Ultrasound‑Guided Fine‑Needle Aspiration of Thyroid Nodules: Indications and Technique

Indications for FNA Based on Nodule Size and EU‑TIRADS Risk

• The American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE) recommend performing FNA only under ultrasound guidance and using a size‑and‑risk algorithm:

• High‑risk (EU‑TIRADS 5) nodules ≥10 mm that show at least one of the following sonographic features—marked hypoechogenicity, spiculated/microlobulated margins, microcalcifications, taller‑than‑wide shape, or extrathyroidal extension—should undergo FNA. 2

• The malignancy risk for EU‑TIRADS 5 nodules ranges from 26 % to 87 %. 3

• For nodules 5–10 mm with high‑risk features, FNA is advised only when accompanied by suspicious cervical lymphadenopathy, extrathyroidal spread, subcapsular or paratracheal location, or a personal/family history of thyroid cancer. 1

• Intermediate‑risk (EU‑TIRADS 4) nodules >15 mm that are slightly hypoechoic with smooth or ill‑defined margins merit FNA. 2

• EU‑TIRADS 4 nodules carry a 6 %–17 % risk of malignancy. 3

• EU‑TIRADS 4 nodules with a definitively benign sonographic appearance should not be biopsied. 1

• Low‑risk (EU‑TIRADS 3) nodules ≥20 mm that are isoechoic with regular margins are candidates for FNA. 2

• EU‑TIRADS 3 nodules have a 2 %–4 % malignancy risk. 3

• FNA of low‑risk nodules is also considered when the nodule shows progressive growth. 1

• Very low‑risk (EU‑TIRADS 2) spongiform or predominantly cystic (>50 %) nodules should not be biopsied unless they are ≥20 mm and demonstrate interval growth. 1

• EU‑TIRADS 2 nodules have a near‑zero malignancy risk. 3

• Critical exceptions—perform FNA regardless of size—include:

Technical Aspects of FNA

• ACE/AACE mandate that all FNA procedures be performed under real‑time ultrasound guidance; this approach improves safety, reliability, and reduces nondiagnostic rates. 1

• Use 23‑ to 27‑gauge needles for capillary or aspiration techniques; larger needles increase bleeding risk and yield more hemorrhagic samples. 4

• Perform 2–5 back‑and‑forth and radial needle movements while maintaining needle position within the target. 4

• Sample at least two distinct sites within the nodule to lower false‑negative results. 5

• In solid nodules, obtain material from both central and peripheral regions; in mixed or partially cystic nodules, target only the solid component. 2

• Eccentric solid components within mixed nodules are associated with a higher malignancy risk. 3

• Do not biopsy more than two nodules in a single patient; prioritize nodules with the highest EU‑TIRADS category and size criteria. 2

• If all nodules appear similarly benign, select the two to three largest nodules (>20 mm) for FNA. 3

Special Situations

• Nodules that are functioning on scintigraphy and lack suspicious ultrasound features should not be biopsied. 1

• Scintigraphy is recommended when serum TSH is suppressed or in multinodular glands to identify autonomously functioning nodules. 1

• Incidentally discovered PET‑avid thyroid nodules with focal FDG uptake require urgent ultrasound evaluation and FNA because of a high malignancy risk. 5

• Thyroid nodules identified on CT or MRI should first undergo dedicated ultrasound assessment before FNA consideration. 5

Management of Nondiagnostic Results

• Persistently nondiagnostic solid nodules should undergo a repeat ultrasound‑guided FNA; the minimum interval between attempts is 1–3 months. 6

• If the second FNA remains nondiagnostic, a core‑needle biopsy is recommended. 1

• Pure colloid obtained from completely cystic nodules should be reported as a colloid cyst and managed with surveillance. 1

Pitfalls and Recommendations

• Never forgo ultrasound guidance, even for palpable nodules; doing so markedly improves diagnostic accuracy. 1

• Do not rely on nodule size alone; always integrate ultrasound risk features into the decision‑making process. 7

• Avoid passing the needle through ultrasound gel, as this can compromise cytologic interpretation. 4

• Routine measurement of serum thyroglobulin or thyroid function tests does not aid cancer detection and should not be performed for nodule evaluation. 7

• Serum calcitonin measurement is indicated only when medullary thyroid carcinoma is clinically suspected based on cytology or history. 1

