Thyroid Nodules

Anatomy of the Thyroid and Parathyroid Glands

• The main function of the thyroid gland in the neck is to make thyroid hormone, which is essential for normal growth and metabolism.
• Nodules are simply lumps that are either solid or fluid-filled.
• Goiter is simply a term for an enlarged thyroid gland.
• Autopsy studies have revealed that up to 50% of all adults die carrying at least one thyroid nodule. These people may or may not have been aware of the presence of their thyroid nodules.
• Thyroid nodules are found more commonly as people age.
• Most thyroid nodules are benign and not cancerous.
• Only 5% of all thyroid nodules will be discovered to be thyroid cancer.
  • Finding cancer in a thyroid nodule is more likely in a person younger than age 30 or older than age 60 years.
  • However, it is important to remember that only a small percentage of people with thyroid cancer die as a result of their thyroid cancer.

Causes of thyroid nodules can be classified as benign (noncancerous) or malignant (cancerous).

Benign Thyroid Nodules

There are a variety of benign thyroid nodules such as

• goiters,
• Hashimoto's thyroiditis,
• thyroid cysts, and
• benign thyroid tumors (thyroid adenomas).

Multinodular Goiter

Multinodular goiter is an overall enlargement of the thyroid gland resulting from nodules, which either contain too many normal thyroid cells (referred to as hyperplasia) and/or have been filled with extra colloid.

• A colloid is a protein-containing substance that normally stores thyroid hormone inside the thyroid gland.

Hashimoto's Thyroiditis

Hashimoto's thyroiditis is the most common form of underactive thyroid disease. This form of hypothyroidism can be associated with thyroid nodules and goiter.

Thyroid Cyst

Commonly caused by a nodule that is bleeding or degenerating (breaking down), these blood or colloid-filled nodules can be associated with thyroid pain.

Benign Thyroid Tumors (Thyroid Adenomas)

Thyroid adenomas are benign abnormal growths of tissue in the thyroid gland. They are generally classified as follicular or papillary.

• Follicular adenomas are the most common type of tumor (adenomas). Cell types of follicular tumors include fetal, colloid, atypical, and Hurthle.
• Papillary adenomas are the least common type of thyroid tumor or adenoma.

Malignant Thyroid Nodules

There are several types of thyroid cancer. At times, thyroid cancer is metastatic cancer (secondary cancer) that has come from other organs in the body that are primary cancers.

6 Types of thyroid cancer (thyroid carcinomas) are:

• Papillary thyroid carcinoma: In the United States, approximately 74% to 80% of thyroid cancers are papillary thyroid cancers, which are more common in women 15 to 84 years of age. Papillary thyroid carcinoma may be caused by exposure to ionizing radiation, history of exposure to X-rays of the head and neck, particularly during childhood, therapeutic radiation, oral contraceptives, late start of menstruation, late age at first birth, and tobacco smoking.
• Follicular thyroid carcinoma: This is an adenoma more common in women aged 15 to 84 years. Follicular thyroid carcinoma may be caused by ionizing radiation, exposure to head and neck X-rays particularly in childhood, therapeutic radiation, radiotherapy for certain cancers, iron deficiency, and research demonstrates from mutations of the ras oncogene.
• Anaplastic thyroid carcinoma: This is the most aggressive type of thyroid cancer and is more common in females. Anaplastic thyroid cancer is thought to occur from previously undetected long-standing papillary or follicular cancer.
• Medullary thyroid carcinoma: This is a type of thyroid cancer that has a genetic association with multiple endocrine neoplasias (the formation of new tumors).
• Thyroid lymphoma: This is a type of lymphoma that originates in the thyroid gland.
• Metastatic cancers from other sources, including breast, kidney, and lung cancers

Most people with thyroid nodules have no symptoms.

Individuals may notice these symptoms include:

• A lump is seen in the front of the neck
• Rapidly growing lump in the front of the neck
• A lump felt in the throat
• Difficulty swallowing if the nodule is positioned such that food has difficulty traveling through the upper portion of the esophagus to the stomach
• Hoarseness of the voice
• Other enlarged glands or lymph nodes in the neck
• Pain is only rarely associated with thyroid nodules

Nodules may be found:

• By a physician during a routine physical exam
• During computed tomography (CT scan), magnetic resonance imaging (MRI), or ultrasound of the front of the neck

A physician will perform an exam of the nodule using the hands.

• Larger and more anteriorly (front) located nodules can be felt by the examiner.
• A physician will ask about any other medical history and any risk factors for thyroid nodules or cancer, including a family history of thyroid cancer or radiation exposure of the head or neck.

• Thyroid stimulating hormone (TSH) levels and levels of thyroid hormone can indicate whether the thyroid is underproducing or overproducing thyroid hormones.
• Anti-thyroid antibody levels can indicate the presence of autoimmune thyroid inflammation that can be seen with Hashimoto's thyroiditis (underactive thyroid disease called hypothyroidism) or Graves' disease (overactive thyroid disease called hyperthyroidism).
• Calcitonin levels in the blood can suggest a specific type of thyroid cancer, known as medullary carcinoma of the thyroid. However, calcitonin testing is generally not recommended as part of an initial evaluation of a thyroid nodule.

This test uses sound waves to take a picture of the thyroid. Similar to the prenatal ultrasound of the fetus, a cold lubricant jelly is placed on the neck. Then, using an external probe, ultrasound images of the thyroid gland are obtained.

An ultrasound can reveal which thyroid nodules are larger than 1.0 to 1.5 centimeters, requiring further evaluation for cancer.

