AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Background

Thyroid nodules are common, perhaps existing in almost half the population, as determined using ultrasonography (US). Only 4-7% of thyroid nodules detected with US are palpable in the adult population in the United States, with women affected more frequently than men. Although the thyroid is the most common endocrine organ to undergo malignant degeneration, thyroid carcinoma accounts for only 1% of diagnosed neoplasms in the United States each year (McNeil, 2006; Wiersinga, 2001). Thyroid cancer is rare; the annual detection rate of clinically significant thyroid cancer in the general population is only 0.004%. Only 5-10% of thyroid cancers are clinically palpable (Bruneton et al, 1994; Nabriski et al, 2003).

Palpable nodules can be visualized as areas of increased (hot) or decreased (cold) tracer activity. However, terms such as hot nodules and cold nodules are misleading unless the nodule can be clearly delineated in several projections. A nonfunctioning (cold) nodule placed in the center of a lobe with functioning normal tissue superficial to it may appear as warm on scans because of integrated activity with depth. Unless oblique views are imaged, the presence of activity concentration cannot be definitively determined. Therefore, nodules should be identified as being functioning (hot), nonfunctioning (cold), or photon deficient. Hot nodules (which are typically adenomas) are more often benign than cold lesions are.

Traditionally, radionuclide imaging was performed to assess possible malignancy. On radionuclide images, 4% of hot nodules are shown to contain tumor, compared with 16% of photon-deficient (cold) nodules (Daumerie et al, 1998). However, radionuclide imaging is not reliable in excluding or confirming the presence of tumor. The classification of thyroid neoplasms has been significantly revised in the last 20 years, and the changes reflect an increased understanding of both the prognosis and histologic characteristics of the tumors. Among asymptomatic patients, 7-21% have palpable nodules found on routine clinical examination. US can be used to identify many more nonpalpable nodules, and it can depict thyroid cysts as small as 2 mm and solid nodules as small as 3 mm (Mandel 2004; Miki et al, 1993).

Sonograms in 40% of the general adult population demonstrate single or multiple nodules. In an autopsy series, 49% of patients who had had clinically normal thyroid glands were found to have one or more grossly visible nodules, whereas the incidence of malignancy in the same autopsy series was 2-4% (Brander et al, 1989; Cannon, 1986).

At examination, the challenge is to differentiate the few clinically significant nodules from the many benign ones. Thyroid nodules are usually clearly identified by using US. No single US criterion is reliable for differentiating all benign thyroid nodules from malignant ones, but many US features may aid in predicting the benign or malignant nature of a given nodule.

For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

Pathophysiology

Pathology

Most thyroid nodules are not true neoplasms but are benign growths caused by cycles of hyperplasia and involution of underlying thyroid tissue. This process results in the fusion of regions of colloid-filled follicles and parenchyma, forming adenomatous or colloid nodules. The classification of thyroid neoplasms has been significantly revised in the last 20 years, and the changes reflect an increased understanding of both the prognosis and the histologic characteristics of the tumors.

Thyroid cysts

Thyroid cysts account for 15-25% of all thyroid nodules. True thyroid cysts lined with epithelium are rare. Most thyroid cysts are macronodules, which undergo degeneration, with the accumulation of serous fluid, colloid substance, or blood.

Inflammatory nodules

• Inflammatory nodules represented by focal chronic thyroiditis and thyroid abscesses are usually symptomatic, but they are rare.
• Hashimoto thyroiditis is much more diffuse and involves the entire thyroid.
• de Quervain thyroiditis is a diffuse disease, although in rare cases, a solitary cold area or multiple ones may be seen on scintigrams.
• Painless thyroiditis is a rare, diffuse disease.
• Acute suppurative thyroiditis may demonstrate diffuse or focal hypofunction on scintigrams, and it may be diffuse or focally hypoechoic.

Thyroid adenoma

Most thyroid nodules (42-77%) represent adenomatous nodules. Most are multiple, and multiplicity is demonstrated at US, scintigraphy, and surgery. The nodules are usually nonfunctioning, although a few may be hyperfunctioning at scintigraphy. When solid, the nodules are poorly encapsulated and not well defined, and they merge into the surrounding tissue. Cystic adenomatous nodules are hemorrhagic, with irregular internal walls and particulate fluid content. Intratumoral calcification is occasionally seen.

Follicular adenomas (15-40%) arise from follicular epithelium and are usually single, well-encapsulated lesions. They may be functioning toxic adenomas (hot on scintigrams), or they may represent a hyperfunctioning adenoma in a multinodular goiter. A nonfunctioning adenoma is cold at scintigraphy. On sonograms, adenomas may be hyperechoic or hypoechoic solid nodules with a regular hypoechoic area surrounding ring called the halo sign. Rarely, a parathyroid adenoma has an ectopic intrathyroid location.

Whether solitary adenomas transform into follicular carcinoma is uncertain. In particular, whether aneuploid cells, which are present in approximately 25% of follicular adenomas, represent carcinoma in situ is unclear.

Thyroid cancer

The incidence of thyroid cancer is 10,000 cases per year, one third of which are clinically silent and are found during surgery or autopsy (Weber et al, 2006). Most commonly, thyroid cancer involves patients under 30 years of age, with a female preponderance. In 20% of cases, other abnormalities in the thyroid gland are associated with thyroid cancer; these include adenomatous hyperplasia, follicular adenoma, colloid nodules, and thyroiditis. Thyroid cancer may be radiation induced, with the incidence increasing with higher doses of radiation. Peak incidence occurs 5-30 years after irradiation.

The presentation is varied, but it involves a rapidly growing, stone-hard thyroid nodule that is usually hypoechoic and has ill-defined borders without a halo; these findings are highly suggestive. Usually, no signs of hemorrhage or liquefaction necrosis are noted.

