Enlargement of the thyroid (goiter) and lumps within it (nodules) are both relatively common findings that may be incidentally noted by people, their friends or family, or their doctor on routine examination. They can also be found incidentally by imaging studies of the neck, such as a sonogramof the carotid arteries or a CT or MR of the spine.
Most goiters and thyroid nodules will not interfere with a person’s health, but a medical evaluation is important to be sure the thyroid gland enlargement is not compressing nearby structures, like the windpipe or swallowing tube; not part of a condition causing overactivity or underactivity of the thyroid gland; and not a thyroid cancer. Fortunately, even for the vast majority of people with these problems, their condition can be effectively treated.
This article explains what goiter and thyroid nodules are, why they can be
important, and how they should be evaluated and, when necessary,
treated.
What is a goiter?
A thyroid nodule is simply a lump or mass in the thyroid gland. Thyroid nodules are relatively common; 6% of adult women and 2% of adult men in the U.S. have a thyroid nodule that can be felt on examination. Moreover, close inspection of the thyroid by sonographic imaging shows that as many as one-third of women and one-fifth of men have small nodules in their glands.
The thyroid may contain just one nodule (solitary thyroid nodule or uninodular goiter) or several of them (multinodular goiter). Thyroid
nodules can be solid if they are comprised of thyroid or other cells or
an accumulation of stored thyroid hormone called colloid. When nodules
contain fluid, they are called cystic nodules. These can be completely fluid filled (simple cysts), or partly solid and partly fluid, (complex cysts). (Figure 3)
Thyroid nodules vary greatly in size. Many are large enough to see and feel (palpable nodules). Some
multinodular goiters can become enormous, bulging out of the neck and
over the collar bones or extending down into the chest behind the
breastbone, a condition called substernal goiter. At the other end of the spectrum, the majority of thyroid nodules are too small to see or feel at all, and are called nonpalpable nodules. Such
small nodules are found when a person has a medical imaging procedure
performed for some other reason, such as a sonogram of the carotid
arteries; a CAT or MRI scan of their neck, head, or chest; or a PET
scan. These very small, incidentally detected thyroid nodules are called thyroid incidentalomas.
Finally,
of course, thyroid nodules can also be classified as benign or
malignant depending on whether the cells of which they are comprised
have the potential to spread beyond the thyroid gland into adjacent
tissues or distant parts of the body. Specific causes of thyroid nodules and how they are distinguished are discussed below.
What does the thyroid gland normally do and what controls it?To understand why some types of goiter develop, it is first important to know what the normal function of the thyroid gland is and how it is regulated. The thyroid gland makes and releases into blood two small chemicals, called thyroid hormones: thyroxine (T4) and triiodothyronine (T3). Each of them is comprised of a pair of connected tyrosine amino acids to which four or three iodine molecules, respectively, are attached. The iodine needed for thyroid hormone production comes from our diet in seafood, dairy products, store bought bread, and iodized salt. Once absorbed, iodine in blood is trapped by a special pump in thyroid cells, called the sodium-iodide symporter. The thyroid also has several specialized biochemical ‘fastening machines,’ called enzymes, that then carry out the steps needed to attach iodine to particular parts of a very big protein called thyroglobulin, which is made only by thyroid cells. Some of this thyroglobulin with iodine molecules attached is stored in the gland in the form of a gooey paste called colloid, which is normally located in the center of follicles, which are balls of thyroid cells with a hollow center.
A
regulated amount of the thyroid hormones is constantly being chopped
off of thyroglobulin and secreted into blood for delivery to tissues
throughout the body. In the nucleus of almost every cell,
thyroid hormones bind to molecules called T3 receptors, which are
attached to segments of DNA that regulate certain genes. Precise control of how many proteins are made from these genetic blueprints maintains the normal or euthyroid thyroid state. Excessive
activation of these genes by abnormally high thyroid hormone levels
causes hyperthyroidism; inadequate gene activation due to insufficient
thyroid hormone production causes hypothyroidism. (See Knols on Hyperthyroidism and Hypothyroidism.)
