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Hyperthyroidism

THYROIDITIS (draft)

Thyroiditis

GOITER AND THYROIDNODULES

Paul W. Ladenson, M.D.

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1. Introduction Hyperthyroidism refers tothe effects on the body of thyroidhormone excess [see below.], acondition...

1. Introduction Thyroiditis meansinflammation of the thyroid gland, whichis a butterfly shaped organ located inthe...

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Enlargement of the thyroid (goiter) andlumps within it (nodules) are bothrelatively common findings that may be...

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Introduction

Thyroid cancers are malignant tumors in the thyroid gland, a butterfly-shaped organ draped around the frontand sides of the windpipe (or trachea) in the lower neck. (Figure 1) There are several types of thyroid cancer,each with its own characteristics (Table 1); papillary thyroid cancer is by far the most common. Thyroid canceroccurs in women three times more often than men. The incidence of thyroid cancer rises with age, and the typesthat occur in older people are generally more aggressive. However, certain forms of thyroid cancer (e.g.,papillary and medullary cancers) can also appear in childhood and adolescence.

Figure 1. The appearance and anatomic relationships of a normal thyroid gland

Thyroid cancers vary widely in their seriousness and the intensity with which they must be treated. Some tumorsare tiny—only detected at surgery or imaging for another reason—and probably would never have affected aperson’s health. Even individuals whose thyroid cancer is found as a thyroid lump (nodule) are usually cured bysurgery and other minimally disruptive treatments. But when thyroid cancer has spread outside of the neck, orwhen thyroid cancer is an aggressive subtype, the disease can be difficult or even impossible to treat. Thyroidcancers that are widespread and have lost the characteristics of normal thyroid cells, so called poorlydifferentiated cancers, can be life-threatening.

Treatment of most thyroid cancers begins with surgical removal of the thyroid gland. Then radioactive iodine,which is taken up by normal thyroid cells and many cancers, is used in selected patients to eradicate residualdisease. After their initial treatment, people with treated thyroid cancer must take thyroid hormone medicationdaily to replace the function of their missing gland, and prevent any potentially remaining thyroid cancer tissuefrom growing back. Because thyroid cancer often comes back after being apparently effectively cured, peoplewho have been treated for thyroid cancer must be monitored—usually for the rest of their lives—to detect andtreat any residual disease at an early stage. Treatments for thyroid cancers that cannot be removed surgically or

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killed with radioactive iodine may include external beam radiotherapy and/or chemotherapy

What Does the Thyroid Gland Normally Do?The thyroid gland’s follicular cells make and release into blood two small chemicals, called thyroid hormones,thyroxine (T4) and triiodothyronine (T3). Each of them is comprised of a pair of amino acids to which iodinemolecules are attached. The iodine needed for thyroid hormone production comes from our diet. Once absorbed,iodine in blood is trapped by a special pump in thyroid cells, called the sodium-iodide symporter. Thyroidfollicular cells also have several specialized biochemical ‘fastening machines,’ called enzymes, that then carry outthe steps needed to attach iodine to particular parts of a very big protein called thyroglobulin, which is made onlyby thyroid cells. These special molecules present in follicular cells of the thyroid, the sodium-iodide symporterand thyroglobulin, are important in evaluating patients with so called differentiated thyroid cancers (i.e., papillary,follicular, and Hürthle cells cancers), as described below.

In the nucleus of almost every cell, thyroid hormones bind to molecules called T3 receptors, which are attachedto segments of DNA that regulate certain genes. Precise control of how many proteins are made from thesegenetic blueprints maintains the normal, or euthyroid, thyroid state. Whether the thyroid hormone come naturallyfrom the thyroid gland itself or from thyroid hormone medication, excessive activation of these genes byabnormally high thyroid hormone levels cause hyperthyroidism; whereas, inadequate gene activation due toinsufficient thyroid hormone production, such as after thyroid surgery, causes hypothyroidism. (See Knols onHyperthyroidism and Hypothyroidism.) The thyroid normally makes precisely the right amount of its hormonesunder the exacting control of the pituitary gland, which is an extension of the brain. Specialized pituitary cellsmake thyroid stimulating hormone (TSH), which travels in blood to the thyroid gland, where TSH binds to its ownreceptors on thyroid cells, prompting them to grow and produce more of the thyroid hormones. Normally, thissystem is kept in balance by the negative feedback of the thyroid hormones on TSH-secreting pituitary cells (aswell as the part of the brain that controls them).