Papillary carcinoma

Papillary carcinomas represent the most common type of thyroid cancer, accounting for 50-81% of cases (Weber). Similar to all thyroid neoplasms, they are more prevalent in women, with a reported female-to-male ratio of 2-4:1. Although the cancer occurs in any age group, it is especially prevalent in patients aged 20-40 years. The most common clinically silent thyroid cancers are papillary carcinomas, which are usually smaller than 1 cm.

Once the patient with papillary carcinoma has symptoms, a thyroid mass is the most typical complaint. Histologically, tumors are nonencapsulated and well differentiated, and they may be purely papillary or mixed with follicular elements. The latter pattern is more common in patients younger than 40 years. Approximately 22% of lesions are pseudoencapsulated. Malignant cells have large nuclei with nuclear grooves and areas devoid of significant chromatin, which produce an appearance of Orphan Annie eyes. These nuclei are identified in 83% of cells. Psammoma bodies, seen in 50% of specimens, represent calcified, dead papillae.

Adenopathy may be found in a significant minority of patients. Reportedly, nodal involvement occurs in 50% of patients at the time of diagnosis and does not appear to affect prognosis. Although recurrence occurs in 15-25% of patients, the long-term outcome is believed to be exceedingly good, with a survival rate higher than 90% after 20 years. The prognosis is poorer in patients who are older at initial diagnosis, who are male, or who have a large tumor. Extracapsular spread is associated with a poorer prognosis. Metastatic spread to the regional nodes occurs in as many as 40% of the patients, with an approximately doubled incidence in children. Hematogenous spread occurs in 5-10% of patients, with a propensity for the lung and bones. Treatment usually involves surgical resection. Suppressive hormonal therapy has been advocated, although its effectiveness has not been confirmed.

Follicular carcinoma

Follicular carcinoma of the thyroid also is considered a well-differentiated neoplasm. Incidence is 5% of thyroid neoplasms if adequate iodine is ingested; however, the incidence can be as high as 40% of malignancies in iodine-deficient populations. Women are affected 2-3 times more often than men. Compared with other lesions, follicular carcinoma occurs in a slightly older age group, commonly in patients aged 40-50 years. Although the neoplasm may be detected as a result of mass effect, it is more likely to be clinically silent at initial presentation.

Nodal disease occurs in approximately 10% of patients with follicular carcinoma. Hematogenously spread metastatic disease in the lung, brain, and bone occurs in fewer than 5%. On pathologic examination, the neoplasm appears as an expansive, encapsulated mass. Differentiating follicular carcinoma from benign follicular adenoma can be difficult. The diagnosis of malignancy relies on the demonstration of vascular invasion or full-thickness capsule invasion.

Histologically, follicular carcinomas are considered to be well or moderately differentiated. Poor prognostic indicators include less-differentiated lesions, larger lesions, extrathyroidal spread, nodal disease, and advanced patient age at the time of initial diagnosis. Treatment involves surgical resection (possibly total thyroidectomy) or the administration of radioactive iodine. Thyroid hormone suppression has been shown to be useful in treating the well-differentiated varieties of follicular carcinoma because they are dependent on thyroid-stimulating hormone.

Medullary carcinoma

Medullary carcinoma, which represents 3-10% of thyroid malignancies, is derived from parafollicular cells (C cells). Calcitonin levels may be increased; the levels are reported to be correlated with the tumor load. Although more common in women than in men, medullary carcinoma is less sex specific than other thyroid malignancies. A familial basis is found in 10-20% of patients, with an autosomal dominant inheritance pattern. Medullary carcinoma is a component of multiple endocrine neoplasia (MEN) syndrome types IIA and IIB and is associated with pheochromocytoma and parathyroid adenoma or parathyroid hyperplasia (Brauckhoff et al, 2004; Weber).

The neoplasms are typically seen as masses, possibly associated with a sensation of pressure or dysphagia, as felt by the patient. Regional lymph node spread is present in 50% of patients at the time of diagnosis. Hematogenous spread to the liver, bone, and lung may occur. The reported 5-year survival rates vary from less than 65% to 80%. A poor prognosis is associated with MEN syndrome type IIB, pleomorphic necrosis, and increased mitotic activity.

Anaplastic carcinoma

Anaplastic thyroid carcinomas are extremely aggressive tumors and represent 8-16% of thyroid neoplasms. These cancers are prevalent in regions in which goiter is endemic. Typically seen in patients aged 60-80 years, they occur slightly later in life, compared with other thyroid neoplasms. A strong female predominance is noted, with a female-to-male ratio of approximately 3:1 (Weber).

Most patients are symptomatic and have a rapidly enlarging neck mass. Neck pain, dysphonia, dysphagia, and dyspnea are common initial complaints. Regional nodal disease and distant metastases are seen in 50-69% of patients at the time of diagnosis. The cause of the tumors is somewhat speculative. Transformation from other thyroid neoplasms is recognized, although this is an uncommon cause. Despite reports suggesting a relationship with prior irradiation, this hypothesis is considered controversial. Unlike other thyroid neoplasms, no effective treatment is available for anaplastic carcinoma, and most patients die within the first year.

Thyroid lymphoma

Thyroid lymphomas are almost always non-Hodgkin lymphomas, and they account for 4-10% of thyroid malignancies. Principally, women older than 50 years are affected, typically in association with Hashimoto thyroiditis. Patients usually present with a rapidly growing neck mass, which may cause symptoms of obstruction, such as dyspnea and dysphagia. In 70-80% of patients, thyroid lymphoma arises in a preexisting chronic thyroiditis with subclinical or overt hypothyroidism. The prognosis depends on the stage of the disease at diagnosis. The 5-year survival rate ranges from 89% in early disease to only 5% in disseminated disease. Signs of cervical invasion in the late stages are also similar to those of an undifferentiated thyroid carcinoma.