Thyroid Nodule Biopsy Frequency: Evidence Against Annual Fine‑Needle Aspiration

Initial Biopsy Indications

• EU‑TIRADS risk stratification combined with nodule size should guide the decision to perform the first fine‑needle aspiration (FNA), rather than the mere presence of a goiter. This recommendation follows the American College of Endocrinology and the American Association of Clinical Endocrinologists guidance. 8
• All FNA procedures must be performed under real‑time ultrasound guidance to enhance safety, reliability, and diagnostic accuracy, as endorsed by the same endocrine societies. 8

Surveillance Strategy After a Benign Cytology (Bethesda II)

• The probability of a subsequent malignancy in nodules with an initial benign cytology is low (approximately 1–3%). This risk estimate is derived from observational data in two 2022 studies. [9][10]
• The first follow‑up ultrasound is recommended at 1–2 years after a benign result; if the nodule remains stable, subsequent scans can be spaced every 2–4 years. Evidence from the 2022 Annales d’endocrinologie publications supports this interval. [9][10]
• Some recent data suggest that the initial reassessment may safely be delayed to 3 years in stable nodules. 9
• In elderly patients with non‑suspicious nodular disease, discontinuation of routine ultrasound monitoring may be considered because the benefit is minimal. 9

Criteria for Repeat FNA (Not Routine Annual Biopsy)

Highly Suspicious Nodules (EU‑TIRADS 5)

• After an initial benign cytology, monitor these nodules with ultrasound every 1–2 years for the first 5 years; if stability is confirmed, the interval can be extended. This schedule is based on the 2022 evidence. 10
• Perform a repeat FNA only if suspicious ultrasound changes develop or if the nodule shows significant growth. The same source defines the trigger for re‑biopsy. 10
• Even in highly suspicious nodules, the residual risk of malignancy after a benign cytology does not exceed 3%. 10

Intermediate/Low‑Risk Nodules (EU‑TIRADS 3–4)

• Repeat FNA is not recommended for these nodules unless there is a change in ultrasound characteristics or a substantial increase in size. Evidence from the 2022 studies advises against routine re‑biopsy. 10
• Significant growth is defined as a volume increase greater than 50 %, a threshold derived from the 2016 endocrine practice guideline. 8

Initially Nondiagnostic Cytology (Bethesda I)

• A repeat FNA should be performed after a minimum interval of 1–3 months to allow for potential cytologic improvement. 10
• If the second FNA remains nondiagnostic, a core‑needle biopsy should be considered as the next diagnostic step. 10

Avoidance of Unnecessary Biopsies

• Routine annual biopsies of stable nodules with benign cytology are not supported by evidence and constitute overutilization without improving patient outcomes. This conclusion is drawn from the 2022 Annales d’endocrinologie data. [9][10]
• Functioning nodules identified on scintigraphy that lack suspicious ultrasound features should not be biopsied. This recommendation follows the 2016 guidance from the American College of Endocrinology and the American Association of Clinical Endocrinologists. 8

Follow‑up and Surveillance Recommendations for Benign Thyroid Nodules

Initial Risk Stratification and Follow‑up Intervals

Malignancy Risk Estimates

Recommendations for Discontinuation of Surveillance

Indications for Repeat Fine‑Needle Aspiration (FNA)

Situations Where Repeat FNA Is Not Required

Management of Large Nodules (> 4 cm)

Nodule Growth and Regression Patterns

Emergence of New Nodules

Common Pitfalls to Avoid

Guideline for Surveillance of Multinodular Goiter with TIRADS 3 Nodules

Surveillance Schedule

• Perform the first follow‑up thyroid ultrasound 1–2 years after a benign cytology result in patients with multinodular goiter and TIRADS 3 nodules; if the nodules remain stable, repeat imaging every 2–4 years. 16
• In low‑risk, stable nodules, the initial reassessment can be safely postponed to 3 years without increasing malignancy risk. 16

Indications for Repeat Fine‑Needle Aspiration (FNA)

• Repeat FNA is warranted only when a nodule shows significant growth (≥50 % volume increase or ≥20 % increase in two dimensions) or when new suspicious ultrasound features appear (marked hypoechogenicity, microcalcifications, irregular/spiculated margins, taller‑than‑wide shape). 16
• Do not repeat FNA based solely on nodule size, even for nodules >4 cm, when ultrasound features remain benign. 16

