ENDOCRINE SURGERY
Management of the
thyroid nodule
Neil Patel
Michael J Stechman
Abstract
Thyroid nodules are common and a frequent reason for referral to sec-
ondary care. Clinical assessment and investigation should aim to
address the possibility of malignancy, functional status of the thyroid
and compressive symptoms. A combination of neck ultrasound and
fine needle aspiration cytology (FNAC) can usually help establish a
plan of management, allowing conservative management of most pa-
tients, and surgical treatment for those with suspected or confirmed
thyroid cancer. The limitations of FNAC include a relatively high rate
of inadequate/non-diagnostic samples, and the inability of cytology
to distinguish between benign and malignant follicular neoplasms.
Surgery may therefore be required to establish the diagnosis in pa-
tients with indeterminate nodules, in addition to its role in treatment
for compressive symptoms or thyrotoxicosis.
Keywords Fine needle aspiration cytology; follicular neoplasm;
molecular testing; thyroid cancer; thyroid function; thyroid nodule;
ultrasound
Thyroid nodules are very common and a frequent reason for
surgical consultation. The thyroid naturally tends to become
nodular with increasing age, and clinically significant nodules
are also more frequent in females compared with males. In
Western society, prevalence has been estimated to be as high as
35e65%, particularly if sensitive methods of detection such as
ultrasound or assessment of the thyroid gland at autopsy are
used. Between 2e6% of the population may have a palpable
thyroid nodule.1
From the patient perspective, the clinical significance of thy-
roid nodules is chiefly related to the exclusion of malignancy.
The risk of malignancy in a thyroid nodule is 4e6.5%, implying
that thyroid cancer is rare and the majority of thyroid nodules are
benign. Nodules usually represent part of the spectrum of dis-
orders that result in thyromegaly (degenerate colloid nodules,
haemorrhagic or hyperplastic nodules, cysts and Hashimoto’s
thyroiditis); however, some are neoplastic (Box 1).2
Clinically, a thyroid nodule presents as a neck lump. Occa-
sionally, a palpable abnormality in the lateral neck may represent
a lymph node metastasis in a patient with thyroid cancer with a
non-palpable thyroid primary. However, frequently thyroid
nodules are identified incidentally with radiology undertaken for
another reason such as:
Neil Patel FRCS is a Specialist Registrar in General Surgery at
University Hospital of Wales, Cardiff, UK. Conflicts of interest: none.
Michael J Stechman MD FRCS is a Consultant Endocrine Surgeon at
the Department of Surgery, University Hospital of Wales, Cardiff, UK.
Conflicts of interest: none.
SURGERY 38:12
Neoplastic thyroid nodule disorders
Benign neoplasms:
C Follicular adenoma
C Hurthle cell adenoma
Neoplasms of indeterminate malignant potentiala:
C Non-invasive follicular thyroid neoplasm with papillary-like nu-
clear features (NIFTP) elacks capsular invasion
C Follicular lesion of uncertain malignant potential (FL-UMP) e in-
vasion into but not through the tumour capsule
C Well-differentiated tumour of uncertain malignant potential (WDT-
UMP) e nuclear features of PTC with incomplete capsular
invasion
Malignant neoplasms:
C Papillary thyroid cancer (and its sub-types)*
C Follicular thyroid cancer*
C Hurthle cell cancer
C Medullary thyroid cancer (arising from the neuro-endocrine C-
cells)
C Anaplastic thyroid cancer
C Primary thyroid lymphoma
C Metastases to the thyroid from cancer elsewhere
a
Defined by the WHO in 2017.
b
PTC and FTC are both derived from follicular cells and termed
differentiated thyroid carcinomas (DTC) and constitute 95% of
malignant thyroid tumours.
Box 1

Ultrasound scanning of the neck for other pathology, e.g.
to assess non-thyroid neck lumps, or for Duplex scanning
of the carotid arteries.

Positron-emission tomography (PET-CT) and contrast CT,
for the staging and follow-up of other cancers.

Chest X-ray or computed tomography (CT) of the chest
performed for respiratory symptoms (a common presen-
tation of retro-sternal nodules and goitres).

MRI for assessment of the cervical spine.
Investigation and management of all incidental nodules can
lead to potential patient harm with overtreatment. Therefore risk
stratification is necessary to identify nodules at high risk of
malignancy.
Clinical evaluation
Assessment of thyroid nodules aims to answer the following
questions:

What is the functional status of the thyroid?