The
thyroid normally makes precisely the right amount of its hormones under
the exacting control of the pituitary gland, which is an extension of
the brain. Specialized pituitary cells make thyroid
stimulating hormone (TSH), which travels in blood to the thyroid gland,
where TSH binds to its own receptors on thyroid cells, prompting them to
grow and produce more of the thyroid hormones. Normally,
this system is kept in balance by the negative feedback of the thyroid
hormones on TSH-secreting pituitary cells (as well as the part of the
brain that controls them). (Figure 4)
Figure 4. Control of the thyroid gland by the hypothalamus and pituitary gland
Three categories of problems are responsible for almost all cases of thyroid gland enlargement: inefficient thyroid hormone production, gland inflammation, and tumors in the thyroid.
First, when the gland is inefficient in making sufficient thyroid hormone, it compensates by getting bigger. Worldwide, the most common cause is dietary iodine deficiency, a condition estimated still to affect 100 million people who live in poverty-stricken societies. (Figure 5) Iodine is an essential building block for thyroid hormones; in the absence of adequate supply, the gland becomes larger. When more than 10% of a population has goiter due to iodine deficiency, it is called endemic goiter. Other
consequences of severe iodine deficiency include hypothyroidism and
cretinism, a syndrome of mental retardation, short stature, deafness,
and characteristic facial deformities that affects children born to
hypothyroid mothers in iodine deficient regions. (For more information, see the International Council for Iodine Deficiency Disorders website: www.iccidd.org.) People
with defects in their genetic blueprints for the proteins that permit
the thyroid gland to make thyroid hormone (e.g., mutations in the
molecular pump that enable the thyroid to concentrate iodine within
itself) typically develop a goiter. Certain drugs can also
interfere with normal thyroid function and lead to compensatory gland
enlargement, such as lithium carbonate, which causes a goiter in 10% of
individuals taking this medicine.
Second, inflammation of the thyroid gland (thyroiditis) can produce gland swelling. Some forms of thyroid inflammation are quite common, such as autoimmune thyroiditis and painless (postpartum) thyroiditis. Autoimmune
thyroiditis (also called Hashimoto thyroiditis) occurs when a person’s
immune system turns against their own thyroid gland, inflaming it,
usually causing the gland to swell, and often making it permanently
underactive. Autoimmune thyroiditis can first appear in
children and young adults, but its incidence increases sharply in middle
aged and elderly people. Other types of thyroiditis
causing goiter include: 1. painless (postpartum) thyroiditis, a
self-limited inflammation of the thyroid that can resolve without
treatment and affects at least five per cent of women in the year after
pregnancy; 2. subacute thyroiditis, which causes painful thyroid
enlargement as the result of viral infection; and 3. other rarer forms
of infectious thyroiditis; and 4. drug-induced thyroiditis, such as
those caused by amiodarone and interferon alfa; and 5. a rare fibrosing
condition called Reidel thyroiditis. (For more information, see Knol on Thyroiditis.)
Third,
goiter can be the result of thyroid tumors, which are usually benign,
but sometimes malignant. Most thyroid tumors present as discrete
nodules, but there are several kinds of thyroid cancer that can cause
generalized swelling of the gland. These include infiltrating papillary thyroid cancer, lymphoma, and anaplastic thyroid cancer. Certain facts make it important to consider the possibility that a goiter might be malignant. These
include one or more of the following symptoms: rapid enlargement of a
goiter over a few weeks, the onset of new thyroid-related pain,
difficulty swallowing, shortness of breath, or coughing up blood; or a
goiter in someone with risk factors for thyroid cancer, such as a person
who had childhood radiation to their neck or who has a close relative
with thyroid cancer. (See below and the Knol on Thyroid Cancer.)
