Thyroid Nodules

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In conjunction with the American Society of Endocrine PAs (ASEPA), Clinician Reviews will be bringing you practical information about topics in endocrinology that may help you to better understand and manage patients with diabetes, thyroid disorders, and other metabolic conditions. In this month’s column, ASEPA President-Elect Christopher Sadler, MA, PA-C, CDE, discusses the role of ultrasonography in the detection of thyroid nodules.


Q: I often detect thyroid nodules in the course of a routine exam or as an incidental finding during diagnostic imaging. How commonly are these found in the general population?

Thyroid nodules are found on routine physical examination in 3% to 7% of patients. It is important to note that 50% of patients with one palpable nodule on physical exam will have additional nodules on ultrasonography.

Incidental finding of thyroid nodules has increased dramatically with the more frequent use of imaging in medicine (eg, carotid Doppler studies and chest/neck CT). The estimated prevalence of clinically undetected nodules in the general population, as detected by ultrasonography, is 20% to 76%. This wide variation results from technical and definitional ­issues.

Q: What tests should I order if I feel a thyroid nodule on examination or find one or more on a nonrelated imaging study?

All patients with a palpable or incidental thyroid nodule should undergo thyroid ultrasonography. A serum thyroid-stimulating hormone (TSH) is the best initial screening test for thyroid function. If the TSH is low, it raises suspicion for a hyperfunctioning nodule or gland; a free T4 (thyroxine) and total T3 (triiodothyronine) should follow. If hyperthyroidism is confirmed, a “hot nodule” should be considered. (See section on thyroid scintigraphy below.)

If the TSH is high, measurement of antithyroid peroxidase antibodies (TPOAb) is appropriate. Measurement of serum thyroglobulin is not usually required in the evaluation of thyroid nodules.

Factors that increase the risk for malignancy are: growing and/or fixed nodule; firm or hard consistency; cervical adenopathy; history of head and neck irradiation; family history of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2 (MEN 2), or papillary thyroid carcinoma (PTC); age < 14 or > 70 years; male sex; and persistent dysphonia, dysphagia, or dyspnea.

Q: When should I order a thyroid uptake and scan (thyroid scintigraphy)?

Thyroid scintigraphy may be helpful primarily in patients with a low serum TSH to detect hot nodules. Based on the pattern of radionuclide uptake, nodules are classified as hyperfunctioning (“hot”), hypofunctioning (“cold”), or indeterminate (neither hot nor cold). Hot nodules are almost never malignancies. Cold and indeterminate nodules may be malignant in 3% to 15% of cases. If the TSH is high or normal, the nodules will likely be cold or indeterminate, which has little predictive value.

Q: When should I consider ordering a thyroid fine-needle aspiration (FNA)?

It was once commonly assumed that a finding of multiple nodules on ultrasonography represented a decreased risk for thyroid malignancy. However, it is now known that the risk for malignancy is similar for solitary nodules, nodules in multinodular glands, or nodules embedded in large goiters. Additionally, the risk for cancer in nodules that are palpable on exam and in clinically undetectable nodules found incidentally is very similar (5.0% to 6.4% vs 5.4% to 7.7%, respectively).

Ultrasonographic characteristics can help identify suspicious nodules. This can be helpful in a multinodular gland, from which the nodule(s) chosen for FNA should be the one(s) with the most suspicious characteristics—not necessarily the largest. FNA is typically done by ultrasonographic guidance for more accurate sampling.

Ultrasound findings that may indicate malignancy include: hypoechogenicity in a solid or complex nodule; microcalcifications; irregular margins; intranodular vascularity; rounded appearance; and shape of the nodule more tall (anteroposterior) than wide (transverse).

When two or more of the characteristics above are present, the risk for malignancy increases. Often, ultrasound reports do not include sufficient information on these characteristics. When unsure about a nodule, the clinician should consult the radiologist, who can review the films with him/her for the presence or absence of the above characteristics.

In general, FNA is recommended for:

• Nodules > 1.0 cm that are solid and hypoechoic

• Nodules of any size with ultrasound findings suggestive of extracapsular growth or metastatic cervical lymph nodes

• Nodules of any size with patient history of neck irradiation in childhood or adolescence; PTC, MTC, or MEN 2 in first-degree relatives; increased calcitonin levels in the absence of interfering factors

• Nodules of diameter < 1.0 cm that have ultrasound findings associated with malignancy; the coexistence of two or more suspicious ultrasound criteria greatly increases the risk of thyroid cancer

• Nodules previously found benign by FNA cytology that have grown significantly or have new suspicious characteristics.

Thyroid ultrasonography is extremely helpful for classification of thyroid nodules based on characteristics that increase the likelihood of malignancy. TSH, thyroid antibody tests, and thyroid scintigraphy assess thyroid function. Serial ultrasonography can follow nodules found to be low-risk and suspicious nodules with benign FNA results. If significant changes occur, reaspiration or surgery should be considered.

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