For people with thyroid cancer who have had their thyroid gland removed surgically, thyroid hormone medication(levothyroxine [L-thyroxine]) must be given to replace the function of the gland. In differentiated thyroid cancerpatients, thyroid hormone treatment is also important to suppress the pituitary’s production of TSH, which couldpromote regrowth of thyroid cancer tissue.

The thyroid gland also contains another population of cells, called parafollicular or C cells, which produce anotherhormone called calcitonin. Although calcitonin appears to have no essential function in humans, it can be usefulto identify people with a malignant C cell thyroid tumor, called medullary thyroid cancer. Furthermore, high bloodlevels of calcitonin in patients with widespread medullary thyroid cancer can cause symptoms of diarrhea,flushing, or itching, as described below.

How Common is Thyroid Cancer?In 2008, there will be more than 37,000 new cases of thyroid cancer in the United Stated, and 1,590 Americanswith thyroid cancer will die of their disease. Because thyroid cancers are usually effectively treated, it isestimated that there are more than 300,000 survivors of thyroid cancer in the U.S. Thyroid cancer is morecommon in women, older persons, and whites. Women whose pregnancies are later in life and obese peoplehave also been found at greater risk of developing thyroid cancer. Thyroid cancer is becoming diagnosed morecommonly in the U.S., and currently has the fastest rising incidence of any malignancy in U.S. women and inolder persons. (Figure 2) This is due, in large part, to detection of small thyroid cancers that previously wentundetected.

What Causes Thyroid Cancer?Scientists are learning how derangements in certain parts of the DNA genetic blueprint that controls thyroid cells’growth can lead to thyroid cancer. For most people with the condition, however, a specific underlying cause oftheir thyroid cancer remains unknown. Certain genetic and environmental factors that increase risk of developingthyroid cancer have been identified. Some types of thyroid cancer are inherited or familial. In one-half of peoplewith medullary thyroid cancer, for example, there is an inherited mutation in a specific part of their geneticblueprint, the Ret gene, that makes it almost inevitable they will develop thyroid cancer, often early in their lives.Genetic testing can be performed to predict which children and other relatives are at risk of acquiring thecondition. Papillary thyroid cancer, a more common type of thyroid malignancy, also affects a close familymember in about one in ten cases; but the genetic mutation(s) responsible for familial papillary thyroid cancerhas not yet been discovered, so testing currently doesn’t exist to predict which relatives are at risk.

by Paul Fitzgerald

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Radiation of the thyroid gland, especially in childhood and adolescence, can predispose to later development ofthyroid cancer. Two kinds of radiation exposure have been implicated. First, x-rays were used to treat a numberof minor diseases in children between the 1920s and early 1950s, mainly in the U.S. These conditions includedinflammation of the tonsils and adenoids, acne, ringworm, and some kinds of birthmarks. As many as one-third ofthese previously irradiated children—now people in their sixties and older—will be found to have a thyroidcancer with careful investigation. Second, radioactive iodine released after nuclear reactor accidents or falloutfrom atmospheric nuclear weapon testing or use predisposes to development of thyroid cancer. For example,higher incidences of thyroid cancer have been seen among the survivors of the World War II atom bombings inJapan, in Pacific islanders accidentally exposed to fallout after nuclear weapon testing, and in children in Belarusand Ukraine after the Chernobyl nuclear power plant accident. In addition, 38 million Americans living in stateseast of Nevada were exposed to radioactive iodine in fallout from atmospheric nuclear testing between 1952 and1958. The extent of this risk in people older than 50 years is uncertain, but can be estimated based on certainpersonal characteristics at:http://ntsi131.nci.nih.gov/.

How Does Thyroid Cancer Present?Most patients with thyroid cancer have no symptoms (i.e., complaints) at all; in some, signs (objective examfindings) can be subtle and easily overlooked. Thyroid cancer is often first detected when an affected person,their doctor, or someone else notices that they have a swelling beneath their Adam’s apple in the front of theneck. Thyroid lumps large enough to see and feel, called palpable nodules, are relatively common, occurring in6% of adult women and 2% of adult men. Many more thyroid nodules, however, are too small to feel. Carefulinspection of the thyroid by sonography, for example, reveals that up to one-third of adult women and one-fifth ofmen have small nodules in their glands. Such small nodules are discovered when a person has a medicalimaging procedure performed for some other reason, such as a sonogram of the carotid arteries; a CAT or MRIscan of their neck, head, or chest; or a PET scan. These very small, incidentally detected thyroid nodules arecalled thyroid incidentalomas. Fortunately, the vast majority of both palpable and smaller nodules are benign (notcancer), but the possibility of cancer must be considered whenever they are found.

