Thyroid nodule

Case presentation
An otherwise healthy 23-year-old female medical
student presents with an asymptomatic neck
mass that was found during a practice head and
neck examination performed by a fellow medical
student.
Physical exam reveals a 3-cm non-tender, firm
mass in the inferior pole of the right thyroid lobe.
The remaining physical exam is normal. She
denies symptoms of hyper- or hypothyroidism and
has no exposure to ionizing radiation. There is no
family history of thyroid disease nor other
endocrinopathies. Serum TSH and T4 levels are
normal.

Questions
What is your next step in management?
What is the most likely diagnosis?
What are the treatment options based on
pathology?

Summary:
A 23-year-old woman presents with an asymptomatic
thyroid mass who is clinically euthyroid without
concerning personal or family history.
Next step: Ultrasound of the thyroid with fine needle
aspiration biopsy of the nodule for cytologic
assessment
Most likely diagnosis: Despite the absence of risk
factors, the non-tender firm mass is consistent with
thyroid carcinoma.
Treatment options: Treatment of thyroid carcinoma
generally consists of thyroidectomy with lymph node
dissection when cervical lymph nodes are involved.
Adjunct therapies are based on the type of carcinoma
and extent of disease.

Objectives
1. Understand the basic approach to evaluation of a
solitary thyroid nodule.
2. Review the diagnostic evaluation and surgical
indications for patients with thyroid nodules.
3. Identify the treatment plan for thyroid nodules
based on FNA cytology.

Considerations
This is a 23-year-old healthy and asymptomatic
woman with a 3-cm nontender mass of the thyroid.
The patient should be questioned carefully about
symptoms such as possible compression on the
trachea or esophagus, or possible symptoms of
hyperthyroidism or pheochromocytoma.
A prior history of head or neck radiation is very
important since the risk of thyroid cancer is much
higher with this history.
A careful family history should be obtained about
thyroid disease but also other cancers, especially
those within MEN II A and B.

Considerations
On physical exam, the mass should be palpated
for location, tenderness, texture, and movement
with the thyroid gland during swallowing. Lymph
nodes should be palpated.
An ultrasound exam of the mass and an FNA
biopsy are reasonable to assess for the possibility
of thyroid carcinoma.

DEFINITIONS
PAPILLARY THYROID CARCINOMA: The most common
type of thyroid carcinoma, usually well-differentiated
and with a favorable prognosis.
FOLLICULAR ADENOMA: Benign thyroid nodules,
which are fairly common in adults. They cannot be
differentiated from follicular carcinoma by fine-needle
aspiration (FNA) due to lack of architecture and
inability to confirm invasion.
MEDULLARY THYROID CARCINOMA (MTC): A more
aggressive type of thyroid cancer which arises from
parafollicular c-cells. It may occur sporadically or in
associated familial clusters such as MEN2.

DEFINITIONS
ANAPLASTIC THYROID CARCINOMA: An extremely aggressive type of
de-differentiated thyroid cancer which has a preponderance for local
invasion. Prognosis is dismal and treatment of is palliative and
multimodal.
CENTRAL NECK DISSECTION: A functional lymph node dissection of
the anterior neck that is bordered laterally by the carotid arteries,
superiorly by the hyoid bone, and inferiorly by the suprasternal
notch. The benefits of routine prophylactic central lymph node
dissection in patients with papillary and follicular thyroid cancers are
controversial.
MULTIPLE ENDOCRINE NEOPLASIA 2A (MEN 2A): An autosomal
dominant genetic syndrome that includes medullary thyroid
carcinoma, pheochromocytoma, and parathyroid hyperplasia.
MULTIPLE ENDOCRINE NEOPLASIA 2B (MEN 2B): An autosomal
dominant genetic syndrome that includes medullary thyroid
carcinoma, pheochromocytoma, marfanoid habitus, and mucosal
neuromas.

CLINICAL APPROACH
The prevalence of thyroid nodules and thyroid
carcinoma is on the rise due to increased diagnoses,
mainly because of advancements in imaging
technology.
Thyroid nodules larger than 1 cm are considered
clinically significant and require further evaluation.
A patient with a thyroid nodule should be questioned
about symptoms of hyper- or hypothyroidism,
compressive symptoms such as dyspnea, coughing,
or choking spells, dysphagia or hoarseness, and a
prior history of head or neck irradiation.
Patients should also be asked about a family history
of thyroid cancer, hyperparathyroidism, or
pheochromocytoma.

CLINICAL APPROACH
Symptoms of hyper- or hypothyroidism may be present in patients
with thyroiditis. Symptoms of hyperthyroidism are also seen in
patients with benign functioning follicular adenomas.
TSH is the single most useful test in the workup for thyroid function,
and thyroid uptake scans now have limited utility except in the
hyperthyroid patient.
Compressive symptoms, which occur from thyroid enlargement and
impingement on adjacent structures (trachea, esophagus, and
recurrent laryngeal nerve) are indications for surgery.
A patient with a solitary thyroid nodule and a prior history of lowdose head or neck irradiation has a 40% risk of carcinoma.
A family history of thyroid cancer should increase the physicians
suspicion of carcinoma in a patient with a thyroid nodule.
An estimated 20% to 30% of medullary thyroid cancers occur as
part of a familial syndrome, most notably MEN 2A and MEN 2B
(Table 44 1). Twenty-five percent of medullary thyroid cancers are
familial cancers with the remainder being sporadic.