Growth and New Nodule Statistics

• Over a 5‑year period, 11–29 % of benign nodules exhibit measurable growth (average increase ≈5.9 mm), while 13–18 % spontaneously shrink. 16
• New thyroid nodules arise in 9–14 % of patients during 5–10 years of follow‑up, supporting continued periodic ultrasound even after the index nodule is stable. 16

Risk Factors Associated with Nodule Growth

• Male gender, age < 45 years, presence of multiple nodules, and a baseline nodule volume > 0.2 cm³ (diameter > 7.5 mm) are linked to a higher likelihood of nodule enlargement. These factors do not alter the surveillance interval but can inform patient counseling. 16

Management of Large Asymptomatic Nodules (>4 cm)

• Newly identified asymptomatic nodules larger than 4 cm should undergo closer initial surveillance (shorter imaging intervals) to characterize growth trajectory and to decide whether surgical or ablative treatment becomes necessary. The focus is on monitoring for compressive symptoms rather than malignancy risk. 16

Key Pitfalls to Avoid

• Annual biopsies of stable, benign nodules constitute over‑utilization and do not improve patient outcomes; such practice should be avoided. 16
• Decisions to repeat FNA must incorporate ultrasound risk features; relying on size alone is insufficient. 16
• Not all nodule growth indicates malignancy—evaluate nodule composition, initial size, and ultrasound characteristics before recommending repeat biopsy. 16
• In multinodular goiter, the presence of multiple nodules does not increase the individual malignancy risk of a nodule when ultrasound features are benign. 16

Guidelines for Fine‑Needle Aspiration of Thyroid Nodules (American College of Endocrinology & American Association of Clinical Endocrinologists)

General Indications & Size Thresholds

• Ultrasound‑guided fine‑needle aspiration (FNA) is required for all thyroid nodules; it is not indicated for nodules < 5 mm regardless of appearance. 17
• High‑risk nodules (EU‑TIRADS 5 / Class 3) should be biopsied when they are ≥ 10 mm and display at least one suspicious ultrasound feature. 17
• Intermediate‑risk nodules (EU‑TIRADS 4 / Class 2) are biopsied when they are > 20 mm and are mildly hypoechoic or isoechoic with an oval/round shape and smooth or ill‑defined margins. 17
• Low‑risk nodules (EU‑TIRADS 3 / Class 1) are biopsied only if they are ≥ 20 mm, iso‑echogenic, spongiform or have a regular halo, and meet any of the following: documented progressive growth; associated with a radiation or familial risk history; or prior to thyroid surgery or minimally invasive ablative therapy. 17

Strength of evidence: expert consensus (Endocrine Practice guideline).

Sonographic Features Defining “Suspicious” (High‑Risk Nodules)

The malignancy risk for high‑risk nodules ranges from *26 % to 90 %, increasing with the number of suspicious features present. 17

Strength of evidence: expert consensus.

Indications for 5–10 mm Nodules with Suspicious Features

Consider FNA for 5–10 mm nodules with suspicious ultrasound findings in the following clinical contexts:

• Subcapsular or paratracheal location. [Citation: 19]
• Presence of suspicious cervical lymph nodes or extrathyroidal extension. [Citation: 18]
• Personal or family history of thyroid cancer. [Citation: 19]
• Co‑existing concerning clinical signs (e.g., hoarseness). [Citation: 19]

Strength of evidence: expert consensus.

Special Situations Requiring FNA Regardless of Size

• FNA is indicated irrespective of nodule size in patients with:

  • Prior head‑and‑neck irradiation. [Citation: 19]
  • Family history of thyroid carcinoma. [Citation: 19]
  • Clinical suspicion of medullary thyroid carcinoma. [Citation: 19]
  • PET‑CT incidentalomas showing focal FDG uptake (high malignancy risk). [Citation: 20]

Strength of evidence: expert consensus.

Contraindications to FNA

• Do not perform FNA on hyperfunctioning (hot) nodules identified on scintigraphy that lack suspicious ultrasound features. [Citation: 19]
• Nodules < 5 mm should never be biopsied; they are managed with observation only. [Citation: 17]

Strength of evidence: expert consensus.

