Thyroid Nodules
Thyroid nodules are extremely common (palpable in ~5%, incidental on US in ~50%). The key clinical question is excluding malignancy, which accounts for approximately 5% of thyroid nodules.
Key Facts
Palpable in ~5% of population; incidental on US in ~50%; the vast majority are benign ~5% of thyroid nodules are malignant; risk increased with: Male sex, age <20 or >60, solitary nodule, rapid growth, hoarseness, radiation exposure, family history U classification (BTA/RCR): U1-U5 based on ultrasound features — guides need for FNA FNA cytology (Thy classification): Thy1-5 — determines management (Thy3f = diagnostic lobectomy; Thy4/5 = surgery) Papillary carcinoma: Most common thyroid cancer (~80%); excellent prognosis (>95% 10-year survival); spreads to lymph nodes Follicular carcinoma: ~10-15%; cannot be distinguished from adenoma on FNA (need capsular/vascular invasion on histology) Medullary thyroid cancer: From parafollicular C cells; produces calcitonin; associated with MEN2A/2B; ~5-8% Anaplastic carcinoma: Rare (~1-2%); rapidly fatal (median survival ~6 months); elderly patients
Overview
Key Facts
Thyroid nodules are one of the most common endocrine findings. The challenge is identifying the ~5% that harbour malignancy while avoiding unnecessary surgery for the majority.
Epidemiology
Palpable nodules in ~5% of adults. Incidental nodules on US in ~50% of adults >50 years. Thyroid cancer incidence: ~3,500/year in UK. Female predominance for benign nodules (F:M ~4:1); malignancy ratio less pronounced.
Aetiology
Benign:
- Colloid/hyperplastic nodule (~60-70%)
- Follicular adenoma (~15-20%)
- Thyroiditis (Hashimoto's, subacute)
- Cyst
Malignant (~5%):
- Papillary carcinoma (~80% of thyroid cancers)
- Follicular carcinoma (~10-15%)
- Medullary carcinoma (~5-8%)
- Anaplastic carcinoma (~1-2%)
- Lymphoma (rare, associated with Hashimoto's)
Pathophysiology
- Papillary: Spread via lymphatics; multifocal in ~30%; Orphan Annie nuclei, psammoma bodies on histology
- Follicular: Spread via blood (haematogenous — lung, bone); needs capsular/vascular invasion for malignancy diagnosis
- Medullary: C-cell origin; calcitonin production; amyloid stroma; RET proto-oncogene (MEN2)
- Anaplastic: Undifferentiated; extremely aggressive; no iodine uptake; rapid local invasion
Clinical Presentation
Assessment of Thyroid Nodule
History:
- Duration and rate of growth
- Compressive symptoms (dysphagia, dyspnoea, hoarseness)
- Hyper/hypothyroid symptoms
- Radiation history (childhood neck irradiation)
- Family history of thyroid cancer, MEN, FMTC
Examination:
- Size, consistency (hard → concerning), mobility
- Fixation to surrounding structures
- Cervical lymphadenopathy
- Signs of thyroid dysfunction
Features Suggesting Malignancy (Red Flags)
- Rapid growth
- Hard, irregular, fixed nodule
- Cervical lymphadenopathy
- Vocal cord palsy (hoarseness)
- Male sex; age <20 or >60
- History of radiation exposure
- Family history of thyroid cancer/MEN
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Colloid/hyperplastic nodule | Benign, most common, variable US appearance | US, FNA if U3-U5 |
| Follicular adenoma | Cannot distinguish from carcinoma on FNA | FNA → diagnostic lobectomy |
| Papillary carcinoma | Microcalcifications, irregular margins, lymph nodes | US (U4-U5), FNA, surgery |
| Thyroid cyst | Simple fluid-filled, benign US features | US, aspiration |