Percutaneous needle aspiration remains the key procedure for the diagnosis of thyroid lymphoma; however, thyroid lymphoma's differentiation from thyroiditis occasionally can be difficult. Currently, the most accurate imaging method for staging thyroid lymphoma is computed tomography (CT) scanning. Lymph node involvement is depicted equally well by using magnetic resonance imaging (MRI) or CT scanning, and both are superior to US. Tumor invasion of the esophagus also is depicted well on MRIs and CT scans but not on sonograms. Accordingly, the diagnosis of thyroid lymphoma by using US-guided fine-needle aspiration (FNA) is recommended. Subsequently, MRI is used to stage the disease and to assess adenopathy and esophageal involvement. Gallium-67 scintigraphy is a useful adjunct to imaging, because thyroid lymphoma is the only thyroid malignancy in which uptake of the radionuclide is reported.

Thyroid metastases

Thyroid metastases are rare and are usually a late manifestation of primary cancer located elsewhere. By far, most metastases are derived from disseminated disease in the liver, bones, lungs, and, invariably, cervical lymph nodes. The incidence of known primary cancer in these patients is 2-17%. Common primary sites include the skin (melanoma, 39%), breast (21%), and kidney (renal cell carcinoma, 10%) (Untch and Olson, 2006).

Frequency

United States

Thyroid nodules are common. In the United States, palpable thyroid nodules are found in 4-7% of the adult population, with women affected more frequently than men. US-detectable thyroid nodules are found in almost half the population. A proportion of nodules discovered with palpation or US are malignant. Thyroid carcinoma is rare and accounts for 1% of neoplasms diagnosed annually; these represent approximately 10,000 cases per year. The annual detection rate of clinically significant thyroid cancer in the general population is only 0.004%. About 40% of the general adult population has a single nodule or multiple ones, as shown on sonograms. In an autopsy series, 49% of patients with clinically normal thyroid glands had one or more grossly visible nodules, whereas the incidence of malignancy was 2-4%. Most thyroid nodules are benign (Papini, Simeone).

International

Thyroid nodules are more common in hilly regions of the world, where the incidence of multinodular goiter thyroid carcinomas is increased. Hashimoto thyroiditis and thyroid lymphoma are more frequently found in Japan than in the rest of the world.

Mortality/Morbidity

Mortality and morbidity depend on the nature of the thyroid nodule. Patients with thyroid cysts and adenomas have a normal life expectancy and are usually asymptomatic. In thyroid cancer, mortality and morbidity rates vary.

• For papillary carcinoma, the 10-year survival rate is 90% with occult cancers and 60% with extrathyroidal disease. The prognosis worsens with advancing age.
• For follicular carcinoma, the 10-year survival rate is 90% with minor vascular invasion, but the rate decreases to 35% with moderate to marked vascular invasion.
• For medullary carcinoma, the 10-year survival rate is 90% without nodal metastases, decreasing to 42% with nodal metastases.
• For anaplastic carcinoma, the prognosis is poor, with a 5-year survival rate of 5% and an average survival of 6-12 months.
• For thyroid lymphomas, the 5-year-survival rate ranges from 89% early in the disease to 5% when the disease is disseminated.

Sex

• Papillary carcinoma is more common in females than in males.
• Follicular carcinoma is more common in females than in males, with a male-to-female ratio of 1:2-3.
• Medullary carcinoma is slightly more common in females, but it is less sex specific than other forms of cancer.
• Anaplastic carcinoma is more common in females than in males, with a male-to-female ratio of 1:3.
• Thyroid lymphoma is more common in females than in males.

Age

• The incidence of papillary carcinoma peaks in those aged 40-50 years.
• The incidence of follicular carcinoma peaks in those aged 40-50 years.
• The mean age of patients with medullary carcinoma is 60 years in sporadic cases. However, in association with MEN types IIA and IIB, the tumor occurs in adolescence.
• The average age of patients with anaplastic carcinoma is 50-70 years.
• Thyroid lymphoma occurs principally after 50 years of age.

Anatomy

The thyroid gland lies in the infrahyoid compartment of the neck, which is outlined by the strap muscles anteriorly and by the parathyroids, larynx, trachea, and esophagus posteriorly. The carotid vessels and the jugular veins constitute the lateral boundaries. The mature thyroid gland comprises a right lobe and left lobe anterior to thyroid cartilage. Each lobe is approximately 5 cm long, 2 cm wide, and as much as 3 cm deep. The lobes are connected by a narrow isthmus.

A pyramidal lobe arising from the isthmus is present in approximately 50% of the population. The pyramidal lobe is seen more frequently on scintigraphy in patients with thyrotoxia. The thyroid gland is slightly larger in women than in men. Embryologically, the thyroid gland descends from the floor of the pharynx. The line of descent is represented by the thyroglossal duct; aberrant thyroid tissue may present anywhere along the path of embryonic migration. Aberrant thyroid tissue is well delineated with scintigraphy.

Clinical Details

Most patients with thyroid nodules are asymptomatic, and most nodules are found on clinical examination or self-palpation. Acute suppurative thyroiditis usually affects children and causes swelling, fever, and pain on swallowing. Neck pain, fever, and lethargy are caused by de Quervain subacute thyroiditis, soon after an upper respiratory infection or a viral illness. A hemorrhagic cyst may present with a sudden onset of pain and swelling in the neck. The presentation of thyroid cancer is variable and depends on the histologic type, causing neck pain resulting from local invasion, with dysphasia or symptoms of distant metastases. Many nodules are identified with US, CT, or MRI performed to stage lymphomas and other head and neck cancers.

Clinicians disagree considerably about the treatment for solitary thyroid nodules after they are discovered. Some clinicians are proponents of scintigraphy for diagnosis, whereas others promote US as the most important diagnostic tool for detection and characterization of thyroid nodules. However, most clinicians agree that the differentiation of functioning toxic nodules and thyroid metastases from follicular and papillary carcinomas is performed best by using iodine-123 uptake studies. Gallium-67 can be useful in the diagnosis of thyroid lymphoma. US is the most useful modality available for the detection and characterization of most thyroid nodules.

