What is the recommended initial evaluation and management of a solitary thyroid nodule?

Management of Solitary Thyroid Nodule

For a solitary thyroid nodule, perform high-resolution ultrasound immediately, measure serum TSH, and proceed with ultrasound-guided fine-needle aspiration (FNA) for any nodule ≥1 cm or for nodules <1 cm with suspicious ultrasound features (microcalcifications, marked hypoechogenicity, irregular margins, solid composition, or absence of peripheral halo) combined with high-risk clinical factors. 1

Initial Diagnostic Workup

Step 1: Clinical Assessment

Obtain focused history specifically evaluating for:

• History of head and neck irradiation (increases malignancy risk approximately 7-fold) 1
• Family history of thyroid cancer, particularly medullary carcinoma or familial syndromes (lowers FNA threshold even for nodules <1 cm) 1
• Age <15 years or male gender (higher baseline malignancy probability) 1
• Rapid nodule growth, compressive symptoms (dysphagia, dyspnea, voice changes), or vocal cord paralysis (suggests invasive disease) 1

Physical examination should identify:

• Firm, fixed nodule on palpation (indicates extrathyroidal extension) 1
• Suspicious cervical lymphadenopathy (warrants immediate FNA regardless of nodule size) 1

Step 2: Laboratory Testing

• Measure serum TSH as the initial thyroid function test 1
• Measure serum calcitonin to screen for medullary thyroid cancer, which has higher sensitivity than FNA alone (detects 5-7% of thyroid cancers that FNA may miss) 1
• If TSH is suppressed, measure free T4 to identify autonomous hormone production (toxic adenoma) 1

Step 3: High-Resolution Ultrasound

Perform ultrasound using high-frequency transducer to characterize: 1

Suspicious features indicating high malignancy risk:

• Microcalcifications (hyperechoic spots ≤1 mm, highly specific for papillary thyroid carcinoma) 1
• Marked hypoechogenicity (darker than surrounding thyroid parenchyma) 1
• Irregular or microlobulated margins (infiltrative borders rather than smooth contours) 1
• Absence of peripheral halo (loss of thin hypoechoic rim) 1
• Solid composition (higher malignancy risk than cystic nodules) 1
• Central hypervascularity (chaotic internal vascular pattern) 1

Reassuring features:

• Peripheral vascularity only (blood flow limited to capsule) 1
• Smooth, regular margins with thin halo 1
• Predominantly cystic composition 1

FNA Decision Algorithm

Proceed with Ultrasound-Guided FNA When:

• Any nodule ≥1 cm with ≥2 suspicious ultrasound features 1
• Any nodule >4 cm regardless of ultrasound appearance (due to increased false-negative rate) 1
• Any nodule <1 cm with suspicious features PLUS high-risk clinical factors (radiation history, family history, suspicious lymphadenopathy, age <15 years) 1
• Suspicious cervical lymphadenopathy present 1
• Focal FDG uptake on PET scan (regardless of nodule size) 1

Exception: Defer FNA If:

• TSH is suppressed AND nodule appears "hot" on radionuclide scan (toxic adenomas are rarely malignant; proceed with radioactive iodine therapy instead) 1
• Pure cystic nodule without solid components or suspicious features (can be safely observed) 1

Critical caveat: For nodules with suppressed TSH, perform radionuclide scan (99mTc preferred) first. If the nodule is "cold" despite suppressed TSH, proceed immediately to FNA as this represents discordant findings with higher malignancy risk. 1

FNA Technique and Interpretation

• Use ultrasound guidance for all FNA procedures (allows real-time needle visualization, confirms accurate sampling, superior to palpation-guided biopsy) 1
• Target the solid portion in mixed solid-cystic nodules (solid component carries highest malignancy risk) 1
• If initial sample is inadequate (occurs in 5-20% of cases), repeat FNA under ultrasound guidance 1

Management Based on Bethesda Classification:

Bethesda II (Benign): Malignancy risk 1-3% 1

• Surveillance with repeat ultrasound at 12-24 months 1
• Monitor for interval growth or development of suspicious features 1
• Surgery only if compressive symptoms, cosmetic concerns, or nodule >4 cm 1
• Important pitfall: False-negative results occur in up to 11-33% of cases—do not override FNA if worrisome clinical findings persist 1

Bethesda III (AUS/FLUS) or IV (Follicular Neoplasm): 1

• Consider molecular testing (BRAF, RAS, RET/PTC, PAX8/PPARγ) to refine malignancy risk 1
• Presence of any mutation indicates 97% probability of malignancy 1
• For Bethesda IV with normal TSH and "cold" scan, surgery is required for definitive diagnosis (cannot distinguish follicular adenoma from carcinoma on cytology alone) 1

Bethesda V (Suspicious) or VI (Malignant): 1

• Immediate referral to endocrine surgeon for total or near-total thyroidectomy 1
• Pre-operative neck ultrasound to assess cervical lymph node status 1
• Compartment-oriented lymph node dissection when lymph node metastases suspected or proven 1

Special Considerations

For Nodules in Hashimoto's Thyroiditis:

• Solid, isoechoic nodules are typically benign hyperplastic/adenomatoid nodules 1
• Still perform FNA if nodule ≥1 cm or has suspicious features 1

For Multiple Nodules:

• Prioritize the largest nodule for FNA (nodules ≥3 cm have 3-times greater malignancy risk) 1
• If largest nodule is benign but clinical suspicion remains, evaluate additional nodules in subsequent procedure 1

For Tender Nodules:

• Defer FNA until acute tenderness resolves 2
• Perform ultrasound to assess for hemorrhage, rupture, or abscess 2
• Repeat ultrasound at 4-6 weeks after symptom resolution, then proceed with FNA if nodule >1 cm or has suspicious features 2

Post-Surgical Management

• Total or near-total thyroidectomy is recommended for nodules ≥1 cm with confirmed malignancy, multifocal disease, or familial thyroid cancer 1
• Surgery typically followed by radioactive iodine (¹³¹I) ablation to eliminate remnant thyroid tissue and decrease recurrence risk 1
• Less extensive surgery (lobectomy) acceptable only for unifocal disease <1 cm, intrathyroidal, with favorable histology (classical papillary or minimally invasive follicular) 1