Thyroid Nodule Evaluation and Management

Initial Assessment and Diagnostic Approach

The American College of Physicians and other guideline societies recommend measuring serum TSH first as it determines the subsequent diagnostic pathway and is the single best initial test of thyroid function 1, 2, 3
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
If TSH is normal or elevated, proceed directly to ultrasound-guided evaluation without radionuclide scanning 3
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

Perform thyroid ultrasound of the thyroid and central neck in all patients with palpable thyroid nodules 1, 2
Ultrasound of the lateral neck can also be performed 1
Microcalcifications are a suspicious ultrasound feature requiring FNA 1
Central hypervascularity is a suspicious ultrasound feature requiring FNA 1
Taller-than-wide shape is a suspicious ultrasound feature requiring FNA 4

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

Initial follow-up at 1, 3, 6, and 12 months during the first year for non-suspicious nodules 5, 4
After 12 months, annual ultrasound for benign nodules 5, 4
Repeat FNA if nodule increases by ≥3 mm in any dimension or develops new suspicious features 4
Low-risk patients with nodules <6 mm without suspicious features may not require routine follow-up 4

The National Comprehensive Cancer Network recommends performing thyroid ultrasound of the thyroid and central neck concurrently with initial evaluation, as part of the diagnostic pathway for thyroid nodules with calcifications 6
Fine-needle aspiration (FNA) should be performed based on TSH results and ultrasound characteristics, as recommended by the Annals of Oncology 7, 8

Microcalcifications are highly suspicious for malignancy and constitute an indication for FNA regardless of nodule size, according to the National Comprehensive Cancer Network 6
The presence of calcification, particularly microcalcification, dramatically elevates malignancy risk and mandates thorough evaluation including TSH measurement 6

Ultrasound assessment should include evaluation for other suspicious features: hypoechogenicity, irregular borders, central hypervascularity, absence of peripheral halo, and regional lymphadenopathy, as recommended by the Annals of Oncology 8
Serum calcitonin measurement may be considered to screen for medullary thyroid carcinoma, which represents 4-7% of thyroid cancers, according to the National Comprehensive Cancer Network and the Annals of Oncology 6, 8