2015 American Thyroid Association

Management Guidelines for Adult

Patients with Thyroid Nodules and
Differentiated Thyroid Cancer
Source : American Thyroid Association
Volume : 26( 1)
Published in : 2016,January.
 Authors

 Bryan R. Haugen  Schlumberger

 Erik K. Alexander Keith
 Gerard M. Doherty
 Susan J. Mandel
 Yuri E. Nikiforov
 Furio Pacini
 Gregory W. Randolph
 Anna M. Sawka Martin
 Kathryn G. Schuff
 Steven I. Sherman
 Julie Ann Sosa
 David L. Steward
 R. Michael Tuttle
 LeonardWartofsky
 Introduction
Thyroid nodule :
 A discrete lesion within the thyroid gland
 Radiologically distinct from the surrounding
thyroid parenchyma.
 May be palpable or non palpable
 Prevalence of palpable thyroid nodules :5% in
women and 1% in men living in iodine-
sufficient parts of the world .
 Introduction

 Non-palpable nodules detected on USG or

other anatomic imaging studies are termed
incidentally discovered nodules or
‘‘incidentalomas.’’
 Introduction (cont..)
 High-resolution USG can detect thyroid
nodules in 19%–68% of randomly selected
individuals, with higher frequencies in women
and the elderly.

 Non-palpable nodules have the same risk of

malignancy as do sonographically confirmed
palpable nodules of the same size.
 Introduction (cont..)
 By 2019, one study predicts that papillary
thyroid cancer will become the third most
common cancer in women at a cost of 19-21
billion dollars in the U.S.
 The clinical importance of thyroid
nodules rests with the need to exclude
thyroid cancer, which occurs in 7%–15% of
cases depending on age, sex, radiation
exposure history, family history, and other
factors.
 Introduction (cont..)
• Generally, only nodules >1cm should be
evaluated, since they have a greater potential
to be clinically significant cancers.

• Occasionally, there may be nodules <1cm that

require further evaluation because of clinical
symptoms or associated lymphadenopathy.
 Introduction (cont..)

With the discovery of a thyroid nodule,

complete history and physical examination
focusing on the thyroid gland and adjacent
cervical lymph nodes should be performed.
 Introduction (cont..)
Pertinent historical factors predicting
malignancy include:
– a history of childhood head and neck
irradiation,
– total body irradiation for bone marrow
transplantation
– exposure to ionizing radiation from fallout
in childhood or adolescence
 Introduction (cont..)

– familial thyroid carcinoma, or thyroid cancer

syndrome in a first-degree relative,
– rapid nodule growth and/or hoarseness.
 Introduction (cont..)
Pertinent physical findings suggesting possible
malignancy include
– vocal cord paralysis,
– cervical lymphadenopathy, and
– fixation of the nodule to surrounding
tissues.
 Purpose

To inform clinicians, patients, researchers, and

health policy makers about the best available
evidence (and its limitations), relating to the
diagnosis and treatment of adult patients with
thyroid nodules.
 Method
• A task force chair of specialists with complementary
expertise (endocrinology, surgery, nuclear medicine,
radiology, pathology, oncology, molecular diagnostics,
and epidemiology) was appointed by the ATA
President with approval of the Board.

• Upon discussion among the panel members and the

Chair with other Chairs of other ATA guideline
committees, the American College of Physicians’ (ACP)
Grading System was adopted
RECOMMENDATIONS
What is the appropriate laboratory and
imaging evaluation for patients with
clinically or incidentally discovered thyroid
nodules?
 Serum thyrotropin measurement ( TSH )

Recommendation
 Serum thyrotropin (TSH) should be measured
during the initial evaluation of a patient with a
thyroid nodule.
 If the serum TSH is subnormal, a radionuclide
(preferably 123I thyroid scan should be
performed.
(Strong recommendation, Moderate-quality
evidence)
Serum thyrotropin measurement(TSH) ( CONT..)

