What are the next steps for a patient with bilateral solid thyroid nodules of mild worrisome appearance, normal thyroid size and shape, and no history of thyroid disease?

Management of Bilateral Solid Thyroid Nodules (TR3)

Both thyroid nodules require ultrasound-guided fine-needle aspiration biopsy (FNA) to exclude malignancy, as they meet size and sonographic criteria warranting tissue diagnosis. 1, 2, 3

Immediate Next Steps

1. Ultrasound-Guided FNA for Both Nodules

Perform FNA on the right lobe nodule (0.38 cm) and the left lobe nodule (0.55 cm) because:

• The left lobe nodule exceeds 0.5 cm with suspicious features (solid composition, internal vascularity), meeting the threshold for FNA in nodules with intermediate-risk sonographic patterns 1, 2
• The right lobe nodule contains a mural calcification, which significantly increases malignancy risk and warrants FNA even at smaller size 1
• Both nodules demonstrate internal vascularity, a concerning feature that elevates suspicion when combined with solid composition 1
• The background heterogeneous echotexture with increased vascularity suggests possible underlying thyroiditis, but this does not exclude malignancy in discrete nodules 1

2. Pre-FNA Laboratory Evaluation

Obtain the following tests before proceeding with FNA:

• Measure serum TSH to assess thyroid function, as higher TSH levels are associated with increased risk for differentiated thyroid cancer 1, 2
• Consider serum calcitonin measurement to screen for medullary thyroid cancer, which has higher sensitivity than FNA alone and detects 5-7% of thyroid cancers that FNA may miss 1, 3
• Measure thyroid peroxidase antibodies if TSH is elevated, to evaluate for underlying autoimmune thyroiditis 4

3. Technical Approach to FNA

• Ultrasound guidance is mandatory for both nodules, as it allows real-time needle visualization, confirms accurate sampling, and is superior to palpation-guided biopsy in terms of accuracy and diagnostic yield 1, 2, 3
• Target the solid components of both nodules, avoiding any cystic areas if present 1
• Document high-risk clinical factors during the procedure, including any history of head and neck irradiation (increases malignancy risk 7-fold) or family history of thyroid cancer 1, 2

Management Based on FNA Results

If Bethesda II (Benign) - Risk of Malignancy 1-3%

• Initiate surveillance with repeat ultrasound at 12-24 month intervals to monitor for growth or development of suspicious features 1, 2
• Surgery is not indicated unless compressive symptoms develop or cosmetic concerns are significant and patient-driven 1
• Molecular testing is not indicated for benign cytology, as the pretest probability of malignancy is too low (1-3%) to add clinical value 1

If Bethesda III-IV (Indeterminate) - Risk of Malignancy 12-34%

• 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, 2
• If TSH is normal and thyroid scan shows "cold" appearance, surgery should be considered for definitive diagnosis, as follicular carcinoma cannot be distinguished from follicular adenoma on cytology alone 1, 3
• Repeat FNA under ultrasound guidance may be considered if initial sample is inadequate 1

If Bethesda V-VI (Suspicious or Malignant) - Risk of Malignancy 96-98%

• Immediate referral to an endocrine surgeon for total or near-total thyroidectomy is recommended 1, 2, 3
• Pre-operative neck ultrasound must assess cervical lymph node status, as lymph node metastases alter surgical planning 1, 3
• Compartment-oriented lymph node dissection should be performed when lymph node metastases are suspected or proven 1

If Nondiagnostic/Inadequate Sample

• Repeat FNA under ultrasound guidance is mandatory, as inadequate samples occur in 5-20% of cases 1
• If repeat FNA remains nondiagnostic, consider core needle biopsy (CNB) for improved diagnostic accuracy 1

Critical Pitfalls to Avoid

• Do not defer FNA based on the "mild worrisome appearance" (TR3) designation alone - the presence of calcification in the right nodule and size >0.5 cm in the left nodule with solid composition and vascularity warrant tissue diagnosis 1, 2
• Do not rely on thyroid function tests (TSH, T3, T4) for malignancy assessment, as most thyroid cancers present with normal thyroid function 1, 2
• Do not perform FNA without ultrasound guidance, as palpation-guided biopsy has inferior accuracy and higher inadequate sample rates 1, 3
• Do not ignore the mural calcification in the right lobe nodule - calcifications significantly increase malignancy risk and are highly specific for papillary thyroid carcinoma 1
• A reassuring FNA should not override concerns if worrisome clinical findings persist, as false-negative results occur in up to 11-33% of cases 1

Follow-Up Strategy

• If both nodules are benign on FNA, perform surveillance ultrasound at 12-24 months initially, then extend intervals if stable 1, 2
• Monitor for development of compressive symptoms including dysphagia, dyspnea, or voice changes 1
• Assess for interval growth or development of new suspicious features on follow-up imaging 1
• If either nodule shows growth >20% in two dimensions or >50% in volume, repeat FNA is indicated 5