Multiple endocrine
neoplasia 2A

Medullary thyroid cancer

Pheochromocytoma
Hyperparathyroidism
Lichen planus amyloidosis
Hirschsprung disease

Multiple endocrine
neoplasia 2B

Medullary thyroid cancer

Pheochromocytoma
Marfanoid habitus
Mucosal neuromas
Ganglioneuromatosis of the gastrointestinal tract

CLINICAL APPROACH
On physical examination, the size and character of
the thyroid nodule should be noted.
The thyroid gland should be examined for other
nodules, and the neck evaluated for associated
cervical lymphadenopathy.
The presence of associated adenopathy should
increase suspicion of malignancy.

Management
The primary challenge in the management of a
thyroid nodule is selecting patients with a high
risk of cancer for surgery while avoiding
operations in patients with benign disease who
would not benefit from surgery.
Ultrasound is an important adjunct in the workup
and management of thyroid nodules.

Ultrasound
Nodule characteristics seen by thyroid ultrasound
are useful in determining risk of carcinoma and to
guide the use of fine needle aspiration biopsy
(FNAB).
Historically, nuclear scintigraphy (thyroid uptake
scan) was a standard part of the workup of thyroid
nodules looking for cold versus hot nodules to
assess malignancy risk.
With the increased access and improved
resolution of thyroid ultrasound, thyroid uptake
scans are reserved for patients with thyroid
nodules and hyperthyroidism to differentiate a
hyperfunctioning nodule from diffuse toxic goiter.

FNAB
Currently, FNAB (FNAC) is the initial and most
important step in the diagnostic evaluation of a
dominant thyroid nodule.
Thyroidectomy is reserved for patients with
progressive nodule enlargement, compressive
symptoms, or a malignant FNAB.
A cytologic diagnosis of malignancy is very
reliable with only a 1% to 2% incidence of falsepositive results. Patients with benign FNAB results
are followed with a yearly physical examination of
the neck and a serum TSH-level test.
The incidence of false-negative FNAB results is
approximately 2% to 5%.

FNAB
A cellular FNAB result refers to a specimen with
cytologic features consistent with either a follicular
or a Hrthle cell neoplasm.
A follicular or Hrthle cell carcinoma cannot be
distinguished from a follicular or Hrthle cell
adenoma using cytologic criteria alone. Diagnosis
of carcinoma is based on the presence of capsular
or vascular invasion as observed in a tissue sample.
Diagnostic thyroid lobectomy is recommended for
patients with a cellular FNAB because of the 20% to
30% incidence of carcinoma.
If pathology returns as invasive carcinoma,
completion thyroidectomy should be performed.

FNAB
In patients with non-diagnostic FNAB results, the
biopsy should be repeated because an adequate
specimen is obtained with a repeated biopsy in
more than 50% of patients.
Surgery is recommended for patients with a
second non-diagnostic FNAB. A 9% incidence of
carcinoma has been reported in the subset of
patients with a persistently non-diagnostic FNAB
results and a hypofunctioning nodule.

Surgery
Patients with FNA proven thyroid cancers are ideally
treated by surgery consisting of total thyroidectomy.
The benefits of prophylactic central lymph node
dissection remains controversial in papillary and
follicular carcinomas because of the marginal
benefits and the high-rate of temporary and
permanent hypoparathyoidism associated with the
procedure.
Postoperative radioactive iodine ablation (RAI) is
recommended for patients with large primary
cancers, metastatic disease, and cancer extension
outside of the thyroid gland.

Surgery
Patients with medullary thyroid carcinoma should
be screened for MEN2 prior to thyroid surgery, and
if a pheochromocytoma is present, it should be
treated before the thyroid procedure.
A central lymph node dissection is indicated at the
time of surgery due to the more aggressive
medullary thyroid carcinoma and ineffectiveness of
RAI.
The prognosis of anaplastic thyroid carcinoma is
dismal and involves multimodality palliative
treatment with a mean survival of less than 6
months.

Review questions
1. A 38-year-old woman is noted to have a 1.2 cm
thyroid nodule. In which of the following
situations would the results of thyroid
scintigraphy most likely impact treatment?
. A. Fine-needle aspiration biopsy (FNAB) results
consistent with a malignant neoplasm
. B. FNAB results consistent with a benign
neoplasm
. C. FNAB results consistent with a follicular
neoplasm
. D. Prior history of head or neck irradiation
. E. FNAB demonstrating non-diagnostic result

1. C. Radionuclide scanning can determine the

function of the nodule. With a fine-needle
aspirate showing a follicular pattern, a cold
hypofunctioning pattern is associated with a
significant risk of cancer (20%-35%), whereas a
warm or hot functioning pattern is associated
with a low (1%) risk of cancer.