Table 1. Causes, Features, and Treatments for Certain Common Causes of Goiter
Type of Goiter
|
Cause
|
Typical Symptoms and Signs
|
Tests for Diagnosis
|
Treatment
|
Iodine deficiency (endemic goiter)
|
Lack of sufficient dietary iodine intake
|
Thyroid gland enlargement (goiter)
Normal or underactive thyroid (hypothyroidism)
|
Urinary iodine measurement
|
Dietary iodine supplementation, usually with iodized salt
|
Graves disease
(diffuse toxic goiter) |
Autoimmune stimulation of the thyroid gland
|
Goiter
Hyperthyroidism
|
T4, T3, and TSH levels to confirm hyperthyroidism
Radioiodine scan
Thyroid-stimulating antibody level
|
Beta-adrenergic blockers for thyrotoxic symptoms
Antithyroid drugs
Radioactive iodine
Surgical thyroidectomy
|
Autoimmune thyroiditis (Hashimoto, chronic lymphocytic)
|
Persistent immune system inflammation of person’s own thyroid
|
Goiter
Hypothyroidism
|
Anti-thyroid peroxidase (anti-TPO)antibody
Anti-thyroglobulin antibody
TSH to detect hypothyroidism
|
Thyroid hormone
(L-thyroxine) for hypothyroidism |
Subacute thyroiditis
(painful, de Quervain) |
Viral infection
|
Painful, tender and swollen gland
Malaise, fever, chills, and night sweats
Thyrotoxicosis, often followed by hypothyroidism
|
Erythrocyte sedimentation rate elevation
Low thyroid uptake of radio iodine & 99mTc-pertechnetate
TSH and T4 levels to detect thyrotoxicosis and hypothyroidism
|
Aspirin, other anti-inflammatory drugs, or Glucocorticoids
Beta-adrenergic blockers for thyrotoxic symptoms
L-thyroxine for hypothyroidism
|
Toxic adenoma and toxic multinodular goiter
|
Benign thyroid tumor(s)
|
Nodular goiter
Hyperthyroidism
|
T4, T3, and TSH levels to confirm hyperthyroidism
Radioiodine scan
|
Radioactive iodine
Surgical thyroidectomy
|
Goiter and thyroid nodules suspicious for malignancy
|
Malignant thyroid tumors
|
No symptoms
Local neck symptoms
Symptoms of tumor spread
|
Thyroid nodules, masses in the thyroid gland, can be the result of benign cell overgrowth (adenomatous hyperplasia) or actual discrete tumors comprised of thyroid cells that can be benign or cancerous. Thyroid nodules can sometimes contain fluid, which usually collects due to bleeding from the fragile blood vessels in thyroid tumors, so called cystic degeneration. This event sometimes causes the sudden onset of pain and swelling in the front of the neck, which typically subsides over several days.
Fortunately, more than 90% of thyroid nodules are not cancers, but malignancy should be considered in every affected person. Often
patients with small thyroid nodules, less than 1 cm in diameter, and no
risk factors for thyroid cancer can simply be reexamined or imaged by
sonography to be sure the nodule is not enlarging. For larger nodules, additional studies are usually indicated, as described below.
How are people who have a goiter or thyroid nodule evaluated?
Whenever a person has a goiter or thyroid nodule, three questions must be answered.
First, is the gland, or a portion of it, so large that it is stretching, compressing, or invading nearby structures? Thyroid swelling can cause a sensation of tightness or, less commonly, pain in the front of the neck. A
goiter or nodule can compress the windpipe (trachea) causing cough or
shortness of breath, while pressure on the swallowing tube (esophagus)
can cause discomfort with swallowing or even the inability to get things
down. When a goiter extends down into the chest, blood
returning from the neck and head can be partially obstructed, causing
neck veins to bulge. When a goiter or nodule is due to
cancer, the tumor may actually grow into nearby structures, causing
pain, hoarseness when nerves to the voice box are invaded, or coughing
up blood when the trachea is penetrated.