Is the nodule benign or malignant?

Is the nodule causing any other symptoms (which might
necessitate treatment, even if benign)?
The clinical history should therefore concentrate on eliciting
any symptoms suggestive of thyroid dysfunction; risk factors for
malignancy; symptoms suggestive of cancer; and compressive
symptoms.
786 Ó 2020 Published by Elsevier Ltd.
 ENDOCRINE SURGERY
Endocrine dysfunction
Symptoms of hyperthyroidism may include weight loss (typically
with a normal or increased appetite), sweating, tremor, anxiety,
tiredness/disturbed sleep, and palpitations (usually with a rapid
heart rate). Conversely, hypothyroidism might be implied by
unexplained weight gain, lethargy, dry skin, and frequently a
decline in cognitive function. It should be recognized, however,
that symptoms might be lacking, even when thyroid function is
abnormal, hence a biochemical assessment of thyroid function
(serum TSH) will always be necessary.
Risk factors for thyroid malignancy
Age: There is a bi-modal distribution of incidence of thyroid
cancer with age, with a small peak in childhood/early adoles-
cence, and a later peak after age 50 years.3 Conversely, most
benign nodules present between ages 30e50 years. Hence, the
probability of an individual nodule proving malignant is highest
at the extremes of the age distribution.
Gender: The incidence of thyroid cancer has an approximately
2.3e2.6:1 female:male ratio, whereas for benign disease this
ratio is closer to 4 to 4.7:1.3e5
Therefore, the probability of a thyroid nodule proving malig-
nant in a man is greater than in a woman.
Family history: Genetic predisposition to thyroid cancer may be
revealed by a careful family history. Around 20e25% of med-
ullary thyroid cancer (MTC) is associated with germ-line muta-
tions in the RET-oncogene, as part of multiple endocrine
neoplasia type 2 (MEN2) or familial medullary thyroid cancer
(FMTC).6,7
The former is associated with phaeochromocytomas and pri-
mary hyperparathyroidism. A history in a family member of
thyroid cancer (especially at an early age) or of premature sud-
den death (suggesting phaeochromocytoma) should raise the
suspicion of MEN2.
Other familial syndromes6 can increase the risk of both
papillary and follicular cancers, including familial papillary thy-
roid cancer (fPTC), Cowden’s syndrome (other features include
multiple skin and mucous membrane hamartomas, breast can-
cer, macrocephaly and mental retardation) and familial adeno-
matous polyposis (FAP, typically associated with multiple
intestinal polyps and colorectal cancer).
History of radiation exposure: Radiation significantly increases
the risk of thyroid cancer, particularly in young individuals. A
history of external beam radiotherapy to the head, neck or upper
chest/breast should specifically be sought (most commonly for
Hodgkin’s lymphoma or breast cancer).
Past history of cancer elsewhere: Clinically significant metas-
tases to the thyroid are uncommon, but can occur in patients
with previous lung, breast, colorectal or renal cancer, or
melanoma.
Symptoms suggestive of cancer
Few features of the history are specific for thyroid malignancy.
However, the following raise suspicion and should be managed
in 2-week wait/urgent suspected cancer pathways:
SURGERY 38:12

Hoarseness of the voice: in association with a thyroid
mass, this is suggestive of vocal cord palsy, secondary to
invasion of the recurrent laryngeal nerve. Benign lesions
seldom compromise this nerve (although hoarseness may
be due to unrelated, benign disease).

A rapidly enlarging mass, growing steadily and swiftly
over a few weeks: very suggestive of aggressive forms of
thyroid cancer, as detailed below. In contrast, a lump
appearing over 24e48 hours is likely to represent a bleed
into a thyroid cyst, most of which are benign.

Symptoms of local invasion of structures in the neck: pain
in the ipsilateral ear (referred otalgia), stridor, dysphagia
or haemoptysis.
Compressive symptoms
Benign thyroid masses, if large enough, can cause compression
of the cervical oesophagus or trachea, causing difficulty swal-
lowing, a sensation of tightness in the neck, or difficulty/noisy
breathing.
Summary of key features in the history

Features of hypo/hyperthyroidism.

Hoarse voice.

Family history of thyroid cancer.

Past history of head/neck irradiation.

