Diagnosing Benign Thyroid Nodules vs. Thyroid Cancer

FINE NEEDLE ASPIRATION BIOPSY (FNAB)

A biopsy is the only way to tell if a thyroid nodule is cancerous. But cancer may be more likely if you have:

• A single, hard lump that feels very different from the rest of the thyroid tissue or other thyroid nodules.
• A nodule that keeps growing for weeks or months.
• A nodule that does not move when you touch it.
• Swollen lymph nodes in your neck.
• A hoarse or scratchy voice that does not go away.

Some other conditions that cause similar symptoms include hyperthyroidism and thyroiditis.

• If a thyroid nodule is larger than 1 cm, or it has other worrisome characteristics seen on ultrasound or other imaging tests, then a 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 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 1-1.5 cm but cannot be felt on physical examination.
  
  
• A sample of the contents of each nodule (to include fluid, blood, or tissue) are removed in the needle and examined by the pathologist under a microscope.
• Pathologists 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 a 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 the FNAB results (for example, papillary thyroid cancer). Other thyroid cancers cannot be diagnosed from the FNAB results (such as follicular thyroid cancer) because the diagnosis rests not simply upon the appearance of the tissue within the nodule, but also on the level of the invasion of surround blood vessels and tissue by the nodule. For these nodules, surgical removal of a portion or 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 or the entire thyroid is typically recommended. Often, a radionuclide scan will be done to obtain functional information (if the nodule is actively producing thyroid hormones) in order to avoid an unnecessary surgery.
  
  
• Non-diagnostic: This means that there are not enough of the tissue cells present in the sample to make a diagnosis. Non-diagnostic FNABs will typically result in a 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.

Thyroid Nodule Diagnosis: The Basics

A physician performs an exam of you neck using his/her 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 family history of thyroid cancer or radiation exposure of the head or neck.

Blood tests

• Thyroid stimulating hormone (TSH) levels and levels of thyroid hormone can indicate whether the thyroid is under- 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) or Graves's disease (overactive thyroid disease).
  
• Calcitonin levels in the blood can indicate 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.

Ultrasound of the thyroid

This is a test that 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 1-1.5 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).

Thyroid Nodules Symptoms

Most people with thyroid nodules have no symptoms. 

Most thyroid nodules do not cause symptoms and are so small that you cannot feel them. They often are found during a physical exam or when another test, such as a CT scan or ultrasound, is done for a different reason. If your thyroid nodule is big, you may be able to feel it or you may notice that your neck is swollen

Patients may notice the following:

• A lump seen in the neck.
  
• A lump felt in the throat.
• Hoarseness of the voice.
• Difficulty swallowing and/or breathing.
• Other enlarged glands or lymph nodes in the neck.
• Rapidly growing lump or swelling 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 neck

Thyroid Nodules Causes

Causes of thyroid nodules can be classified as benign or malignant. 

                     

Experts do not know the exact cause of thyroid nodules. But they do know that people who have been exposed to radiation have a greater chance of developing thyroid nodules. Exposure to environmental radiation or past radiation treatment to the head, neck, and chest (especially during childhood) raises your risk for thyroid nodules.

Experts know that thyroid nodules run in families. This means you are more likely to have a thyroid nodule if one of your parents has had a thyroid nodule. Also, if you have another thyroid condition (such as goiter), you may have a greater chance of developing thyroid nodules.

Benign Thyroid Nodules

• Multinodular goiter: Multinodular goiter is an overall enlargement of the thyroid gland (called goiter) can result from nodules containing too many normal thyroid cells (referred to as hyperplasia) and/or filled with extra colloid. Colloid is the protein-containing substance normally storing 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 which is bleeding or degenerating (breaking down), these blood or colloid-filled nodules can be associated with thyroid pain.

