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  1. 1. Thyroid Nodules – Evaluation with Sonography Author: R. Brooke Jeffrey, MD Objectives: Upon the completion of this CME article, the reader will be able to: 1. Describe the sonographic appearance of benign thyroid lesions. 2. Describe the sonographic appearance of Hashimoto’s Thyroiditis. 3. Describe the sonographic appearance of malignant thyroid lesions. 4. List the factors that place a patient at increased risk for thyroid cancer. Introduction The human thyroid gland develops in the fetus in the first trimester as an outgrowth of cells from the pharynx near the base of the tongue. It then descends (or moves down) somewhat over the following weeks to its final position in the anterior neck region. Remnants of thyroid tissue can persist into childhood or adulthood along this pathway leading to thyroglossal cysts or nodules. The normal adult thyroid gland contains two lobes joined in the midline by an isthmus and its normal location is anterior and slightly caudad (or lower) to the cartilages of the larynx. There are fibrous septa that divide the gland up into what are called pseudolobules. These pseudolobules are made up of follicles or acini that are surrounded by networks of capillaries. The cells of the thyroid follicles produce the thyroid hormones called T4 and T3. When these cells undergo malignant transformation, they lead to papillary, follicular and aplastic carcinomas (discussed below). There is a second set of cells in the thyroid gland (called C cells) that produce the hormone calcitonin, which is involved in calcium homeostasis. If these cells undergo malignant transformation, they lead to medullary carcinoma. Thyroid disorders are very common in medicine presenting as an overactive gland (hyperthyroidism), as an under active gland (hypothyroidism), as an overall enlargement (goiter), or as palpable nodules. Ultrasound of the thyroid gland is an extremely valuable adjunct to the clinical assessment in patients with thyroid nodules. The first task of ultrasound is to detect and characterize nodules and determine which lesions require biopsy. Secondly, the use of ultrasound can be highly effective in guiding fine-needle aspiration biopsy of thyroid nodules that are difficult to palpate.
  2. 2. Technical Aspects Due to the superficial location of the thyroid, high frequency linear array transducers should be employed routinely. In general, frequencies of 10 MHz and higher are preferred, except in patients with very thick necks who are difficult to penetrate and in patients with an extensive goiter. Lower frequency transducers (7-10 MHz) may be required for adequate penetration in these patients. Both longitudinal and transverse grayscale images should be obtained of both the right and left lobes as well as the thyroid isthmus. Any detected lesions should be routinely evaluated with color Doppler. The normal thyroid appears as the uniformly echogenic gland (figure 1). The vascularity is symmetric bilaterally with color and power Doppler. Both surface and parenchymal thyroid blood vessels can readily be detected by the use of current high- resolution power Doppler. The use of Color Doppler is particularly valuable in assessing thyroid lesions that may be predominantly cystic or have internal hemorrhage. With high- resolution scanners, the lack of internal flow or avascular debris indicates a low likelihood of tumor. Imaging Approach The imaging approach to the management of patients with thyroid nodules varies from institution to institution. In patients with palpable nodules, it is often accepted clinical practice to perform biopsy by palpation alone without the use of imaging. Other institutions prefer to initially screen with thyroid scintigraphy to evaluate for non-functioning cold nodules, which have a much higher likelihood of being malignant. At many institutions, high-resolution ultrasound has largely replaced scintigraphy as the imaging method of choice in evaluating the patient with the possible thyroid nodule. In addition to determining the size and location of the nodule or nodules, an assessment should be made of whether a biopsy is indicated or not. In general, patients with nodules less than 1 cm are not appropriate for biopsy unless the nodule has suspicious features or unless the patient is in a high-risk group for thyroid cancer. In these patients, the most likely diagnosis is a hyperplastic or adenomatous nodule. The patient can simply be followed by clinical evaluation with palpation. Similarly, patients with purely cystic lesions (colloid cysts) should not undergo biopsy because these are invariably benign.