CT and MRI are useful in the detection of local and mediastinal cancer extension and regional lymphadenopathy. FNA is used because of the inability of imaging to precisely define the nature of the thyroid nodule. For palpable nodules, FNA can be performed with palpation. Guided FNA provides specimens for cytologic studies. The procedure is safe and inexpensive and provides direct information. Although the sensitivity and specificity of scintigraphy are 100% and 5.5%, respectively, these can be considerably improved with FNA to 100% and 91.2%, respectively.

Preferred Examination

Usually, US is the first modality used to investigate a palpable thyroid nodule and in searching for a primary lesion in a patient with systemic metastases. US may be the only examination required in cases of hemorrhagic cyst and multinodular goiter. Doppler US is an extension of US and provides valuable information regarding the vascularity of nodules. Most intervention in the thyroid, such as FNA and guided thyroid ablation, are performed under US guidance.

Currently, scintigraphy is reserved for characterizing functioning nodules and for staging follicular and papillary carcinomas. Lymphoma of the thyroid is the only gallium-67–avid thyroid nodule.

Plain radiographs are used to detect retrosternal thyroid extension, thyroid calcification, bony or mediastinal lymph nodes, and lung metastases.

CT is an effective method for detecting regional and distant metastasis from thyroid cancer.

At the present time, MRI has a limited role in characterizing thyroid nodules, although it appears to be effective in the diagnosis of cervical lymph node metastasis.

Percutaneous needle aspiration remains the key procedure in the diagnosis of thyroid lymphoma; however, thyroid lymphoma's differentiation from thyroiditis occasionally can be difficult. US helps in diagnosing thyroid lymphoma most accurately, and CT helps in staging the disease most accurately. However, MRI also can be useful in staging the lymphoma. A tissue-specific diagnosis of a lymphoma can be achieved by using US-guided FNA.

Limitations of Techniques

In the past, radionuclide imaging was performed to differentiate malignant from benign lesions. On radionuclide imaging, 4% of hot nodules are shown to contain tumor, compared with 16% of cold nodules. Thus, radionuclide imaging is unreliable in excluding or confirming the presence of cancer. Technetium-99m pertechnetate, an inexpensive and readily available isotope, delivers a low dose of radiation because of its 6-hour half-life; it has a favorable decay scheme without particulate emission. A gamma camera using a 140-keV photon is ideal for imaging. The disadvantages of technetium-99m pertechnetate studies are that they can delineate only the trapping function and not organification, and 3-dimensional distortion occurs with pinhole imaging and decreased sensitivity in the mediastinum.

Currently, iodine-123 is the radioisotope of choice. The 13.3-hour half-life, the 159-keV principal photon, and the absence of particulate emission allow for good imaging with modest patient exposure. However, this isotope is cyclotron produced and relatively expensive, and the short half-life necessitates frequent shipments from the producer. Metastatic cancer is imaged well with iodine-123 because one half of papillary carcinomas and two thirds of follicular carcinomas are sufficiently iodine avid to allow their visualization.

US is an alternative method and can be used to evaluate local tumor recurrence because, unlike iodine-123 scintigraphy, it does not require the cessation of thyroid hormone therapy for as long as 5-6 weeks.

Gallium-67 has not enabled sufficient differentiation between the degree of uptake in malignant lesions and that of benign lesions to warrant its routine use, but it appears to be useful when thyroid lymphoma is suspected. US is the most sensitive method for diagnosing intrathyroid lesions; it can depict 2-mm cystic lesions and 3-cm solid intrathyroid lesions. The challenge is to differentiate a few malignant nodules from common benign nodules, because no single US criterion can be used to reliably differentiate all benign thyroid nodules from malignant ones. However, many US features may aid in predicting the benign or malignant nature of a given nodule.

Similarly to MRI, CT is not sensitive in the prediction of intrathyroid lesions; however, it is useful for evaluating lymphadenopathy, local tumor extension, and extension into the mediastinum or retrotracheal region. Guided FNA provides specimens for cytologic studies. The procedure is safe and inexpensive and provides direct information.

DIFFERENTIALS

Section 3 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Other Problems to be Considered

Benign thyroid tumors
Thyroid cysts
Inflammatory thyroid masses
Malignant thyroid tumors
Aberrant thyroid tissue

RADIOGRAPH

Section 4 of 11  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

The role of plain radiography in the evaluation of thyroid disease is limited. Plain radiographs can show soft-tissue masses and tracheal deviation. Retrosternal extension and metastatic lung disease also can be detected on a chest radiograph.

Calcifications in thyroid tumors can be seen on plain radiographs. Stippled calcification in the thyroid is suggestive of carcinoma, whereas peripheral rim calcification suggests a benign lesion. However, because of the overlap in findings, the sensitivity is reduced. Medullary carcinomas and their metastases can become calcified. Plain radiographs can show metastases in bone; these are vascular and can cause expansion of the bone.

Degree of Confidence

Plain radiograph findings are neither sensitive nor specific. Retrosternal goiters caused by tracheal stenosis that are large enough to cause symptoms may be shown on plain radiographs, but CT is more sensitive and specific. Findings of calcification in thyroid cancers overlap with those of benign disease. Similarly, lung and bone metastases can be derived from several primary sites.

False Positives/Negatives

Tracheal stenosis or deviation can result from causes other than retrosternal goiters. Similarly, calcification in the neck can have several causes other than thyroid cancer.

CT SCAN

Section 5 of 11  

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• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Similarly to MRI, CT is not a sensitive technique for demonstrating intrathyroid lesions. However, CT is useful in evaluating lymphadenopathy, local tumor extension, and extension into the mediastinum or retrotracheal region. Therefore, US is used for primary detection of intrathyroid lesions, and CT or MRI is used for staging. Attempts to differentiate benign from malignant nodules by measuring the iodine content and enhancement characteristics of the nodules on CT scans have been unsuccessful.

Degree of Confidence

CT of the thyroid is neither sensitive enough nor specific enough to allow the characterization of thyroid nodules. Thyroid cancer is suggested when certain patterns of calcification are seen in a thyroid mass and when extension to the surrounding soft tissues is visualized. Regional lymphadenopathy in association with a thyroid mass also is suggestive of thyroid malignancy.

