What is the appropriate evaluation and management approach for a patient presenting with a thyroid nodule?

Evaluation and Management of Thyroid Nodules

Initial Diagnostic Approach

Begin with serum TSH measurement as the first laboratory test for any patient presenting with a thyroid nodule, followed by thyroid ultrasound—this two-step approach determines all subsequent management decisions. 1, 2, 3

Step 1: TSH Measurement

• TSH guides the entire diagnostic pathway and must be obtained before proceeding to imaging studies 1, 2
• If TSH is low (suppressed): proceed to ultrasound first, then radionuclide thyroid uptake scan to identify hyperfunctioning "hot" nodules 1, 3
• If TSH is normal or elevated: proceed directly to ultrasound evaluation without radionuclide scanning 1, 2, 3

Step 2: Thyroid Ultrasound

• Ultrasound is the preferred first-line imaging modality for all thyroid nodules with normal or elevated TSH 1
• Perform ultrasound for all palpable thyroid nodules to confirm thyroid origin and characterize malignancy risk 3, 4
• Do not use ultrasound as a screening test in asymptomatic patients without palpable nodules 5

Risk Stratification by Ultrasound Features

High-Risk Sonographic Features Requiring Biopsy

• Solid composition with hypoechogenicity 6, 3, 4
• Microcalcifications 6, 3, 4
• Irregular or infiltrative margins 6, 3, 4
• Taller-than-wide shape (anteroposterior diameter greater than transverse) 3
• Absence of peripheral halo 6
• Intranodular vascularity on Doppler 3

Low-Risk Features (Observation Acceptable)

• Cystic or spongiform appearance suggests benign process 4
• Pure cysts rarely require biopsy 4

Fine-Needle Aspiration Biopsy (FNAB) Indications

Perform ultrasound-guided FNAB for nodules ≥1 cm with suspicious features, or for nodules <1 cm if there are high-risk clinical or sonographic characteristics. 6, 3, 5

Clinical Risk Factors Lowering Size Threshold

• History of head and neck irradiation 6
• Family history of thyroid cancer 6
• Presence of cervical lymphadenopathy 6
• Rapid growth or compressive symptoms 6
• Vocal cord paralysis 7

Pre-Biopsy Considerations

• Check coagulation function if patient is on anticoagulation 2
• Consider complete blood count and blood type determination 2
• Ensure experienced cytopathologist will interpret specimens 5

Management Based on TSH and Uptake Scan Results

For Low TSH (Thyrotoxicosis)

• After ultrasound, perform radionuclide thyroid uptake scan to determine if nodule is hyperfunctioning 1, 3
• Hyperfunctioning "hot" nodules are rarely malignant (malignancy risk <1%) and typically do not require biopsy 3, 8
• Hot nodules causing thyrotoxicosis can be treated with radioactive iodine therapy (98% success rate) 1

For Normal or Elevated TSH

• Proceed directly to ultrasound-guided FNAB based on size and sonographic features 3, 8
• Do not perform radionuclide scanning—it has low positive predictive value for malignancy in euthyroid patients 1, 2

Cytology Interpretation and Follow-Up

Bethesda Classification System

• Bethesda II (Benign): Very low malignancy risk (1-3%), surveillance acceptable 3, 9
• Bethesda III-IV (Indeterminate): Occurs in 20-30% of biopsies, consider molecular testing 4, 9
• Bethesda V-VI (Suspicious/Malignant): Surgical referral indicated 9, 8

Indeterminate Cytology Management

• Molecular testing can help differentiate benign from malignant nodules in indeterminate cases 3, 4, 9
• Consider surgery when TSH is normal and nodule appears "cold" on thyroid scan 3
• Molecular testing not yet validated in pregnant women or children 8

Surgical Indications

Refer for surgery when cytology shows malignancy or suspicious findings, or for nodules >2 cm even without suspicious features due to increased malignancy risk. 6, 3

Additional Surgical Considerations

• Compressive symptoms (dysphagia, dysphonia, dyspnea) 6, 7
• Substernal extension with respiratory compromise 1
• Follicular neoplasm on cytology (requires lobectomy minimum) 7
• Toxic multinodular goiter not responding to medical management 5

Critical Pitfalls to Avoid

• Never proceed directly to radionuclide scan without checking TSH first—this wastes resources and provides no useful information in euthyroid patients 1, 2
• Do not use radionuclide scanning to determine malignancy in patients with normal TSH—it has low diagnostic value 1, 3
• Do not perform ultrasound as a screening test in asymptomatic patients without palpable abnormalities 5
• Do not skip ultrasound evaluation before radionuclide scanning even in hyperthyroid patients—coexisting malignant nodules can be missed 1
• Do not rely on clinical examination alone—up to 50% of nodules are non-palpable but detectable on ultrasound 5

Special Populations

Pregnancy

• Management is similar to non-pregnant adults with TSH measurement and ultrasound 5, 8
• Molecular testing has not been validated in pregnancy 8
• FNAB can be safely performed during pregnancy if indicated 5

Children

• Evaluation approach mirrors that of adults 8
• Molecular testing not validated in pediatric populations 8
• Higher index of suspicion warranted as pediatric nodules have higher malignancy rates 5