Thyroid Nodules

Picture of the thyroid gland

The term thyroid nodule refers to any abnormal growth that forms a lump in the thyroid gland.

The thyroid gland is located low in the front of the neck, below the Adam's apple. The gland is shaped like a butterfly and wraps around the windpipe or trachea. The two wings or lobes on either side of the windpipe are joined together by a bridge of tissue, called the isthmus, which crosses over the front of the windpipe.

A thyroid nodule can occur in any part of the gland. Some nodules can be felt quite easily. Others can be hidden deep in the thyroid tissue or located very low in the gland, where they are difficult to feel.

A goiter is simply an enlarged thyroid gland. Multiple conditions can lead to goiter, including hypothyroidism, hyperthyroidism, excessive iodine intake, or thyroid tumors. Goiter is a nonspecific finding that warrants medical evaluation.

Thyroid nodules may be single or multiple.

1. A thyroid gland that contains multiple nodules is referred to as a multinodular goiter.
2. If the nodule is filled with fluid or blood, it is called a thyroid cyst.
3. If the nodule produces thyroid hormone in an uncontrolled manner (without regarding the body's needs), the nodule is referred to as autonomous.
   • Such a nodule may cause signs and symptoms of too much thyroid hormone, or hyperthyroidism.
   • Less often, patients with a thyroid nodule may have too little thyroid hormone or hypothyroidism
   • Hypothyroidism is most common in the context of Hashimoto's thyroiditis, a condition characterized by painless autoimmune destruction of the thyroid.
4. The most common types of single thyroid nodules are noncancerous colloid nodules or follicular adenomas.
5. Another type of benign nodule that may be seen is called a Hurthle cell adenoma. Up to 24% of Hurthle cell nodules are cancerous.
6. Few nodules are cancerous.
7. Cancerous nodules are classified by the types of malignant thyroid cells they contain. These cell types include papillary, follicular, medullary, or poorly differentiated (anaplastic) cells. The prognosis for the patient depends largely on the cell type and how far the cancer has spread at the time of diagnosis.
8. In addition to thyroid cancer of the cell types mentioned previously, thyroid nodules may contain lymphoma (a cancer of the cells of the immune system). Cancer from other sites, such as the breast and kidney, can also spread (metastasize) to the thyroid.

The cause of most thyroid nodules is unknown. In certain cases, insufficient iodine in the diet can cause the thyroid to develop nodules, but this is no longer common in the U.S. Certain genes may contribute to the development of thyroid nodules.

The vast majority of thyroid nodules do not cause symptoms. However, if the cells in the nodules are functioning and producing thyroid hormone on their own, the nodule may produce signs and symptoms of too much thyroid hormone (hyperthyroidism).

A small number of patients complain of pain at the site of the nodule that can travel to the ear or jaw. If the nodule is very large, it can cause difficulty swallowing or shortness of breath by compressing the esophagus (tube connecting the mouth to the stomach) or trachea (windpipe).

In rare instances, a patient may complain of hoarseness or difficulty speaking because of compression of the larynx (voice box).

Thyroid nodules usually are discovered by the health care professional during a routine physical examination of the neck. Occasionally, a patient may notice a nodule as a small lump in their neck when looking in the mirror. Once a nodule is discovered, a physician will carefully evaluate the nodule.

History

The doctor will take a detailed history, evaluating both past and present medical problems. If the patient is younger than 20 or older than 70 years, there is an increased likelihood that a nodule is cancerous. Similarly, the nodule is more likely to be cancerous if there is any history of radiation exposure, difficulty swallowing, or a change in the voice. It was customary to apply radiation to the head and neck in the 1950s to treat acne! Significant radiation exposures include the Chernobyl and Fukushima disasters. Although women tend to have more thyroid nodules than men, the nodules found in men are more likely to be cancerous. Despite its value, the history cannot differentiate benign from malignant nodules. Thus, many patients with risk factors uncovered in the history will have benign lesions. Others without risk factors for malignant nodules may still have thyroid cancer.

Physical examination

The physician should determine if there is one nodule or many nodules, and what the remainder of the gland feels like. The probability of cancer is higher if the nodule is fixed to the surrounding tissue (unmovable). In addition, the physical exam should search for any abnormal lymph nodes nearby that may suggest the spread of cancer. In addition to evaluating the thyroid, the physician should identify any signs of gland malfunction, such as thyroid hormone overproduction (hyperthyroidism) or underproduction (hypothyroidism).

Blood tests

Initially, blood tests should be done to assess thyroid function. These tests include:

• The free T4 and thyroid stimulating hormone (TSH) levels. Elevated levels of the thyroid hormones T4 or T3 in the context of suppressed TSH suggest hyperthyroidism
• Reduced T4 or T3 in the context of high TSH suggests hypothyroidism
• Antibody titers to thyroperoxidase or thyroglobulin may be useful in diagnosing autoimmune thyroiditis
• (for example, Hashimoto's thyroiditis).
• If surgery is likely to be considered for treatment, it is strongly recommended that the physician also determine the level of thyroglobulin. Produced only in the thyroid hormone in the blood. Thyroglobulin carries thyroid hormone in the blood. Thyroglobulin levels should fall quickly within 48 hours if the thyroid gland is completely removed. If thyroglobulin levels start to climb.

