Thyroid Nodules and Cancer

1

What is the prevalence of thyroid nodules and cancer?

The prevalence of thyroid nodules increases throughout life and is dependent on the method of detection—by palpation 5%, by ultrasound (US) 35%, and by autopsy 50%. Thyroid nodules are four times more common in females than in males. After exposure to radiation, nodules develop at approximately 2% annually, reaching a peak at 25 years. Up to 35% of thyroid glands examined at autopsy contain occult papillary cancer (<1.0 cm). SEER database information suggests a thyroid cancer prevalence of about 637,000 in the United States and predicts 64,300 new cases in 2016.

2

What concerns are associated with thyroid nodules?

Thyroid nodules are clinically relevant to patients because of the ability to grow and cause compressive symptoms, the possibility of being functional adenomas, and the small risk of malignancy.

3

What is the importance of the distinction between solitary and multiple thyroid nodules?

Traditionally, multiple thyroid nodules were considered benign and solitary thyroid nodules malignant. However, multiple series suggest that a dominant nodule in a multinodular gland carries the same risk of cancer as a solitary nodule (5%). With improvements in US, each nodule should be assessed individually based on imaging characteristics.

4

What features of the history and physical examination indicate a higher risk of cancer?

• Nodules occurring at the extremes of age are more likely to be cancerous, particularly in males.

• Rapid growth and local invasion raise the possibility of malignancy, but associated symptoms (e.g., hoarseness, dysphagia) are uncommon.

• History of radiation exposure increases the frequency of both benign and malignant nodules.

• Family history of medullary or papillary thyroid cancer or Gardner syndrome (i.e., familial polyposis) increases the risk of cancer.

• Firm, solitary nodules, fixation to adjacent structures, vocal cord paralysis, and enlarged lymph nodes also are associated with an increased risk of malignancy.

5

What laboratory tests should be included in the evaluation of a patient with a thyroid nodule?

The only biochemical test that is routinely needed is a serum thyroid-stimulating hormone (TSH) concentration to identify patients with unsuspected hyperthyroidism.

Thyroglobulin and serum calcitonin should not be routinely tested. Thyroglobulin can be measured in patients with differentiated thyroid carcinoma, while calcitonin should be measured only in patients with suspected medullary thyroid carcinoma (MTC). Patients with known MTC should also have lymphocyte-derived DNA analysis for ret proto-oncogene mutation analysis .

In patients with known multiple endocrine neoplasia (MEN) 2, serum calcium levels and 24-hour urine collection for assessment of catecholamines and their metabolic products should be done to evaluate for hyperparathyroidism and pheochromocytoma before thyroidectomy.

6

What imaging should be done in the evaluation of a thyroid nodule?

• Thyroid US should be performed on all patients with nodules. It determines if there is a nodule that corresponds to a palpable abnormality, evaluates for other nodules, determines if a nodule is cystic, solid, or mixed, and is the best measure of the size of a nodule. Sonographic features are superior to size for determining risk of malignancy, and suspicious characteristics include microcalcification, hypoechogenicity of a solid nodule, and intranodular hypervascularity. US improves the accuracy of fine-needle aspiration (FNA) biopsy, which should be performed on nodules that are concerning.

• Radioactive iodine uptake scans are reserved for patients with suppressed TSH (<0.5 μIU/mL) to evaluate for hyperthyroidism resulting from Graves’ disease, toxic multinodular goiter, or an autonomous nodule. Patients with a normal or elevated TSH do not require scanning because it cannot reliably distinguish benign from malignant nodules.

7

What is the differential diagnosis of thyroid nodules?

• Adenoma: Macrofollicular (colloid), microfollicular, embryonal, Hürthle cell

• Cancer: Papillary, follicular, medullary, anaplastic, lymphoma, metastatic

• Cyst

• Multinodular goiter with a dominant nodule

• Other: Inflammatory diseases (e.g., Hashimoto’s thyroiditis), developmental abnormalities (e.g., thyroglossal duct cyst)

8

What is the single most important test in the evaluation of thyroid nodules?

The single best test is FNA. The overall accuracy exceeds 95% in experienced hands. If an adequate specimen is obtained, results are grouped by Bethesda Criteria (see Table 62.1 ) to predict the risk of malignancy and recommend a treatment plan.

9

Is levothyroxine suppression treatment useful in the management thyroid nodules?

Levothyroxine suppression treatment is generally not recommended, except in regions of the world with low iodine uptake where TSH suppression to subnormal serum levels using levothyroxine may decrease benign nodule size.