Technical Recommendations for Performing FNA

• Real‑time ultrasound guidance is mandatory for all procedures, enhancing safety, diagnostic accuracy, and reducing non‑diagnostic samples. [Citation: 17]
• Use 23–27 gauge needles. [Citation: 19]
• Perform 2–5 back‑and‑forth (to‑and‑fro) passes while maintaining needle position within the target area. [Citation: 19]
• Sample at least two distinct locations within the nodule to lower false‑negative rates. [Citation: 19]
• In solid nodules, obtain material from both central and peripheral regions. [Citation: 19]
• In mixed or partially cystic nodules, target only the solid component (solid eccentric areas carry higher malignancy risk). [Citation: 17]

Strength of evidence: expert consensus.

Management of Multinodular Goiter

• Limit biopsies to no more than two nodules per patient, prioritizing those with the highest EU‑TIRADS category and meeting size criteria. [Citation: 17]
• Do not biopsy hyper‑capturing (hot) areas when scintigraphy is available. [Citation: 17]

Strength of evidence: expert consensus.

Handling Non‑Diagnostic FNA Results

• If the initial FNA is non‑diagnostic, repeat the procedure after a minimum interval of 1–3 months. [Citation: 17]

• Repeat FNA is warranted only when:

  • The nodule shows significant growth (volume increase > 50 % or ≥ 20 % increase in two dimensions). [Citation: 19]
  • New suspicious ultrasound features emerge. [Citation: 19]

Strength of evidence: expert consensus.

Guideline Recommendations for Imaging and Fine‑Needle Aspiration of Thyroid Nodules

1. Required Imaging Modality for FNA

• Ultrasound is the sole imaging modality required before fine‑needle aspiration, and all FNAs must be performed under real‑time ultrasound guidance. The American College of Endocrinology and the American Association of Clinical Endocrinologists state this as a core requirement. 21

2. Ultrasound as Diagnostic and Procedural Tool

• Ultrasound serves both for risk stratification and as the procedural guide for FNA. This dual role is emphasized by the Endocrine Practice guidelines. 21

3. Standard Ultrasound Technique

• Gray‑scale B‑mode ultrasound with a high‑frequency linear probe (7–18 MHz) is the foundational technique for evaluating thyroid nodules and determining FNA eligibility. 21
• A complete thyroid examination must include transverse and longitudinal scans of both lobes, the isthmus, and cervical lymph‑node assessment (levels VI, III, IV). Recommended by the European Thyroid Association. 22

4. Risk Stratification Systems

• EU‑TIRADS, ACR TI‑RADS, and ATA ultrasound risk‑stratification systems should be applied to guide FNA decisions. These systems integrate nodule composition, echogenicity, margins, calcifications, and size. 23

5. Ultrasound Features Defining FNA Indications

High‑Risk (EU‑TIRADS 5)

• Nodules with marked hypoechogenicity, spiculated or microlobulated margins, microcalcifications, taller‑than‑wide shape, or extrathyroidal extension warrant FNA when ≥10 mm. Strong recommendation from the Endocrine Practice guideline. 24

Intermediate‑Risk (EU‑TIRADS 4)

• Nodules with mild hypoechogenicity and smooth or ill‑defined margins require FNA when >15–20 mm. 23

Low‑Risk (EU‑TIRADS 3)

• Isoechoic nodules with regular margins are biopsied only if ≥20 mm and demonstrate growth or additional risk factors. 24

6. Advanced Ultrasound Techniques (Selective Use)

• Elastography and contrast‑enhanced ultrasound (CEUS) are not primary decision tools for FNA indications. The American College of Endocrinology and AACE advise against routine use. 25
• Elastography may be used as a complementary tool in nodules with indeterminate ultrasound or cytology, but it cannot replace gray‑scale assessment. 25
• CEUS is not recommended for routine thyroid nodule evaluation and lacks regulatory approval in many countries. 23

7. Cross‑Sectional Imaging (CT/MRI)

• CT and MRI are not indicated for routine thyroid nodule evaluation prior to FNA. Endocrine Practice guidelines consider them unnecessary in standard work‑up. 23
• CT/MRI should be reserved for specific scenarios that do not affect the FNA decision, such as:

8. Thyroid Scintigraphy

• Scintigraphy is not routinely required before FNA; it is indicated when serum TSH is suppressed (<0.4 mIU/L) to identify hyperfunctioning (hot) nodules. 23
• FNA should be avoided for hyperfunctioning nodules that lack suspicious ultrasound features. 24
• When TSH is ≥1 mU/L, scintigraphy is not recommended as a first‑line investigation. 23