Compressive features e noisy breathing, dysphagia.
Physical examination
Assessment of thyroid functional status
Hyperthyroidism may be manifest by resting tachycardia, agita-
tion, tremor, palmar sweating and signs of weight loss. Brady-
cardia, dry skin and thinning hair, obesity and slow mentation
may imply hypothyroidism.
Neck examination
This should determine the lump’s consistency, volume, rela-
tionship to surrounding structures and whether or not the pre-
senting lump is within the thyroid. If found within the thyroid,
assessment should be made of whether the lump is clinically:

a solitary nodule

a dominant nodule within a multi-nodular gland (‘domi-
nant’ implying the largest, most symptomatic or most
suspicious nodule)

a smooth, symmetrical goitre (usually suggestive of auto-
immune thyroid disease).
Sub centimetre nodules, those located posteriorly or in a ret-
rosternal location, are usually not clinically palpable.
Examination of the neck should also look for lymphadenop-
athy and assess for tracheal deviation and the presence of stridor.
Red flag signs for malignancy include a fixed hard mass,
cervical lymphadenopathy, stridor, and hoarseness.
Investigation
A blood test for thyroid function should be performed. Serum
thyroid-stimulating hormone (TSH) alone is usually adequate if
the patient is clinically euthyroid and there is no suspicion/his-
tory of pituitary disease. Thyroid cancer is rare in patients that
are not euthyroid. If the serum TSH level is outside the reference
787 Ó 2020 Published by Elsevier Ltd.
 ENDOCRINE SURGERY

range, the serum free thyroxine (T4) and free tri-iodothyronine The BTA guidelines7 for the management of thyroid cancer
(T3) should be measured. suggest that the cumulative sonographic features of thyroid
Optimal further investigation depends upon the clinical pic- nodules should be summarized in a U1e5 classification, as
ture. The following scenarios are most frequently observed. follows:

The euthyroid, solitary (or dominant) thyroid nodule
1: normal thyroid

These are patients with a normal TSH and a solitary thyroid mass
or a ‘dominant’ or large nodule in a background multi-nodular
goitre. The risk of the dominant nodule being malignant is
similar to that for solitary nodules,8 hence management is
similar. The main clinical concern is to establish whether or not
the lesion is malignant.
First-line investigations are an ultrasound scan of the neck,
with or without fine-needle aspiration cytology.
Ultrasound: When undertaken by an appropriately trained and
experienced sonographer, ultrasound can reliably be used to
guide subsequent management and forms the first step of eval-
uation outlined in the British Thyroid Association guidelines.7
Sonographic characteristics of a thyroid nodule can be used to
assess the likelihood of malignancy and determine if any further
clinical evaluation is required.7 The features of thyroid lesions
that can be used to help differentiate benign from malignant on
ultrasonography are illustrated in Figure 1. Lesions with ill-
defined margins, that are taller than they are wide, hypoechoic,
and those with punctate calcification have the greatest suspicion
of malignancy.9

2: benign

3: equivocal

4: suspicious

5: malignant
Although FNAC is the gold standard for diagnosis of thyroid
nodules, recent guidelines demonstrate a move towards fewer
FNAC procedures for lesions that are benign on ultrasound. Le-
sions classified as benign (U2) do not necessarily require fine-
needle aspiration to confirm their benign nature, unless there
are suspicious clinical features such as increasing size of the
lesion, or risk factors for thyroid cancer. Indeed, unless there are
additional symptoms, most patients can be reassured and dis-
charged at this stage.
Lesions classified as U3e5 should undergo fine-needle aspi-
ration cytology (FNAC), as should any associated abnormal
cervical lymph nodes. Depending on local expertise, this may be
performed guided by palpation alone (‘freehand’) or using ul-
trasound guidance. NICE recommend US guidance due to its
associated lower non-diagnostic (Thy1) rate, and US guidance is
mandated if the nodule is impalpable.10 US is also useful when

British Thyroid Association 2014 classification of ultrasound scoring of thyroid nodules

U1 Normal U1 U2 U3 U4 U5
U2 Benign:
(a) halo, iso-echoic/mildly hyper-echoic
(b) cystic change +/- ring down sign (colloid) a
(c) micro- cystic/spongiform

(f) peripheral vascularity.

b
U3 Indeterminate/equivocal:
(a) homogenous, hyper-echoic (markedly), solid, halo (follicular lesion).
(b) ? hypo-echoic, equivocal echogenic foci, cystic change
(c) mixed/central vascularity. c

U4 Suspicious:
(a) solid, hypo-echoic (cf thyroid)
(b) solid, very hypo-echoic (cf strap muscle) a a>b
d b

(d) lobulated outline.

