Key Facts

Most thyroid nodules are benign. Systematic evaluation with USS grading and FNA cytology identifies the ~5% that are malignant. The BTA guidelines provide a clear pathway for investigation.

Epidemiology

Palpable nodules ~5% of population. USS-detected nodules ~50% (especially in women, elderly). ~5% of thyroid nodules are malignant.

Aetiology

Benign: colloid nodules (most common), follicular adenoma, cysts, Hashimoto nodule. Malignant: papillary (~80%), follicular (~10%), medullary (~5%), anaplastic (~2%), lymphoma.

Pathophysiology

Most nodules represent focal thyroid hyperplasia, colloid accumulation, or benign neoplasia. Malignant transformation involves genetic mutations: RET/PTC rearrangements (papillary), RAS mutations, BRAF V600E (papillary — associated with poorer prognosis), PAX8-PPARγ (follicular).

Presentation

• Often asymptomatic — found incidentally on imaging or examination
• Neck swelling (patient or clinician finds lump)
• Compressive symptoms (large goitre): dysphagia, dyspnoea, hoarseness (recurrent laryngeal nerve)

Features Suggesting Malignancy

• Hard, fixed, non-tender nodule
• Rapid growth
• Cervical lymphadenopathy
• Hoarseness (recurrent laryngeal nerve involvement)
• Family history of thyroid cancer or MEN2
• History of neck irradiation
• Age <20 or >60
• Male sex (higher proportion malignant)

Red Flags

• Rapidly enlarging nodule → anaplastic carcinoma or lymphoma
• Hoarseness + thyroid mass → malignancy involving RLN
• Compressive symptoms → urgent assessment

TFTs

• First investigation: if TSH suppressed → uptake scan (hot nodule rarely malignant → no FNA needed)
• If TSH normal/raised → USS

Thyroid USS + BTA U-Classification

• U1: normal
• U2: benign (isoechoic, halo, spongiform cyst)
• U3: indeterminate/equivocal
• U4: suspicious (solid hypoechoic, lobulated)
• U5: malignant (solid hypoechoic, irregular margins, microcalcifications, taller-than-wide, nodal metastasis)
• FNA indicated: U3 (if >1 cm), U4, U5

Fine Needle Aspiration Cytology

• Thy classification (RCPath):
  • Thy1: non-diagnostic → repeat FNA
  • Thy2: benign → monitor
  • Thy3a: neoplasm possible → repeat FNA or surveillance
  • Thy3f: follicular neoplasm → diagnostic lobectomy (cannot distinguish adenoma from carcinoma on FNA)
  • Thy4: suspicious of malignancy → surgery
  • Thy5: malignant → surgery

Other

• Calcitonin: if medullary thyroid cancer suspected (MTC) or family history of MEN2
• Molecular testing: BRAF, RAS, RET/PTC — increasingly used for Thy3 nodules to guide management

Benign (Thy2, U2)

• Reassurance; follow-up USS at 3-6 months, then annually for 3-5 years
• Repeat FNA if growing

Indeterminate (Thy3)

• Thy3a: repeat FNA or surveillance USS
• Thy3f: diagnostic lobectomy (histological assessment needed to distinguish follicular adenoma from carcinoma)

Suspicious/Malignant (Thy4/5)

• Thyroidectomy: total thyroidectomy for confirmed malignancy (see thyroid cancer)
• MDT discussion: thyroid cancer MDT

Observation

• Small benign nodules: monitor with USS
• Growing benign nodule: repeat FNA or surgery

Referral Criteria

• 2WW (NICE NG12): unexplained thyroid lump in a child or adult (palpable thyroid nodule)
• Endocrine surgery: U3-5 or Thy3-5

~95% of thyroid nodules are benign. Benign nodules on FNA: <3% false-negative rate. Follicular neoplasm (Thy3f): ~20-30% are malignant on final histology. Most thyroid cancers (especially papillary) have excellent prognosis (>95% 10-year survival). Anaplastic thyroid cancer: very poor prognosis (median survival ~6 months).

BTA U-Classification and Action

Thy Classification and Management