Goitre, nodular thyroid disease, and thyroid cancer

Epidemiology
More common in women in men
Present in examination in up to 9% of population
Majority are painless, but pain and discomfort can occur in acute presentation
Large goitres can produce dysphagia and breathing difficulty, and
superior vena cava obstruction
Can be physiological or pathological

Clinical history and examination

History
Often first noticed as a cosmetic deficit
Medication: iodine-containing preparations, and possible exposure to
radiation
Examination
Clinical thyroid status: euthyroid, hypothyroid or hyperthyroid?

Hyperthyroid--toxic means the goitre is actively producing

hormone
Document the pathological nature:
Size
Shape
Consistency
Mobility
Can you feel the lower margin? (retrosternal extension)
Bruit (carotid or thyroid)
Examine the cervical lymph nodes and trachea (deviation).
Then Pembertons sign
Aetiology
Physiological, resulting in a diffuse increase in thyroid size
Puberty
Pregnancy
Graves, Hashimotos
Painful goitre:
Thyroiditis
Bleeding into cyst (sudden onset)
Thyroid tumour (rarely)
Drug-induced:
Carbimazole
Propylthiouracil
Iodine problems:
Deficiencyendemic goitre esp in mountainous areas such as Himalayas, Africa,
Netherlands, Western Pacific. Mechanism is thought to be borderline
hypothyroidism leading to TSH stimulation and thyroid enlargement. Solution:
iodinated salt.

Dyshormonogenesis (due to genetic defects in the synthesis of thyroid

hormones)

Diffuse

Nodular

Solitary:
Tumours
Adenoma

Misc

Simple: physiological

Multinodular goitre

Autoimmune: Graves Solitary nodular

Hashimotos

Carcinoma

Tuberculosis

Thyroiditis: Acute (de

Quervains
thyroiditis)

Fibrotic (Reidels
thyroiditis, form of
autoimmune)

Lymphoma

Iodine deficiency
(endemic goitre)
Dyshormonogenesis
Goitrogens (eg
sulfonylureas)

Cysts

Sarcoidosis

Diffuse non-toxic goitre:

Simple: no clear cause, and thyroid usually smooth and soft. May be associated
with thyroid growth-stimulating antibodies.
o Presents between ages of 15 and 25, or in pregnancy
o Noticed not by the patients but by their friends and relatives
o Recedes on its own, but sometimes 10-20 years later can develop
autonomous nodules

Autoimmune: firm diffuse goitre, variable size.

Thyroiditis: acute, diffuse swelling, sometimes with severe pain. Suggestive of

acute viral thyroiditis (de Quervains)
o Infection with Coxsackie, mumps or adenoviruses
o Period of transient clinical hyperthyroidism (releases colloid and stored
thyroid hormones), hypothyroidism (follicular cells are damaged and
impaired synthesis), then euthyroidism

Diffuse toxic goitre:

Graves, often presents with bruit
De Quervains thyroiditis
Nodular goitre:
Multinodular colloid goitre: common in older patients. They are usually euthyroid
(normal thyroid function), but may be hyperthyroid/borderline with suppressed
TSH and normal T3 and T4.
o Most common cause of tracheal and/or oesophageal compression
Can cause laryngeal nerve palsy
May extend retrosternally
Stridor, dysphagia and superior vena cava obstruction in severe
disease
Pain can be due to sudden haemorrhage into a nodule or a cyst

Hyperthyroidism may develop because of progression to toxic

multinodular goitre; hypothyroidism and malignancy are rare

o Late-stage goitre--it has had the time to become lumpy

o Large nodules are present clinically, but smaller nodules that are not
clinically detected can be visualised by high-resolution ultrasound,
which are associated with autoimmune thyroid disease and present in
40% of the population.
o Aetiology uncertain; perhaps developed from simple goitre or uneven TSH
exposure
o Thyroxine does not help but radioactive iodine does.

Solitary: multiple causes, assume almost all are non-toxic

o Malignancy (10%) should be considered, but the majority are cystic
or benign
History of rapid enlargement, associated lymph nodes suggests
possibility of thyroid carcinoma.
o Risk factors for malignancy:
Previous irradiation
Long-standing iodine deficiency
Occasional familial cases
o Sometimes, they are just the most prominent nodule of a multinodular
goitre.
o Investigations are needed to confirm

Solitary toxic nodules are uncommon and may be associated with T3 toxicosis,
or are toxic adenomas (follicular in origin).