9. PET‑CT Findings

• Thyroid nodules with focal FDG uptake on PET‑CT require urgent ultrasound evaluation and FNA regardless of size because of a high malignancy risk. Endocrine Practice guidelines emphasize this urgent approach. 24
• PET‑CT is not recommended for routine diagnostic evaluation of thyroid nodules due to limited accuracy, high cost, and limited accessibility. 25

10. Procedural Pitfalls and Reporting Standards

• Never perform FNA without ultrasound guidance, even for palpable nodules; this markedly improves diagnostic accuracy and reduces nondiagnostic rates. 24
• Do not order CT or MRI as part of the initial thyroid nodule work‑up; if incidental findings appear on these studies, obtain a dedicated ultrasound before considering FNA. 24
• Do not rely on nodule size alone; always integrate ultrasound risk features (EU‑TIRADS or equivalent) into the FNA decision. 24
• Avoid biopsying nodules <5 mm regardless of appearance; such lesions should be monitored rather than sampled. 24
• Ultrasound reports must include: EU‑TIRADS (or equivalent) classification, nodule dimensions, composition (solid vs. cystic), echogenicity, margins, calcifications, and cervical lymph‑node status to guide FNA decisions. These reporting elements are mandated by the European Thyroid Association and the American College of Endocrinology/AACE. 23

Size Thresholds for Fine‑Needle Aspiration of Low‑Suspicion Thyroid Nodules

ACR TI‑RADS Recommendations

• The American College of Radiology’s ACR TI‑RADS assigns three points to mildly suspicious (TR3) nodules, defining a low‑suspicion sonographic pattern. 26
• ACR TI‑RADS recommends performing fine‑needle aspiration (FNA) on TR3 nodules only when they are ≥ 2.5 cm in maximal dimension. This higher threshold is intended to balance cancer detection with avoidance of unnecessary biopsies. 27
• The 2.5 cm cutoff is based on analysis of a database of > 3,000 proven thyroid nodules, which showed a malignancy risk of approximately 5 % for TR3 lesions. 26
• SEER registry data incorporated by the ACR committee indicate that distant metastases begin to rise modestly at 2.5 cm, with incremental mortality effects becoming apparent at 3 cm. 26
• Ultrasound tends to overestimate nodule size by ~0.7 cm on average, a systematic bias accounted for in the size threshold. 26

AACE/ACE and EU‑TIRADS Recommendations

• The American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) classify low‑risk nodules (Class 1 or EU‑TIRADS 3) as isoechoic or spongiform with regular margins, carrying a 1–4 % malignancy risk. 28
• These guidelines advise FNA for low‑risk nodules only when they exceed 2.0 cm (20 mm) in size. 28
• Additional qualifiers for FNA at ≥ 2.0 cm include:

Sonographic Features Defining Low‑Suspicion Nodules & Malignancy Risk

• Low‑suspicion nodules typically demonstrate:
• The expected malignancy risk for nodules with this low‑suspicion pattern ranges 2–5 % across the classification systems. 26

Clinical Exceptions to Size‑Based Thresholds

• Regardless of size, FNA is indicated when any high‑risk clinical feature is present, including:

Technical and Surveillance Guidelines

• All FNA procedures must be performed under real‑time ultrasound guidance; palpation‑only biopsies are not acceptable. 28
• For low‑suspicion nodules that do not meet the size criteria, the first follow‑up ultrasound is recommended at 12 months. If stable, repeat imaging at 24 months, then every 2–3 years for up to 5–7 years. 27
• Nodules < 5 mm should not be biopsied regardless of appearance; they are monitored with imaging alone. 28
• Hyperfunctioning (“hot”) nodules identified on scintigraphy with suppressed TSH should not be biopsied, even if they appear suspicious on ultrasound, because they are almost universally benign. 28

Guideline Comparison & Practical Recommendations

• The ACR TI‑RADS threshold (≥ 2.5 cm) is more conservative than the AACE/ACE threshold (≥ 2.0 cm). Comparative research indicates that when similar size criteria are applied, the unnecessary biopsy rate falls from 0–33.8 % to 0–8.7 % without a meaningful loss in sensitivity.
• In clinical practice, adopting the more conservative 2.5 cm threshold (ACR TI‑RADS) is reasonable for truly low‑suspicion nodules to minimize overdiagnosis. The 2.0 cm threshold (AACE/ACE) may be appropriate when additional risk factors (e.g., growth, family history) are present. [26][28]