U5 Malignant: e
(a) solid, hypo-echoic, lobulated/irregular outline,

(b) solid, hypo-echoic, lobulated/irregular outline, globular

f
(c) intra-nodular vascularity
(d) shape (taller >wide) (AP>TR)
(e) characteristic associated lymphadenopathy.

From Perros P, Boelaert K, Colley S et al. Guidelines for the management of thyroid cancer. Clinical Endocrinology. 2014 Jul; 81: 1–122.
With kind permission from John Wiley & Sons, Ltd.

Figure 1

SURGERY 38:12 788 Ó 2020 Published by Elsevier Ltd.

 ENDOCRINE SURGERY
targeting small lesions, lymph nodes and the solid component of
a partially cystic lesion. Suspicious lymph nodes can also be
assessed for thyroglobulin (Tg) by washout testing whereby the
material in the hub of a biopsy needle is diluted with 1mL of
0.9% saline and Tg concentration is measured. Detectable Tg
would confirm a malignant thyroid cancer node. Core biopsy is
an alternative to FNAC, although it is more invasive and like
FNAC, unable to distinguish follicular neoplasms from carci-
nomas. It may be better than FNAC for the diagnosis of larger,
rapidly growing masses, where the additional information on
tissue architecture and immunohistochemistry can help to
distinguish lymphoma, anaplastic or metastatic cancers, in bi-
opsy of lymph nodes, or if FNAC is repeatedly non-diagnostic.
Subsequent management of these U3-5 lesions is then
dependent upon the outcome of FNAC, as detailed below.
Fine-needle aspiration cytology (FNAC): is a simple, fast and
inexpensive investigation that can be performed in the outpatient
clinic. Furthermore, it is associated with relatively few compli-
cations. A small gauge 25e27 needle is used to draw a sample of
cells either by gentle negative pressure or capillary-action, which
are then fixed onto slides for analysis by an appropriately trained
thyroid cytopathologist. Meta-analysis has demonstrated that
capillary action with smaller gauge (25e27G) needles yields the
lowest rate of non-diagnostic samples.11
Results can be reliably used to guide subsequent manage-
ment. The Royal College of Pathologists12 recommends classifi-
cation of the cytology result into Thy1e5 categories, similar to
those for ultrasound above:
Thy1: Inadequate/non-diagnostic e This category implies
an inadequate yield of well-visualized thyroid epithelial cells
from which to make a diagnosis. At least six groups with each
containing ten thyroid epithelial cells need to be present for a
satisfactory sample. Unsatisfactory samples may arise due to a
poor technique in taking/preparing the aspirate, or due to the
lesion being predominantly cystic, degenerate or necrotic, where
the yield of viable epithelial cells may be expected to be poor.
The FNAC should be repeated in this scenario. If Thy1 still per-
sists, the patient’s clinical and radiological risk factors are
reviewed and the patient is put into a low level of suspicion or a
high level of suspicion of thyroid cancer group. Low-risk patients
may be monitored with serial ultrasound and high-risk patients
should be discussed in an multidisciplinary team meeting (MDT)
with a decision made to undertake diagnostic surgery if
appropriate.
Thy2: Benign/non-neoplastic e the yield of thyroid epithelial
cells is adequate, there is no cellular atypia; and other features,
such as the presence of colloid or macrophages, suggest a benign
process.
Thy3: Neoplasm possible e this category is usually sub-
divided into:

Thy3a (‘atypia’): subtle or focal atypical features, of un-
certain significance.