Review questions
2. A 40-year-old woman presents with a single
thyroid nodule. Which of the following situations
would be associated with the highest risk of
malignancy?
. A. A prior history of head or neck irradiation
. B. Hyperfunction of the nodule seen on thyroid
scintigraphy
. C. Hypofunctioning of the nodule seen on
scintigraphy (cold nodule)
. D. History of Graves disease
. E. The presence of a dominant nodule within a
goiter.

2. A. A history of head and neck irradiation greatly

increases the risk of a thyroid nodule being
malignant. A cold nonfunctioning nodule
increases the risk of cancer, but not as
significantly as the history of irradiation.
Dominant nodules arising from a goiter do not
have an increased risk of being cancerous;
however, a clinical diagnosis based on the
physical examination can be difficult because of
the background abnormality.

Review questions
3. A 55-year-old man is noted to have a 1.4-cm
nodule in the right thyroid lobe. For which of the
following situations is thyroidectomy the best
treatment option?
. A. Initial nondiagnostic FNAB results
. B. Hypothyroidism
. C. A mother who had papillary carcinoma
. D. FNAB results consistent with a benign
neoplasm when compressive symptoms are
present
. E. Patient has underlying hyperplastic thyroid
disease (goiter).

3. D. Compressive symptoms can become life

threatening; therefore, urgent surgical
intervention is considered the best therapy.

Review questions
4. Which of the following procedures should be
performed routinely in a patient with a thyroid
nodule who is clinically euthyroid?
. A. FNAB and determination of a screening serum
TSH level
. B. Measurement of radioiodine uptake and thyroid
scintiscanning
. C. Measure of serum T4, triiodothyronine (T3), and
TSH levels
. D. Ultrasound examination of the thyroid gland to
distinguish a solid from a cystic nodule
. E. Thyroid scintigraphy 44.5 A 60-year-old man is
noted to have.

4. A. FNAB and a TSH level test for the assessment

of thyroid function and determination of the
histology of the lesion are the two most
important initial tests for evaluating a thyroid
nodule.

Review questions
5. A 60-year-old man is noted to have a 2-cm nodule in the
right lobe of the thyroid. He is asymptomatic, and FNAB
has been attempted on three separate occasions
demonstrating nondiagnostic findings. Ultrasound has
shown a solid thyroid nodule without other abnormalities,
and iodine-123 scintigraphy has revealed a nonfunctioning
nodule. Which of the following management approaches is
most appropriate?
. A. Place patient on suppressive dose of levothyroxine and
repeat FNA in 3 months
. B. Right thyroidectomy
. C. Place patient on suppressive dose of levothyroxine and
repeat ultrasound in 3 months
. D. Total thyroidectomy with central neck dissection
. E. Ethanol injection of the nodule under ultrasound
guidance

 B. Right thyroidectomy or total thyroidectomy are

appropriate options for this patient because an
overall cancer rate of 9% has been reported for
this population. Thyroxine suppression would not
change the fact that this is a nonfunctioning
nodule. Ethanol injection is a reasonable option
for the ablation of recurrent, benign thyroid cysts.
However, this is not an appropriate treatment for
a nodule of unknown significance.

6. A 52-year-old woman with a history of asymptomatic

carotid stenosis undergoes follow-up ultrasound of
the neck that revealed stable stenosis of the carotid
and an incidental finding of several solid and fluidfilled nodules seen in both lobes of the thyroid gland.
The largest of these nodules measure 0.3 cm in
diameter. Her serum TSH is within the normal range.
Which of the following is the most appropriate
management for this patient?
. A. Total thyroidectomy
. B. I131-radioablation of the thyroid
. C. Observation
. D. Placement on suppressive dose of levothyroxine
. E. Aspiration of the fluid-filled nodules

6. C. Thyroid nodules less than 1 cm in diameter

are common findings in women, and most of
these are of no clinical consequences, do not
progress, and have low probability of being
malignant. The probability of cancer in this
patient is further reduced because there are
multiple nodules seen. Observation with repeat
ultrasound is generally appropriate for these
patients.

CLINICAL PEARLS
FNAB is the initial and most important step in the
diagnostic evaluation of a dominant thyroid nodule
and guides subsequent management
The role of thyroid uptake scans has been replaced
by ultrasound but may be useful in the setting of
thyroid nodules in the hyperthyroid patient.
A patient with a prior history of neck irradiation or a
family history consistent with MEN syndromes has a
high risk of thyroid cancer.
Indications for surgical removal are compressive
symptoms, functioning nodules, or suspicion of
malignancy (history, size, growth, ultrasound
characteristics, FNA findings)

CLINICAL PEARLS
Papillary and follicular thyroid carcinomas are
treated with total thyroidectomy with
postoperative RAI in high-risk patients.
Prophylactic central neck dissection is
controversial.
Initial treatment of a follicular neoplasm is a
diagnostic thyroid lobectomy to look for invasive
carcinoma which cannot be determined by FNA
biopsy.
Medullary thyroid carcinoma is associated with
familial genetic syndromes in 25% of cases.
MEN2 or pheochromocytoma should be assessed
prior to thyroidectomy in patients with MTC.