Management of a 1.2 cm Thyroid Nodule

Initial Diagnostic Workup

• Serum TSH should be measured first to determine thyroid functional status and guide subsequent testing (American College of Endocrinology and the American Association of Clinical Endocrinology) [29][30].
• If TSH is suppressed (< 0.4 mIU/L), a thyroid scintigraphy is required to identify hyperfunctioning (“hot”) nodules, which are almost universally benign and should not be biopsied regardless of ultrasound appearance (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.
• When TSH is elevated, thyroid peroxidase antibodies and free T4 should be measured to evaluate for autoimmune thyroiditis (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.
• With a normal TSH, proceed directly to ultrasound risk stratification and selective fine‑needle aspiration (FNA) based on sonographic features (American College of Endocrinology and the American Association of Clinical Endocrinology; Annales d’endocrinologie) [29][30].

Ultrasound Risk Stratification

• A high‑resolution thyroid ultrasound must include transverse and longitudinal scans of both lobes, the isthmus, and cervical lymph‑node levels III, IV, and VI (Annales d’endocrinologie) 30.
• Nodules should be classified using EU‑TIRADS or ACR TI‑RADS, evaluating composition, echogenicity, margins, calcifications, and shape (American College of Endocrinology and the American Association of Clinical Endocrinology; Endocrine Practice 2021) [29][31].

FNA Indications by EU‑TIRADS Category

• EU‑TIRADS 5 (high risk; malignancy risk 26‑87 %) – Perform ultrasound‑guided FNA immediately for nodules ≥10 mm that display any high‑risk sonographic feature (American College of Endocrinology and the American Association of Clinical Endocrinology; Annales d’endocrinologie) [29][30].
• EU‑TIRADS 5 nodules 5‑10 mm with high‑risk features – FNA is indicated only if accompanied by suspicious cervical lymphadenopathy, subcapsular or paratracheal location, or a personal history of head‑and‑neck irradiation (American College of Endocrinology and the American Association of Clinical Endocrinology) 32.
• EU‑TIRADS 4 (intermediate risk; malignancy risk 6‑17 %) – Do NOT perform FNA on a 1.2 cm nodule because the size threshold for biopsy is >15 mm (American College of Endocrinology and the American Association of Clinical Endocrinology; Annales d’endocrinologie) [29][30].
• EU‑TIRADS 4 nodules are typically slightly hypoechoic with smooth or ill‑defined margins and lack definitive benign features (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.
• EU‑TIRADS 4 nodules should be managed with ultrasound surveillance (Annales d’endocrinologie) 30.
• EU‑TIRADS 3 (low risk; malignancy risk 2‑4 %) – Do NOT perform FNA on a 1.2 cm nodule because the size threshold is ≥20 mm (American College of Endocrinology and the American Association of Clinical Endocrinology; Annales d’endocrinologie) [29][30].
• EU‑TIRADS 3 nodules are usually isoechoic with regular margins or have a spongiform appearance (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.
• FNA for EU‑TIRADS 3 nodules ≥20 mm is indicated only when there is documented progressive growth or a high‑risk personal/family history (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.
• EU‑TIRADS 2 (very low risk; malignancy risk < 1 %) – Never perform FNA on spongiform or predominantly cystic (> 50 %) nodules unless they are ≥20 mm and show interval growth (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.

Technical Standards for FNA (When Indicated)

• All FNA procedures must be performed under real‑time ultrasound guidance; palpation‑guided FNA has unacceptably high nondiagnostic rates (American College of Endocrinology and the American Association of Clinical Endocrinology; Annales d’endocrinologie) [29][32]33.
• Use 23‑27 gauge needles with 2‑5 back‑and‑forth passes while maintaining needle position (American College of Endocrinology and the American Association of Clinical Endocrinology; Annales d’endocrinologie) [32][33].
• Sample at least two distinct sites within the nodule to reduce false‑negative results (American College of Endocrinology and the American Association of Clinical Endocrinology) 32.
• In solid nodules, obtain material from both central and peripheral regions (American College of Endocrinology and the American Association of Clinical Endocrinology) 32.
• Avoid passing the needle through ultrasound gel, as this compromises cytologic interpretation (Annales d’endocrinologie) 33.