When a thyroid cancer grows to the extent that it stretches the capsule around the gland, presses on or invadesnearby structures, or spreads to lymph nodes or other organs outside of the thyroid, then symptoms may appear.Some patients with thyroid cancer may feel a lump, tightness, or pain in the front of the neck. Pain from thethyroid gland can sometimes seem to be coming from the jaw, ear, or throat. Pressure on or invasion of thewindpipe (trachea) can cause cough, coughing up blood, and shortness of breath. Growth surrounding orinvading the swallowing tube (esophagus) can produce difficulty swallowing or pain with swallowing. The nervesthat control the vocal cords (recurrent laryngeal nerves) run right behind the thyroid gland, so pressure on orinvasion of them by tumor can cause hoarseness, difficulty swallowing liquids, and shortness of breath.

Sometimes, the first evidence that a person has thyroid cancer arises from disease spread (metastasis) that hasalready occurred. Some people, especially affected children, present with an enlarged lymph node or multiplenodes in the neck. Other patients come to the doctor with new and persistent bone pain reflecting the presenceof a metastasis to the skeleton. Spread to lungs can present with chest pain, coughing up blood, or shortness ofbreath. When there is pressure on the spinal cord from a thyroid cancer metastasis, a person could haveweakness or numbness of an extremity, or difficulty with control of urination or bowel movements. In all of thesecircumstances, the presence of thyroid cancer is often not established until the offending metastasis has beenbiopsied and found to be comprised of cells from the thyroid gland.

It is important to remember that most people who have any one of the symptoms noted above do not havethyroid cancer. Hoarseness, coughing, chest and skeletal pain, and enlarged lymph nodes in the neck are muchmore likely to be due to something else. However, when a symptom or sign, such as those noted above, is newfor that person, has no other obvious explanation (e.g., a cold), lasts two weeks, or is getting worse, the affectedindividual should seek medical attention.

How is Thyroid Cancer Diagnosed?Thyroid cancer is usually diagnosed in the course of evaluating patients with a thyroid nodule or, less commonly,diffuse gland enlargement (goiter) that has been either palpated (felt) or identified on an imaging study performedfor another reason. (See Knol on Goiter and Thyroid Nodules.) Although more than 90% of thyroid nodules arebenign tumors or cysts—not cancers—malignancy should, nonetheless, be considered in every affected personby, at least, determining certain key facts from a careful medical history and physical examination. Often patientswith small thyroid nodules, less than one cm in diameter, and no risk factors for thyroid cancer can then simplybe reexamined or imaged by sonography to be sure the nodule is not enlarging. For larger nodules, additionalstudies are usually indicated, as described below.

The clinical evaluation, knows as a history and physical examination, for patients with one or more thyroid

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nodules or a goiter collects facts about potential risk factors for developing thyroid cancer, local neck symptoms,complaints suggesting metastatic disease, features of hyperthyroidism or hypothyroidism, and the presence ofdiseases associated with thyroid cancer (Table 2). Particularly important facts from this history include child neckradiation exposure, gland or nodule enlargement over a few weeks or months, gland pain, persistent hoarsenessor cough, coughing up blood, difficulty swallowing, or a family history of thyroid cancer or related illnesses. Onexamination, worrisome findings include a hard nodule or entire gland that does not move freely with swallowingand is associated with lymph node enlargement in the neck.

The history and examination on their own rarely establish the presence or absence of thyroid cancer, soadditional tests are usually needed. (Figure 3) A thyroid sonogram, in which inaudible sound waves are beamedinto the neck and the returning echoes depict thyroid and surround tissues, can confirm that a lump in the neckis actually in the thyroid gland, show whether it is cystic or solid, and precisely measure its size. Sometimes,sonographic features of a thyroid nodule make it more suspicious for cancer (e.g., fine calcium deposits, a roughborder, and abnormal lymph nodes nearby in the neck) or, alternatively, make it less likely to be malignant (e.g.,a small purely fluid-filled cyst). A blood test for TSH is useful in evaluating people with a thyroid nodule because,if the TSH is low, the person may have a benign, but hyperfunctioning thyroid tumor, called a toxic adenoma.The next step in evaluation is a radionuclide thyroid scan to see if the gland enlargement is, in fact, a “hot”nodule. However, if the blood TSH level is now low, then people with a thyroid nodule larger than 1.0 to 1.5 cm(1/2 inch) in diameter, as well as those with any other features suspicious for cancer, need to have a fine needleaspiration biopsy to obtain thyroid cells for evaluation by an expert cytopathologist. A blood calcitonin level mayalso be checked if there is any reason to suspect that the patient or a family member has medullary thyroidcancer due to symptoms associated with high calcitonin or of other medical conditions known to be associatedwith this particular thyroid cancer type (see Table 2). Other special testing for medullary thyroid cancer isdiscussed in the section dedicated to that tumor type below.