False Positives/Negatives

Thyroid cancers may be missed on CT scans in the presence of a multinodular goiter. An intrathyroidal parathyroid gland and/or adenoma may lead to a false-positive diagnosis of thyroid cancer.

MRI

Section 6 of 11  

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• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

MRI is not as sensitive as US in depicting intrathyroid lesions. Early optimism regarding the use of MRI in the diagnosis of intrathyroid lesions is fading. However, MRI is helpful in the evaluation of local extension of thyroid neoplasms or the spread of disease into the mediastinum or retrotracheal region. In addition, MRI is useful in assessing lymphadenopathy. High–field-strength and specially configured coils have improved the resolution of MRI.

Thyroid lymphoma

Once the diagnosis is made, MRI is suggested for staging the cancer, including the assessment of adenopathy and esophageal involvement. On T2-weighted MRIs, the lesions tend to be homogeneous and isointense to hyperintense as compared with normal tissue. (Typically, however, the lesions are isointense to normal thyroid tissue, with more T1 weighting in approximately one third of the patients.) Tracheal compression, extrathyroidal extension, and the presence of a pseudocapsule are described.

Lymph node involvement is depicted equally well by MRI and CT, and both are superior to US. Tumor invasion of the esophagus is demonstrated well on MRIs and CT scans but not on sonograms.

Gallium-67 scintigraphy is a useful adjunct to imaging because thyroid lymphoma is the only thyroid malignancy in which the uptake of the radionuclide is reported.

Magnetic resonance spectroscopy

Magnetic resonance spectroscopy has been tried with FNA and surgical specimens. Performing hydrogen spectroscopy at 360 MHz has demonstrated a ratio of the peaks at 1.7 and 0.9 ppm, and it can be used to differentiate benign from malignant lesions. Values higher than a ratio of 1.1 are normal, and ratios lower than 1.1 indicate malignancy. In addition, normal tissue can be distinguished from papillary and medullary carcinoma, with a sensitivity of approximately 95%. The employment of this technique may be useful in differentiating malignant from benign follicular lesions when cytologic analysis is difficult.

Degree of Confidence

The specificity of MRI is not adequate to preclude further imaging or FNA. Once the diagnosis has been achieved by using alternative methods, MRI is particularly good for the detection of tumoral extension into the surrounding tissues, particularly the trachea and esophagus.

False Positives/Negatives

The differentiation of the various thyroid nodules localized to the thyroid gland can be difficult with MRI. A thyroid carcinoma in a multinodular goiter may be missed.

ULTRASOUND

Section 7 of 11  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

US is the most sensitive method for diagnosing intrathyroid lesions. It can depict 2-mm cystic lesions and 3-mm solid intrathyroid lesions. The challenge is differentiating a few malignant nodules from common benign nodules. Despite US's ability to clearly identify nodules, no single US criterion is reliable in differentiating benign ones from malignant thyroid nodules. Even so, many US features may aid in predicting the benign or malignant nature of a given nodule.

Most cystic lesions are benign masses that contain internal debris with a solid component that is hyperechoic relative to the adjacent thyroid tissue. Typically, benign nodules are well defined (96% benign). Lesions demonstrating eggshell calcification and a thin echolucent halo around the entire lesion are most often benign. Some authors have found that the halo sign is present in 21-33% of thyroid cancers.

Typically, malignant nodules are mostly solid and hypoechoic, with irregular margins and, at times, fine punctate calcification in the nodule, particularly in papillary carcinomas. Thyroid cancer has a hypoechoic texture, as compared with that of a normal thyroid gland, because a malignancy contains many cells that lack colloid. Carcinoma is hypoechoic in 68-100% of patients; however, a hypoechoic nodule is more likely to be benign than malignant, because benign nodules are highly prevalent in the general population. Considerable overlap may exist between benign nodules and malignant nodules. Some malignant nodules can have a cystic component. Cystic degeneration is reported in 4-33% of thyroid cancers.

Caution should be taken in relying on US features alone.

Thyroid cyst

On sonograms, thyroid cysts are anechoic, fluid-filled, smooth-walled structures. Most cysts are colloid-filled, dilated macrofollicles, which represent colloid accumulation in goiter. Simple cysts of the thyroid are rare. Cysts with irregular walls and particulate fluid content usually represent hemorrhagic colloid cysts; hemorrhagic adenoma (30% of cases); necrotic papillary carcinoma (15% of cases); liquefaction necrosis in adenoma or goiter; thyroid abscess; and, occasionally, a cystic parathyroid tumor. Some colloid cysts have a characteristic US appearance; in addition to the well-defined cyst, several echogenic foci with comet tails are visualized in the cyst (de los Santos ET et al, 1990; Perlmutter et al, 1975).

Thyroid lymphoma

On US, a thyroid lymphoma has the appearance of a hypoechoic mass, often a large one with lobulated margins and large, anechoic necrotic areas. Doppler US findings are unremarkable and are comparable to those of an undifferentiated carcinoma. Signs of cervical invasion in the late stages also are similar to those of an undifferentiated thyroid carcinoma; however, thyroid tissue surrounding undifferentiated tumors is a normal finding, whereas tissue surrounding lymphomas shows evidence of chronic thyroiditis.

Thyroid metastases

Involvement can be diffuse or focal. In diffuse disease, a heterogeneous hypoechoic pattern resembles that of thyroid lymphoma. Focal disease is usually confined to the lower pole, which is typically large and appears solid, well defined, noncalcified, and hypoechoic. Color Doppler images may occasionally show hypervascularity.

Color Doppler imaging

Recently, color Doppler US has been applied to the evaluation of thyroid nodules, but again, many similarities are noted between the appearance of benign nodules and that of malignant nodules. No consistent correlation has been found between the pathologic findings and either the presence of internal flow or its amount. Color Doppler findings depend more on lesion size than on the histologic features. In fact, papillary carcinomas are usually less vascular than benign lesions. Cold nodules demonstrated with scintigraphy are usually hypervascular at the periphery and internally hypovascular. Most nodules with this pattern of vascularity are benign.

