What is the next best investigation for a patient with a solitary thyroid nodule and a normal Thyroid-Stimulating Hormone (TSH) level?

Next Best Investigation for Solitary Thyroid Nodule with Normal TSH

Fine needle aspiration (FNA) biopsy is the next best investigation for a patient with a solitary thyroid nodule and normal TSH. 1

Rationale for FNA as First-Line Investigation

FNA should be performed for any thyroid nodule >1 cm, regardless of ultrasound characteristics or TSH level, to exclude malignancy. 1 This recommendation is consistent across multiple guideline societies including the American College of Radiology, National Comprehensive Cancer Network, and American Thyroid Association. 1

Why FNA Takes Priority Over Other Modalities

• Radioiodine uptake scanning is NOT indicated when TSH is normal, as thyroid scintigraphy is now rarely used except in the presence of a low (suppressed) TSH value. 2 The scan would only be useful if the nodule were autonomously functioning (causing hyperthyroidism), which is excluded by the normal TSH. 1

• CT neck is NOT the appropriate next step as ultrasound is the only appropriate initial imaging study for thyroid nodule characterization, providing superior visualization compared to CT or MRI. 1 CT would only be considered later for surgical planning if malignancy is confirmed. 1

• Thyroid antibodies are NOT helpful for determining malignancy risk in a solitary nodule, as most thyroid cancers present with normal thyroid function. 1

• PET scan is NOT indicated as a primary diagnostic tool for thyroid nodules. 1

Evidence Supporting FNA as Gold Standard

FNA is recognized as the most accurate and cost-effective method for evaluating thyroid nodules and remains the gold standard for preoperative diagnosis of thyroid malignancy. 1 The diagnostic accuracy approaches 95% for thyroid nodules. 1, 3

Performance Characteristics

• Sensitivity: 55-80% for detecting thyroid neoplasia 3, 4
• Specificity: 73.7-86.6% 3, 4
• False-negative rate: 11-33% 1
• Malignant cytology has NO false positives when properly interpreted 4

Clinical Algorithm for Solitary Thyroid Nodule Management

Step 1: Confirm Normal TSH

• TSH is already confirmed as normal in this case, ruling out autonomous function 1

Step 2: Perform High-Resolution Ultrasound

• Characterize nodule features before FNA 1
• Assess for suspicious features: microcalcifications, marked hypoechogenicity, irregular margins, absence of peripheral halo, solid composition, central hypervascularity 1
• Evaluate cervical lymph nodes for suspicious features 1

Step 3: Proceed with Ultrasound-Guided FNA

• Ultrasound guidance is mandatory as it allows real-time needle visualization, confirms accurate sampling, and is superior to palpation-guided biopsy in terms of accuracy, patient comfort, and cost-effectiveness 1
• FNA should target the solid portion if the nodule has mixed solid-cystic components 1

Step 4: Interpret Results Using Bethesda Classification

• Bethesda II (Benign): Surveillance with repeat ultrasound at 12-24 months, malignancy risk only 1-3% 1
• Bethesda III/IV (Indeterminate): Consider molecular testing for BRAF, RAS, RET/PTC, PAX8/PPARγ mutations 1
• Bethesda V/VI (Suspicious/Malignant): Immediate referral for total or near-total thyroidectomy 1

High-Risk Features That Strengthen FNA Indication

Even though FNA is already indicated for any nodule >1 cm, these features increase urgency: 1

• History of head and neck irradiation (increases malignancy risk 7-fold) 1
• Family history of thyroid cancer, particularly medullary carcinoma 1
• Age <15 years or male gender (males with solitary nodules have 22.7% cancer rate vs 11.9% in females) 4
• Rapidly growing nodule 1
• Firm, fixed nodule on palpation 1
• Vocal cord paralysis or compressive symptoms 1
• Suspicious cervical lymphadenopathy 1

Critical Pitfalls to Avoid

• Do NOT delay FNA waiting for additional imaging studies - FNA is the definitive diagnostic test 1, 5
• Do NOT rely on thyroid function tests alone to assess malignancy risk, as most thyroid cancers present with normal thyroid function 1
• Do NOT override a benign FNA if worrisome clinical findings persist, as false-negative results occur in up to 11-33% of cases - consider repeat FNA 1
• Do NOT perform radioiodine scanning in euthyroid patients - it does not help determine malignancy and delays appropriate diagnosis 1
• If initial FNA is inadequate (occurs in 5-20% of cases), repeat FNA under ultrasound guidance is mandatory 1

Additional Diagnostic Considerations

Measure serum calcitonin as part of the diagnostic workup 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

The correct answer is C. Fine needle aspiration.