Surveillance Strategy for Nodules Not Meeting FNA Criteria

• For EU‑TIRADS 3 or 4 nodules with benign appearance or size below the FNA threshold, the first follow‑up ultrasound should be performed at 12‑24 months (Annales d’endocrinologie) 30.
• For EU‑TIRADS 5 nodules <10 mm, the initial surveillance interval is 12 months (Annales d’endocrinologie) 30.
• If the nodule remains stable at the first follow‑up, repeat ultrasound every 2‑4 years for up to 5‑7 years (Annales d’endocrinologie) 30.

Indications for Repeat FNA During Surveillance

• Significant growth defined as a volume increase > 50 % or ≥20 % increase in two dimensions (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.
• Appearance of new suspicious ultrasound features such as microcalcifications, irregular margins, or marked hypoechogenicity (Annales d’endocrinologie) 30.
• Development of suspicious cervical lymphadenopathy (American College of Endocrinology and the American Association of Clinical Endocrinology; Annales d’endocrinologie) [29][30].

Critical Pitfalls to Avoid

• Do not biopsy nodules <5 mm regardless of appearance; these should be monitored with ultrasound only (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.
• Do not rely on nodule size alone to determine FNA indication; always integrate ultrasound risk features (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.
• Do not perform FNA on hyperfunctioning nodules identified on scintigraphy when TSH is suppressed, even if ultrasound features appear suspicious (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.
• Do not order routine serum thyroglobulin or calcitonin for nodule evaluation; calcitonin is indicated only when medullary thyroid carcinoma is clinically suspected (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.

Management of Nondiagnostic FNA Results

• If the initial FNA is nondiagnostic (Bethesda I), repeat the procedure after a minimum interval of 1‑3 months (American College of Endocrinology and the American Association of Clinical Endocrinology; Annales d’endocrinologie) [29][33].
• If the second FNA remains nondiagnostic, consider an ultrasound‑guided core‑needle biopsy for micro‑histologic assessment (American College of Endocrinology and the American Association of Clinical Endocrinology) [29][32].
• Pure colloid obtained from a completely cystic nodule should be labeled as a colloid cyst and managed with surveillance only (American College of Endocrinology and the American Association of Clinical Endocrinology) 29.

Management of Thyroid Nodules TIRADS 3 in Patients with Prior Partial Thyroidectomy

Definition and Malignancy Risk of TIRADS 3

• TIRADS 3 (EU‑TIRADS 3) nodules are iso‑echogenic, have regular margins, an oval shape, and lack high‑risk ultrasound features; they carry a malignancy risk of 2–4 %. 34

Impact of Prior Thyroid Surgery

• A history of partial thyroidectomy does not alter the size threshold for performing fine‑needle aspiration (FNA) in TIRADS 3 nodules. 34

Indications for Fine‑Needle Aspiration (FNA)

• Size criterion: FNA is recommended only when the nodule’s maximum diameter is ≥20 mm (2 cm). 34
• Nodules <20 mm: These should be managed with ultrasound surveillance, irrespective of prior thyroid surgery. 34

Exceptions to the Size Threshold (When FNA Is Indicated Regardless of Size)

• Documented progressive growth (volume increase > 50 % or ≥20 % increase in two dimensions). 34
• Appearance of new suspicious ultrasound features: marked hypoechogenicity, microcalcifications, irregular or spiculated margins, or a taller‑than‑wide shape. 34
• Personal history of cervical irradiation. 35
• Family history of thyroid cancer or hereditary syndromes (e.g., Cowden, MEN 2, DICER1). 35
• Suspicious cervical lymphadenopathy (loss of fatty hilum, round shape, microcalcifications). 35

Ultrasound Surveillance Protocol for TIRADS 3 Nodules Not Meeting FNA Criteria

• First follow‑up scan: 12–24 months after the initial diagnosis. 34
• If stable: repeat ultrasound at 3 years. 34
• If still stable: continue scans every 2–4 years until a total of 5–7 years of follow‑up is reached. 34
• Discontinuation of surveillance: after 5 years of documented stability, surveillance may be stopped, indicating reliable benign behavior. 36