In addition to size, other nodule characteristics that can be noted on a thyroid ultrasound include the following:

• Number of nodules
• Location of nodules
• Distinctness of borders
• Fluid versus solid contents
• Other nodule contents (such as calcium deposits) or
• The amount of blood flow; certain newer ultrasound machines can assess blood flow to the thyroid and its nodules

• If a thyroid nodule is larger than 1 cm, or it has other worrisome characteristics seen on ultrasound or other imaging tests, then FNAB may be performed.
• This office procedure does not require anesthesia and consists of passing small needles (similar to those used to draw blood from the arm) into the thyroid nodule(s) in the neck. This is a quick and usually painless procedure.
• This procedure may be done on multiple nodules.
• Ultrasound guidance may be used to assist in the FNAB of nodules that are bigger than 1.0 to 1.5 cm but cannot be felt by physical examination.
• A sample of the contents of each nodule (including fluid, blood, or tissue) is removed from the needle and examined by the pathologist under a microscope.
• Pathologists often can identify certain features in the nodule sample.

FNAB results are characterized as one of the following:

• Benign: This is the most common outcome of FNAB. The typical finding is a nodule filled with colloid protein, a normal component of the thyroid. Benign nodules can be followed over time with serial physical exams or ultrasound exams. Further intervention is only necessary if enlargement occurs or new symptoms develop.
• Malignant: Some thyroid cancers can be diagnosed directly from FNAB results (for example, papillary thyroid cancer). Other thyroid cancers cannot be diagnosed from FNAB results (such as follicular thyroid cancer). This is because the diagnosis rests not simply upon the appearance of the tissue within the nodule, but also on the level of the invasion of surrounding blood vessels and tissue by the nodule. For such nodules, surgical removal of a portion of the entire thyroid is recommended.
• Indeterminate: This is neither definitively benign nor malignant. Given that the risk for cancer is increased by 20% in such cases, surgical removal of a portion of the entire thyroid is typically recommended. Often, a radionuclide scan will be done to obtain functional information (determine whether the nodule is actively producing thyroid hormones) in order to avoid unnecessary surgery.
• Non-diagnostic: This means that there are not enough tissue cells present in the sample to make a diagnosis. Non-diagnostic FNABs will typically result in repeat FNAB or definitive surgery.

Cystic nodules more often result in a non-diagnostic FNAB due to higher fluid content than solid content in the sample obtained from the nodule.

• The use of radioisotope scanning has nearly been abandoned in the initial workup of a thyroid nodule. This test is performed by a nuclear medicine specialist. After a small, safe amount of radioisotope (123-iodine or Tc99) is taken by mouth or injected into a vein, the radiologist obtains pictures of the thyroid.
• Nodules can be seen as dark spots (called "cold," because they do not take up the radioisotope) or bright spots (called "hot," because they do take up the radioisotope).
• Nodules that concentrate the radioisotope are "hot" and usually make excessive thyroid hormone. "Hot" nodules are rarely associated with cancer and may not require FNAB investigation.
• Nodules that do not concentrate iodine are "cold" and usually take less than normal amounts of thyroid hormone
  • More than 80% to 85% of all thyroid nodules are "cold," but only 10% of these represent a malignancy.
  • These nodules are typically more worrisome for cancer and require evaluation with FNAB or surgery.

As stated previously, the majority of thyroid nodules are benign and may not require any intervention. In particular, nodules that are benign and/or less than 1 cm wide may not require immediate treatment. Instead, periodic evaluation by a physician's examination and/or ultrasound may be sufficient.

Treatments for thyroid nodules are:

Radioactive Iodine

131-IODINE (I-131) concentrates in the thyroid tissue and cause tissue destruction. I-131 can be administered as a capsule or in liquid form.

• I-131 can be used to treat multinodular goiters with nodules that are producing extra thyroid hormone. Such cases are indicated by a low TSH level and elevated thyroid hormone level in the blood or a "hot" nodule on radionuclide (I-123) thyroid scan.
• After I-131 destroys the thyroid, the patient develops an underactive thyroid (hypothyroidism) and requires thyroid hormone replacement for life to maintain a normal level of thyroid hormones in the blood. Thyroid hormone replacement consists simply of taking a pill once daily by mouth.
• Thyroid hormone replacement is safe, easily tolerated, and relatively inexpensive.

Thyroid Surgery

Thyroidectomy is the removal of the thyroid by surgery. Partial or complete thyroidectomy is recommended for:

• Thyroid cancer or indeterminate lesions that cannot be classified from a fine needle aspiration biopsy (FNAB)
• Large thyroid nodules that cause obstructive symptoms, such as problems breathing or swallowing
• Thyroid nodules that cause pain
• Cosmetic reasons, to remove large visible thyroid nodules

Thyroid Hormone Suppression

There is controversy regarding whether physician-supervised administration of thyroid hormone may shrink the size of thyroid nodules. Many doctors believe that thyroid hormone does not effectively shrink nodules. Furthermore, there is the risk of high blood levels of thyroid hormone in patients with multiple thyroid nodules (multinodular goiter). Two major studies have shown that thyroid suppression does not make a difference.

• The American Thyroid Association does not recommend thyroid suppression of the benign thyroid nodules in iodine-sufficient populations.
• Doctors may make this decision on a case-by-case basis and research is still ongoing to determine the efficacy of this type of treatment. It is important to discuss the pros and cons of suppressive thyroid hormone therapy with your doctor.