Patient education: Thyroid nodules (Beyond the Basics)

OVERVIEW — The thyroid is a butterfly-shaped gland in the middle of the neck, located below the larynx (voice box) and above the clavicles (collarbones) (figure 1). Thyroid nodules are round or oval-shaped areas within the thyroid (figure 2) that can be caused by a number of conditions, most of which are not serious.

This topic discusses the tests that may be performed on thyroid nodules, as well as the treatments that are available. Other thyroid conditions are discussed separately. (See "Patient education: Hyperthyroidism (overactive thyroid) (Beyond the Basics)" and "Patient education: Hypothyroidism (underactive thyroid) (Beyond the Basics)" and "Patient education: Antithyroid drugs (Beyond the Basics)".)

WHAT DOES THE THYROID DO? — The thyroid produces two hormones, triiodothyronine (T3) and thyroxine (T4), which regulate how the body uses and stores energy. Thyroid function is controlled by the pituitary gland, which is located just below the brain (figure 3). The pituitary produces a hormone that stimulates the thyroid to produce T3 and T4. This hormone is called thyroid-stimulating hormone (TSH).

Thyroid nodules are very common (figure 2); up to half of all people have at least one thyroid nodule, although most do not know about it. Thyroid nodules can be caused by many different conditions (table 1). Reassuringly, approximately 95 percent of all thyroid nodules are caused by benign (noncancerous) conditions.

THYROID NODULE DIAGNOSIS — Diagnostic tests can determine if a thyroid nodule is benign or malignant (cancerous); this information can help to guide treatment decisions. There are several diagnostic tests, and each provides unique information about the thyroid nodule. However, not every person with a thyroid nodule needs all of these tests.

Often, a test will provide a definitive answer about the type and cause of a nodule. In other cases, a test may be inconclusive, and further testing will be required. Your health care provider can talk to you about which tests you will need and what the results mean.

Thyroid-stimulating hormone — Thyroid-stimulating hormone (TSH) can be measured with a blood test.

●If the blood test shows that your TSH level is normal, the next step is to have a thyroid ultrasound. Depending upon the appearance of the nodule on ultrasound, a fine-needle aspiration (FNA) biopsy may be recommended. (See 'Thyroid ultrasound' below and 'Fine-needle aspiration' below.)

●Low levels of TSH in the blood may indicate that a nodule is producing high levels of thyroid hormone. If your TSH level is lower than normal, the next step is to have a thyroid scan. (See 'Thyroid scan' below.)

●High levels of TSH may indicate autoimmune inflammation of the thyroid (called Hashimoto's thyroiditis). Another blood test, to measure levels of thyroid antibodies, is sometimes recommended in this case (see "Pathogenesis of Hashimoto's thyroiditis (chronic autoimmune thyroiditis)"). An FNA biopsy may also be needed.

Thyroid ultrasound — A thyroid ultrasound should be done if you have a suspected thyroid nodule or nodular goiter after a physical examination. Ultrasound should also be done if nodules are found through imaging studies done for other reasons (for example, carotid ultrasound, computed tomography [CT], magnetic resonance imaging [MRI], or positron emission tomography [PET] scan). Thyroid ultrasonography provides information about the size and anatomy of the thyroid gland and nearby structures in the neck as well as the characteristics of the nodule. This information can be used to identify which nodules require FNA biopsy.

Fine-needle aspiration — In most cases, the TSH level is normal, and if the ultrasound shows features that are suspicious for cancer, the next step is fine-needle aspiration (FNA). FNA uses a thin needle to remove small tissue samples from the thyroid nodule. The tissue is then examined with a microscope.

FNA biopsy can be done in a doctor's office with a local anesthetic (medicine to numb the area). It can be performed by palpation (meaning the doctor uses their fingers to feel the nodule) but is usually done using ultrasound guidance. You may feel mild discomfort as the anesthesia is injected, and you may feel some pressure during the biopsy, but it should not be very painful.

