What is the appropriate management for a patient with chronic thyroiditis on ultrasound and a thyroid nodule under surveillance, who has normal thyroid function tests?

Management of Thyroid Nodule with Chronic Thyroiditis and Normal Thyroid Function

Continue surveillance with ultrasound at 12-24 month intervals without immediate fine-needle aspiration, unless the nodule is ≥1 cm or demonstrates high-risk sonographic features such as marked hypoechogenicity, microcalcifications, irregular margins, or absence of peripheral halo. 1

Initial Diagnostic Approach

Laboratory Evaluation

• Measure serum TSH as the first laboratory test to confirm euthyroid status, which has already been established in this case with normal thyroid function tests. 2
• Consider measuring serum calcitonin to screen for medullary thyroid carcinoma, which has higher sensitivity than FNA alone and can detect 5-7% of thyroid cancers that FNA may miss. 1
• Thyroid peroxidase antibody (TPOAb) levels may already be elevated given the ultrasound diagnosis of chronic thyroiditis, though this does not change immediate management. 3

Ultrasound Risk Stratification

• Perform high-resolution ultrasound to characterize the nodule for the following high-risk features: marked hypoechogenicity (darker than surrounding thyroid parenchyma), microcalcifications (≤1 mm hyperechoic spots representing psammoma bodies), irregular or microlobulated margins, absence of peripheral halo, solid composition, and central hypervascularity with chaotic internal blood flow. 1, 4
• Document nodule size precisely in all three dimensions, as growth ≥3 mm in any dimension during surveillance constitutes significant progression requiring cytological evaluation. 1

Critical Context: Hashimoto Thyroiditis Increases Malignancy Risk

The presence of chronic thyroiditis (Hashimoto thyroiditis) significantly elevates the risk of thyroid malignancy. 3 This is a crucial consideration that modifies your surveillance strategy:

• Patients with Hashimoto thyroiditis have a 1.6-fold increased relative risk of any nodule proving malignant compared to patients without thyroiditis (24.5% vs 16.3% in solitary nodules; 22.1% vs 15.4% in multinodular goiter). 3
• The prevalence of indeterminate cytology is higher in Hashimoto thyroiditis (26.3% vs 21.8%), and malignant cytology is also more common (10.0% vs 6.4%). 3
• Diffuse sonographic heterogeneity and/or TPOAb positivity should be used for risk assessment at the time of evaluation. 3

Sonographic Pitfalls in Hashimoto Thyroiditis

• Focal presentation of Hashimoto thyroiditis may mimic malignant nodules, appearing as hypoechoic masses with irregular borders, but carcinomas also occur in this setting. 5
• Hyperplastic/adenomatoid nodules in Hashimoto thyroiditis are typically solid, isoechoic nodules that are usually benign. 1
• Hypoechoic nodules in Hashimoto thyroiditis have a higher frequency of malignancy, with most carcinomas found in hypoechoic masses (96.7% of malignant nodules vs 48.3% of benign nodules are hypoechoic). 4
• Markedly hypoechoic masses may represent lymphoma, which is indistinguishable from pseudotumor or adenomatous hyperplasia on ultrasound alone. 6

Indications for Fine-Needle Aspiration

Size-Based Criteria

• Perform FNA for any nodule ≥1 cm, regardless of ultrasound features, because size alone is a critical determinant for malignancy risk in the setting of Hashimoto thyroiditis. 1, 7
• For nodules <1 cm, perform FNA only if suspicious ultrasound features are present plus high-risk clinical factors (history of head/neck irradiation, family history of thyroid cancer, age <15 years, suspicious cervical lymphadenopathy, or subcapsular location). 1