Figure 3. Typical diagnostic testing for a person with a thyroid nodule (Sonographic Features of ThyroidNodules)

The test needed to sort out most thyroid nodules is the fine needle aspiration biopsy, a simply outpatientprocedure performed with the patient wide awake. A physician uses a small needle to withdraw representativethyroid cells from the nodule, usually guided by an ultrasound machine to show the location of the nodule duringthe procedure. The microscopic examination of cells acquired then leads to the categorization of nodules intofour categories. (Figure 4) First, the specimen may be inadequate with insufficient thyroid tissue to make adiagnosis; people with this finding need another biopsy. Second, and fortunately, most often, the biopsy report isbenign. People whose nodule falls into this category seldom need surgery and can be seen by their doctorperiodically to sure their goiter or nodule is not progressively enlarging. Third, the biopsy can strongly suggestthe presence of thyroid cancer. When the biopsy findings are interpreted as malignant, 95% of the time, theperson actually proves to have thyroid cancer at subsequent surgery, so an operation is indicated (unless theindividual has other serious medical problems). The fourth category of thyroid biopsy finding is uncertain orindeterminate. One in five biopsies fall into this group, if features of the cells seen are simply not characteristicenough of a benign or malignant nodule for the cytopathologist to be sure

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Specific Types of Thyroid Cancer (Table 1)

ThyroidCancer Type

Incidence AffectedFamily

Member(s)

Typical Management Comments

Papillary

10% Surgery to remove both

sides of thyroid gland(bilateral thyroidectomy)

After surgery, sometimesradioactive iodine to ablateremaining thyroid tissue andtreat metastases

Lifelong thyroid hormonemedication to replace glandfunction and suppresspituitary TSH

Usually low-grade cancer thatis curable

Spread is by extension intoneck tissues or metastasis tolymph nodes and/or lung

Mortality is rare, butrecurrence is common (1/4cases)

Follicular

<1% Bilateral thyroidectomy,although unilateral thyroidlobectomy may be sufficientfor minimally invasive tumors

Postoperative radioactiveiodine for vascular invasivetumors to ablate remainingnormal thyroid and treatiodine-concentratingmetastases

Lifelong thyroid hormone

Minimally invasive follicularcancers (i.e., capsularinvasion only) behave like low-grade papillary cancer

Vascular invasive follicularcancers can spread in blood tolung, bone, and other sites

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medication to replace glandfunction and suppresspituitary TSH

Hürthle cell

None Same as follicular thyroidcancer, except that thetumor rarely concentratesradioactive iodine

Behaves like follicular thyroidcancer

Usually does not concentrateradioactive iodine used forscan detection or treatment

Medullary

50% Bilateral thyroidectomy,especially for individuals withrelated familial syndromes

Lifelong thyroid hormonemedication to replace glandfunction, but no need forTSH suppression

Tumor arising fromparafollicular or C cells, whichproduce calcitonin

May occur as familial medullarythyroid cancer or as acomponent of multipleendocrine neoplasia syndromeII, along with adrenal andparathyroid gland tumors

Anaplastic

None Surgical removal of thetumor is rarely possible, solimited to biopsy fordiagnosis and relief of airwayobstruction

Combined chemotherapyand radiation therapy

Usually presents in olderpersons

Very aggressive cancer withrapid growth and early spreadto other parts of the body

Extremely difficult to treat

Papillary thyroid cancer, which accounts for 80-90% of all thyroid malignancies, most commonly arises inadults, but it is also the most common type of thyroid cancer in older children and adolescents. The namepapillary refers to the fern leaf-like organization of the cells. The nuclei of papillary thyroid cells have atypicalfeatures that often permit diagnosis to be made by biopsy before surgery. This kind of thyroid cancer has beenassociated with mutations in genes that define the structure of proteins normally involved in thyroid cell growthand proliferations, for example, Ret, Ras, and BRAF. Papillary cancer affects another family member in 10% ofaffected people. In a minority of individuals with papillary cancer, the tumor is one aspect of an inheritedsyndrome with other features, such as colon polyps in Gardner’s syndrome; skin and mouth lining lumps inCowden’s syndrome; or kidney cancer, moles, and lung blebs in Birt-Hogg-Dube syndrome.