The results of a biopsy will be one of the following:

●Benign (noncancerous) (see 'Benign thyroid nodules' below)

●Malignant (cancerous) (see 'Malignant thyroid nodules (thyroid cancer)' below)

●Suspicious for malignancy (see 'Suspicious for malignancy' below)

●Indeterminate – This means that the findings are neither clearly benign nor malignant, the risk of malignancy is low, and further testing may be advised. The following classifications are considered indeterminate, and require further evaluation:

•Follicular neoplasm (microfollicular nodules, including Hürthle cell lesions) (see 'Follicular neoplasm' below)

•Follicular lesion or atypia of undetermined significance (nodules with atypical cells or some microfollicles) (see 'Follicular lesion or atypia of undetermined significance' below)

●Nondiagnostic or insufficient – In this case, the biopsy does not contain enough tissue to make a diagnosis, and a repeat biopsy is necessary.

"Indeterminate" results make up approximately 15 percent of cases. Surgical removal of a nodule may be recommended for indeterminate nodules for a definitive diagnosis. However, in most cases in the United States (and some other countries where the technology is available), a biopsy sample is tested for specific "molecular markers" (genetic characteristics that affect how likely a nodule is to be malignant) instead of being removed with surgery. This information is used to determine whether the nodule should be observed or removed surgically for closer examination.

Thyroid scan — While most people do not have to have a thyroid scan, it may be recommended if a blood test shows that your TSH level is low. In this case, the thyroid scan (rather than a biopsy) is the first step after the blood test.

A thyroid scan can help to determine if a thyroid nodule is "hot," meaning it produces too much thyroid hormone, or "cold," meaning it does not. The scan is typically performed after taking a small dose of radioiodine (in the form of pill); alternatively, a substance called technetium may be injected into a vein, but this is less reliable. Because the dose of radioiodine (or technetium) is small, the amount of radiation exposure you get from a thyroid scan is relatively low. The risk of exposure is considered small compared with the benefit of knowing if you will need treatment. However, if you are pregnant or breastfeeding, you should not have a thyroid scan

●Thyroid nodules that absorb the radioiodine are usually not cancerous (called autonomous, hot, or toxic). (See '"Hot" thyroid nodules' below.)

●Thyroid nodules that do not absorb the radioiodine are called cold and have a 5 percent risk of being cancerous. Approximately 95 percent of thyroid nodules are cold.

THYROID NODULE TREATMENT — The appropriate thyroid nodule treatment depends upon the type of thyroid nodule that is found.

Benign thyroid nodules — Benign thyroid nodules usually develop as a result of overgrowth of normal thyroid tissue. Surgery is not usually recommended, and a benign nodule can be monitored with ultrasound over time. If it grows, a repeat biopsy or surgery may be recommended. Some surgeons recommend excision of nodules over 4 cm.

Large benign thyroid nodules may also be treated with radiofrequency ablation. With this technique, a needle-like probe is inserted in the nodule using ultrasound guidance. The probe uses thermal energy (heat) to destroy most of the nodule and reduce its size.

Suppressive (thyroid hormone) treatment — If a thyroid nodule is not cancerous, but the nodule is large, some health care providers will suggest a trial of thyroid hormone (thyroxine [T4]) to shrink the nodule; this is called suppressive treatment. The American Thyroid Association guidelines do not recommend this treatment, because only a small percentage of nodules shrink and suppressive therapy may have side effects (eg, abnormal heart rhythm or loss of calcium from bone). Thyroid hormone levels should be monitored carefully during suppressive treatment.

Malignant thyroid nodules (thyroid cancer) — Only approximately 5 percent of all thyroid nodules are malignant. Most people with thyroid cancer have an excellent chance of cure or long-term survival.

The exact treatment approach will depend on the type and size of cancer. Thyroid cancers require surgical removal of all or part of the thyroid gland and sometimes one or more treatments with radioiodine, followed by thyroid hormone (T4). The goal of taking thyroid hormone is to keep your thyroid-stimulating hormone (TSH) in the lower portion of the normal range or even slightly below normal. If your entire thyroid is removed with surgery, you will need to take daily thyroid hormone for life.

Suspicious for malignancy — Nodules in this category have a 50 to 75 percent risk of malignancy. People with nodules that are suspicious for malignancy frequently have a lobectomy (in which part of the thyroid is removed) or a total thyroidectomy (removal of the entire thyroid) because the chance that the nodule is a cancer is higher than the chance it is benign.

