Thyroid Nodules

What is the thyroid and what are thyroid nodules?

The thyroid is a small, butterfly-shaped gland located at the base of the neck that produces thyroid hormones, primarily thyroxine (T4) and some triiodothyronine (T3). These hormones travel throughout the body and regulate metabolism by telling the cells in the body how fast to use energy and produce proteins. The thyroid gland also makes calcitonin, a hormone that helps to regulate calcium levels in the blood by preventing the breakdown (reabsorption) of bone and increasing calcium elimination from the kidneys.

The body has an elaborate feedback system to control the amount of T4 and T3 in the blood.

When blood levels of the hormones decrease, the hypothalamus releases thyrotropin-releasing hormone, which in turn causes the pituitary gland to release thyroid-stimulating hormone (TSH). TSH stimulates the thyroid gland to produce and release T4 (primarily) and T3.
As thyroid hormone levels increase in the blood, the pituitary gland produces less TSH and the thyroid produces less T4 and T3.

Under normal circumstances, this feedback system regulates thyroid activity to maintain relatively stable levels of thyroid hormones in the blood.

Thyroid nodules are abnormal growths of thyroid tissue that form a swelling or lump within the thyroid gland. These nodules can happen at any age but become increasingly common as you get older, and are more common in women than men. The American Thyroid Association estimates that by age 60 as many as half of all people have a thyroid nodule that would be visible on imaging (e.g., ultrasound), although only about 5% of adults have nodules that are large enough to detect by physical exam.

In fact, most thyroid nodules do not cause symptoms and are found by chance, such as during an imaging scan for another condition or during a neck evaluation as part of a routine health exam. Occasionally, you may notice a lump in your neck and bring it to your healthcare practitioner's attention.

Once found, both the nodule and the thyroid gland need to be evaluated. More than 90% of thyroid nodules are not harmful (benign), but a small percentage are cancerous.

Thyroid nodules may:

Be solid or filled with fluid (cystic), or have aspects of both
Exist as a single nodule or be present as multiple nodules
Be small or large
Typically grow very slowly, but some nodules may grow rapidly while others may shrink
Occasionally be large enough to compress structures in the throat, causing pain, or difficulty swallowing or breathing
Rarely affect the vocal cords and cause hoarseness; these are more likely to be cancerous thyroid nodules.
Produce thyroid hormones (T4, T3), but most do not (non-functional thyroid nodules)

About Thyroid Nodules

Tests
Initial testing

A combination of laboratory testing and imaging tests may be used to evaluate your thyroid as well as any thyroid nodules.

Blood tests for thyroid-stimulating hormone (TSH), sometimes free T4, and occasionally free or total T3 may be done to help determine whether your thyroid gland is functioning normally. These tests may also help determine whether the thyroid nodule is producing excess thyroid hormone.

An ultrasound of the thyroid gland is also one of the first tests ordered to evaluate a thyroid nodule. Results of the ultrasound may show the nodule's location, size, shape and other characteristics and whether more than one nodule is present. Ultrasound may also be used to:

Evaluate the remainder of the neck structures, including lymph nodes

Help determine whether a fine needle aspiration biopsy (FNA, see below) will be done; if so, it can be used to guide needle placement during the FNA.

Monitor nodules and/or the thyroid gland over time

Fine needle aspiration biopsy (FNA, FNAB) – for this procedure, a healthcare practitioner inserts a thin needle into the thyroid and removes a small amount of tissue and/or fluid from a thyroid nodule. The cells collected are examined by a pathologist to determine whether cancer is present, or if the biopsy is suspicious for cancer.
A standardized system (Bethesda System) is used to report biopsy results. With each finding, there is an associated risk of cancer. Generally, results may be reported as:

Nondiagnostic or unsatisfactory—not enough cells were collected to make a diagnosis. There is a 5-10% risk of cancer. Typically, a repeat FNA will be done guided by ultrasound.

Benign—there is a 0-3% risk of cancer.

Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS)—risk of cancer is 10-30%.

Follicular lesion—cancerous about 25-40% of the time.
AUS or FLUS and follicular lesions are indeterminate (unclear) results. This means that even though enough cells were present in the sample to be examined using a microscope, it is not possible to reliably diagnose them as benign or cancerous.

Suspicious for malignancy—about 50-75% risk of cancer.

Malignant—97-99% risk of cancer.

Depending on results of an initial biopsy, a second biopsy or surgery may be needed.

Additional tests

Molecular tests—if the findings from a fine needle aspiration biopsy are indeterminate or unclear as described above, genetic testing of the biopsy material may be performed to detect cancer-causing variants (mutations) in certain genes (such as BRAF, KRAS, NRAS, and fusion genes such as RET/PTC, Pax8/PPARG).

Panels of genetic tests are available that can help determine the risk that the nodule is cancerous.

These tests may be used to help determine whether surgery is necessary.

The American Thyroid Association acknowledges that molecular tests can be useful supplemental information and recommends them but cautions they will not replace the ultrasound results, other clinical findings, and clinical judgement.

Molecular tests are helpful in diagnosing thyroid cancer; however, the absence of mutations in genes associated with thyroid cancer does not exclude thyroid cancer in the patient.

Calcitonin test—this blood test is not routinely used in the evaluation of a thyroid nodule, but it may sometimes be ordered to see if the thyroid gland is producing elevated amounts. Significantly elevated levels of calcitonin are an indicator of C-cell hyperplasia or medullary thyroid cancer; however, a healthcare practitioner will use other procedures, such as a thyroid biopsy, scan, and ultrasound, to establish a diagnosis.

Thyroid scans

FDG-PET scan (fluorodeoxyglucose (FDG)-positron emission tomography (PET)—the role of this scan in evaluating the thyroid and helping to detect cancer is still being studied. It uses a small amount of radioactively labeled glucose. Depending on the results, follow up testing (e.g., ultrasound, FNA) may be done.

Radioactive iodine scan—this scan is not routinely done anymore because ultrasound and FNAs are very good at evaluating thyroid nodules. However, it may be done in rare cases when a person has a thyroid nodule and hyperthyroidism. Thyroid nodules that produce excess thyroid hormone (causing hyperthyroidism) take up more of the radioactively labeled iodine than normal thyroid tissue, which shows up on the scan.
Treatments
Treatments for thyroid nodules depend primarily on the type of nodule as determined by results from the tests previously described.

Benign or small (less than one centimeter) nodules—these usually do not require treatment. Instead, they are monitored with physical exams, repeat ultrasounds, and/or fine needle aspiration biopsies to detect growth or changes in the nodule(s). The frequency of repeat testing depends on the risk of cancer. Surgery may be recommended if the nodule grows or compresses nearby structures.

Indeterminate nodules—treatment depends on the type of nodule and the cancer risk. Molecular testing may help determine cancer risk. A repeat fine needle aspiration biopsy may be done or surgery performed to remove the part of the thyroid containing the nodule. This surgical biopsy is evaluated and if cancer is found, the rest of the thyroid is surgically removed. If there is no cancer found, no further surgery is usually necessary.

Suspicious for malignancy and malignant nodules—most of these are treated with surgery to remove all or part of the thyroid, followed by one or more therapies to kill or control remaining cancer cells. Most thyroid cancers are curable.

If your entire thyroid is surgically removed, you will need lifelong thyroid hormone replacement therapy. This is manufactured thyroid hormone taken as a pill by mouth that replaces your body's own thyroid hormone.

Surgery may also be needed for relief of symptoms. Sometimes a nodule causes pain or grows large enough to make it difficult to breathe or swallow, requiring surgery to remove all or part of the thyroid.

Testing and treatments are always evolving. Talk to your healthcare practitioner about what is best for you. For additional details on treatment, see the links in Related Content.

For more, read the articles on Thyroid Cancer and Thyroid Diseases.

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