The majority of papillary thyroid cancers remain confined to the thyroid gland when they are diagnosed, butseparate tumors are found in other parts of the gland in 40% of cases, so called multifocality. Papillary cancercan spread beyond the thyroid gland by direct growth into nearby tissues or by traveling through lymphatic orblood vessels to distant sites. Involvement of lymph nodes in the neck is common, occurring in one-third ofpeople with the condition. Papillary cancer can also spread to the lungs and, less commonly, to other parts of thebody. Certain subtypes of papillary thyroid cancer behave more aggressively, such as tall cell, columnar cell,insular, and poorly differentiated variants. Treatment of papillary thyroid cancer is discussed below.

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Follicular thyroid cancer, which represents less than 10% of all thyroid malignancies, typically occurs in olderadults. Their individual cells look and are oriented in follicles like those in normal thyroid tissue and some benignthyroid tumors. However, when follicular thyroid cancers are removed and examined microscopically, their cellscan be seen to penetrate through their surrounding capsule and/or blood vessels within the tumor. Follicularcancers with capsular invasion alone are called minimally invasive. These cancers generally behave like low-grade papillary thyroid cancers and remain confined to the gland. Follicular thyroid cancers that also invadeblood vessels are called invasive or angioinvasive follicular thyroid cancers; these cancers can spread via bloodto lung, bone, and less commonly, other distant organs around the body.

Hürthle cell cancer, accounting for less than 5% of all thyroid cancers, is similar in most respects to follicularthyroid cancer, except that its cells have swollen cytoplasm that are filled with microscopic structures calledmitochondria. Hürthle cell cancers can, like follicular tumors, be either minimally invasive or vascular invasivemalignancies. The former are usually confined to the thyroid gland; whereas, the latter having the potential forspread to the lungs, bones, and, rarely, other distant sites. Hürthle cell cancers differ in that they rarelyconcentrate iodine efficiently, making it more difficult to locate and treat metastatic disease.

Medullary thyroid cancer, representing less than 10% of thyroid cancers, arises from the thyroid’s parafollicularC cells, which make calcitonin. Medullary thyroid cancers are evenly divided between those that affect a singleindividual, so called sporadic medullary thyroid cancer, and those that occur as a component of several differentinherited familial medullary thyroid cancer syndromes. Medullary thyroid cancers are closely linked to a set ofgenetic derangements in the Ret gene, which can unleash cancerous growth of C cells in the thyroid as well astumors in other adrenal and parathyroid cell types. Inherited forms of thyroid C cell cancers include familialmedullary cancer alone and the multiple endocrine neoplasia II (MENII) syndromes. MEN IIa is comprised ofmedullary thyroid cancer; pheochromocytoma, a tumor of the central part of the adrenal (medulla) secreting the‘fight or flight’ hormones (e.g., epinephrine) that cause high blood pressure that is often severe, unstable, andhard to control; and parathyroid tumors that make an excess of parathyroid hormone causing high blood calciumand related symptoms, kidneys stones, and bone mineral loss. MEN IIb includes medullary thyroid cancer;pheochromocytoma, and characteristic benign tumors beneath the mucosa of the mouth and eyelids along with alanky body build.

The behavior of medullary thyroid cancers ranges from incidentally detected microscopic tumors detected thenthe thyroid is removed for another reason to aggressive widely metastatic cancer with symptoms related to bothsites of disease and excess calcitonin production (see above). The state of a patient’s disease can be monitoredwith the blood calcitonin level; another substance called carcinoembryonic antigen (CEA) can also be useful inmonitoring.

In people with an affected family member, tests to analyze the DNA comprising the Ret gene can identify most ofthose with risk of developing medullary thyroid cancer. Blood testing for calcitonin, especially after calciumstimulation, can also be useful in testing potentially affected relatives of a medullary thyroid cancer patient.Based on the results of such testing, young family members with high risk of future disease may be well advisedto have their thyroid removed before the cancer develops, spreads, and becomes incurable.

Anaplastic thyroid cancer is a high-grade malignancy arising from thyroid tissue that grows rapidly and spreadsaggressively to both adjacent structures in the neck and distant sites in the body. Anaplastic thyroid cancers areoften impossible to remove surgically. Their cells lose the microscopic and functional characteristics of normalthyroid cells, and as a result, they do not concentrate iodine or respond to radioactive iodine treatment. Theprospects have been pretty dismal for people with this condition unless their disease is detected very early andtreated aggressively with combined chemotherapy and external beam radiation. New drugs may offer hope forsome individuals with this previously incurable form of cancer.