Warm nodules demonstrated on scintigraphy are always internally and peripherally hypervascular, with a significant increase in blood velocity in the vessels that supply them compared with that of vessels in the normal parenchyma. When a cold nodule is internally hypervascular, the likelihood of malignancy increases. Papillary carcinoma can be hypovascular. If associated with Hashimoto thyroiditis, the tumor can be seen as a hypovascular area surrounded by an intensely hypervascular parenchyma.

Degree of Confidence

Typical benign nodules are well defined, mostly cystic, and hyperechoic relative to adjacent parenchyma (96% benign). These nodules have eggshell calcification and a thin, echolucent halo around the entire lesion (in many benign nodules), and they always contain internal debris.

Typical malignant nodules have irregular margins at times and are solid (most nodules) and mostly hypoechoic. Fine punctate calcification may be present within the nodule, particularly in papillary carcinoma.

False Positives/Negatives

Significant overlap exists between benign and malignant thyroid nodules; therefore, FNA biopsy is necessary in many cases with equivocal findings.

NUCLEAR MEDICINE

Section 8 of 11  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

In the past, radionuclide imaging was performed to differentiate malignant from benign lesions. With radionuclide imaging, 4% of hot nodules are shown to contain tumor, compared with 16% of cold nodules. Thus, radionuclide imaging is unreliable in excluding or confirming the presence of cancer. Currently, several radionuclides are used in thyroid scintigraphy.

Technetium-99m pertechnetate study

This radionuclide delivers a low dose of radiation because of its 6-hour half-life and favorable decay scheme without particulate emission. The 140-keV photon is ideal for imaging with the gamma camera. The isotope is inexpensive and readily available. The disadvantages are that the technique can delineate only the trapping function and not organification. With pinhole imaging, 3-dimensional distortion of the image occurs and sensitivity is decreased in the mediastinum.

Iodine-123 study

Currently, iodine-123 is the radioisotope of choice. The 13.3-hour half-life, 159-keV principal photon, and absence of particulate emission allow for good imaging with modest patient exposure. However, this isotope is cyclotron produced and relatively expensive, and the short half-life necessitates frequent shipments from the producer. Scintigraphy with iodine-123 is the preferred modality for functional evaluation of the thyroid. Palpable nodules can be visualized as areas of increased (hot) or decreased (cold) tracer activity.

Terms such as hot nodules and cold nodules are misleading unless the nodule can be clearly delineated in several projections. A nonfunctioning (cold) nodule placed in the center of a lobe with functioning normal tissue superficial to it may appear as warm on scans because of integrated activity with depth. Unless oblique views are obtained, the presence of activity concentration cannot be determined with certainty. Therefore, nodules should be identified as being functioning (hot), nonfunctioning (cold), or photon deficient. Most nodules are cold; hot nodules account for only about 10% of the lesions. A hot nodule is usually a benign lesion; typically, it is an adenoma. Hot nodules have a risk of malignancy of approximately 1-4%.

All thyroid carcinomas are likely to be cold, as are lymphoma, metastases, and many benign thyroid abnormalities, such as adenomas, nodular goiter, focal thyroiditis, and cysts. As a result of the relative frequencies of these benign abnormalities, most cold nodules are benign. Approximately 80% of cold lesions are benign. Low iodine-123 uptake in a single palpable nodule indicates that it has a risk of malignancy of approximately 10-25%, but this percentage decreases to only 1-3% if multiple nodules are demonstrated at scintigraphy. The risk of cancer in nodules with increased technetium-99m pertechnetate uptake is approximately 29%, whereas the risk of cancer in nodules with increased iodine-123 uptake is only 4%.

A thyroid nodule may have decreased or absent iodine organification. In this case, pertechnetate uptake (which is not organified) may still be present, but the nodule may lack radioiodine uptake (which is organified). Therefore, the nodule may be cold on radioiodine images but hot on pertechnetate images. Therefore, hot nodules on pertechnetate images are usually rescanned by using iodine-123 for further characterization. Technetium-99m pertechnetate study is not sensitive for nodules smaller than 5 mm, but its sensitivity increases to 100% in nodules larger than 2 cm.

Metastatic cancer is imaged well by using iodine-123 because one half of papillary and two thirds of follicular carcinomas are sufficiently iodine avid to allow their visualization. US is an alternative method that can be used to evaluate local tumor recurrence because, unlike iodine-123 scintigraphy, it does not require the cessation of thyroid hormone use for as long as 5-6 weeks.

Gallium-67 study

Scans performed by using this radionuclide have not demonstrated sufficient differentiation between the uptake in malignant nodules and the uptake in benign lesions to warrant its routine use. However, gallium-67 is useful when lymphoma of the thyroid is suspected.

Thallium-201 study

Thallium uptake is better visualized than gallium-67 uptake in the evaluation of cold nodules. Imaging at 3-5 hours after the administration of the agent demonstrates washout of activity from benign lesions, with intensely persisting activity in cancers.

Iodine fluorescence imaging

This technique is used only in a few centers in which dedicated equipment is available. An external beam of monoenergy gamma rays irradiates the thyroid, and the fluorescence of the intrinsic stores of stable iodine in the thyroid is studied. This technique provides a slightly different metabolic marker of thyroid function. The radiation dose used in this technique is low.

Degree of Confidence

Radionuclide imaging is not reliable in excluding or confirming the presence of cancer. However, metastatic cancer is imaged well by using iodine-123, because one half of papillary and two thirds of follicular carcinomas are sufficiently iodine avid to allow their visualization. Scintigraphy provides a specific imaging tool for functional thyroid studies and for demonstrating aberrant thyroid tissue and nodules. Gallium-67 studies can be useful in assessing thyroid lymphoma, but their employment does not preclude the use of FNA.