Benign thyroid tumors (thyroid adenomas)

• Hurthle cell adenoma
• Follicular adenoma

Malignant Thyroid Nodules

Thyroid Cancer (also called thyroid carcinomas)

• Papillary thyroid carcinoma
• Follicular thyroid carcinoma
• Anaplastic thyroid carcinoma
• Medullary thyroid carcinoma
• Thyroid lymphoma
• Metastatic cancers from other sources, including breast, kidney and lung cancers

Thyroid Nodules Overview

Most thyroid nodules do not cause problems and are not cancerous. They are often hard to notice because they are so small. Lots of people have thyroid nodules that are never found or treated. There are three kinds of thyroid nodules: solid nodules, nodules that are filled with fluid (cystic nodules), and nodules that are partially cystic. You can have one thyroid nodule or several thyroid nodules (multinodular goiter). 

You can also have some nodules that are solid and some that are cystic. Solid nodules may grow slowly over time. In rare cases, cystic nodules bleed, which can cause them to grow suddenly and become painful. Thyroid nodules usually do not prevent the thyroid gland from doing its job. But sometimes a noncancerous thyroid nodule can cause:

• Hyperthyroidism. - when one or more nodules makes too much thyroid hormone. Hyperthyroidism is treated with antithyroid medicine, possibly radioactive iodine, and very rarely, surgery. Hyperthyroidism from thyroid nodules is not very common. It occurs in fewer than 1 out of 100 people who have thyroid nodules.

• Difficulty breathing or swallowing. -Sometimes, one or more large nodules can press on your windpipe (trachea) or on your esophagus. These kinds of nodules have to be surgically removed.

FAST FACTS: 

• Only about 5 out of 100 thyroid nodules are cancerous.
• Thyroid nodules are simply "lumps" which are either solid or fluid-filled. 
• The main function of the thyroid gland in the neck is to make thyroid hormone, which is essential for normal growth and metabolism.
• 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 of these 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 under the age of 30 or over the age of 60.

Your Thyroid Gland: The Basics Review

The thyroid is an organ that is considered part of the endocrine, or hormone, system. It is located in the neck below the Adam's apple. The thyroid's main purpose is to produce thyroid hormones. These hormones then travel through the bloodstream to all the other tissues and organs to help control metabolism in adults and growth, development, and metabolism in children.

• The thyroid is shaped like a butterfly. The two "wings" of the butterfly are the right and left lobes of the thyroid, with lie on both sides of the trachea or main breathing tube. The connection between the wings is called the isthmus.
  
  
• The two hormones that the thyroid produces are L-thyroxine(T4) and tri-iodothyronine (T3).

• The thyroxine (T4) and tri-iodothyronine (T3) hormones regulate your body's metabolic functions such as heat generation, and the utilization of carbohydrates, proteins, and fats. In children, thyroid hormones are responsible for growth and development.
  
  
• Regulatory hormones from different parts of the brain control the thyroid's production of T4 and T3. In the pituitary gland, thyrotropin-stimulating hormone (TSH) is released when more thyroid hormone is needed and travels via the bloodstream to the thyroid gland. TSH then stimulates the thyroid to produce T4 and T3.
  
  
• The pituitary gland acts like a thermostat. When there is too much thyroid hormone in the bloodstream, the pituitary releases less TSH to signal the thyroid to produce less thyroid hormone. When there is too little thyroid hormone in the bloodstream, the pituitary releases more TSH to signal the thyroid to increase thyroid hormone production. Through this "feedback" system, the production of thyroid hormone is tightly controlled.

Thyroid Health Problems Overview

The thyroid gland is located on the front part of the neck below the thyroid cartilage (Adam's apple). The gland produces thyroid hormones, which regulate body metabolism. Thyroid hormones are important in regulating body energy, the body's use of other hormones and vitamins, and the growth and maturation of body tissues.

Diseases of the thyroid gland can result in either production of too much (overactive thyroid disease or hyperthyroidism), too little (underactive thyroid disease or hypothyroidism) thyroid hormone,thyroid nodules, and/or goiter. All types of thyroid problems in women are much more common than thyroid problems in men.