Rarer forms of thyroid malignancy. The thyroid cancer can sometimes give rise to or become involved withtumors of the lymph system, called thyroid lymphomas. Unlike other forms of thyroid cancer that are usuallytreated surgically, thyroid lymphomas can sometimes be effectively treated with a combination of chemotherapyand radiation. Squamous cell cancers, like those affecting the upper airway, can also develop in the thyroidgland. Sometimes cancers that originate from malignancies in other parts of the body—kidney, colon, lung, andbreast—can secondarily spread to the thyroid.

Table 2. Key Facts in a Patient with a Thyroid Nodule

History

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Age and gender

Pattern of gland enlargement

Local neck symptoms Pain or tenderness of the thyroid

Persistent cough or hoarseness

Coughing up blood

Difficulty or pain with swallowing

Shortness of breath

Swelling of lymph nodes in the neck

Symptoms potentially due to thyroid cancer spread

Bone pain

Chest pain

Weakness or numbness or an arm or leg

Symptoms potentially due to of too much or too little thyroid hormone

Hyperthyroidism: weight loss, heat intolerance, tremor, palpitations, insomnia, anxiety, nervousness,increased bowel movement frequency, anxiety, and muscle weakness

Hypothyroidism: weight gain, cold intolerance, constipation, dry skin and hair, slowed thinking, depressedmood, and muscle cramps

Symptoms potentially due to a high calcitonin level in blood: diarrhea, flushing, or itching

Past history of childhood neck irradiation

Past illnesses potentially associated with thyroid cancer (as in Family History below)

Family history of thyroid disease or related illnesses

Benign goiter or thyroid nodulesThyroid cancer

Colon polyps

Kidney stones, high blood calcium level, or parathyroid gland tumor

Severe high blood pressure or adrenal gland tumor

Physical Examination

Nodule or goiter

Size

Consistency (hard, rubbery, fluctuant)

Tender

Mobility, i.e., move freely with swallowing

Lymph node enlargement in the neck

Signs suggesting an overactive or underactive thyroid gland

Hyperthyroidism: fast heart rate, jitteriness, trembling hands, pounding heart, warm moist skin, muscleweakness

Hypothyroidism: slow heart rate, lethargic, puffy tissues, dry skin and hair, slowed speech and thinking

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Signs suggesting features of conditions associated with thyroid cancer

High blood pressure

Lumps beneath the mucosal linings of the lips and eyelids

Tall lanky body build with loose jointedness

How is Thyroid Cancer Treated? (Figure 5)Thyroid surgery is the initial treatment for most people with known or suspected thyroid cancer to remove eitherall or only one side of the thyroid gland. When the diagnosis of thyroid cancer has already been established by abiopsy, the preferred operation is bilateral thyroidectomy. This removes other sites of thyroid cancer that areoften present in patients with the most common form, papillary thyroid cancer, and it prepares the patient foreradication of any small thyroid tissue remnant with postoperative radioactive iodine. On the other hand, removalof a single thyroid lobe is sometimes preferable, in patients with an indeterminate biopsy because the majority ofthese patients will not, in fact, prove to have thyroid cancer and will not thereafter have to take thyroid hormonemedication.

Thyroid surgery requires general anesthesia and hospitalization. All patients have some postoperative discomfortand a small scar in the front of the neck. Injury to nearby structures occurs in a small percentage (2-10 %) ofpatients. Such injury may include damage to the recurrent laryngeal nerves causing permanent hoarseness,difficulty swallowing fluids, and even trouble breathing, or removal or other injury to the adjacent parathyroidglands, causing a low blood calcium level and related symptoms of tingling, numbness, or muscle crampsrequiring prolonged calcium and vitamin D medications.

Surgery is also used to remove lymph nodes containing thyroid cancer tissue, either at the time of initialthyroidectomy or later when remaining thyroid cancer tissue is detected during the course of long-termmonitoring.