Thy3f (‘follicular lesion’): cellular specimens, with fea-
tures suggestive of follicular neoplasms.
Epithelial cells obtained from benign hyperplastic nodules,
follicular adenomas and follicular carcinomas are indistinguish-
able cytologically in 20e30% of samples:13 the differentiation
between these lesions relies on architectural features of the
SURGERY 38:12
lesion. For follicular cancer, this specifically requires demon-
stration of capsular or vascular invasion. This can only be
accurately assessed by histological analysis of the whole lesion,
which will usually mandate a diagnostic operation (hemi-thy-
roidectomy on the side of the lesion, or occasionally isthmusec-
tomy, for a solitary nodule confined to the isthmus). Where such
surgery is undertaken for Thy3 cytology, around 25% prove to be
malignant (follicular and papillary cancer), a further 37% are
benign (i.e. follicular adenomas4), and the rest are entirely non-
neoplastic (hyperplastic or colloid lesions).
Molecular markers e are novel and evolving modalities that
are used in some units for the assessment of indeterminate thy-
roid nodules from FNAC washings and to distinguish minimally
invasive and low-risk thyroid cancers from benign lesions.
Commercially available tests involve mutational analysis and
gene expression analysis of FNA samples to evaluate the mol-
ecular background of thyroid tumours. The most commonly re-
ported tests in the literature are the AfirmaÒ and ThyroSeqÒ
tests. The results are used in different ways: the AfirmaÒ and
ThyroSeqÒ test have high negative predictive values and are
used by some to ‘rule out’ cancer in a nodule and thereby avoid
diagnostic surgery. However, a gene mutation and rearrange-
ment analysis panel including BRAF V600E (classical papillary
cancer), TERT and KRAS alterations (follicular pattern thyroid
cancer) are used by others as a ‘rule in’ test for cancer in thyroid
nodules.14 The limitations appear to be they are not 100% ac-
curate in all indeterminate nodules and, moreover, there is a
paucity of data for Hurthle cell nodules. Furthermore, positive
and negative predictive values of the test are dependent on local
institutional prevalence of cancer and so need to be validated to
each institution. Where a thyroidectomy is preferred for clinical
reasons, there is no role for molecular testing in the diagnostic
pathway nor is there a need for nodules that are benign on
cytology.15 In the future, molecular testing offers the potential to
facilitate highly individualized treatment and follow up of inde-
terminate nodules and thyroid cancer.
Thy4: Suspicious of malignancy e Suspicious features, but
the diagnosis cannot be made with sufficient confident for
definitive treatment to be planned.
Thy5: Malignant e Diagnostic of malignancy, where the
subtype of cancer can often also be stated (papillary, medullary,
anaplastic, lymphoma).
Management: The management of thyroid nodules is guided by
symptoms, thyroid function and the suspicion of malignancy
based on clinical features, ultrasound and cytology.
Cytology results should be interpreted in light of the clinical
and radiological setting, bearing in mind the potential for sam-
pling error and the limitations in the interpretation of cytology
specimens. The reliability of FNAC in large nodules is conten-
tious. The false negative rate of benign cytology in nodules under
3 cm is around 4.8% compared with 11.7% for those above
3 cm.16
As mentioned above, lesions classified as U2 may require no
further action, unless there are other symptoms or clinical con-
cerns mandating intervention. Routine surveillance/follow-up is
not usually necessary.
Lesions classified as U3, with Thy2 cytology, may also be
treated conservatively if there are no other reasons to consider
789 Ó 2020 Published by Elsevier Ltd.
 ENDOCRINE SURGERY
surgical excision. To be sufficiently confident of a benign diag-
nosis for conservative management of such lesions, however, a
repeat ultrasound (with or without a further FNAC) is advised.7
Thy3f cytology is more challenging as the risk of cancer is
highly variable (5e75%) and will usually require diagnostic
surgery, as outlined above, unless there are clinical features
which suggest conservative treatment/surveillance is more
appropriate, e.g. competing comorbidities, patient preference, or
more recently molecular markers.
Thy5 results will usually lead to definitive management for
cancer, usually surgery for papillary or medullary cancer.
Where there is conflict between results, e.g. U4/5 lesion with
Thy2 cytology, or where FNAC is Thy4, discussion at a thyroid
MDT is advisable to determine the next steps.
Table 1 summarizes the malignancy risk associated with each
Thy-category, and the commonest course of action
recommended.
It can be seen that the combination of ultrasound and FNAC