• Production of thyroid hormones: The process of hormone synthesis begins in a part of the brain called the hypothalamus. The hypothalamus releases thyrotropin-releasing hormone (TRH). The TRH travels through the venous plexus located in the pituitary stalk to the pituitary gland, also in the brain. In response, the pituitary gland then releases thyroid-stimulating hormone (TSH) into the blood. The TSH travels to the thyroid gland and stimulates the thyroid to produce the two thyroid hormones, L-thyroxine (T4) and triiodothyronine (T3). The thyroid gland also needs adequate amounts of dietary iodine to be able to produce T4 and T3.

• Regulation of thyroid hormone production: To prevent the overproduction or underproduction of thyroid hormones, the pituitary gland can sense how much hormone is in the blood and adjust the production of hormones accordingly. For example, when there is too much thyroid hormone in the blood, TRH and TSH production are both decreased. The sum effect of this is to decrease the amount of TSH released from the pituitary gland and to reduce production of thyroid hormones from the thyroid gland to restore the amount of thyroid hormone in the blood to normal. Defects in these regulatory pathways may result in hypothyroidism (underactive thyroid problem) or hyperthyroidism  (overactive thyroid problem).
  
  
• Thyroid goiter: Thyroid goiter is any enlargement of the thyroid that can occur with hyperthyroidism or hypothyroidism but also with benign and malignant (cancerous) nodules. Worldwide, the most common cause of goiter is iodine deficiency. Although it used to be very common in the U.S., it is now less common with the use of iodized salt. Multiple nodules in the thyroid are very common, but only about 5% of the nodules are a thyroid cancer. Thyroid cancer is diagnosed after a thyroid ultrasound exam and a needle aspiration biopsy of the nodule.

Pregnant? Talk To Your Doctor About Thyroid Health Conditions Today

Hypothyroidism in Pregnancy

Newly diagnosed hypothyroidism in pregnancy is rare because most women with untreated hypothyroidism do not ovulate or produce mature eggs in a regular manner, which makes it difficult for them to conceive.

It is a difficult new diagnosis to make based on clinical observation. The signs and symptoms of hypothyroidism (fatigue, poor attention span, weight gain, numbness, and tingling of the hands or feet) are also prominent symptoms of a normal pregnancy.

Undiagnosed hypothyroidism during pregnancy increases the chance of stillbirth or growth retardation of the fetus. It also increases the chance that the mother may experience complications of pregnancy such as anemia, eclampsia, and placental abruption.

Probably the largest group of women who will have hypothyroidism during pregnancy are those who are currently on thyroid hormone replacement. The ideal thyroxine replacement dose (for example, levothyroxine [Synthroid, Levoxyl, Levothroid, Unithroid]) during pregnancy may rise by 25% to 50% during pregnancy. 

It is important to have regular checks of T4 and TSH blood levels as soon as pregnancy is confirmed; and frequently through the first 20 weeks of pregnancy to make sure the woman is taking the correct medication dose.

Hyperthyroidism in Pregnancy

Newly diagnosed hyperthyroidism occurs in about 1 in 2,000 pregnancies. Grave's disease accounts for 95% of cases of hyperthyroidism newly diagnosed during pregnancy.

As with hypothyroidism, many symptoms of mild hyperthyroidism mimic those of normal pregnancy. However, anyone experiencing symptoms such as significant weight loss, vomiting, increased blood pressure, or persistently fast heart rate should have blood tests to evaluate whether hyperthyroidism is present.

Untreated hyperthyroidism does cause fetal and maternal complications including poor weight gain and tachycardia (an abnormally fast heart rate).

Treatment of hyperthyroidism during pregnancy is primarily medical.Propylthiouracil or methimazole (Tapazole) are the usual first-line agents to block the synthesis of thyroid hormone. They appear to be equally effective and have the same rate of side effects. The rate of side effects of each medication is not increased in pregnancy.

Iodine will cross the placenta, so its use in either a thyroid scan or in treatment with radioactive iodine is prohibited in pregnancy. One positive note for women with hyperthyroidism is that those with Grave's disease or Hashimoto's thyroiditis may have improvement in their symptoms during pregnancy.

