Diagnostic Workup for Thyroid Nodules
The recommended diagnostic workup for thyroid nodules should begin with 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
Initial Assessment
- Ultrasound (US) of the thyroid and central neck should be performed for all thyroid nodules, as it is essential for detecting and characterizing nodular thyroid disease 1
- Serum TSH measurement should ideally be obtained 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 1
Ultrasound Evaluation
Suspicious ultrasound features that warrant FNA include:
- Hypoechogenicity 1, 2
- Microcalcifications 1
- Irregular borders/margins 1, 3
- Solid composition 2, 3
- Central hypervascularity 1
- Absence of peripheral halo 1
- Shape (taller than wide) 1, 4
Clinical Risk Factors
The probability of malignancy increases with:
- 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)
- US-guided FNA is more accurate, economical, safe, and effective than palpation-guided FNA 1, 3
- FNA specimens should be categorized according to the Bethesda System for Reporting Thyroid Cytopathology 1
- Cytologic examination typically categorizes specimens as: carcinoma or suspicious for malignancy; follicular or Hürthle cell neoplasm; follicular lesion of undetermined significance; thyroid lymphoma; benign; or insufficient biopsy 1
Additional Testing
- For indeterminate cytology results, molecular testing (BRAF/RAS, TERT, PIK3CA, TP53) can assist in diagnosis of benign versus malignant subtypes 1
- Serum calcitonin measurement should be considered as part of the diagnostic evaluation to detect medullary thyroid cancer, which has higher sensitivity compared with FNA 1
- If TSH is suppressed, thyroid scintigraphy with 99Tc should be performed to evaluate for autonomously functioning thyroid nodules 5, 6
- Cervical lymph nodes should be evaluated by US when thyroid nodules are found 1
Management of FNA Results
- If FNA is inadequate or nondiagnostic, it should be repeated 1
- For follicular neoplasia with normal TSH and "cold" appearance on thyroid scan, surgery should be considered 1
- Pathology and cytopathology slides should be reviewed at the treating institution by a pathologist with expertise in diagnosing thyroid disorders 1
Follow-up
- For benign nodules, follow-up with ultrasound is recommended at regular intervals 1
- For malignant nodules, treatment planning should include careful exploration of the neck by ultrasound to assess lymph node chains 1
Important Caveats
- A reassuring FNA should not override concerns in the presence of worrisome clinical findings, as false-negative results can occur 1
- Neither FNAB nor CNB can distinguish thyroid follicular adenoma from adenocarcinoma 1
- Routine thyroid cancer screening is not recommended except in high-risk individuals 5
- Nodules with a long-to-short axis ratio greater than 2.5 are highly likely to be benign 4