can be used to facilitate conservative management of benign
solitary thyroid nodules (the majority of patients in this clinical
scenario), while also guiding the use of surgery for diagnosis,
and for definitive therapy of those cases which prove to be
malignant.
Some patients with benign disease may still require surgical
intervention for other reasons, such as local compressive symp-
toms, cosmetic concerns or patient preference. Therefore, a
comprehensive clinical assessment and good counselling of the
patient following initial investigation are important.
Special situations:
The rapidly expanding thyroid mass e Occasionally, patients
will present with a thyroid mass which has rapidly and steadily
increased in size over a few weeks (Figure 2). Frequently, there
are associated worrying symptoms such as hoarseness,
dysphagia, stridor or referred otalgia. This presentation is highly
suggestive of aggressive thyroid cancer, and in particular
Risk estimates for Thy1-5 cytology categories12 and
usual course of action
Category Risk of malignancy Usual action
(%)
Thy1 0e10 Repeat FNAC
Thy2 0e3 Correlate with clinical/USS findings
Repeat FNAC if U3-5 (equivocal/
suspicious)
Usually conservative treatment
Thy3a 5e15 Correlate with clinical/USS findings
Repeat FNAC
Frequently conservative treatment
Thy3f 15e30 Diagnostic hemi-thyroidectomy
Thy4 60e75 Diagnostic hemi-thyroidectomy
Thy5 97e100 Definitive therapy, depending on
tumour type (usually surgery for
papillary/medullary cancer)
Table 1
SURGERY 38:12
anaplastic thyroid cancer, thyroid lymphoma or poorly
differentiated carcinoma metastasis to the thyroid from a
remote site. A past history of long-standing hypothyroidism/
Hashimoto’s thyroiditis raises further the probability of primary
thyroid lymphoma.
Initial investigation is similar to that described above, though
additional cross-sectional imaging (computed tomography (CT)
or magnetic resonance imaging (MRI)) may help assess the
extent of local invasion and potential resectability (in the event
that the final diagnosis is primary thyroid cancer).
FNAC may be diagnostic, though wide-bore core biopsy can
often be more useful in these tumours as it provides a larger
tissue sample for immuno-histochemistry and flow cytometry.
This may help in differential diagnosis, and allow subtype anal-
ysis in lymphoma.
Where the clinical course is particularly rapid, consideration
should be given to urgent admission to hospital to monitor for
impending airway crisis and multi-disciplinary review by the
haemato-oncolgy team with a view to an empirical course of
steroids, which in the case of lymphoma, can lead to rapid
resolution of the thyroid mass. A biopsy should be obtained
before steroid treatment in suspected lymphoma, as steroid-
induced tumour lysis can be dramatic. The resolution of large
masses within days of treatment is diagnostic of lymphoma.
Such rapid tumour lysis can lead to acute urate nephropathy.
Hence, if steroids are to be used, renal protection should be
considered and diuresis encouraged with oral or intravenous
fluids. The administration of oral allopurinol 300e600 mg
daily also helps in this situation; the first dose to be given 1e2
hours before the first dose of steroids. An effective steroid
regime is oral dexamethasone 4 mg four times daily, tapered
down after a few days according to response (and dis-
continuing if no response is observed, or if the biopsy result
excludes lymphoma).
A diagnosis of lymphoma will require further imaging for
staging, and referral to the appropriate haemato-oncology MDT.
The management of anaplastic cancer will depend on the pa-
tient’s performance status and require discussion at the thyroid
MDT. Further investigation requires staging with CT thorax,
abdomen and pelvis. More recently identification of patients with
wild KRAS mutations can aid in decision making for patients
responding to chemotherapy.17 Treatment may comprise a
combination of surgery, radical external beam radiotherapy and/
or chemotherapy. The prognosis is, however, generally very
poor. Patients who have undergone molecular testing and have
tumours positive for the BRAF V600E mutation are now
considered for treatment with BRAF inhibitors such as dabrafe-
nib and MEK inhibitor trametinib. Although experience is
limited, initial results are encouraging.17
The lateral neck node e A palpable lateral compartment
lymph node often represents non-thyroidal pathology such as
lymphadenopathy secondary to pathology elsewhere in the head
and neck region, or systemic illness. However, this is also an
occasional presentation of thyroid cancer, where the primary
thyroid lesion is small and non-palpable. Cystic degeneration of
such metastatic nodes is characteristic of papillary thyroid can-
cer. The finding of a cystic mass in the lateral neck, especially in
a young patient, should therefore raise the suspicion of papillary
