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Am Fam Physician. 2020;102(5):298-304

Patient information: A handout on this topic is available at https://familydoctor.org/condition/thyroid-nodules.

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Author disclosure: No relevant financial affiliations.

Thyroid nodules can be detected by ultrasonography in up to 68% of the general population. They are typically benign and are often discovered incidentally. The primary goal of thyroid nodule evaluation is to determine whether it is malignant. After thyroid ultrasonography has been performed, the next step is measurement of serum thyroid-stimulating hormone. If levels are low, a radionuclide thyroid uptake scan is indicated. Hyperfunctioning nodules are rarely malignant and do not require tissue sampling. Nonfunctioning nodules and nodules in a patient with a normal or high thyroid-stimulating hormone level may require fine-needle aspiration based on ultrasound characteristics and size. Nodules with suspicious features and solid hypoechoic nodules 1 cm or larger require aspiration. The Bethesda System (categories 1 through 6) is used to classify samples. Molecular testing can be used to guide treatment when aspiration yields an indeterminate result. Molecular testing detects mutations associated with thyroid cancer and can help inform decisions about surgical excision vs. continued ultrasound monitoring. Treatment of pregnant women with nonfunctioning thyroid nodules and of children with thyroid nodules is similar to that for nonpregnant adults, with the exception of molecular testing, which has not been validated in these populations. (Am Fam Physician. 2020;102(5):298–304. Copyright © 2020 American Academy of Family Physicians.)

New advances in molecular testing have changed the management of thyroid nodules. This article reviews the workup for thyroid nodules, including how to interpret ultrasound findings and fine-needle aspiration (FNA) cytopathology, and a comparison of new molecular testing modalities to determine the appropriate management strategy.

WHAT'S NEW ON THIS TOPIC

Over the past few years, molecular testing of fine-needle aspiration specimens has changed the way thyroid nodules with indeterminate cytology are managed. A benign pattern on molecular testing significantly decreases the risk of malignancy in indeterminate thyroid nodules. However, these nodules still require ultrasound surveillance.

There is growing evidence that low-risk micropapillary thyroid cancers smaller than 1 cm can be followed with observation as an alternative to immediate surgical excision.

Clinical recommendationEvidence ratingComments
Thyroid ultrasonography with a survey of the cervical lymph nodes should be performed in all patients with thyroid nodules.11,12 CCross-sectional prevalence studies and expert opinion
The serum thyroid-stimulating hormone level should be measured during the initial evaluation of a thyroid nodule.If it is low, a radionuclide thyroid uptake scan should be performed.11,12 CCross-sectional prevalence studies and expert opinion
Fine-needle aspiration is recommended for thyroid nodules 1 cm or larger that have a suspicious pattern on ultrasonography.11,12 CCross-sectional prevalence studies and expert opinion
Before molecular testing is performed, patients should be counseled about the potential benefits and limitations of the test.11 CExpert opinion
RecommendationSponsoring organization
Do not use nuclear medicine thyroid scans to evaluate thyroid nodules in patients with normal thyroid gland function.Society of Nuclear Medicine and Molecular Imaging

Epidemiology

Thyroid nodules are detected by ultrasonography in up to 68% of healthy patients.1 Most thyroid nodules are detected incidentally when imaging is performed for another indication. They are found on about 16% of computed tomography or magnetic resonance imaging studies of the neck.2

Thyroid nodules are more common in countries with iodine-deficient populations. The introduction of iodized salt in 1924 virtually eliminated iodine deficiency disorders in the United States.3 Thyroid nodules are four times more common in women than in men, and their prevalence increases with age and body mass index.46

Most thyroid nodules (90% to 95%) are benign.4,6 Risk factors for thyroid cancer include ionizing radiation (e.g., from cancer treatments, occupational exposure, or nuclear fallout, especially when the exposure occurs at a young age), rapid nodule growth, hoarseness, and a family history of thyroid cancer or cancer syndromes (e.g., multiple endocrine neoplasia type 2, familial adenomatous polyposis).7 Patients with Graves disease who have hypofunctioning nodules have a higher prevalence of papillary thyroid cancer (33% to 42%).8

The U.S. Preventive Services Task Force recommends against screening for thyroid cancer with neck palpation or ultrasonography.9 Screening results in overdiagnosis and overtreatment without improving patient outcomes. In South Korea, a widespread cancer screening program increased the thyroid cancer diagnosis rate 15-fold but did not change the mortality rate.10

Evaluation

The first step in evaluating a thyroid nodule is to measure the thyroid-stimulating hormone (TSH) level and perform thyroid ultrasonography with a survey of the cervical lymph nodes.7,11,12 A normal or elevated TSH level indicates that the thyroid nodule is nonfunctioning; a low or suppressed TSH level suggests the diagnosis of primary hyperthyroidism, and a radionuclide thyroid uptake scan (technetium-99 or iodine-123) should be performed. Focal increased uptake in the region of the thyroid nodule is consistent with a hyperfunctioning or “hot” nodule. Hyperfunctioning nodules are unlikely to be malignant and do not require FNA. Nonfunctioning or “cold” nodules should be further evaluated with FNA if they meet clinical or ultrasound criteria.

Figure 1 suggests a management approach for thyroid nodules based on laboratory and ultrasound features.11 Nonfunctioning nodules have a 14% to 22% risk of malignancy.13 The risk of malignancy should be further stratified by ultrasound findings, which can be used to distinguish suspicious nodules that require further evaluation with FNA. According to the American College of Radiology, the American Thyroid Association, and the European Thyroid Association, ultrasound features that strongly suggest malignancy include hypoechoic echogenicity, solid composition, irregular margins, microcalcifications, height greater than width, extrathyroidal extension, disrupted rim calcification, and cervical lymph nodes with suspicious features.11,14,15 FNA should not be performed on nodules smaller than 1 cm.11 Micropapillary thyroid cancers typically have an indolent course. However, patients younger than 40 years may have more progressive disease.16 Most nodules smaller than 1 cm that have highly suspicious ultrasound features (with the exception of extrathyroidal extension and suspicious cervical lymph nodes) can be followed with close surveillance and repeat thyroid ultrasonography in six to nine months. FNA can be considered for younger patients or if the patient requests it.11 Conversely, pure cystic nodules are rarely malignant and do not require evaluation with FNA. Spongiform and predominantly cystic nodules also have very low risk of malignancy, and biopsy should be considered only if the nodule is 2 cm or larger.11 These nodules can also be followed with thyroid ultrasonography in 12 to 24 months without FNA.

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