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Chapter 4
Evaluation ofThyroid Nodules
PanagiotisBletsis andJoyceShin
Evaluation
History
• Symptomatic patients can present with a neck mass which may or may not be
painful, cause compressive symptoms (e.g., the 3 D’s: dysphagia, dysphonia, and
dyspnea), or result in voice changes.
• Asymptomatic patients may have nodules discovered on physical exam or more
commonly on imaging studies performed for other purposes (e.g., CT, MRI,
PET, chest X-ray, carotid duplex).
• It is important to ask patients if they have signs/symptoms of hypo−/hyperthyroidism, pain, compressive symptoms, voice changes, personal history of head
and neck radiation, family history of thyroid cancer, or hereditary syndromes
(e.g., multiple endocrine neoplasia (MEN) syndromes, familial adenomatous
polyposis (FAP) , PTEN hamartoma tumor syndrome), or a past history of neck
operations including cervical spine procedures.
Physical Exam
• Inspect the patient, paying particular attention to any signs that may suggest
underlying pathology including: scars on the neck, visible neck masses, voice
quality, dyspnea or stridor, body habitus, signs of sympathetic hyperactivity
P. Bletsis · J. Shin (*)
Department of Endocrine Surgery, Endocrinology and Metabolism Institute, Cleveland
Clinic, Cleveland, OH, USA
e-mail: shinj2@ccf.org
Switzerland AG 2024
R. M. Gartland, J. A. Lee (eds.), Endocrine Surgery Clerkship, Contemporary
Surgical Clerkships, https://doi.org/10.1007/978-3-031-62091-1_4
25© The Author(s), under exclusive license to Springer Nature
26
(e.g., anxiety, sweating, skin ushing), exophthalmos, and if their clothes are
appropriate for the weather.
• Pemberton’s sign is when patients have facial ushing, dizziness, or shortness of
breath when raising their arms above their shoulders and may indicate a substernal goiter.
• Palpate the thyroid assessing for its size, consistency, tracheal deviation, and
presence of nodules. If nodules are palpated, then the size, consistency, and
movement in relation to the surrounding tissues should be noted.
• Auscultate for a systolic or continuous bruit of the thyroid, which may suggest
increased vascularity of an enlarged and hyperactive gland; however, this has
largely been replaced by point-of-care ultrasound.
P. Bletsis and J. Shin
Laboratory Tests
• All patients with newly diagnosed thyroid nodule(s) should initially have TSH
checked to determine whether the nodule(s) are functional or non-functional.
• If the TSH (reference range, 0.5–5mIU/L) is low, free T4 and free T3 should be
ordered to conrm hyperthyroidism.
• Additionally, thyroid stimulating immunoglobulin (TSI or TRAb) can be checked
if the patient is hyperthyroid to differentiate Graves’ disease from toxic adenoma/toxic multinodular goiter.
Imaging
• Neck ultrasound is the best imaging modality to evaluate and characterize all
thyroid pathology, including thyroid nodules.
– Two systems for evaluation and risk stratication of thyroid nodules exist.
Endocrinologists, endocrine surgeons, and other thyroidologists performing point-of-care ultrasound typically use the American Thyroid Association
(ATA) Thyroid Nodule Guidelines [1], while radiologists use the Thyroid
Imaging Reporting and Data System (TI-RADS) [2] shown in Figs.4.1 and 4.2.
• If the patient is hyperthyroid, a radioactive iodine uptake scan can be done to
determine whether there are discrete toxic nodules.
Fine Needle Aspiration (FNA) andCytopathology
• Ultrasound-guided FNA, typically with a 22- to 25-gauge needle, provides the
most accurate and safest way to sample thyroid nodules for malignancy.
– High sensitivity (65–98%) and specicity (72–100%) for thyroid cancer [3].
4 Evaluation ofThyroid Nodules
27
Fig. 4.1 Sonographic patterns of thyroid nodules and risk of malignancy
28
P. Bletsis and J. Shin
Fig. 4.2 TI-RADS scoring system. (From Tessler etal., White Paper of the ACR TI-RADS Committee 2017)
4 Evaluation ofThyroid Nodules
29
ab
Fig. 4.3 Performing FNA. (a) Technique for performing ultrasound-guided FNA. (b) Ultrasound
appearance of needle (green arrow) sampling thyroid nodule
• FNA is a well-tolerated ofce-based procedure that can be performed with or without local anesthesia. An example of FNA being performed is shown in Fig.4.3.