Feature-Based Criteria

• Perform FNA if ≥2 suspicious ultrasound features are present in nodules >1 cm: solid composition, marked hypoechogenicity, irregular margins, microcalcifications, central hypervascularity, or absence of peripheral halo. 1
• Microcalcifications are highly specific for papillary thyroid carcinoma (71.7% of malignant nodules vs 30.0% of benign nodules in Hashimoto thyroiditis). 4
• Ill-defined margins are present in 95.0% of malignant nodules vs 41.7% of benign nodules in Hashimoto thyroiditis. 4
• Absence of regular halo is seen in 96.7% of malignant nodules vs 65.0% of benign nodules in Hashimoto thyroiditis. 4

Procedural Approach

• Use ultrasound-guided FNA rather than palpation-guided biopsy, as it provides real-time needle visualization, confirms accurate sampling, and has superior diagnostic accuracy (sensitivity 100% for differentiating benign from malignant disease in Hashimoto thyroiditis). 6
• Ultrasound-guided FNA is particularly beneficial in Hashimoto thyroiditis because it can detect non-palpable malignancies and help select patients who need surgery, avoiding unnecessary procedures for nonneoplastic disorders. 6

Surveillance Protocol When FNA Not Performed

Follow-Up Intervals

• Repeat ultrasound at 12-24 months to assess for interval growth or development of suspicious features. 1
• Monitor for compressive symptoms including dysphagia, dyspnea, or voice changes, which warrant immediate FNA regardless of nodule size. 1
• For nodules with initially benign cytology (Bethesda II), continue surveillance ultrasound at 12-24 month intervals, as the malignancy risk remains very low (1-3%). 1

Definition of Significant Growth

• Growth ≥3 mm in any dimension during surveillance constitutes significant progression and mandates cytological evaluation, as this represents 5-6 times the threshold for measurement error. 1
• Rapid growth is one of the strongest predictors of malignancy and is an independent risk factor that outweighs baseline size considerations. 1

What to Avoid

• Do not rely on thyroid function tests (TSH, T3, T4) for malignancy assessment, as most thyroid cancers present with normal thyroid function. 1
• Do not order radionuclide scanning in euthyroid patients, as these studies do not add value for malignancy risk assessment; ultrasound findings should guide management decisions. 1, 7
• Avoid performing FNA on nodules <1 cm without high-risk features, as this leads to overdiagnosis and overtreatment of clinically insignificant papillary microcarcinomas. 1

Management Based on FNA Results (If Performed)

Bethesda II (Benign)

• Continue surveillance with repeat ultrasound at 12-24 months, as the malignancy risk is only 1-3%. 1
• A reassuring FNA should not override worrisome clinical findings, as false-negative results occur in up to 11-33% of cases. 1
• Consider surgery only if compressive symptoms develop, cosmetic concerns are significant, or suspicious features develop on follow-up ultrasound despite initially benign cytology. 1

Bethesda III (AUS/FLUS) or IV (Follicular Neoplasm)

• Consider molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations to refine malignancy risk, as 97% of mutation-positive nodules are malignant. 1
• Repeat FNA under ultrasound guidance if initial sample is inadequate or consider core needle biopsy for indeterminate results. 1
• For follicular neoplasm with normal TSH and "cold" appearance on thyroid scan (if performed), surgery should be considered for definitive diagnosis. 1, 8

Bethesda V (Suspicious) or VI (Malignant)

• Refer immediately for total or near-total thyroidectomy with pre-operative assessment of cervical lymph node compartments. 1
• Perform compartment-oriented lymph node dissection when lymph node metastases are suspected or proven. 1

Special Considerations in Hashimoto Thyroiditis

• Solid, isoechoic nodules in Hashimoto thyroiditis are typically benign hyperplastic/adenomatoid nodules, but FNA is still indicated if ≥1 cm. 1
• Central hypervascularity is concerning for malignancy only when associated with a discrete nodule with irregular borders and microcalcifications. 1
• If repeat FNA remains nondiagnostic after ultrasound-guided sampling, assess the number of suspicious ultrasound features to determine whether surgery is warranted. 1