 If the serum TSH is normal or elevated, a

radionuclide scan should not be performed as
the initial imaging evaluation.
(Strong recommendation, Moderate-quality
evidence)
 Serum thyrotropin measurement ( TSH) ( CONT.. )

• A higher serum TSH level, even within the

upper part of the reference range, is
associated with increased risk of malignancy
in a thyroid nodule, as well as more advanced
stage thyroid cancer
 Serum thyrotropin measurement ( TSH) ( CONT.. )

• If TSH low, risk of malignancy depends

on radio uptake scan:
– Tracer uptake : hyperfunctioning
“hot” nodule- rarely harbor malignancy,
no cytologic evaluation is necessary.
– Tracer uptake is equal to the surrounding
thyroid isofunctioning “warm” nodule
– Uptake : nonfunctioning
“cold”nodule
 Thyroid sonography

Recommendation
Thyroid sonography with survey of the cervical
lymph nodes should be performed in all
patients with known or suspected thyroid
nodules.
(Strong recommendation, High-quality
evidence)
 Thyroid sonography (cont…)

Thyroid US can answer the following:

– Is there truly a nodule?
– How large is the nodule?
– What is the nodule’s pattern of ultrasound
imaging characteristics?
 Thyroid sonography (cont…)

– Is suspicious cervical lymphadenopathy

present?
– Is the nodule greater than 50% cystic?
– Is the nodule located posteriorly in
the thyroid gland?
 Thyroid sonography (cont…)
• Sonography features that are associated with thyroid
cancer include:
– microcalcifications,
– nodule hypoechogenicity compared with the
surrounding thyroid or strap muscles,
– irregular margins (defined as either infiltrative,
microlobulated or spiculated), and
– A shape taller than wide measured on a transverse
view.
Sonographic patterns, estimated risk of malignancy, and fine-needle
aspiration guidance for thyroid nodules
Sonograp US features Estimat FNA size
hic ed risk cutoff
pattern of (largest
malign dimension)
ancy %
High Solid hypoechoic nodule or >70–90 Recommend
suspicion solid hypoechoic component FNA at
of a partially cystic ≥1 cm
nodule with one or more of
the following features:
a)Irregular margins
(infiltrative, microlobulated),
b)Microcalcifications,
c)Taller than wide shape,
 d)Rim
calcifications with
small extrusive
soft tissue
component,
e)Evidence
of ETE
Intermed Hypoechoic solid 10–20 Recommend
iate nodule with smooth FNA at ≥1 cm
suspicion margins without mic
rocalcifications, ETE,
or taller than wide
shape
Low Isoechoic or 5–10 Recommend
suspicion hyperechoic solid FNA at
nodule, or partially ≥1.5 cm
cystic nodule with
eccentric solid
areas, without micr
ocalcification,
irregular margin or
ETE, or taller than
wide shape.
Very low Spongiform or <3 Consider
suspicion partially cystic FNA at
nodules without any ≥2 cm
of the sonographic Observation
features described in without FNA
low, intermediate, or is also a
high suspicion reasonable
patterns option

b
Benign Purely cystic nodules <1 No biopsy
(no solid component)
 Serum thyroglobulin (Tg)

Recommendation
Routine measurement of serum thyroglobulin
(Tg) for initial evaluation of thyroid nodules is
not recommended.
(Strong recommendation, Moderate-quality
evidence)
 Serum calcitonin measurement

Recommendation :
The panel cannot recommend either for or
against routine measurement of serum
calcitonin in patients with thyroid nodules.
(No recommendation, Insufficient
evidence)
 FNAC

Recommendation

FNA is the procedure of choice in the evaluation

of thyroid nodules, when clinically indicated.

(Strong recommendation, High-quality

evidence)
 Recommendation for Diagnostic FNA of a thyroid
nodule based on sonographic pattern

Recommendation

1.Thyroid nodule diagnostic FNA

is recommended for :
(A)Nodules ≥1cm in greatest dimension with
high suspicion sonographic pattern.

(Strong recommendation, Moderate quality

evidence)
 Recommendation for Diagnostic FNA of a thyroid
nodule based on sonographic pattern

B)Nodules ≥1cm in greatest dimension with

intermediate suspicion sonographic pattern.
(Strong recommendation, Low-quality evidence)
C)Nodules ≥1.5cm in greatest dimension with
low suspicion sonographic pattern.
(Weak recommendation, Low-quality evidence)
 Recommendation for Diagnostic FNA of a thyroid
nodule based on sonographic pattern

2) Thyroid nodule diagnostic FNA may be

considered for:
(D) Nodules ≥2cm in greatest dimension with
very low suspicion sonographic pattern (e.g.,
spongiform). Observation without FNA
is also a reasonable option.
(Weak recommendation, Moderate-quality
evidence)
 Recommendation for Diagnostic FNA of a thyroid
nodule based on sonographic pattern