| Thyroiditis nodule | Diffuse changes, may be tender | TFTs, anti-TPO antibodies |
| Medullary carcinoma | Raised calcitonin, may have MEN2 features | Calcitonin, RET testing |
Diagnosis / Investigation
Bedside
- TFTs: If suppressed TSH → radionuclide scan (hot/cold nodule); hyperfunctioning nodules rarely malignant
Bloods
- TFTs: TSH, FT4
- Calcitonin: If medullary carcinoma suspected or family history of MEN2
- Thyroid antibodies: If thyroiditis suspected
Imaging
- Ultrasound neck: First-line — classify using U classification (BTA/RCR)
- U1: Normal
- U2: Benign (isoechoic, halo, egg-shell calcification)
- U3: Indeterminate (solid, hypoechoic, mixed solid/cystic)
- U4: Suspicious (irregular margins, microcalcifications, tall > wide)
- U5: Malignant (features of U4 + invasion/nodes)
- FNA: Guided by U classification (U3-U5)
- Radionuclide scan (Tc99m): If TSH suppressed — hot nodule (autonomous, rarely malignant) vs cold (requires FNA)
- CT neck: If compressive symptoms or staging for malignancy
Cytology (Thy Classification)
- Thy1: Non-diagnostic → repeat
- Thy2: Benign → observation
- Thy3a: Atypical → repeat FNA or lobectomy
- Thy3f: Follicular neoplasm → diagnostic lobectomy
- Thy4: Suspicious → surgery
- Thy5: Malignant → surgery
Management
Benign (Thy2)
- Observation: Clinical and US follow-up
- Repeat US at 3-6 months then annually for 3-5 years
- If growing or changing → repeat FNA
Indeterminate (Thy3)
- Thy3a: Repeat FNA; if persistent → diagnostic lobectomy
- Thy3f: Diagnostic lobectomy — histology determines if benign adenoma or follicular carcinoma
Malignant (Thy4/5)
Papillary/follicular (differentiated thyroid cancer):
- Total thyroidectomy (if >4cm, bilateral, or high-risk features) or hemithyroidectomy (if low-risk, <4cm, unifocal)
- Radioactive iodine (RAI) ablation: Post-operatively for intermediate/high-risk disease
- TSH suppression: Levothyroxine to suppress TSH (reduces recurrence in differentiated cancer)
- Surveillance: Thyroglobulin (tumour marker), neck US
Medullary thyroid cancer:
- Total thyroidectomy + central neck dissection
- RAI NOT effective (C cells do not take up iodine)
- Screen for RET mutation; screen family members for MEN2
Anaplastic carcinoma:
- Palliative approach in most cases — surgery rarely curative
- External beam radiotherapy ± chemotherapy
- Tracheostomy may be needed for airway compromise
Referral Criteria
- U3-U5 on ultrasound → FNA → specialist thyroid MDT
- 2WW referral (NICE NG12) if unexplained thyroid lump
Prognosis
- Papillary carcinoma: 10-year survival >95%; 20-year survival >90%
- Follicular carcinoma: 10-year survival ~85-90%
- Medullary carcinoma: 10-year survival ~70-80%; worse with MEN2B
- Anaplastic carcinoma: Median survival ~6 months; near 100% mortality at 1 year
- Benign nodules: Excellent prognosis; ~5% annual growth rate; malignant transformation very rare
Other Relevant Information
Thyroid Cancer Comparison
| Type | Frequency | Origin | Spread | Marker | 10-Year Survival |
|---|---|---|---|---|---|
| Papillary | ~80% | Follicular cells | Lymph nodes | Thyroglobulin | >95% |
| Follicular | ~10-15% | Follicular cells | Haematogenous (bone, lung) | Thyroglobulin | ~85-90% |
| Medullary | ~5-8% | Parafollicular C cells | Lymph + haematogenous | Calcitonin, CEA | ~70-80% |
| Anaplastic | ~1-2% | Undifferentiated | Rapid local invasion | None | <5% |
| Lymphoma | ~1-2% | Lymphoid (Hashimoto's) | Nodal | None specific | Variable |