Ultrasonography

A physician may order an ultrasound examination of the thyroid to:

• Detect nodules that are not easily felt
• Determine the number of nodules and their sizes
• Determine if a nodule is solid or cystic
• Assist in obtaining tissue for diagnosis from the thyroid with a fine needle aspirate (FNA)

Despite its value, the ultrasound cannot determine whether a nodule is benign or cancerous.

Radionuclide scanning

Radionuclide scanning with radioactive chemicals is another imaging technique a physician may use to evaluate a thyroid nodule. The normal thyroid gland accumulates iodine from the blood and uses it to make thyroid hormones. Thus, when radioactive iodine (123-iodine) is administered orally or intravenously to an individual, it accumulates in the thyroid and causes the gland to "light up" when imaged by a nuclear camera (a type of Geiger counter). The rate of accumulation indicates how the thyroid gland and any nodules are functioning.

A "hot spot" appears if a part of the gland or a nodule is producing too much hormone. Non-functioning or hypo-functioning nodules appear as "cold spots" on scanning. A cold or non-functioning nodule carries a higher risk of cancer than a normal or hyper-functioning nodule.

Cancerous nodules are more likely to be cold because cancer cells are immature and don't accumulate the iodine as well as normal thyroid tissue. However, cold spots can also be caused by cysts. This makes the ultrasound a much better tool for determining the need to do an FNA.

Fine needle aspiration

Fine needle aspiration (FNA) of a nodule is a type of biopsy and the most common, direct way to determine what types of cells are present. The needle used is very thin. The procedure is simple and can be done in an outpatient office, and an anesthetic is injected into tissues traversed by the needle. FNA is possible if the nodule is easily felt. If the nodule is more difficult to feel, fine needle aspiration can be performed with ultrasound guidance. The needle is inserted into the thyroid or nodule to withdraw cells.

Usually, several samples are taken to maximize the chance of detecting abnormal cells. These cells are examined microscopically by a pathologist to determine if cancer cells are present. The value of FNA depends upon the experience of the physician performing the FNA and the pathologist reading the specimen.

Diagnoses that can be made from FNA include:

• Benign thyroid tissue (non-cancerous) can be consistent with Hashimoto's thyroiditis, a colloid nodule, or a thyroid cyst. This result is reported from approximately 60% of biopsies.
• Cancerous tissue (malignant) can be consistent with a diagnosis of papillary, follicular, or medullary cancer. This result is reported from approximately 5% of biopsies. The majority of these are papillary cancers.
• Suspicious biopsy can show a follicular adenoma. Though usually benign, up to 20% of these nodules are found ultimately to be cancerous.
• Non-diagnostic results usually arise because insufficient cells were obtained. Upon repeat biopsy, up to 50% of these cases can be distinguished as benign, cancerous, or suspicious.

One of the most difficult problems for the pathologist is to be confident that a follicular adenoma - usually a benign nodule - is not a follicular cell carcinoma or cancer. In these cases, it is up to the physician and the patient to weigh the option of surgery on a case-by-case basis, with less reliance on the pathologist's interpretation of the biopsy. It is also important to remember that there is a small risk (3%) that a benign nodule diagnosed by FNA may still be cancerous. Thus, even benign nodules should be followed closely by the patient and physician. Another biopsy may be necessary, especially if the nodule is growing.

Most thyroid cancers are not very aggressive; that is, they do not spread rapidly. The exception is poorly differentiated (anaplastic) carcinoma, which spreads rapidly and is difficult to treat.

Follicular adenomas are difficult to distinguish from follicular cancers. Follicular nodules, and other nodules, are highly suspicious for cancer, and definite cancer should be treated by surgery. Most thyroid cancers are curable and rarely cause life-threatening problems. Any nodule not removed needs to be watched closely by follow-up with the physician every 6 to 12 months. This follow-up may involve a physical examination, ultrasound examination, or both.

Occasionally, a physician may attempt to shrink the nodule by using suppressive doses of thyroid hormone. Some physicians believe that if a nodule shrinks on suppressive therapy, it is more likely to be benign. Recent large studies have shown that treating with thyroid suppression does not make a difference.

If a nodule causes hyperthyroidism, it is usually noncancerous. Treatment is aimed at preventing the signs, symptoms, and complications of hyperthyroidism, such as heart failure, osteoporosis, and rapid heart rate. Treatments include destroying the gland using radioactive iodine (131-iodine), blocking the production of thyroid hormone with medications, or conservatively following the patient with mild hyperthyroidism.

"Subclinical hyperthyroidism" refers to an adult patient with a hyperfunctioning nodule, but TSH is minimally suppressed and the blood levels of thyroid hormones are normal. Treatment is individualized based on age, the presence of other medical conditions, and patient preference.

Modern imaging techniques - such as ultrasound (US), computerized tomography (CT), and magnetic resonance imaging (MRI) - have revealed more thyroid nodules incidentally. This means that nodules are being found during studies that were done for reasons other than an examination of the thyroid per se. Up to 4%-8% of adult women and 1%-2% of adult men have thyroid nodules detectable by physical examination. Closer to 30% of adult women have nodules detectable by ultrasound. In fact, the diagnosis of a thyroid nodule is the most common endocrine problem in the United States.

Although the majority of thyroid nodules are benign (not cancerous), about 10% of nodules do contain cancer. Therefore, the primary purpose for evaluating a thyroid nodule is to determine whether cancer is present.