Fibrotic goitre: rare condition, Reidels thyroiditis

o Woody glandthe feeling
o Associated with other midline fibrosis
o Difficult to distinguish from carcinoma, as it is irregular and hard
o Clinical clues: systemic symptoms of inflammation and elevation in inflammatory
markers

Tumours
Thyroid carcinoma
Rarely the site of a metastatic deposit or the site of origin of lymphoma
Investigation
TEST
TFTs
Thyroid antibodies
Ultrasound

Chest and thoracic inlet X-rays

EXPLANATION
TSH and Free T4 or T3
To exclude autoimmune aetiology
High-resolution can delineate nodules, esp
clinically undetectable multinodular goitre
Differentiates between cystic and solid
FNA usually also performed (for possibly
malignant cystic tumours and thyroid
tumours)
Tracheal compression, large retrosternal
extensions

Fine-needle aspiration

Thyroid nuclear scan (radioactive

iodine)

In patients with a solitary nodule/dominant

nodule in multinodular goitre, there is a 5%
chance of malignancy.
5% false-negative rate
Distinguishes between functioning (hot) and
non-functioning (cold) nodules.
A hot nodule is rarely malignant and a cold
nodule is malignant only in 10% of cases, but
should always raise suspicion of malignancy.

Thyroid Function Tests

TSH (0.3-3.5 mU/L)
Thyrotoxicosis
Primary
hypothyroidism
TSH deficiency
T3 toxicosis
Compensated
euthyroidism

Suppressed
(<0.05 mU/L)
Increased (>10
mU/L)
Low-normal or
subnormal
Suppressed (<0.05
mU/L)
Slightly
increased (5-10
mU/L)

Free T4 (10-18.7
pmol/L)
Increased

Free T3 (3.5-6.5
pmol/L)
Increased

Low/low-normal

Normal/low

Low/low-normal

Normal/low

Normal

Increased

Normal

Normal

Detailed management
Many goitres are small, cause no symptoms and can be observed (includes patient
self-monitoring). When it is physiological it is likely to spontaneously resolve.
When thyroid function is abnormal, the patient should be treated so that they are
euthyroid.
Surgical intervention is indicated when:
Malignancy is suspected
o Rapid growth
o Pain
o Cervical lymphadenopathy
o Change in voice (recurrent laryngeal nerve compression)
o Previous radiation
o Positive or suspicious FNA
Pressure symptoms on the trachea or more rarely, the oesophagus are detected
(retrosternal extension)
Cosmetic reasonspatients may be anxious over appearance
Radioactive iodine is an option in euthyroid goitre, particularly when surgery is
unattractive.
Toxic nodules are managed with antithyroid drugs, but surgery or radioiodine is often
required.
Thyroid carcinoma

Epidemiology
Not common, and more common in females
Mortality from it not that high
In 90% of cases they present as thyroid nodules
Occasionally with cervical lymphadenopathy (5%), or with lung, cerebral,
hepatic or bone metastases

A minimum of hemithyroidectomy is required to confirm capsular invasion

for dx follicular or Hurthle cell CA.
Cell type
Papillary
(intranuclear
holes and
grooves,
orphan-Annie
eyes and
psammoma
bodies)

Follicular
(Hurthle cells)

Frequen
cy
70%-most
common

20%

Behavio
ur
Occurs in
young
people

More
common
in
females

Spread

Prognosis Treatment

Local lymph
nodes,
sometimes
lung/bone
metastasis via
blood

Good,
especially
in young

Metastasises
to lung/bone
via blood

Good if
resectable,
has
propensity
to take up

Total thyroidectomy
+/- node excision +/radioiodine; thyroxine
to suppress TSH and
growth
Monitor with
thyroglobulin
antibodiesshould
have no thyroglobulin
left
Same as above

131Iodine and
so maybe
good
prognosis
Very poor

Anaplastic
(dedifferentiation
)
Medullary cell
(neuroendocri
ne tumour)

<5%

Aggressi
ve, in
elderly

Locally
invasive

5%

Often
familial
(Multiple
Endocrin
e
Neoplasi
a 2)

Local
invasion;
lymphatic
spread and
eventually via
blood to the
liver

Poor, but
indolent
course
(causing
little or no
pain)

Lymphoma;
non-Hodgkin,
non B-cell

2%

Variable;
may
present
with
stridor or
dysphagi
a

Lymphatic
spread

Sometime
s
responsive
to
radiothera
py

Papillary or follicular: differentiated

Both from simple cuboidal epithelium (follicle cells)
Anaplastic: undifferentiated
Medullary: C (calcitonin) cells
History and examraising suspicion
Demographic
o Male
o Age <20 or >70
History
o Rapid growth
o Compressiondysphagia, dyspnoea, hoarseness
o Previous neck irradiation
o FHx of MEN or familial MTC
Exam
o Firm hard nodule
o Tethering to adjacent structures
o Cervical lymphadenopathy