Limits on the Number of FNAs in Multinodular Glands

• In patients with multiple nodules, limit FNA to a maximum of two nodules, prioritizing those with the highest TIRADS category and that meet size criteria. 35

Functional Thyroid Assessment Prior to FNA

• Measure serum TSH as the first step to determine thyroid functional status. 35
• Suppressed TSH (<0.4 mIU/L): perform thyroid scintigraphy to identify “hot” (hyperfunctioning) nodules, which should not be biopsied even if they have suspicious ultrasound features. [35][37]

Technical Recommendations for Performing FNA

• All FNAs must be performed under real‑time ultrasound guidance; palpation‑guided biopsies have unacceptably high nondiagnostic rates. 34

Management of Nondiagnostic FNA Results

• If the initial FNA is nondiagnostic (Bethesda I), repeat the procedure after a minimum interval of 1–3 months. 34
• If the second FNA remains nondiagnostic, consider a core‑needle (large‑gauge) biopsy for microhistological evaluation. 34

Guideline societies referenced:

• European Thyroid Association (EU‑TIRADS) – citations 34 38
• American College of Endocrinology & American Association of Clinical Endocrinologists – citations 35 37
• American College of Radiology – citation 36

EU‑TIRADS Thyroid Nodule Risk Stratification and Fine‑Needle Aspiration Guidelines

Risk Categories and Malignancy Probabilities

• The EU‑TIRADS system classifies thyroid nodules into five categories, each linked to a specific malignancy risk ranging from ≈0 % for EU‑TIRADS 2 up to 26‑87 % for EU‑TIRADS 5【39】.
• EU‑TIRADS 2 nodules have an estimated malignancy risk of ≈0 %【39】【40】.
• EU‑TIRADS 3 nodules carry a malignancy risk of 2‑4 %【39】【40】.
• EU‑TIRADS 4 nodules have a malignancy risk of 6‑17 %【39】【40】.
• EU‑TIRADS 5 nodules exhibit a malignancy risk of 26‑87 %【39】【40】.

Prevalence of EU‑TIRADS Categories in Thyroid Nodule Populations

• Approximately 5 % of all thyroid nodules are classified as EU‑TIRADS 2【39】.
• About 63 % of nodules fall into the EU‑TIRADS 3 category【39】.
• EU‑TIRADS 4 accounts for roughly 27 % of nodules【39】.
• EU‑TIRADS 5 comprises about 5 % of nodules【39】.

Ultrasound Features Defining Each Category

• EU‑TIRADS 2: Purely cystic (anechoic) or spongiform appearance【39】.
• EU‑TIRADS 3: Iso‑echoic nodules with regular margins and no high‑suspicion characteristics【39】【40】.
• EU‑TIRADS 4: Mildly hypoechoic nodules lacking high‑suspicion signs, with smooth or ill‑defined margins【39】【40】.
• EU‑TIRADS 5: Presence of at least one high‑suspicion feature, such as marked hypoechogenicity, spiculated or microlobulated margins, microcalcifications, taller‑than‑wide shape, or extrathyroidal extension【39】【40】.

Size Thresholds for Fine‑Needle Aspiration (FNA)

• EU‑TIRADS 3: FNA recommended for nodules ≥ 20 mm in maximal diameter【39】【41】.
• EU‑TIRADS 4: FNA recommended for nodules > 15 mm in maximal diameter【39】【41】.
• EU‑TIRADS 5: FNA recommended for nodules ≥ 10 mm in maximal diameter【39】【41】; for nodules 5‑10 mm, FNA is advised only when there is a suspicious cervical lymph node, subcapsular or paratracheal location, or a history of cervical irradiation【39】.

Technical Recommendations for Performing FNA

• All fine‑needle aspirations should be performed under real‑time ultrasound guidance; palpation‑only guidance is associated with unacceptably high rates of nondiagnostic samples【41】.
• When suspicious cervical lymph nodes are present, both the thyroid nodule and the lymph node should be aspirated, and thyroglobulin measurement should be performed on the washout fluid【41】.

Special Situations Requiring FNA Independent of Size

• Progressive nodule growth (volume increase > 50 %), personal history of cervical irradiation, family history of thyroid cancer, or suspicious cervical lymphadenopathy are indications for FNA regardless of nodule size (derived from the EU‑TIRADS criteria)【39】【40】.