False Positives/Negatives

The diagnosis of thyroid nodules is based on activity patterns of the radionuclide. Most malignant thyroid nodules are photon deficient, but so are thyroid cysts, some adenomas, and inflammatory nodules. Conversely, most benign thyroid nodules are hot, but 4% of thyroid cancers also can be hot.

INTERVENTION

Section 9 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

FNA biopsy

FNA is used because of the inability of imaging to precisely define the nature of the thyroid nodule. For palpable nodules, FNA can be performed with palpation. Guided FNA provides samples for cytologic studies. The procedure is safe and inexpensive and provides direct information. The sensitivity and specificity are 100% and 91.2%, respectively. The overall accuracy of cytologic diagnosis with this method approaches 95%.

A study demonstrated that in practices in which FNA was used instead of other methods of thyroid nodule evaluation, the percentage of patients undergoing thyroidectomy decreased by 25%. In the same study, the identification of carcinoma in patients who underwent surgery more than doubled, from 14% to 39%, and the overall cost of the evaluation for patients with thyroid nodules decreased by 25%. In most thyroid nodules, FNA can be performed with palpation guidance.

US-guided FNA is indicated when the nodule is not palpable with certainty in patients with a family history of thyroid carcinoma, in those who underwent previous neck irradiation, and in individuals with nonpalpable sonographically depicted nodules. In addition, US-guided FNA is used in patients with previous nondiagnostic results at palpation-guided FNA. In the procedure, the needle can be placed in the peripheral solid and cellular portions of the nodule that provide the greatest diagnostic yield when aspirated.

No serious complications have been reported with FNA. The introduction of infection is unlikely with the careful use of aseptic procedure.

US-guided alcohol ablation

In this procedure, ethyl alcohol is used for ablation. Reports on US-guided alcohol ablation of autonomous, hyperfunctioning thyroid nodules are encouraging. Cures have been reported in more than 90% of patients. The incidence of hypothyroidism is less than 1% in patients who have undergone alcohol ablation of thyroid nodules, compared with a 45% incidence in patients treated with radioiodine (Goletti et al, 1992; Livraghi et al, 1990; Paracchi et al, 1992). The results of cold-nodule alcohol ablation as an alternative to surgery also are encouraging. In addition, US-guided tetracycline or alcohol injection has been successful in sclerosing recurrent thyroid cysts.

Percutaneous ethanol ablation of thyroid cysts and autonomously functioning nodules are usually well-tolerated procedures. The most common adverse effects are transient pain or a burning sensation at the site of injection. The pain may radiate to the mandible or the auricular area. Local hematoma, transient dysphonia, and transient headache are other minor adverse effects reported.

Potentially, the most serious complication is recurrent laryngeal nerve palsy, which is reported in 1-4% of procedures. The complication is usually transient, and full recovery typically occurs within 1-3 months. The nerve damage is probably induced by chemicals or compression; it is unlikely to happen during surgery because no transaction of the nerve occurs.