Radioactive iodine is recommended after surgery for some patients with differentiated thyroid cancers (i.e.,papillary, follicular, and Hürthle cell cancers) to ablate (destroy) the small amount of thyroid tissue that remains inmost patients after thyroidectomy. The two reasons for this treatment are that 1) patients who initially have moreadvanced disease are known to have fewer recurrences of cancer if radioactive iodine is used after surgery; and2) the tests used to monitor patients with previously treated thyroid cancer—blood thyroglobulin levels andradioactive iodine scans—are most accurate once all normal thyroid tissue has been completely removed. Thisadditional treatment is usually advisable for patients who are older with larger tumors that have spread beyondthe gland, have not been completely removed surgically, or have other microscopic features that suggest theyare more aggressive. Tests of tumor tissue for molecular mutations, such as in BRAF, can also predict greaterrisk of recurrence and, some believe, the need for radioactive iodine treatment. Radioactive iodine is also used totreat metastatic disease that still can concentrate iodine, a characteristic that is often retained by follicular thyroidcancers and papillary thyroid cancers in younger people.

Radioactive iodine is a relatively simple treatment administered by mouth as a capsule or liquid; this is usuallydone without hospitalization in the U.S. Side effects include inflammation of the salivary and lacrimal (tear)glands, causing short-term swelling and mild pain, and rarely, long-term dry mouth or eye, respectively. In orderto stimulate radioactive iodine uptake by thyroid tissue, the blood level of TSH must be elevated. There are twoways to accomplish this: 1) stopping thyroid hormone medication so the patient’s own thyroid makes more TSH,or 2) giving genetically engineered recombinant human TSH as injections to patients who remain onuninterrupted thyroid hormone treatment. The latter approach avoids symptoms related to thyroid hormonedeficiency (hypothyroidism), which otherwise occur.

Thyroid hormone medication, L-thyroxine (T4), is an essential part of long-term treatment for patients withthyroid cancer. It replaces the function of their missing gland, ensuring that they will not suffer symptoms andcomplications of hypothyroidism. L-thyroxine also feeds back on the pituitary gland, suppressing its production ofTSH, which might otherwise promote regrowth of thyroid cancer tissue.

Other thyroid cancer treatments may be required for people with more extensive and poorly differentiatedthyroid malignancies that cannot be removed surgically or radiated with radioactive iodine. External beamradiation may be administered to control remaining cancer in the neck that cannot be removed surgically ormetastatic disease causing bone pain or pressure on adjacent structures. Chemotherapy for thyroid cancer,which previously had limited effectiveness and many serious side effects, has recently advanced with the

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introduction of new agents, called tyrosine kinase inhibitors, which more directly target thyroid cancer cells withgreater likelihood of stabilizing disease, and less risk of injury to other body tissues.

How are thyroid cancer patients monitored after initial treatment?In the past, thyroid cancers had a reputation for recurring even many years after apparent cure. Recentimprovements in the techniques for monitoring patients after primary treatment permit the earlier detection ofresidual disease and its retreatment. Foremost among these tests is measurement of tumor markers in blood:thyroglobulin for differentiated thyroid cancers (papillary, follicular, and Hürthle cell cancers) and calcitonin andCEA for medullary thyroid cancers. For example, after complete thyroid removal with surgery and radioactiveiodine, there should be no thyroglobulin remaining in the blood of a treated papillary thyroid cancer patient. Fordifferentiated thyroid cancers capable of concentrating iodine, radioactive iodine scanning can also be helpful inidentifying and locating residual disease. Unfortunately, many thyroid cancers lose the ability to capture iodineand be seen or treated. TSH stimulation improves the accuracy of both thyroglobulin blood testing andradioactive iodine scanning, and recombinant TSH administration achieves this without causing the patient tosuffer a period of thyroid hormone deficiency.

Radiological imaging techniques can also help identify residual thyroid cancer after initial treatment. Sonographyof the neck is especially useful to find remaining cancer tissue in the thyroid bed or lymph nodes in the neck.CT, MR, and PET scanning all have roles to play in locating residual thyroid cancer tissue when it persists.When potential sites of remaining disease are identified by these techniques, the present of thyroid cancer canoften be confirmed by biopsy. Repeat surgery may then be recommended to remove residual cancer tissue if thisis feasible.

Most patients with thyroid cancer enjoy lives that are, otherwise, as healthy and long as anyone else. Theiranxiety about having cancer, their pain after surgery and other symptoms related to treatments, and theinconvenience and expense typically fade into the background for most people with the condition. For some,however, more aggressive thyroid cancer is not completely cured after initial treatment. Their condition mayrequire close medical follow-up to detect, locate, and treat residual disease. For a less than 5% of thyroidcancer patients, their disease is currently incurable and life-threatening. For them, recent advances inchemotherapy hold great promise of halting their disease’s progression.