• FNA should only be performed in euthyroid or hypothyroid patients.
• Core needle biopsies are reserved for very specic indications (e.g., suspected
lymphoma or anaplastic thyroid cancer).
• For an adequate sample, the cytopathologist must typically see at least 6 groups
of cells with each group composed of at least 10 cells. Therefore, multiple passes
of each thyroid nodule being sampled are performed to increase the likelihood of
a satisfactory biopsy [4].
• Cytopathologists classify the sampled thyroid cells according to the Bethesda
System summarized in Table4.1 [4]. Figure4.4 provides representative cytology
slides of each Bethesda category. Each category has its own associated risk of
malignancy that inuences clinical management.
Molecular Testing
• Molecular testing was developed as an adjunct to help stratify cytopathologically
indeterminate lesions (Bethesda III and IV) into benign or potentially malignant
lesions. The goal here is to decrease the need for unnecessary diagnostic surgery
and aid surgeons in planning the extent of initial surgery (thyroid lobectomy
versus total thyroidectomy).
• As of this publication, three companies provide molecular testing: Arma GSC
(RNA sequencing), ThyroSeq v3 (DNA and RNA sequencing), and ThyGenXT/
ThyraMIR (DNA and RNA sequencing, analysis of miRNA) [5].
30
Table 4.1 Bethesda system for reporting thyroid cytopathology
Diagnostic
category Description
Bethesda I Non-diagnostic or unsatisfactory 5–10% Repeat FNA
Bethesda II Benign 0–3% Clinical surveillance
Bethesda III Atypia of undetermined signicance
(AUS) or follicular lesion of
undetermined signicance (FLUS)
Bethesda IV Follicular neoplasm (FN) or suspicious
for follicular neoplasm (SFN)
Bethesda V Suspicious for malignancy 50–75% Thyroidectomy
Bethesda VI Malignant 97–99% Thyroidectomy
Risk of
malignancy Usual management
10–30% Repeat FNA with
25–40% Repeat FNA with
P. Bletsis and J. Shin
molecular testing
molecular testing
abc
def
Fig. 4.4 Cytology appearance of each Bethesda group. (a) Bethesda 1—Non-diagnostic: Cyst
contents only. (b) Bethesda 2—Benign: Abundant colloid and at sheets of follicular cells with
small, round dark nuclei. (c) Bethesda 3—AUS: Rare groups of follicular cells with poor cellular
preservation arranged in small microfollicles. (d) Bethesda 4—SFN: Highly cellular sample of
follicular cells arranged in microfollicles and syncytial groups with small dark round nuclei. (e)
Bethesda 5—Suspicious for malignancy: Rare groups of follicular cells with marked nuclear
atypia (pale chromatic, grooves) but insufcient for diagnosis of papillary thyroid carcinoma. (f)
Bethesda 6—Malignant: Sheets of follicular cells with enlarged nuclei, grooves, nuclear crowding,
overlapping, and pseudoinclusion (at arrow)
4 Evaluation ofThyroid Nodules
31
Treatment
• For any functional nodules, the preferred denitive treatment is surgical removal
with thyroid lobectomy for a single toxic adenoma versus total thyroidectomy
for toxic multinodular goiter or Graves’ disease. Patients who wish to avoid surgery or high-risk surgical candidates can be treated with radioactive iodine ablation or with antithyroid medications (methimazole or propylthiouracil) as
acceptable alternatives.
• Any symptomatic nodules, including those with benign cytopathology, should be
offered surgical removal.
• Treatment of asymptomatic thyroid nodules is guided by cytopathology and
molecular testing as summarized by the algorithm in Fig.4.5 [1, 2, 6].
• Interventional endocrine techniques such as percutaneous radiofrequency ablation or ethanol ablation may be considered for select nodules. See Chap. 11 for
details.
