In an adult patient with a hypoechoic thyroid nodule located in the left mid‑gland, what is the appropriate work‑up and management?

Management of a Hypoechoic Thyroid Nodule in the Left Mid-Gland

Proceed directly to ultrasound-guided fine-needle aspiration (FNA) biopsy for any hypoechoic thyroid nodule ≥1 cm, as hypoechogenicity is a well-established suspicious sonographic feature that substantially increases malignancy risk and warrants tissue diagnosis. 1

Initial Diagnostic Work-Up

Step 1: Measure Serum TSH

• Obtain serum thyroid-stimulating hormone (TSH) level to determine if the nodule is autonomously functioning 2, 3
• If TSH is suppressed (low), proceed to radionuclide thyroid uptake scan with 99mTc 2, 3
  • Hot (hyperfunctioning) nodules are rarely malignant and do not require FNA 2
  • Cold nodules require the same evaluation as nodules with normal/elevated TSH 3
• If TSH is normal or elevated, proceed directly to ultrasound characterization 2, 3

Step 2: Perform High-Resolution Ultrasound

Document the following features to stratify malignancy risk:

High-risk features that increase suspicion for malignancy:

• Marked hypoechogenicity (nodule darker than surrounding thyroid parenchyma) 1, 4
• Solid composition (higher risk than cystic) 1
• Microcalcifications (highly specific for papillary thyroid carcinoma) 1, 4
• Irregular or microlobulated margins 1, 4
• Absence of peripheral halo 1
• Central hypervascularity (chaotic internal blood flow) 1

Assess cervical lymph nodes systematically:

• Evaluate both central and lateral cervical lymph node compartments for suspicious features: loss of fatty hilum, microcalcifications, cystic change, or abnormal vascularity 1

Step 3: Determine FNA Indication Based on Size and Features

For nodules ≥1 cm:

• Perform ultrasound-guided FNA for any nodule ≥1 cm with hypoechoic appearance, regardless of other features 1, 4, 2
• The combination of solid composition and hypoechogenicity represents intermediate-to-high suspicion (TI-RADS 4) that warrants tissue diagnosis 1

For nodules <1 cm:

• Perform FNA only if hypoechogenicity is present plus high-risk clinical factors 1:
  • History of head and neck irradiation (increases risk 7-fold) 1
  • Family history of thyroid cancer (especially medullary carcinoma or familial syndromes) 1
  • Suspicious cervical lymphadenopathy 1
  • Age <15 years 1
  • Subcapsular location 1
• Do not perform FNA on nodules <1 cm without these high-risk factors to avoid overdiagnosis of clinically insignificant papillary microcarcinomas 1

Step 4: Consider Additional Diagnostic Testing

• Measure serum calcitonin as part of the initial workup to screen for medullary thyroid cancer, which has higher sensitivity than FNA alone (detects 5-7% of thyroid cancers that FNA may miss) 1
• Calcitonin testing is particularly important because medullary thyroid cancer may not show typical ultrasound features associated with papillary cancer 5

FNA Technique and Interpretation

Procedural Approach

• Use ultrasound guidance for FNA rather than palpation-guided biopsy, as it provides real-time needle visualization, confirms accurate sampling, and is superior in accuracy, patient comfort, and cost-effectiveness 1, 4
• If the initial sample is inadequate (nondiagnostic), repeat FNA under ultrasound guidance 1
• Consider core needle biopsy (CNB) if repeat FNA remains nondiagnostic or for follicular neoplasms requiring histological examination 1

Bethesda Classification and Management

Bethesda II (Benign):

• Malignancy risk: 1-3% 1
• Management: Surveillance with repeat ultrasound at 12-24 months 1
• Surgery indicated only for compressive symptoms or nodules >4 cm 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 (97% of mutation-positive nodules are malignant) 1
• Follicular neoplasm with normal TSH and "cold" scan requires surgical excision for definitive diagnosis 1

Bethesda V (Suspicious) or VI (Malignant):

• Immediate referral to endocrine surgeon for total or near-total thyroidectomy 1
• Pre-operative neck ultrasound to assess lymph node status 1
• Surgical consultation should be arranged within 2-4 weeks of pathology report 1

Critical Pitfalls 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 override a reassuring FNA when worrisome clinical findings persist, as false-negative results occur in up to 11-33% of cases 1
• Do not perform radionuclide scanning in euthyroid patients to determine malignancy risk, as ultrasound features are far more predictive 1
• Do not delay FNA for observation in solid hypoechoic nodules ≥1 cm, as palpation alone cannot reliably differentiate benign from malignant nodules 1

Special Considerations

If Multiple Nodules Are Present

• Prioritize the largest nodule for initial FNA, as nodule size ≥3 cm is associated with 3-times greater malignancy risk 1
• If the larger nodule is benign but clinical suspicion remains high, evaluate additional suspicious nodules in subsequent procedures 1

If Nodule Shows Rapid Growth

• Growth of ≥3 mm in any dimension during surveillance warrants immediate FNA, as rapid growth is one of the strongest predictors of malignancy 1
• Dramatic enlargement (>10 mm) far exceeds measurement error and represents true progression requiring urgent evaluation 1