3) Thyroid nodule diagnostic FNA is not required

for :
(E)Nodules that do not meet the above
criteria.
(F) Nodules that are purely cystic.
(Strong recommendation, Moderate-quality
evidence)
Thyroid nodule FNA cytology should be
reported using diagnostic groups outlined in
the:
Bethesda System for Reporting Thyroid
Cytopathology
 Nondiagnostic cytology

Recommendation
(A) For a nodule with an initial nondiagnostic
cytology result, FNA should be repeated with
US guidance and, if available, on-site cytologic
evaluation
(Strong recommendation, Moderate-quality
evidence)
 Nondiagnostic cytology

(B) Repeatedly nondiagnostic nodules without a

high suspicion sonographic pattern require
close observation or surgical excision for
histopathologic diagnosis
(Weak recommendation, Low-quality evidence)
 Nondiagnostic cytology

Recommendation
(C) Surgery should be considered for
histopathologic diagnosis if the cytologically
nondiagnostic nodule has a high suspicion
sonographic pattern, growth of the nodule
(>20% in two dimensions) is detected during
US surveillance, or clinical risk factors for
malignancy are present
(Weak recommendation, Low-quality evidence)
 Benign cytology

Recommendation
If the nodule is benign on cytology, further
immediate diagnostic studies or treatment are
not required

(Strong recommendation, High-quality evidence)

 Malignant cytology

Recommendation
If a cytology result is diagnostic for primary
thyroid malignancy, surgery is generally
recommended.
(Strong recommendation, Moderate-quality
evidence
An alternative active surveillance management
approach can be considered in:
 patients with very low risk tumors
 patients at high surgical risk because of co-
morbid conditions,
 patients expected to have a relatively short
remaining life span
 Patients with concurrent medical or surgical
issues that need to be addressed prior to
thyroid surgery.
 Indeterminate cytology
(AUS/FLUS, FN, SUSP)

What are the principles of the molecular

testing of FNA samples?
Recommendation
If molecular testing is being considered, patients
should be counseled regarding the potential
benefits and limitations of testing and about the
possible uncertainties in the therapeutic and
long-term clinical implications of results.
(Strong recommendation,Low-quality evidence)
Recommendation
If intended for clinical use, molecular testing
should be performed in Clinical Laboratory
Improvement Amendments/College of American
Pathologists (CLIA/CAP)-certified molecular
laboratories, or the international equivalent
because reported quality assurance practices
may be superior compared to other settings.
(Strong recommendation, Low-quality evidence)
 AUS/FLUS cytology

Recommendation
(A) For nodules with AUS/FLUS cytology, after
consideration of worrisome clinical &
sonographic features, investigations such as
repeat FNA/molecular testing may be used to
supplement malignancy risk assessment in lieu
of proceeding directly with a strategy of either
surveillance or diagnostic surgery. Informed
patient preference & feasibility should be
considered in clinical decision-making.
(Weak recommendation, Moderate-quality
 AUS/FLUS cytology

(B) If repeat FNA cytology, molecular testing, or

both are not performed or inconclusive, either
surveillance or diagnostic surgical excision
may be performed for an AUS/ FLUS thyroid
nodule, depending on clinical risk factors,
sonographic pattern, and patient preference.

(Strong recommendation, Low-quality evidence)

Follicular neoplasm/suspicious for follicular neoplasm
cytology

Recommendation
(A) Diagnostic surgical excision is the long-established
standard of care for the management of FN/SFN
cytology nodules. However, after consideration of
clinical and sonographic features, molecular testing
may be used to supplement malignancy risk
assessment data in lieu of proceeding directly with
surgery. Informed patient preference and feasibility
should be considered in clinical decision-making.
(Weak recommendation, Moderate-quality
evidence)
 Follicular neoplasm/suspicious for follicular
neoplasm cytology

(B) If molecular testing is either not performed

or inconclusive, surgical excision may be
considered for removal and definitive diagnosis
of an FN/SFN thyroid nodule.
(Strong recommendation, Low-quality
evidence)
 Suspicious for malignancy cytology
Recommendation

If the cytology is reported as suspicious for

papillary carcinoma (SUSP), surgical
management should be similar to that of
malignant cytology, depending on clinical
risk factors, sonographic features, patient
preference, and possibly results of
mutational testing (if performed).
(Strong recommendation, Low-quality evidence)
 What is the utility of 18FDG-PET scanning to
predict malignant or benign disease when FNA
cytology is indeterminate (AUS/FLUS, FN, SUSP)?
 18 FDG-PET scan
Recommendation

18FDG-PET imaging is not routinely

recommended for the evaluation of thyroid
nodules with indeterminate cytology.