Goiter in Pregnancy

It is common for a goiter to enlarge slightly during pregnancy. It is more common when the mother lives in an area of iodine deficiency. In the United States, the average intake of iodine is adequate but can be low if someone avoids consumption of milk, eggs, and iodized salt. Not all prenatal vitamins contain iodine, but it is recommended that only prenatal vitamins that contain iodine should be used during pregnancy.

Postpartum Thyroid Disease

Some women may have thyroiditis that usually occurs within 3 to 6 months after giving birth. It also may occur after miscarriage. The classic clinical picture is a woman who will first have symptoms of hyperthyroidism, followed by hypothyroidism, culminating in normal thyroid function.

Women with type I diabetes have a 25% risk of developing postpartum thyroid dysfunction.  Consult your doctor if you have symptoms of hypothyroidism or hyperthyroidism after pregnancy or miscarriage.

STUDY: Thyroid and Parathyroid Surgical Outcomes In Pregnant Women

Thyroid and parathyroid surgery outcomes may be worse in pregnant women. Pregnant women appear to have worse clinical and economic outcomes after thyroid and parathyroid surgery compared with women who are not pregnant, according to a report in the May issue of Archives of Surgery, one of the JAMA/Archives journals.

Thyroid and parathyroid surgery are used to treat cancer and other conditions. The incidence of thyroid cancer has increased by almost 250 percent over the last 30 years, increasing from 3.6 to 8.7 cases per 100,000 persons, according to background information in the article. The rate is almost double in pregnant women, with 14.4 cases per 100,000 persons. "Hyperthyroidism [overactive thyroid] has been reported in 0.1 percent to 0.4 percent of pregnancies. Inadequately treated hyperthyroidism during pregnancy poses significant risks to both mother and fetus," the authors write. "Outcomes after thyroid and parathyroid procedures during pregnancy have not been well characterized in the surgical literature."

SreyRam Kuy, M.D., of Yale University School of Medicine, New Haven, Conn., and United States Department of Veterans Affairs, Washington, and colleagues compared clinical and economic outcomes of thyroid and parathyroid surgery performed on 201 pregnant women (average age 29) and a group of 31,155 age-matched, non-pregnant women from 1999 to 2005. Fetal, maternal and surgical complications as well as in-hospital death, length of stay and hospital costs were measured.

Of the 201 pregnant women, 165 underwent thyroid procedures and 36 underwent parathyroid procedures. "Compared with non-pregnant women, pregnant patients had a higher rate of endocrine [relating to glands that secrete hormones](15.9 percent vs. 8.1 percent) and general complications (11.4 percent vs. 3.6 percent), longer unadjusted lengths of stay (two days vs. one day) and higher unadjusted hospital costs ($6,873 vs. $5,963)," the authors write. "The fetal and maternal complication rates were 5.5 percent and 4.5 percent, respectively," Additionally, pregnant patients had higher surgical complications than non-pregnant patients for benign (27 percent vs. 14 percent) and malignant (21 percent vs. 8 percent) thyroid diseases while undergoing thyroidectomy (the surgical removal of part or all of the thyroid gland).

"Differences between pregnant and non-pregnant women in complication rates were most pronounced by diagnosis, race and hospital size," the authors note. When compared to non-pregnant women of the same race, white pregnant patients had double the complication rate (21 percent vs. 10 percent), black pregnant patients had nearly five times the complication rate (48 percent vs. 10 percent) and Hispanic pregnant patients had an almost three-fold higher complication rate (30 percent vs. 12 percent).

"These data suggest that thyroid and parathyroid surgery during pregnancy should be approached with caution and careful deliberation about whether the risks are outweighed by the benefits," the authors conclude. "Surgeon volume is an important predictor of outcomes, so pregnant women undergoing thyroid and parathyroid procedures should be directed to high-volume surgeons whenever possible. Disparities in outcomes based on race and insurance must be overcome. Optimizing maternal and fetal outcomes requires the collaboration of surgeons, endocrinologists, obstetricians, neonatologists, anesthesiologists, insurers and policy makers."