Second, is the gland functioning normally, or is it overactive or underactive? Goiter is a characteristic feature of all the common forms of hyperthyroidism. For
example, in hyperthyroid Graves disease, there is usually a diffuse or
generalized goiter; and in toxic adenomas and toxic multinodular goiter,
there are solitary and multiple nodules, respectively in the gland. Individuals
with hyperthyroidism due to either painless thyroiditis or subacute
thyroiditis also usually have a modest diffuse goiter. Conversely, people with hypothyroidism also often have a goiter. For
example, the most common cause of hypothyroidism, autoimmune
thyroiditis, typically causes diffuse gland enlargement that is 1½ to
3-times normal size. Consequently, thyroid function must be assessed in
all patients presenting with goiter or a thyroid nodule. The
best single test to screen for both conditions is the serum thyroid
stimulating hormone (TSH) concentration, which is suppressed to a low
level in people with hyperthyroidism, and elevated in those with
hypothyroidism.
Third, is the goiter or thyroid nodule due to malignancy? Fortunately, most patients with a goiter or thyroid nodule do not have thyroid cancer. Often
other findings in a patient with a goiter, such as the features of
hyperthyroid Graves disease, make it unnecessary to do additional tests
to rule out cancer. However,
when a goiter is enlarging rapidly, causing local symptoms, or develops
in a person with risk factors for or other symptoms suggesting a
malignancy, this possibility must be considered. On
the other hand, almost everyone with a thyroid nodule larger than 1.0
to 1.5 cm in diameter must be investigated for the possibility of
thyroid cancer. The approach to these diagnostic evaluations is discussed below.
Answering
these three important questions begins with collecting certain facts
about the person’s medical history and any recent symptoms. (Table 2)
Table 2. Key Facts to Evaluate in a Person with a Goiter or Thyroid Nodule
Fact
|
Comments
|
Gender and Age
|
Goiter
and nodules are more common in women and older people, but nodules in
men and younger are somewhat more likely to be cancer
|
Local Neck Symptoms
|
Swelling or pain in the front of the neck
Hoarseness that is new and persistent Cough that is new and persistent Coughing up blood Shortness of breath |
Symptoms of Possible Cancer Spread
|
Bone pain in one spot without relief
Weakness or numbness of an arm or leg that persists |
Hyperthyroid Symptoms
|
Weight
loss, heat intolerance, trembling hands, palpitations, insomnia,
anxiety, increased bowel movement frequency – especially if the
symptoms are new or persistent
|
Hypothyroid Symptoms
|
Weight
gain, cold intolerance, constipation, very dry skin, slowed thinking,
depressed mood, muscle cramps – especially if the symptoms are new or
persistent
|
Risk factors for thyroid cancer
|
Childhood neck radiation
Family history of thyroid cancer Family history of colon polyps Family history of parathyroid or adrenal tumors |
Then, a doctor will look on physical examination for signs related to the thyroid enlargement: the entire
gland or nodule size; its firmness, mobility, and tenderness; and whether there is any
nearby lymph node enlargement. The doctor will also look for signs of thyroid hormone excess or deficiency. (See Knols on Thyroid Cancer, Hyperthyroidism, and Hypothyroidism.) Although the history and physical examination sometimes provide important clues, it is almost always necessary to perform additional diagnostic tests to answer the key
clinical questions with certainty. (Figure 6)
gland or nodule size; its firmness, mobility, and tenderness; and whether there is any
nearby lymph node enlargement. The doctor will also look for signs of thyroid hormone excess or deficiency. (See Knols on Thyroid Cancer, Hyperthyroidism, and Hypothyroidism.) Although the history and physical examination sometimes provide important clues, it is almost always necessary to perform additional diagnostic tests to answer the key
clinical questions with certainty. (Figure 6)
A
thyroid sonogram beams inaudible sound waves into the neck and the
returning echoes depict thyroid and surrounding tissues; this can
confirm that a lump in the neck is in the thyroid gland, show whether it
is cystic or solid, and precisely measure its size. A blood test for TSH can rule in or out all of the common causes of hyperthyroidism and hypothyroidism. If
the TSH is low, then there is a possibility the person has a benign,
but hyperfunctioning thyroid adenoma; so the next step for these
individuals is often a radionuclide thyroid scan to see if the gland
enlargement is, in fact, a “hot” nodule. (Figure 7) This is important,
because almost all cancerous thyroid nodules are “cold” on radionuclide
scanning; unfortunately, so are many benign thyroid nodules, so the test
is not very helpful in people who do not already have a low TSH blood
test suggesting hyperthyroidism. If the TSH is elevated,
the person probably has an underactive thyroid gland, and its
enlargement may be a sign of autoimmune thyroiditis. If
the TSH is normal or high, then most individuals with a thyroid nodule
larger than 1.0 to 1.5 cm (1/2 inch) in diameter as well as those with a
suspicious goiter need to have a fine needle aspiration biopsy to
obtain thyroid cells for cytological evaluation by an expert
pathologist.