(Weak recommendation, Moderate-quality evidence)

 18 FDG-PET scan

Recommendation
 Focal [18 F]fluorodeoxyglucose emission
tomography
positron (18FDG-PET) uptake within a
sonographically confirmed thyroid nodule conveys an
increased risk of thyroid cancer, and FNA is
recommended for those nodules ≥ 1cm.
(Strong recommendation, Moderate-quality evidence)
 18 FDG-PET scan

 Diffuse 18FDG-PET uptake, in conjunction

with sonographic and clinical evidence of
chronic lymphocytic thyroiditis, does not
require further imaging or FNA.
(Strong recommendation, Moderate-qualityevidence)
What is the appropriate operation for
cytologically indeterminate thyroid
nodules?
Recommendation
When surgery is considered for patients with a
solitary, cytologically indeterminate nodule,
thyroid lobectomy is the recommended initial
surgical approach. This approach may be
modified based on clinical or sonographic
characteristics, patient preference, and/or
molecular testing when performed

(Strong recommendation, Moderate-quality evidence)

Recommendation
Because of increased risk for malignancy, total
thyroidectomy may be preferred in patients with
indeterminate nodules that are cytologically
suspicious for malignancy, positive for known
mutations specific for carcinoma, sonographically
suspicious, or large (>4cm), or in patients with
familial thyroid carcinoma or history of radiation
exposure, if completion thyroidectomy would be
recommended based on the indeterminate nodule
being malignant following lobectomy.

(Strong recommendation, Moderate-quality

evidence)
How should multinodular thyroid glands
(i.e., two or more clinically relevant
nodules) be evaluated for malignancy?
Recommendation

Patients with multiple thyroid nodules˃1cm should

be evaluated in the same fashion as patients with a
solitary nodule ˃1cm, excepting that each nodule that
is >1cm carries an independent risk of malignancy
and therefore multiple nodules may require FNA.

(Strong recommendation, Moderate-quality

evidence)
When multiple nodules˃1cm are present, FNA
should be performed preferentially based upon
nodule sonographic pattern and respective size
cutoff
(Strong recommendation, Moderate-quality
evidence)
Recommendation

If none of the nodules has a high or moderate

suspicion sonographic pattern, and multiple
sonographically similar very low or low suspicion
pattern nodules coalesce with no intervening
normal parenchyma, the likelihood of malignancy is
low and it is reasonable to aspirate the largest
nodules (≥2cm) or continue surveillance without
FNA.
(Weak recommendation, Low-quality evidence)
Recommendation
 A low or low-normal serum TSH concentration
in patients with multiple nodules may suggest
that some nodule(s) may be autonomous.

In such cases, a radionuclide (preferably

123I) thyroid scan should be considered and
directly compared to the US images to
determine functionality of each nodule ≥1cm.
FNA should then be considered only for those
isofunctioning or nonfunctioning nodules,
among which those with high
sonographic pattern should suspicion be
preferentially. aspirated

(Weak recommendation, Low-quality evidence)

What are the best methods for long term
follow-up of patients with thyroid nodules ?
 Recommendations for initial follow-up of
nodules with benign FNA cytology

Recommendation
 Nodules with high suspicion US pattern:
repeat US and US-guided FNA within 12
months.
(Strong recommendation, Moderate-quality
evidence)
• Nodules with low to intermediate
suspicion US pattern: repeat US at 12–24
months.
(Weak recommendation, Low-quality evidence)
 Recommendations for initial follow-up of
nodules with benign FNA cytology

Nodules with very low suspicion US

pattern (including spongiform nodules):
repeating FNA to detect a missed malignancy is
limited. If US is repeated, it should be done at
24 months.

(Weak recommendation, Low-quality

evidence)
Recommendation for follow-up of nodules with
two benign FNA cytology results

If a nodule has undergone repeat US-

guided FNA with a second benign cytology
result, US surveillance for this nodule for
continued risk of malignancy is no longer
indicated.