Follicular neoplasm — Nodules in this category have a 10 to 40 percent risk of malignancy. If your biopsy shows follicular neoplasm, your health care provider may do a thyroid scan, especially if your TSH level is in the lower portion of the normal range. If the scan shows a "cold" (non-hormone-producing) nodule or your TSH is not low, your provider may test a biopsy sample for certain molecular markers (if available). This information is used to determine whether the nodule should be observed or removed surgically for closer examination.

If surgery is necessary, a hemithyroidectomy (removal of half of the thyroid) or a total thyroidectomy (removal of the entire thyroid) may be recommended depending on the results of the molecular testing, the size of the nodule, and your preferences. "Hot" thyroid nodules are usually not cancerous, and treatment options are based on the results of thyroid function tests and other factors. (See '"Hot" thyroid nodules' below.)

Follicular lesion or atypia of undetermined significance — Nodules in this category have a 6 to 18 percent risk of malignancy. Molecular markers are frequently used to select low-risk nodules for observation rather than surgery. Many people whose biopsy shows nodules with atypical cells require repeat fine-needle aspiration (FNA). However, in some centers, a sample for molecular testing is obtained with all FNAs. The sample is submitted for analysis if the result is follicular lesion or atypia of undetermined significance. The optimal treatment depends upon individual factors, such as your personal risk for thyroid cancer and your past test results (including biopsy, molecular testing, and ultrasound).

Nondiagnostic — A nondiagnostic (or insufficient) biopsy does not have enough cells for interpretation. It should not be considered a negative biopsy. If your biopsy came back as nondiagnostic, the FNA should be repeated using ultrasound guidance.

"Hot" thyroid nodules — Some thyroid nodules produce thyroid hormone, similar to the thyroid gland, but do not respond to the body's hormonal controls. These nodules are called "hot" or "autonomous" thyroid nodules. They are almost always benign, but they can produce too much thyroid hormone, a condition known as hyperthyroidism. (See "Patient education: Hyperthyroidism (overactive thyroid) (Beyond the Basics)".)

If you have an autonomous thyroid nodule and high levels of thyroid hormone, you will probably be advised to have surgery to remove the thyroid nodule, or to undergo radioiodine treatment to destroy the nodule. Long-term treatment with the antithyroid drug methimazole is also an option, although methimazole cannot be taken during pregnancy.

If you have an autonomous nodule and normal thyroid function or minimal hyperthyroidism, the appropriate treatment will depend on your age and other health factors:

●In young adults, autonomous nodules may be monitored over time.

●In older adults, radioiodine treatment or surgery may be recommended because high thyroid hormone levels pose a risk of an abnormal heart rhythm (atrial fibrillation) and bone loss (osteoporosis).

Cystic thyroid nodules — Cystic thyroid nodules are usually benign nodules that have filled with fluid. These nodules may simply collapse when the fluid is removed. Cystic nodules are usually monitored for changes. If the cyst comes back or if the nodule bleeds more than once, surgery can be performed to remove the thyroid nodule. Sometimes the fluid is removed and the cyst is treated by injecting ethanol, which causes the sides of the cyst to become stuck to each other. This prevents the cyst fluid from building up again.

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Thyroid nodules (The Basics)
Patient education: Nodular goiter (The Basics)
Patient education: Thyroid cancer (The Basics)
Patient education: Seroma (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Hyperthyroidism (overactive thyroid) (Beyond the Basics)
Patient education: Hypothyroidism (underactive thyroid) (Beyond the Basics)
Patient education: Antithyroid drugs (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Atlas of thyroid cytopathology
Cystic thyroid nodules
Diagnostic approach to and treatment of thyroid nodules
Papillary thyroid cancer: Clinical features and prognosis
Differentiated thyroid cancer: Overview of management
Overview of thyroid nodule formation
Thyroid hormone suppressive therapy for thyroid nodules and benign goiter
Pathogenesis of Hashimoto's thyroiditis (chronic autoimmune thyroiditis)
Treatment of toxic adenoma and toxic multinodular goiter
Follicular thyroid cancer (including oncocytic carcinoma of the thyroid)

The following organizations also provide reliable health information.

●National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)

●The American Thyroid Association

(www.thyroid.org)

●Thyroid Foundation of Canada

(www.thyroid.ca)

●Hormone Health Network

(www.hormone.org, available in English and Spanish)

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