ‘ ground glass ’ appearance. Nucleoli are
prominent, and the nuclei have clefts, grooves and ‘ holes ’ due to
intranuclear cytoplasmic inclusions ( ‘ Orphan Annie eyes ’ ). About
50% of papillary carcinomas contain calcified psammoma bodies, the
scarred remnants of tumour papillae that presumably infarcted.
Follicular carcinoma
This type of epithelium - derived thyroid carcinoma shows follicular
differentiation and capsular or vascular invasion. The peak incidence of
follicular carcinomas is between ages 40 and 60 years.
Fine needle aspiration specimens may show microfollicles with varying
nuclear atypia and little colloid. However, it is difficult to differentiate
between benign follicular adenomas and malignant follicular
carcinomas on cytology. The distinction between follicular adenoma
and carcinoma can only be made through histological identification of
capsule and/or vascular invasion. Follicular carcinomas may be
minimally or widely invasive. Spread is more likely to be
haematogenous (to lung and bones) than to regional lymph nodes.
Hurthle cell carcinoma is a variant of follicular thyroid carcinoma and is
characterized by the presence of oncocytic cells, which have an
abundant oxyphillic cytoplasm (due to the accumulation of altered
mitochondria) and round oval nuclei with prominent nucleoli.
Anaplastic carcinoma
Anaplastic thyroid carcinoma occurs more
frequently in older patients (60 – 80 years of
age). Patients usually present with a rapidly
enlarging neck mass. The spread is
haematogenous, and distant metastases are
found in 15 – 50% of patients at initial disease
Thyroid lymphoma
Thyroid lymphoma may be part of a systemic
disease or may primarily involve the thyroid
gland. The risk of thyroid lymphoma is increased
in patients with autoimmune thyroiditis.
Treatment of papillary and follicular
Papillary and follicular carcinoma
Treatment includes initial thyroidectomy, postoperative TSH
suppression with thyroxine and, in high - risk patients, postoperative
radio - iodine ablation.
Surgery is the primary treatment and should be performed by an
experienced thyroid surgeon to minimize the risk of
hypoparathyroidism and recurrent laryngeal nerve injury. Total
thyroidectomy is appropriate when the primary tumor is 1.0 cm or
more, or if there is extra - thyroidal extension or metastasis. This
aggressive initial surgical approach is associated with lower rates of
local and regional recurrence and overall mortality.
Lobectomy plus isthmusectomy may be appropriate for tumours of
less than 1.0 cm confined to one lobe of the gland. Lymph node status
should be assessed by neck ultrasound scans, and regional neck
dissection is carried out in cases of central or lateral nodal
Treatment of papillary and follicular
TSH suppression
After initial surgery, all patients should receive
thyroxine to prevent hypothyroidism and to
minimize potential TSH stimulation of tumour
growth. The dose of levothyroxine should be
adjusted by 25 μ g every 6 weeks until the serum
TSH is below 0.1 mU/L. Most patients require 175 –
200 μ g daily. A lower level of TSH suppression may
be appropriate in those with heart disease or low
bone mineral density.
Treatment of papillary and follicular
Radio – iodine
Thyroid follicular cells can take up radio – iodine (131 I), which causes cell
death by the emission of beta rays. Postoperatively (at about 4 – 6 weeks),
radio - iodine ablation is given to high - risk patients (those aged ≥ 45
years, tumours > 3 – 4 cm, aggressive histological variants, extra thyroidal disease with direct invasion or metastases). The need for radio iodine ablation in low - risk patients is controversial.
Radio - iodine ablation destroys residual normal thyroid as well as
microscopic malignant tissue and improves the specifi city of subsequent
radio - iodine scans and serum thyroglobulin for detecting recurrent or
metastatic cancer. Follow – up scanning with 123 I and further radio iodine treatment with 131 I in cases of positive uptake is done 6 – 12
months after initial radio - iodine and is repeated until the patient has a
negative scan.
Complications of radio - iodine include radiation thyroiditis, painless neck
oedema, sialoadenitis, tumour haemorrhage or oedema, and nausea. An
increased risk of secondary malignancies has been reported.
Treatment of anaplastic thyroid
carcinoma and thyroid lymphoma
Anaplastic thyroid carcinoma
The treatment of anaplastic thyroid carcinoma
includes total thyroidectomy with lymph node
clearance, chemotherapy (e.g. doxorubicin and
cisplatin) and external beam irradiation.
Thyroid lymphoma
Disease limited to the thyroid is treated with