The use of a multihole needle appears to preclude this complication. The aggravation of toxic symptoms is reported in the treatment of thyrotoxic nodules. Thyroid crisis was reported in a single case. Therefore, when severely thyrotoxic patients are treated, the use of beta blockers may be appropriate.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Media file 1:  Coned apical radiograph of the upper thorax shows curvilinear calcification in a thyroid adenoma, at the root of the neck, on the right side.
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Media file 2:  Posteroanterior chest radiograph shows a large retrosternal goiter (G) that displaces the trachea to the left (arrow).
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Media file 3:  Plain anteroposterior radiograph of the neck shows punctate calcification to the right of the cervical spine (straight arrow) and further multiple conglomerates of calcification at the root of the neck (curved arrow), also on the right.
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Media file 4:  Standard posteroanterior chest radiograph (in the same patient as in Image 3) shows widening of the superior mediastinum on the right in a lobulated fashion.
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Media file 5:  Plain radiograph of the upper abdomen (in the same patient as in Images 3-4) shows multiple conglomerates of punctate calcification in the right hypochondrium encroaching on the left hypochondrium. The final diagnosis was a medullary carcinoma of the thyroid (calcified), lymph node metastases at the root of the neck (calcified), right superior mediastinal metastases, and gross hepatomegaly with multiple calcified hepatic metastases.
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Media file 6:  Posteroanterior chest radiograph shows a large, lytic, expanding metastasis in the anterior aspects of the right fifth and sixth ribs, secondary to an anaplastic thyroid carcinoma in an 85-year-old woman. Note displacement of the trachea to the left by a mass lesion at the root of the neck.
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Media file 7:  Anteroposterior chest radiograph of an 86-year-old woman who had been unwell for a few months and was losing weight. The radiograph shows a right superior mediastinal mass.
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Media file 8:  Ten-millimeter computed tomography section through the thorax shows a heterogeneous mass (m) at the root of the neck, on the left, that displaces the trachea to the right. The mass appears to be growing in the caudal direction and is reaching the arch of the aorta (same patient as in Image 7).
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Media file 9:  Ten-millimeter computed tomography section through the thorax shows a heterogeneous mass (m) at the root of the neck, on the left, that displaces the trachea to the right. The mass appears to be growing in the caudal direction and is reaching the arch of the aorta (same patient as in Images 7-8).
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Media file 10:  Ten-millimeter computed tomography section through the thorax shows a heterogeneous mass at the root of the neck, on the left, that displaces the trachea to the right. The mass appears to be growing in the caudal direction and is reaching the arch of the aorta (arrow) (same patient as in Images 7-9).
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Media file 11:  Computed tomography scan shows a mass in the posterior mediastinum (P), which displaces the air-filled esophagus to the right (arrow) (same patient as in Images 7-10).
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Media file 12:  Iodine-123 thyroid scan shows that a mass is a multinodular goiter (G). The posterior mediastinal mass is a hiatus hernia (H); the stomach (S) is shown. Further investigation revealed that thyrotoxicosis was the cause of the patient's symptoms (same patient as in Images 7-11).
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Media file 13:  Technetium-99m pertechnetate thyroid scan demonstrates normal findings in a thyroid gland.
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Media file 14:  Technetium-99m pertechnetate thyroid scan demonstrates an autonomous nodule with increased activity. Uptake in the remainder of the thyroid is suppressed.
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Media file 15:  Technetium-99m pertechnetate thyroid scan demonstrates intense activity in a large thyroid gland in a patient who was hypothyroid. The patient had Pendred syndrome. Note the pyramidal lobe (P).
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Media file 16:  Technetium-99m pertechnetate thyroid scan demonstrates a thyrotoxic goiter. Note the pyramidal lobe (arrow).
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Media file 17:  Technetium-99m pertechnetate thyroid scan demonstrates a multinodular goiter.
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Media file 18:  Technetium-99m pertechnetate thyroid scan demonstrates a cold nodule in the left lobe of the thyroid (C).
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Media file 19:  Technetium-99m pertechnetate thyroid scan shows a photon-deficient mass in the upper pole of the left lobe in a 53-year-old woman with a sudden onset of pain in the anterior aspect of the neck.
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Media file 20:  Sonogram demonstrates a multilocular benign cyst (same patient as in Image 19).
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Media file 21:  Repeat 3-month follow-up sonogram in a 53-year-old woman with a sudden onset of pain in the anterior part of the neck shows that the septa have resolved. However, debris and strands are noted at the bottom of the cyst (same patient as in Images 19-20).
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Media file 22:  Further 3-month follow-up sonogram shows a considerable reduction in the size of the cyst, with a tiny debris level at the base of the cyst, in a 53-year-old woman with a sudden onset of pain in the anterior part of the neck. The final diagnosis was hemorrhage in a benign cyst (same patient as in Images 19-21).
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Media file 23:  Sonogram demonstrates a cystic colloid cyst with a comet tail artifact, in the thyroid.
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Media file 24:  Sonogram demonstrates a benign cystic lesion in the thyroid, with a surrounding halo and ragged walls.
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Media file 25:  Sonogram demonstrates a multilocular benign cyst in the thyroid.
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Media file 26:  Sonogram demonstrates thyroid cystic lesions in a 13-year-old female adolescent with cystic papillary thyroid carcinoma.
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Media file 27:  Technetium-99m pertechnetate thyroid scan shows a large cold nodule in the left lobe of the thyroid and a further, smaller cold nodule in right lobe.
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Media file 28:  Sonogram shows a 4-cm, hypoechoic, left-lobe thyroid mass (in the same patient as in Image 27).
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Media file 29:  Sonogram displaying a palpable, asymptomatic thyroid nodule (same patient as in Images 27-28) shows a solid mass in the thyroid, with a completely surrounding halo. The final diagnosis was a follicular carcinoma of the left lobe and a benign adenoma of the right lobe.
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Media file 30:  Image in a patient with a palpable, asymptomatic thyroid nodule shows a solid mass in the left lobe, with a complete surrounding halo (thyroid adenoma).
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Media file 31:  Power Doppler sonogram shows peripheral vascularity but no detectable flow in the tumor. The final diagnosis was benign thyroid adenoma (same patient as in Image 30).
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Media file 32:  A 56-year-old man underwent subtotal thyroidectomy for a familial medullary carcinoma 2 years previously. On routine follow-up examination, a mass was felt in the thyroid. Coronal, T1-weighted magnetic resonance imaging scan shows a carcinoma recurrence (R) and lymph node (L) metastases.
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Media file 33:  A 56-year-old man underwent subtotal thyroidectomy for a familial medullary carcinoma 2 years previously (same patient as in Image 32). On routine follow-up examination, a mass was felt in the thyroid. Coronal, short-tau inversion recovery magnetic resonance imaging scan shows carcinoma recurrence (R) and lymph node (L) metastases.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

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• Ahuja AT, Metreweli C. Ultrasound of thyroid nodules. Ultrasound Q. 2000;16(3):111-22.
• Barroeta JE, Wang H, Shiina N. Is fine-needle aspiration (FNA) of multiple thyroid nodules justified?. Endocr Pathol. 2006;17(1):61-5.
• Bartolotta TV, Midiri M, Runza G, et al. Incidentally discovered thyroid nodules: incidence, and greyscale and colour Doppler pattern in an adult population screened by real-time compound spatial sonography. Radiol Med (Torino). Oct 2006;111(7):989-98.
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• Brauckhoff M, Lorenz K, Ukkat J, et al. Medullary thyroid carcinoma. Scand J Surg. 2004;93(4):249-60.
• Bruneton JN, Balu-Maestro C, Marcy PY, et al. Very high frequency (13 MHz) ultrasonographic examination of the normal neck: detection of normal lymph nodes and thyroid nodules. J Ultrasound Med. Feb 1994;13(2):87-90.
• Cannon CR. Evaluation of the thyroid nodule. Am Fam Physician. May 1986;33(5):147-52.
• Danese D, Centanni M, Farsetti A, et al. Diagnosis of thyroid carcinoma. J Exp Clin Cancer Res. Sep 1997;16(3):337-47.
• Daumerie C, Ayoubi S, Rahier J, et al. [Prevalence of thyroid cancer in hot nodules]. Ann Chir. 1998;52(5):444-8.
• Dworkin HJ, Meier DA, Kaplan M. Advances in the management of patients with thyroid disease. Semin Nucl Med. Jul 1995;25(3):205-20. [Medline].
• Freitas JE, Freitas AE. Thyroid and parathyroid imaging. Semin Nucl Med. Jul 1994;24(3):234-45. [Medline].
• Gharib H. Current evaluation of thyroid nodules. Trends Endocrinol Metab. 1994;5:365-9.
• Gharib H. Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations, and effect. Mayo Clin Proc. Jan 1994;69(1):44-9. [Medline].
• Goletti O, Monzani F, Lenziardi M, et al. Cold thyroid nodules: a new application of percutaneous ethanol injection treatment. J Clin Ultrasound.