What are the necessary steps to evaluate and manage a lump on the thyroid gland?

Evaluation and Management of a Thyroid Lump

Perform ultrasound-guided fine needle aspiration (FNA) for any thyroid nodule ≥1 cm, and for nodules <1 cm if suspicious ultrasound features or high-risk clinical factors are present. 1, 2

Initial Diagnostic Workup

History and Physical Examination

Obtain specific historical details that modify malignancy risk:

• Age <15 years or male gender increases baseline malignancy probability 3, 2
• History of head and neck irradiation increases malignancy risk approximately 7-fold 1, 2
• Family history of thyroid cancer, particularly medullary carcinoma or familial syndromes (MEN 2A/2B, familial adenomatous polyposis, Carney complex, Cowden's syndrome) 3, 2
• Rapidly growing nodule suggests aggressive biology 1, 2
• Hoarseness, dysphagia, or compressive symptoms may indicate invasive disease 3, 4

Physical examination must assess:

• Nodule characteristics: firm, fixed nodules suggest extrathyroidal extension 1, 2
• Cervical lymphadenopathy: palpable nodes increase malignancy probability 3, 2
• Vocal cord function: paralysis indicates nerve invasion 3, 2
• Tachycardia or tremor: suggests autonomous thyroid hormone production 4

Laboratory Testing

• Measure serum TSH before FNA, as higher TSH levels are associated with increased risk of differentiated thyroid cancer 1, 2
• Consider serum calcitonin measurement to screen for medullary thyroid cancer, which has higher sensitivity than FNA alone (detects 5-7% of thyroid cancers that FNA may miss) 1, 2

Ultrasound Evaluation

High-resolution ultrasound is the only appropriate initial imaging study for thyroid nodule characterization 1. Radionuclide scanning is not helpful in euthyroid patients for determining malignancy 1.

Suspicious ultrasound features that warrant FNA include:

• Microcalcifications (hyperechoic spots ≤1 mm representing psammoma bodies, highly specific for papillary thyroid carcinoma) 1, 2
• Marked hypoechogenicity (darker than surrounding thyroid parenchyma) 1, 2
• Irregular or microlobulated margins (infiltrative borders rather than smooth contours) 1, 2
• Absence of peripheral halo (loss of thin hypoechoic rim) 1, 2
• Central hypervascularity (chaotic internal vascular pattern) 1, 2
• Taller-than-wide shape on transverse view 2
• Solid composition carries higher malignancy risk than cystic nodules 1

Fine Needle Aspiration Biopsy

Indications for FNA

Perform ultrasound-guided FNA when:

• Any nodule >1 cm regardless of ultrasound appearance if ≥2 suspicious features present 1, 2
• Any nodule >4 cm regardless of ultrasound appearance (due to increased false-negative rate) 1
• Nodules <1 cm only if suspicious ultrasound features PLUS high-risk clinical factors (radiation history, family history, suspicious lymphadenopathy, age <15 years) 1, 2
• Suspicious cervical lymphadenopathy is present 1, 2

Technical Approach

Ultrasound guidance is mandatory as it allows real-time needle visualization, confirms accurate sampling, and is superior to palpation-guided biopsy in accuracy, patient comfort, and cost-effectiveness 1, 2. For mixed solid-cystic nodules, target the solid portion as it carries the highest malignancy risk 1.

Bethesda Classification System

FNA results are categorized using the Bethesda System for Reporting Thyroid Cytopathology 1, 2:

• Bethesda I (Nondiagnostic/Inadequate): Repeat FNA under ultrasound guidance 1, 2
• Bethesda II (Benign): Malignancy risk 1-3%; surveillance with repeat ultrasound at 12-24 months 1
• Bethesda III (AUS/FLUS): Consider molecular testing (BRAF, RAS, RET/PTC, PAX8/PPARγ) or repeat FNA 1, 2
• Bethesda IV (Follicular Neoplasm): Surgery required for definitive diagnosis, as FNA cannot distinguish adenoma from carcinoma 1, 2, 4
• Bethesda V (Suspicious for Malignancy): Immediate referral for total or near-total thyroidectomy 1, 2
• Bethesda VI (Malignant): Immediate referral for total or near-total thyroidectomy 1, 2

Management Based on FNA Results

Benign Nodules (Bethesda II)

Surveillance is the standard of care for Bethesda II nodules without concerning features 1:

• Repeat ultrasound at 12-24 months to assess for interval growth or development of suspicious features 1
• Monitor for compressive symptoms (dysphagia, dyspnea, voice changes) 1
• Surgery indicated only for: compressive symptoms clearly attributable to the nodule, significant patient-driven cosmetic concerns, or large nodules >4 cm (due to increased false-negative rate) 1

Indeterminate Nodules (Bethesda III/IV)

• Molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations assists in management decisions; 97% of mutation-positive nodules are malignant 1, 2
• Core needle biopsy may be considered if repeat FNA remains nondiagnostic 1, 2
• Follicular neoplasm (Bethesda IV) with normal TSH and "cold" appearance on thyroid scan requires surgical excision for definitive diagnosis 1, 2

Malignant or Suspicious Nodules (Bethesda V/VI)

Immediate referral to endocrine surgeon for total or near-total thyroidectomy 1, 2:

• Pre-operative neck ultrasound must assess cervical lymph node status 1, 2
• Compartment-oriented lymph node dissection indicated when lymph node metastases suspected or proven 1
• Surgery typically followed by radioactive iodine (¹³¹I) ablation to eliminate remnant thyroid tissue and microscopic residual tumor 1

Critical Pitfalls to Avoid

• Do not override a reassuring FNA when worrisome clinical findings persist, as false-negative results occur in up to 11-33% of cases 1
• Drains do not prevent hematoma formation after thyroidectomy; clot formation may prevent free drainage while hematoma continues to develop 5
• Stridor is a late sign of airway compromise post-thyroidectomy; intervention should occur well before stridor develops using DESATS criteria (Difficulty swallowing, increased Early warning score, Swelling, Anxiety, Tachypnea, Stridor) 5
• Avoid FNA on nodules <1 cm without high-risk features, as this leads to overdiagnosis and overtreatment of clinically insignificant cancers 1
• Cystic lesions are as likely as solid lesions to harbor malignancy (14% vs 23%); most cysts not abolished by aspiration should be surgically excised 6
• FNA is slightly less reliable for cystic lesions (88% sensitivity) compared to solid nodules (100% sensitivity); insufficient material for diagnosis occurs in 20% of cystic papillary cancers 6