Initial Evaluation and Management of Thyroid Nodules
The initial evaluation of a thyroid nodule should include ultrasound-guided fine needle aspiration (FNA) of the nodule and clinically suspicious lymph nodes as the first diagnostic test, along with measurement of serum thyroid-stimulating hormone (TSH). 1
Diagnostic Approach
Initial Assessment
- Ultrasound of the thyroid and central neck should be performed for all thyroid nodules to detect and characterize nodular thyroid disease 2, 1
- Serum TSH measurement should be obtained ideally before FNA, as higher TSH levels are associated with increased risk of differentiated thyroid cancer 1
- FNA should be performed in any thyroid nodule >1 cm and in those <1 cm if there are suspicious clinical or ultrasonographic features 2, 3
Ultrasound Features Warranting FNA
- Suspicious ultrasound features include: 1
- Microcalcifications
- Central hypervascularity
- Absence of peripheral halo
- Irregular borders
- Hypoechogenicity
- Shape (taller than wide)
Clinical Risk Factors for Malignancy
- Age <15 years and male gender 1
- Family history of thyroid cancer 1
- History of head and neck irradiation 1
- Firm nodule fixed to adjacent structures 1
- Rapidly growing nodule 1
- Enlarged regional lymph nodes 1
- Vocal cord paralysis 1
- History of diseases associated with thyroid carcinoma (familial adenomatous polyposis, Carney complex, Cowden's syndrome, MEN 2A or 2B) 1
Fine Needle Aspiration (FNA)
- Ultrasound-guided FNA is more accurate, economical, safe, and effective than palpation-guided FNA 1
- FNA specimens should be categorized according to the Bethesda System for Reporting Thyroid Cytopathology 1
- If FNA is inadequate or nondiagnostic, it should be repeated 1
- Pathology and cytopathology slides should be reviewed at the treating institution by a pathologist with expertise in diagnosing thyroid disorders 1
Additional Testing
- Measurement of serum calcitonin should be considered as part of the diagnostic evaluation to detect medullary thyroid cancer, which has higher sensitivity compared with FNA 3, 2
- For indeterminate cytology results, molecular testing (BRAF/RAS, TERT, PIK3CA, TP53) can assist in diagnosis of benign versus malignant subtypes 1
- If TSH is suppressed, a thyroid scan with 99Tc can distinguish between a solitary hot nodule, toxic multinodular goitre, or less commonly, thyroiditis or Graves' disease 4
Management Based on FNA Results
Benign Cytology (Bethesda II)
- Active surveillance with regular ultrasound follow-up is recommended 2, 5
- Most thyroid nodules are benign, clinically insignificant, and safely managed with a surveillance program 5
Malignant or Suspicious Cytology (Bethesda V-VI)
- Total or near-total thyroidectomy is recommended for nodules ≥1 cm, or regardless of size if there is metastatic, multifocal or familial differentiated thyroid carcinoma 3, 2
- Surgery should be preceded by careful exploration of the neck by ultrasound to assess the status of lymph node chains 3
Indeterminate Cytology (Bethesda III-IV)
- For follicular neoplasia with normal TSH and "cold" appearance on thyroid scan, surgery should be considered 3, 1
- Molecular testing may help reduce unnecessary surgical procedures 6
Important Caveats
- A reassuring FNA should not override concerns in the presence of worrisome clinical findings, as false-negative results can occur 1
- Neither FNA nor core needle biopsy can distinguish thyroid follicular adenoma from adenocarcinoma 1
- The quality of thyroid nodule evaluations varies significantly; a complete evaluation should include both TSH measurement and high-quality ultrasound 7
Emerging Treatment Options
- For benign nodules causing compressive symptoms, non-surgical approaches include: 6
- Ethanol ablation for predominantly cystic nodules
- Thermal techniques such as radiofrequency ablation, laser ablation, microwaves, and high-intensity focused ultrasound
- Active surveillance is an option in select cases of micropapillary thyroid cancer 6