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SJCCF Thy-NET Editor's Note: The study was supported by the Robert Wood Johnson Foundation and the United States Department of Veterans Affairs. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. Available pre-embargo to the media at http://www.jamamedia.org/ (Arch Surg. 2009;144[5]:399-406.)

For More Information Contact: Helen Dodson
Email:  helen.dodson@yale.edu
Telephone: 203-436-3984
JAMA and Archives Journals

Could it be thyroid cancer? When To Call The Doctor

When To Call a Doctor

Call your doctor if you have any of these signs of thyroid nodules:

• Swelling in your neck for more than 2 weeks
• A hoarse or scratchy voice that is not caused by a cold or throat infection and lasts longer than 1 month
• A hard time swallowing or breathing
• Symptoms of a thyroid problem such as feeling tired, weak, or nervous, losing weight, having trouble sleeping, or having a fast heartbeat

If you have had part of your thyroid gland removed because of noncancerous thyroid nodules, you will need regular medical checkups to make sure your thyroid gland is working well.

Watchful Waiting

For some kinds of health problems, you can wait and see what happens for a while before you and your doctor decide what kind of treatment you should have. This is called watchful waiting.

Because of the small risk of cancer, watchful waiting is not recommended for people with thyroid nodules.

Call your doctor if you have swelling in your neck that does not go away, problems swallowing, a hoarse or scratchy voice that has lasted several weeks, or any other symptoms of a thyroid problem.

Who To See

Different types of health professionals can help treat a thyroid problem.

• Family medicine doctor or general practitioner
• Internist
• Pediatrician
• Your doctor may also refer you to an endocrinologist for further tests and treatment.

If you need a special exam or treatment, you may see one of these types of doctors:

• Nuclear medicine physician (a doctor who specializes in medicine using different types of radioactive substances)
• Surgeon and/or Otolaryngologist (an ear, nose, and throat specialist)

Risk Factors Associated with Thyroid Nodules or Tumors

You are more likely to develop a thyroid nodule if:

• You are older. Thyroid nodules are more common in older people.
• You are female. Women are more likely than men to develop thyroid nodules.
• You have been exposed to radiation. Exposure to environmental radiation or past radiation treatment to your head, neck, and chest (especially during childhood) increases your risk for thyroid nodules.
• You do not get enough iodine. Iodine deficiency is rare in the United States but it is common in areas where iodine is not added to salt, food, and water. An iodine deficiency may result in an enlarged thyroid gland (goiter), with or without nodules.
• You have Hashimoto's thyroiditis. Hashimoto's thyroiditis can cause an underactive thyroid gland (hypothyroidism).
• One or both of your parents have had thyroid nodules.

Most thyroid nodules are not cancerous. But a nodule is more likely to be cancerous if:

• You have had radiation treatment, or you were exposed to radiation in the environment. In rare cases, thyroid cancer could appear up to 20 years after radiation exposure.
• You have family members who have had cancer in their endocrine glands, including the thyroid gland.
• You are younger than 30 or older than 60.
• You are male.
• The nodule grows quickly over a period of weeks or months. But just because a nodule has changed in size does not mean it is cancerous.
• You develop a nodule while you are pregnant.
• You have Graves' disease.
• You have Hashimoto's thyroiditis. Hashimoto's thyroiditis can cause an underactive thyroid gland (hypothyroidism).
• One or both of your parents have had thyroid nodules.

Most thyroid nodules are not cancerous, but a thyroid nodule is more likely to be cancerous if:

You have had radiation treatment, or you were exposed to radiation in the environment. 

In rare cases, thyroid cancer could appear up to 20 years after radiation exposure.

You have family members who have had cancer in their endocrine glands, including the thyroid gland.

You are younger than 30 or older than 60.

You are female (Women and girls are three times more likely to be diagnosed with thyroid cancer)

The thyroid nodule grows quickly over a period of weeks or months. 

You develop a thyroid nodule while you are pregnant.

You have Graves' disease.

You have Hashimoto's thyroiditis.