MORE INFORMATION ABOUT THYROID CANCER

Web Resources

American Thyroid Association

Thyroid Cancer: http://www.thyroid.org/patients/patient_brochures/cancer_of_thyroid.html

Thyroid Nodules: http://www.thyroid.org/patients/patient_brochures/nodules.html

Thyroid Surgery: http://www.thyroid.org/patients/patient_brochures/surgery.html

Radioactive Iodine Use for Thyroid Diseases: http://www.thyroid.org/patients/patient_brochures/radioactive.html

Up to Date Patient Information: http://patients.uptodate.com/indexResults.asp?index=41887&title=Thyroid%20cancer

Mayo Clinic: http://www.mayoclinic.com/health/thyroid-cancer/DS00492

Medline Plus: http://www.nlm.nih.gov/medlineplus/

National Cancer Institute: http://www.cancer.gov/cancertopics/wyntk/thyroid

Books

Quick FACTS Thyroid Cancer. American Cancer Society, 2008

Thyroid Cancer: A Guide for Patients. D. Van Nostrand, 2004 (also available in Spanish as: Cancer de Tiroides:Guia Para Pacientes.)

The Thyroid Cancer Book. M.S. Rosenthal, 2006

THYROID CANCER - a knol by Paul W. Ladenson, M.D.

https://knol.google.com/k/paul-w-ladenson-md/thyroid-cancer/uR0IJFRYF/mjri92[11/11/2008 3:45:46 PM]

Patient Support Organizations

Thyroid Foundation of America, Inc.One Longfellow Place Suite 1518Boston, MA 02114phone (toll-free) 800 832-8321phone 617 534-1500 fax 617 534-1515e-mail info@allthyroid.org www.allthyroid.org

Cutting Edge Thyroiditis Research

Clinical trials in progress: http://www.clinicaltrials.gov/ct2/results?term=Thyroid Cancer

Recently published clinical research: http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=DetailsSearch&Term=(%22ThyroidCancer%22%5BMeSH+Terms%5D+OR+ThyroiAnalysis%5Bptyp%5D+OR+Randomized+Controlled+Trial%5Bptyp%5D))&WebEnv=0LNqYZeXefVU

References

Sherman SI. Thyroid carcinoma. Lancet. 2003;361(9356):501-11. PMID: 12583960

Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA.2006;295:2164-7. PMID: 16684987

Cooper DS, Doherty GM, Haugen BR, et al.; The American Thyroid Association Guidelines Taskforce.Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006;16:109-42. PMID: 16420177

AACE/AME Task Force on Thyroid Nodules. American Association of Clinical Endocrinologists and AssociazioneMedici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroidnodules. Endocr Pract. 2006;12:63-102. PMID: 16596732

Mazzaferri EL, Kloos RT. Clinical review 128: Current approaches to primary therapy for papillary and follicularthyroid cancer. J Clin Endocrinol Metab. 2001;86:1447-63. PMID: 11297567

Jonklaas J, Sarlis NJ, Litofsky D, et al.. Outcomes of patients with differentiated thyroid carcinoma following initialtherapy. Thyroid 2006;16:1229-1242.

Sawka AM, Thephamongkhol K, Brouwers M, Thabane L, Browman G, Gerstein HC.Clinical review 170: A systematic review and metaanalysis of the effectiveness of radioactive iodine remnantablation for well-differentiated thyroid cancer. J Clin Endocrinol Metab. 2004;89:3668-76. PMID: 15292285

Pacini F, Ladenson PW, Schlumberger M, et al. Radioiodine ablation of thyroid remnants after preparation withrecombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized,controlled study. J Clin Endocrinol Metab 2006;91:926-32

Mazzaferri EL, Robbins RJ, Spencer CA, et al. A consensus report of the role of serum thyroglobulin as amonitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab. 2003;88:1433-41. PMID: 12679418

Torlontano M, Crocetti U, Augello G, et al. Comparative evaluation of recombinant human thyrotropin-stimulatedthyroglobulin levels, 131I whole-body scintigraphy, and neck ultrasonography in the follow-up of patients withpapillary thyroid microcarcinoma who have not undergone radioiodine therapy. J Clin Endocrinol Metab.2006;91:60-3. PMID: 16219716

Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J ClinEndocrinol Metab. 2001;86:5658-71. PMID: 11739416

THYROID CANCER - a knol by Paul W. Ladenson, M.D.

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Cornett WR, Sharma AK, Day TA, Richardson MS, Hoda RS, van Heerden JA, Fernandes JK. Anaplastic thyroidcarcinoma: an overview. Curr Oncol Rep. 2007 Mar;9(2):152-8.

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