Excision or
radiotherapy if it is
resectable
Do
phaeochromocytoma
screen; screen
asymptomatic
relatives,
thyroidectomy and
node clearance. Does
not respond to radioiodine.
Stage lymphoma pre
treatment;
chemoradiotherapy. If
MALT origin, good
prognosis

Pathophysiology
Uncertain, but papillary carcinoma can be familial (eg inherited MAPK defects) and
those related to previous head and neck irradiation or ingestion of radioactive iodine.
Hormonally, these tumours are minimally active but secrete thyroglobulin, which
can act as a tumour marker. Also used after adjuvant radiotherapy for any
cancer activity.
Medullary cell carcinoma: calcitonin levels as tumour marker.
Medullary carcinoma: a neuroendocrine tumour, often associated with multiple
endocrine neoplasia type 2 (RET proto-oncogene mutation, familial cancer syndrome,
often with other mucosal neuromas/parathyroid hyperplasia).
In detail
Papillary
Young, good prognosis
Tends to spread to
o Pretracheal and prelaryngeal nodes, usually a small occult tumour
o Deep cervical chain following superior and middle thyroid veins
o Nodes around RLN and anterior mediastinum following inferior thyroid
veins
o Does not metastasise beyond head and neck
Treatment
General
Ablation radio-iodine
Thyroxine after surgeryreplace and to suppress TSH
Papillary and follicular carcinoma:
Surgical, normally total or near-total thyroidectomy for local disease
Regional or more extensive neck dissection is needed where there is local nodal
spread or involvement of local structures

Radioactive iodine is recommended to ablate residual thyroid tissue postoperatively for most patients with differentiated thyroid cancer
If it recurs, local thyroid invasion and lymph node involvement is common
Lungs and bone are most common sites of distant metastasis
Suppressive doses of levothyroxine to minimise TSH levels below the normal
range, and minimises risk of recurrence.
Serum thyroglobulin levels are used to monitor patient progress

o This is most sensitively detected when TSH in high, so either levothyroxine

has to be stopped or recombinant TSH is given.

Prognosis is extremely good when they are confined to the thyroid gland
o Higher riskage >40
o Larger primary tumour size (>4cm)
o Macroscopic invasion of capsule and surrounding tissues

Anaplastic carcinomas and lymphoma

Do not respond to radioactive iodine and external radiotherapy only produces
brief respite
Medullary carcinoma
Total thyroidectomy and wide lymph node clearance
Local invasion or metastasis is frequent and the tumour responds poorly to
treatment even though its progression is slow
Children with MEN 2a/2b or familial medullary thyroid carcinoma advised to
undergo prophylactic thyroidectomy
o MEN 2abefore 5 years
o MEN 2bbefore 1year
o Familial MTCafter 10 years

Assessment of a solitary thyroid nodule

Definition
Clearly defined discrete mass, separated from the thyroid parenchyma
Palpable nodules are found in approximately 4% of the population
M:F = 1:4
Work-up
Take history, do exam to ascertain patients clinical thyroid status
Ddxes
o Benign tumours eg follicular adenoma
o Thyroid malignancy
o Hyperplastic area in a MNGPlummer syndrome
o Cyst: true thyroid cysts, area of cystic degeneration in MNG
Investigations
o Ultrasound: differentiates between cystic and solid lesions, sizing
Look for intra-epithelial growths which could be neoplasia
Calcifications strongly suggests carcinoma
Vascular lesionreferral to tertiary hospital
o Thyroid scan only if TSH is low to determine if nodule is hot (significant
131I uptake) which signifies very low malignant potential
Minimal value in the investigation of the thyroid nodule
o FNA + cytology
FNA for all nodules >1-1.cm, or nodules >5mm with suspicious US
features (particularly microcalfication)
Thyroid epithelium is cuboidal epithelium
Benign: colloid goitre
Carcinoma:
Papillary: appears like a frond

Follicular: has eroded through the capsule containing it so

need hemithyroidectomy at least! Cannot see on FNA!

Screening for disease recurrence

Recurs in approx. 30% of patients
Thyroglobulin
o After surgery and ablation, levels should be very low.
o Check for antithyroglobulin Abspresent in up to 25%
o 5% of tumours do not secrete thyroglobulin
Thyroid scanthyroid tissue takes up iodine
o Requires stopping thyroxine
Ultrasoundusually annually

MENmultiple endocrine neoplasia

Neoplastic syndrome involving multiple endocrine glands

Tumours of neuroectodermal origin
Autosomal dominant inheritance with variable penetrance
Genetic screening for RET proto-oncogene on chromosome 10 has long-term
benefit
o Early cure and prevention of medullary thyroid cancer