(Strong recommendation, Moderate-quality

evidence)
 Follow-up for nodules that do not meet
FNA criteria
Recommendation
• Nodules with high suspicion US pattern:
repeat US in 6–12 months.
(Weak recommendation, Low-quality
evidence)

 Nodules with low to intermediate suspicion

US pattern: consider repeat US at 12–24
months.
(Weak recommendation, Low-quality
 Follow-up for nodules that do not
meet FNA criteria
Recommendation:
• Nodules >1cm with very low suspicion US
pattern and pure cyst: the utility and time
interval of surveillance US for risk of
malignancy is not known. If US is repeated, it
should be at≥24 months.
(No recommendation, Insufficient evidence)
• Nodules ≤1cm with very low suspicion US
pattern (including spongiform nodules) and
pure cysts do not require routine sonographic
follow-up.
(Weak recommendation, Low-quality evidence)
What is the role of medical or surgical therapy
for benign thyroid nodules?
Recommendation

Routine TSH suppression therapy for benign

thyroid nodules in iodine sufficient populations
is not recommended. Though modest responses
to therapy can be detected, the potential harm
outweighs benefit for most patients.

(Strong recommendation, High-quality

evidence)
Recommendation

Individual patients with benign, solid, or mostly

solid nodules should have adequate iodine
intake. If inadequate dietary intake is found or
suspected, a daily supplement (containing 150lg
iodine) is recommended.

(Strong recommendation, Moderate-quality

evidence)
Recommendation

(A) Surgery may be considered for growing

nodules that are benign after repeat FNA if they
are large (>4cm), causing compressive or
structural symptoms, or based upon clinical
concern.
(Weak recommendation, Low-quality
evidence)
(B) Patients with growing nodules that are
benign after FNA should be regularly monitored.
Most asymptomatic nodules demonstrating
modest growth should be followed without
intervention.
(Strong recommendation, Low-quality
evidence)
Recommendation
Recurrent cystic thyroid nodules with benign
cytology should be considered for surgical
removal or percutaneous ethanol injection (PEI)
based on compressive symptoms and cosmetic
concerns. Asymptomatic cystic nodules may be
followed conservatively.

(Weak recommendation, Low-quality evidence)

Recommendation

There are no data to guide recommendations on

the use of thyroid hormone therapy in patients
with growing nodules that are benign on
cytology.

(No recommendation, Insufficient evidence)

How should thyroid nodules In pregnant
women be managed ?
 FNA for thyroid nodules discovered during
pregnancy

Recommendation

• FNA of clinically thyroid nodules

should be performed in euthyroid and
relevant
hypothyroid pregnant women.
(Strong recommendation, Moderate-quality
evidence)
 FNA for thyroid nodules discovered
during pregnancy
• For women with suppressed serum TSH levels
that persist beyond 16 weeks gestation, FNA
may be deferred until after pregnancy and
cessation of lactation. At that time,
a radionuclide scan can be
evaluate tonodule function if the serum
performed
TSH remains suppressed.
(Strong recommendation, Moderate-quality
evidence)
 Approaches to pregnant patients with
malignant or indeterminate cytology
• PTC discovered by cytology in early
pregnancy should be monitored
sonographically.

• If it grows progressively before 24-26 weeks

gestation, or if US reveals cervical lymph
nodes that are suspicious for metastatic
disease, surgery should be considered during
pregnancy.
Approaches to pregnant patients with
malignant or indeterminate cytology
• However, if the disease remains stable by mid-
gestation,or if it is diagnosed in the second
half of pregnancy, surgery may be deferred
until delivery

• In pregnant women with FNA that is

suspicious for or diagnostic of PTC, thyroid
hormone therapy to keep the serum TSH 0.1-
1.0mU/L is recommended.
 Take home message
• The clinical importance to evaluate thyroid
nodule is to exclude thyroid carcinoma.
• High resolution US can detect thyroid nodules
upto 19-68% with higher frequencies in
women & elderly.
• Minimize potential harm from overtreatment
of patients at low risk and appropriately treat
and monitor those patients at higher risk.
 Take home message
• Non-palpable nodules have the same risk of
malignancy as do sonographically confirmed
palpable nodules of the same size.
• FNA is choice , most accurate & cost effective
method of procedure in evaluation of thyroid
nodule.
• FNA should be repeated after 3 month to
prevent false-positive interpretation due to
biopsy induced reactive/ reparative changes.
 Take home message
• Most nodules with non-diagnostic cytology
interpretation are benign.
• Slight enlargement of nodules throughout
gestation dose not implies malignant
transformation.
• Avoid radio-nuclied scan in pregnancy.