cancer. A full head and neck examination, and an examination of
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 ENDOCRINE SURGERY
Figure 2 CT scan of the lower neck, demonstrating a large right thyroid
mass. Tissue planes between the mass and the trachea, oesophagus
and pre-vertebral fascia are indistinct, implying locally advanced ma-
lignancy. Patient’s history suggests development of this lesion over 4
weeks.
other lymph nodes (axilla, groin) and abdomen (splenomegaly)
should be undertaken, to exclude other pathology.
Investigation with ultrasound þ FNAC/core biopsy of the
index lymph node is usually diagnostic.
The toxic solitary nodule
In this situation, clinical assessment indicates a solitary (or
dominant) thyroid mass and the patient is thyrotoxic (confirmed
by a suppressed serum TSH and raised serum free T4 and/or T3).
Here, the probability of malignancy is much lower, and the
main question is whether or not the palpable lesion is the (sole)
source of the thyrotoxicosis.
The most likely diagnosis is a toxic hyperplastic nodule or
toxic follicular adenoma. Other possibilities include a dominant
nodule within a toxic multi-nodular goitre, or auto-immune
thyroiditis, e.g. Graves’ disease, with a co-incidental nodule.
For diagnosis, a combination of thyroid scintigraphy and ul-
trasound are most useful, while, if Graves’ disease is suspected,
testing for anti-TSH receptor antibodies (TRab) is usually diag-
nostic. FNAC is not advised in the setting of a toxic nodule since
it is likely to yield a Thy3f result and not only cause patient
anxiety, but also adds little to guide management.
Scintigraphy involves the administration of a tracer dose of a
radio-isotope taken up by thyroid tissue and subsequent imaging
of the neck using a gamma camera. The radio-isotope is
commonly technetium-99m pertechnetate, or radio-iodine (123I).
In patients where ultrasound shows a solitary (or dominant)
nodule without overt malignant features, and scintigraphy shows
intense uptake in the nodule with suppression of the remaining
thyroid (Figure 3), the diagnosis of a toxic hyperplastic nodule or
adenoma is secure.
Where ultrasound shows benign features (U2) in the index
nodule, and isotope uptake is diffusely increased, diagnosis of
a toxic multi-nodular goitre or Graves’ disease, with a co-
incidental benign nodule, may also be made without
recourse to FNAC.
Where the nodule does not take up the radio-isotope (a ‘cold’
nodule), ultrasound should be used to determine the need for
FNAC, exactly as for the euthyroid nodule. The risk of
SURGERY 38:12
Figure 3 Thyroid scintigraphy using Technetium-99m pertechnetate.
Gamma camera image in the anteroeposterior plane, showing intense
isotope uptake in a left thyroid nodule, with suppression of uptake in
the remaining thyroid, diagnostic of a toxic solitary thyroid nodule.
Patient was subsequently treated with left thyroid lobectomy, with
resolution of thyrotoxicosis.
malignancy is slightly higher within cold nodules compared with
those which take up radio-isotope.18 However, many benign le-
sions, such as simple cysts and degenerate nodules, may be cold
on scintigraphy. Management of the thyroid nodule will then
depend upon the outcome of FNAC, as described above.
The need for surgical treatment will depend upon the results
of the above investigations, patient preference and nodule size,
but the initial aim is adequate control of thyroid function by
administration of oral anti-thyroid drugs.
Anti-thyroid drugs, such as carbimazole or propylthiouracil
are recommended, in order to reduce T3/T4 levels to within the
normal reference range. This is essential prior to any invasive
treatment, including surgery, or radio-iodine therapy, in order to
avoid the risk of precipitating a thyrotoxic crisis. For toxic nod-
ules, doses can be titrated to response, with most patients
adequately controlled on oral carbimazole, 5e20 mg daily or
propylthiouracil 50e200 mg daily. Higher doses may be required
in patients with auto-immune thyrotoxicosis. A rare risk of anti-
thyroid drugs is agranulocytosis, and patients should be warned
of the need for an urgent full blood count in case of pyrexial
illness or sore throat (and to stop anti-thyroid drugs if this shows
neutropenia).
Thyrotoxic symptoms can also be controlled with beta-
blockers. Propranolol is favoured, as not only does it manage
sympathetic symptoms such as tremor and tachycardia, but it
also inhibits the conversion of T4 to the more active T3. An oral
dose of 10e40 mg daily will usually be adequate for toxic ade-
noma, although in Graves’ disease doses up to 160 mg daily may
be necessary.
In toxic adenoma and toxic multi-nodular goitre, spontaneous
remission of thyrotoxicosis is not anticipated, hence definitive
791 Ó 2020 Published by Elsevier Ltd.
 ENDOCRINE SURGERY
