What is the recommended workup for a thyroid nodule?

Thyroid Nodule Workup

The initial workup of a thyroid nodule should begin with serum TSH measurement followed by thyroid ultrasound, with fine-needle aspiration (FNA) reserved for nodules meeting specific size and sonographic criteria.

Initial Laboratory Assessment

• Measure serum TSH first as it determines the subsequent diagnostic pathway and is the single best initial test of thyroid function 1, 2, 3, 4.
• If TSH is low or suppressed, proceed to radioiodine uptake scan to identify hyperfunctioning ("hot") nodules, which are rarely malignant and do not require FNA 3, 5, 4.
• If TSH is normal or elevated, proceed directly to ultrasound-guided evaluation without radionuclide scanning 3, 4.
• Do not routinely measure serum calcitonin in all patients with thyroid nodules, as this remains controversial and cost-effectiveness is not established in the United States 1, 6.

Ultrasound Evaluation

• Perform thyroid ultrasound of the thyroid and central neck in all patients with palpable thyroid nodules 1, 2, 6.
• Ultrasound of the lateral neck can also be performed 1.
• Do not use ultrasound as a screening test in asymptomatic patients without palpable abnormalities 6.

Suspicious Ultrasound Features Requiring FNA:

• Solid composition with hypoechogenicity 7, 5, 4
• Microcalcifications 1, 7, 4
• Irregular or infiltrative margins 7, 4
• Taller-than-wide shape 8, 4
• Central hypervascularity 1

Benign-Appearing Features (Lower Priority for FNA):

• Cystic or spongiform appearance 7
• Purely cystic nodules 7

Fine-Needle Aspiration Criteria

• Perform FNA for nodules ≥10 mm with any suspicious ultrasound features 6, 5.
• For nodules <10 mm, FNA is indicated only if clinical risk factors or suspicious ultrasound features are present 6.
• Nodules ≥1.0 cm should undergo FNA depending on clinical and sonographic risk factors 5.
• Use ultrasound-guided FNA for optimal accuracy 6.
• FNA specimens should be interpreted by an experienced cytopathologist using the Bethesda Classification System (categories 1-6) 5, 4.

Clinical Risk Assessment

High-Risk Clinical Features:

• Age <15 years or male gender 1
• History of head and neck irradiation 1
• Family history of thyroid cancer or associated syndromes (MEN 2A/2B, familial adenomatous polyposis, Carney complex, Cowden's syndrome) 1
• Nodule that is firm, fixed, rapidly growing 1
• Associated cervical lymphadenopathy 1
• Vocal cord paralysis or symptoms of invasion 1

Symptoms to Assess:

• Dysphagia, dysphonia, pressure, or pain 6
• Symptoms of hyperthyroidism or hypothyroidism 6
• Note: Absence of symptoms does not exclude malignancy 6

Common Pitfalls to Avoid

• Do not proceed directly to radionuclide uptake scan in euthyroid patients—this wastes resources and has low diagnostic value 8, 3.
• Do not use radionuclide scanning to determine malignancy in euthyroid patients with nodules 8, 3.
• Do not perform routine thyroid cancer screening except in high-risk individuals, as early detection has not been shown to improve survival 5.
• Do not skip TSH measurement before selecting imaging modality, as this can lead to unnecessary testing and radiation exposure 3.

Management Based on FNA Results

• Benign nodules: Follow-up with ultrasound at 3,6, and 12 months in the first year, then annually 1, 8, 6.
• Malignant or suspicious cytology: Surgical treatment is indicated 6, 5.
• Indeterminate cytology (20-30% of biopsies): Consider molecular testing to guide management decisions between surgery and surveillance 7, 4.
• Hyperfunctioning nodules on radionuclide scan: Do not require FNA as they are rarely malignant 4.

Follow-Up for Non-Suspicious Nodules

• Initial follow-up at 1,3,6, and 12 months during the first year 1, 8.
• After 12 months, annual ultrasound for benign nodules 1, 8.
• Repeat FNA if nodule increases by ≥3 mm in any dimension or develops new suspicious features 8.
• Low-risk patients with nodules <6 mm without suspicious features may not require routine follow-up 8.