Thyroid biopsy results fall into four categories. (Figure 8) First is an inadequate specimen in which there simply is not enough thyroid tissue to make a diagnosis. People with this finding need another biopsy. Second, and fortunately, most often, the biopsy report is benign. People
with this category of nodule usually need no surgery and can be seen by
their doctor periodically to sure their goiter or nodule is not
progressively enlarging. Third, the biopsy can strongly suggest the presence of thyroid cancer. When
the biopsy findings are malignant, 95% of the time, the person will
actually prove to have thyroid cancer at subsequent surgery, so an
operation is indicated unless the individual has other serious medical
problems. The fourth category of thyroid biopsy finding is uncertain or indeterminate. One
in five biopsies fall into this group, in which adequate tissue has
been obtained, but the features of the cells seen just are not
characteristic enough of a benign or malignant nodule to be sure.
Surgery is usually also indicated for this last group (see below),
because among people with this biopsy outcome, 15% will prove to have
thyroid cancer once the nodule is removed surgically and fully examined.
(See Knol on Thyroid Cancer.)
Whether a goiter needs treatment depends on the answers to the three key clinical questions. If the thyroid is so large as to cause symptoms by stretching or compressing adjacent structures, or if it is so big as to be unsightly, surgical removal of the thyroid gland (thyroidectomy) may be required. If the goiter is related to a condition causing hyperthyroidism, as in Graves disease or toxic nodular goiter, treatment with radioactive iodine may be effective in both controlling gland overactivity and decreasing its size. Some normally functioning (nontoxic) nodular goiters can also be shrunk with radioactive iodine therapy. If the thyroid is enlarged as the result of autoimmune (Hashimoto) thyroiditis and the gland is also underactive with a high blood TSH level, then starting thyroid hormone medication (L-thyroxine) may both treat the hypothyroidism and partially shrink the gland.
Similarly,
thyroid nodules may also require surgical removal or radioactive iodine
based on their size and whether they are causing hyperthyroidism. In
addition, thyroid nodules that are found to be suspicious for
malignancy must be removed along with the remainder of the thyroid gland
to prevent the spread of thyroid cancer. Most people with
a cytologically uncertain finding are also advised to have at least the
half of their thyroid gland with the nodule removed because one in
seven of these individuals will be found to have thyroid cancer. The
use of thyroid hormone to put the thyroid gland to rest and shrink
thyroid nodules—often prescribed in the past—has now been found to be
relatively ineffective.
What are the benefits and risks of surgery for a goiter or thyroid nodule?Thyroid surgery can remove one-half (thyroid lobectomy or hemi-thyroidectomy) or all of the thyroid gland (total thyroidectomy) to establish with certainty whether a goiter or nodule is cancer or not. Surgery to remove an enlarged thyroid can relieve compression of nearby structures and improve symptoms in patients with related difficulty swallowing, cough, or shortness of breath. Thyroid surgery can also cure certain forms of thyroid gland overactivity associated with goiter or nodules.
Thyroid surgery almost always requires hospitalization and being put to sleep under anesthesia. The incision causes pain for a day or two after surgery, and it leaves a scar, which is usually relatively inapparent after a year. As with any operation, bleeding and infection can complicate thyroid surgery.