32
4T
P. Bletsis and J. Shin
Toxic Nodules
Single or Multiple
I scan
123
US, and/or
Order FT4/FT3, TSI,
Low TSH
R5
FNA ≥1cm
Follow ≥0.5cm
High
Suspicion Pattern
FNA ≥1cm
Intermediate
Suspicion Pattern
TR
Normal/High TSHGraves’ disease
Diagnostic US
Low Suspicion
FNA ≥1.5cm
Follow ≥1cm
Cytology
Pattern
FNA ≥1.5cm
Thyroidectomy
Repeat FNA with
Molecular Testing
MalignantIntermediate
Thyroid Nodule TSH
T1-RADS Guidelines
ATA Guidelines
Very Low
Suspicion Pattern
TR1/TR2 TR3
Benign
Pattern
FNA ≥2.5cm
Follow ≥1.5cm
No FNA No FNA FNA ≥2cm
Non-diagnosticBenign AUS/FLUS SFN/FN Suspicious Malignant
Benign
Surveillance
Repeat FNA
Fig. 4.5 Evaluation and treatment algorithm for thyroid nodules
4 Evaluation ofThyroid Nodules
33
References
1. Haugen BR, Wartofsky L.American Thyroid Association management guidelines for adult
patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid
Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid.
2015;26:1–133.
2. Cibas ES, Ali SZ.The 2017 Bethesda system for reporting thyroid cytopathology. Thyroid.
2017;27:1341–6.
3. Salvatore D, Larsen PR.Thyroid pathophysiology and diagnostic evaluation. In: Williams textbook of endocrinology. 14th ed. Philadelphia, PA: Elsevier; 2020. p.332–63.
4. Tessler FN, Stavros AT.ACR thyroid imaging, reporting and data system (TI-RADS): white
paper of the ACR TI-RADS Committee. J Am Coll Radiol. 2017;14:587–95.
5. Patel SG, Lee AJ.Molecular testing for thyroid nodules including its interpretation and use in
clinical practice. Ann Surg Oncol. 2021;28:8884–9.
6. Russell JO, Tufano RP.Management of thyroid nodules. In: Current surgical therapy. 13th ed.
Philadelphia, PA: Elsevier; 2020. p.756–60.
Suggested Reading
Nguyen XV, Sipos J.Thyroid incidentalomas: practice considerations for radiologists in the age of
incidental ndings. Radiol Clin North Am. 2020;58:1019–31.
Dean DS, Gharib H.Epidemiology of thyroid nodules. Best Pract Res Clin Endocrinol Metab.
2008;22:901–11.
Chapter 5
Goiter andBenign Thyroid Nodules
AbhinayTumati andBrendanM.Finnerty
Introduction
A visible or palpable nodule on physical exam of the thyroid is considered a goiter.
Goiters can also be detected incidentally on imaging studies obtained for other purposes. They are subclassied based on their distribution (nodular or diffuse), etiology, and thyroid hormone production (normal, increased, or decreased). While
goiters may harbor underlying malignancy, the focus of this chapter will be to dene
goiters that represent benign thyroid pathology.
Anatomy [1]
• The thyroid is a buttery-shaped endocrine gland that lies inferior to the larynx
and is bordered by the trachea and esophagus posteriorly and carotid sheath
laterally.
• A normal thyroid gland measures 4.0–4.8×1.0–1.8×0.8–1.6 cm in size and
weighs 10–20g.
• Goiters growing in the neck can also extend retrosternal into the mediastinum.
• With marked growth, structures such as the trachea, esophagus, blood vessels
within the carotid sheath (e.g., common carotid artery and internal jugular vein),
and nerves (e.g., recurrent laryngeal nerve) can become displaced and/or compressed (Fig.5.1).
A. Tumati (*) · B. M. Finnerty
Department of Surgery, Weill Cornell Medical Center, New York, NY, USA
e-mail: abt9022@nyp.org; bmf9002@med.cornell.edu
Switzerland AG 2024
R. M. Gartland, J. A. Lee (eds.), Endocrine Surgery Clerkship, Contemporary
Surgical Clerkships, https://doi.org/10.1007/978-3-031-62091-1_5
35© The Author(s), under exclusive license to Springer Nature