therapy with either surgery or therapeutic radio-iodine is usually
necessary, allowing for competing comorbidities. If surgery is
favoured, for a solitary toxic adenoma an ipsi-lateral thyroid lo-
bectomy will both remove the lump and achieve a cure of the
thyrotoxicosis. However, where the nodule is part of a toxic
multi-nodular goitre, total thyroidectomy will be necessary to
guarantee a cure of thyrotoxicosis. It should be noted that
enthusiasm has waned for subtotal thyroidectomy in the setting
of toxic multi-nodular goitre and Graves’ disease because of the
risk of recurrence and the attendant risks of re-operative surgery
and this is reflected in the NICE guidelines.10
Thyroid ‘incidentaloma’
Given the high prevalence of thyroid nodules in the normal
population, it is not surprising that thyroid lumps are frequently
seen as a coincidental pathology on imaging performed for non-
thyroid disease. The liberal use of ultrasound, in particular, has
led to a large increase over recent years in the incidence of thy-
roid nodules undergoing investigation, and possibly also in the
detection of small thyroid cancers of uncertain biological signif-
icance (papillary micro-carcinoma).19
Where ultrasound was the original imaging modality,
comment may already have been made on the likely nature of the
thyroid pathology. However, thyroid function tests should still be
performed. Repeat ultrasound  FNAC may also be necessary if
findings were equivocal on the initial scan or if this scan had not
been performed by an operator suitably skilled at interpretation
of thyroid ultrasound.
Positron-emission computed tomography (PET-CT, usually
with fluoro-deoxyglucose (FDG) as the tracer) is now frequently
performed to stage cancers and in immunological or rheumato-
logical conditions. It is common to observe incidental ‘hot-spots’
within the thyroid. Again, it is essential to assess thyroid function
status, as some lesions represent toxic adenomas. The thyroid
uptake on PET scans (hot-spots) may be diffuse (frequently seen
with benign disease, such as auto-immune thyroiditis or multi-
nodular goitre) or focal e (where the risk of malignancy, usu-
ally papillary thyroid cancer, is more significant and as high as
40%).20
The need for further investigation should be considered in
light of the patient’s comorbidities, including the stage and likely
prognosis of the disease for which PET-CT was requested. Many
incidental, PET-detected papillary cancers are small, slow-
growing lesions, and may not require investigation in a patient
with disseminated cancer or advanced frailty. If investigation is
deemed necessary, ultrasound  FNAC, as for the euthyroid
solitary nodule should be used. The interpretation of results
should bear in mind the probable increased underlying risk of
cancer in PET-positive lesions.
Chest X-ray or thoracic CT frequently detect retrosternal thy-
roid nodules/masses. Most are benign. Clinical assessment
should include assessment of thyroid function and compressive
symptoms. In the absence of clinical or radiological features to
suggest significant compression or malignancy, further investi-
gation may not be necessary. Conversely, a patient with dysp-
noea and tracheal narrowing of >35% on CT scanning may
derive significant benefit from thyroidectomy.21
SURGERY 38:12
Surgery for the thyroid nodule
Surgery may be necessary for diagnostic purposes, as outlined
above, or as definitive therapy for thyrotoxicosis or primary
thyroid malignancy.
In all cases, thyroid function should be assessed pre-
operatively, and any dysfunction corrected. Assessment of
vocal cord function by fibre-optic laryngoscopy should take place
if there is a history of voice change, evidence on imaging of
locally advanced cancer, or for re-operative surgery.
Preoperative counselling should include discussion of the
risks of surgery, including bleeding, voice change and swallow-
ing problems, and in the case of bilateral surgery, hypocalcaemia
and levo-thyroxine replacement.
Surgery should be performed by an appropriately trained
surgeon, and outcomes should ideally be entered into the rele-
vant national registry.
For diagnostic purposes, surgery should comprise a total ipsi-
lateral resection of the affected thyroid lobe and the isthmus,
preserving the recurrent laryngeal nerve and parathyroid glands.
Simple excision of the nodule or sub-total lobar resection should
be avoided, as there is a risk of breaching the tumour capsule;
also, subsequent completion thyroidectomy, if indicated, will be
made more hazardous, as it would require re-operation in a
previously dissected central compartment of the neck.
As mentioned above, if bilateral surgery is required (e.g. in
nodules which are part of toxic multinodular goitre), total thy-
roidectomy is favoured over traditional subtotal resections.4 A
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