Behind
the thyroid gland, there are two sets of important structures that can
be accidentally injured during the course of a thyroid operation. The
recurrent laryngeal nerves run along side the windpipe on their way to
the voicebox (larynx), where they control the muscles that move the
vocal cords. If one of these nerves is cut, smashed, or has its blood supply cut off, then a person will suffer some degree of voice loss. This
vocal cord paralysis can lead to a range of voice changes, ranging from
losing a high octave or two while singing to the inability to shout to a
severely disabling whisper of a voice. If both recurrent
laryngeal nerves are injured, then a person may have difficulty
breathing and require that a hole be created connecting the windpipe
with the front of the neck (tracheostomy). Four parathyroid glands are also located behind the thyroid: two on each side. If
the parathyroids are accidentally removed or injured, then the
patient’s blood calcium levels drops—resulting in tingling, numbness,
and muscle cramps. Rarely, a severely low calcium level can lead to throat spasm or a seizure. Fortunately,
these complications are unusual in the hands of an experienced thyroid
surgeon; mild injuries often resolve spontaneously over days or weeks
after surgery; and there are treatments that can improve matters.
What are the benefits and risks of radioactive iodine for a goiter or thyroid nodule?Radioactive iodine is mainly used for treated of a goiter or nodule when it is the cause of an overactive thyroid gland. The benefits and risks of this outpatient treatment, which is taken as a pill by mouth, are discussed in the Knol on Hyperthyroidism. Radioactive iodine is also sometimes used to shrink a goiter that is not overactive.
MORE INFORMATION ABOUT GOITER AND THYROID NODULES
American Thyroid Association:
· Thyroid Nodules: http://www.thyroid.org/patients/patient_brochures/nodules.html
UptoDate Patient Information on Thyroid Nodules : http://patients.uptodate.com/topic.asp?file=endocrin/11828
Mayo Clinic:
· Thyroid Nodules: http://www.mayoclinic.com/health/thyroid-nodules/DS00491
Medline Plus:
· Thyroid Nodule: http://www.nlm.nih.gov/medlineplus/ency/article/007265.htm
Web MD:
Thyroid Nodule: http://www.webmd.com/a-to-z-guides/thyroid-nodules-topic-overviewBooks
Wood LC, Cooper DS, Ridgway EC. Your Thyroid: A Home Reference., Ballantine Books, New York, 1995
Surks MI. The Thyroid Book. Consumer Reports Books, Yonkers, New York, 1993
Garber J, White SS. Harvard Medical School Guide to Overcoming Thyroid Problems. McGraw-Hill, 2005
Public Health and Patient Support Organizations
International Council for the Control of Iodine Deficiency Disorders (ICCIDD): http://www.iccidd.org/
The Johns Hopkins Thyroid Tumor Center: www.thyroid-cancer.net
ThyCa: Thyroid Cancer Survivors Association, Inc.: www.thyca.org
Cutting Edge Goiter and Thyroid Nodule Research
Clinical trials in progress:
Thyroid nodules: http://www.clinicaltrials.gov/ct2/results?term=Thyroid%20nodules
Multinodular goiter: http://www.clinicaltrials.gov/ct2/results?term=multinodular%20goiterRecently published clinical research: http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=(nodular
goitre[Text Word] OR "goiter, nodular"[MeSH Terms] OR nodular
goiter[Text Word]) OR ("thyroid nodule"[MeSH Terms] OR thyroid
nodule[Text Word]) AND ("2007/02/19"[PDat] : "2008/02/18"[PDat] AND
"humans"[MeSH Terms] AND English[lang] AND (Clinical Trial[ptyp] OR
Meta-Analysis[ptyp] OR Practice Guideline[ptyp] OR Randomized Controlled
Trial[ptyp] OR Review[ptyp]))
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Hermus AR, Huysmans DA. Treatment of benign nodular thyroid disease. N Engl J Med. 1998;338:1438-47. PMID: 9580652
Frates MC, Benson CB, Charboneau JW, et al.; Society of Radiologists in Ultrasound. Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Radiology. 2005;237:794-800. PMID: 16304103
Ross DS. Nonpalpable thyroid nodules--managing an epidemic. J Clin Endocrinol Metab. 2002;87:1938-40. PMID: 11994320
Boyages SC. Clinical review 49: Iodine deficiency disorders. J Clin Endocrinol Metab. 1993;77:587-91. PMID: 8370679