  3. 3. Characterization of Thyroid Nodules It is important to characterize the echogenicity of nodules because hypoechoic lesions tend to have a greater clinical likelihood for malignancy compared to echogenic or isoechoic nodules. Areas of cystic change within the nodule should be identified because this indicates a lesion that is likely benign. Finally, areas of calcification within the nodule should also be assessed. Fine punctate areas of calcification often appear sonographically as high amplitude echoes without acoustic shadowing. These are typical for malignant calcifications related to psammoma bodies. Color Doppler of thyroid nodules is not highly specific in differentiating benign from malignant as both may demonstrate prominent internal vascularity. Benign Lesions Benign lesions of the thyroid include: colloid cysts, hyperplastic nodules, and adenomatous nodules. In general, benign lesions are isoechoic or echogenic compared to normal background echogenicity of the thyroid. Hyperplastic and adenomatous nodules often have a thin, well-defined hypoechoic halo on the periphery of the lesion. There frequently are cystic areas within these nodules (figure 2). Color Doppler may reveal avascular debris within the nodules that have undergone hemorrhagic degeneration. A fluid level may be noted in nodules that have acute internal hemorrhage. Although calcification is relatively uncommon with benign nodules, it is frequently curvilinear and peripheral. This is often referred to as “eggshell” calcification. Not infrequently, multiple adenomas or hyperplastic nodules result in diffuse enlargement of the gland with multi-focal disease known as multinodular goiter. True cystic lesions of the thyroid are most often colloid cysts. They are predominantly anechoic but may have the presence of tiny high amplitude echoes casting reverberation artifacts known as comet-tails that are highly characteristic (figure 3). A benign inflammatory condition of the thyroid is known as Hashimoto’s Thyroiditis. In more chronic cases of Hashimoto’s Thyroiditis, the typical sonographic features include: a diffusely enlarged gland demonstrating hypoechoic areas with a very disorganized and heterogeneous pattern (figure 4). Due to the chronic inflammation, color Doppler may demonstrate prominent vascularity within areas of Hashimoto’s Thyroiditis.
  4. 4. Malignant Lesions Papillary carcinoma is the most common thyroid malignancy. It comprises nearly 75% of all thyroid cancers. Follicular, Medullary and Aplastic carcinomas and lymphoma make up the remaining 25% of all primary thyroid malignancies. Although uncommon, metastases to the thyroid gland may occur with lung, breast, and colon cancers. Lymphoma may also involve the thyroid gland and is characteristically a sequela of long-standing Hashimoto’s Thyroiditis with lymphocytic infiltration of the gland. Sonographic features suggesting a malignant thyroid nodule include a poorly defined margin, hypoechoicity and punctate calcifications (psammomatous calcification). These calcifications may be present in 25% of carcinomas (figures 5 & 6). There is often increased internal flow on color Doppler within carcinomas but this is a nonspecific finding encountered with benign nodules as well. Although a thin hypoechoic halo within an isoechoic lesion is felt to be a feature of benign thyroid nodule, halos may be seen on the periphery of malignant lesions as well. Typically, the halos in malignant lesions are incomplete and irregular in their appearance often thicker than the usual thin 1-2 mm halo around a benign appearing lesion. In all patients with a possible malignant thyroid lesion, an attempt should be made to search for cervical lymphadenopathy along the internal jugular chain. The Incidental Thyroid Nodule Nearly 40% of the population has sonographically demonstrable thyroid nodules. The overwhelming majority of these are benign. Therefore, there is often concern about pursuing small, non-palpable, thyroid nodules that are discovered incidentally by CT, MRI, or ultrasound examinations for other reasons. For example, it is not uncommon for an incidental thyroid nodule to be discovered during carotid ultrasound. In general, unless there is a clinical increased risk for cancer (such as prior-neck radiation, multiple endocrine neoplasia type II or MEN-II Syndrome, known prior thyroid cancer or a positive neck node), biopsy should be deferred in small lesions particularly when there is no sonographic evidence of malignancy.
  5. 5. In patients with a possible malignant lesion discovered on sonography, careful examination should be formed of the cervical lymph nodes along the jugular vein to assess for possible nodal metastases. Lymphadenopathy may demonstrate abnormal flow patterns on color Doppler sonography and may have fine punctate calcifications typical of papillary carcinoma. Although primary thyroid cancers are rarely cystic, metastases to lymph nodes may produce complex cystic masses that should not be mistaken for benign lesions such as a branchial cleft cyst or thyroglossal duct cyst. Color Doppler may be of particular value in identifying the solid component of the cyst, which should be used to guide the biopsy approach. Biopsy Technique One of the most useful aspects of ultrasound of the thyroid is to guide percutaneous biopsy. Although a variety of techniques may be utilized, usually fine needle aspiration technique performed properly can achieve a high rate of diagnostic yield. Unlike biopsy with palpation, the key feature of sonographic guidance is that precise needle placement can be determined with high-resolution ultrasound. Following informed consent, and a detailed explanation of the nature of the procedure, ultrasound color Doppler mapping is performed to delineate vessels in and around the thyroid nodule that should be avoided. A 25-gauge needle yields excellent results with fine needle aspiration biopsy. The author’s prefer to use subcutaneous and dermal local anesthetic as well as injecting local anesthetic over the capsule of the thyroid because multiple aspirates may be required. It is not uncommon to perform 4 to 6 aspirations of a thyroid nodule because many of the benign nodules contain a hemorrhagic component and thus only blood will be obtained. Following sonographic puncture of the nodule, the relatively hypovascular areas of the nodule are biopsied using a slight rotatory motion with 2 to 3 ml of suction applied by an attached syringe. After the first 4 aspirates are performed, slides are assessed to determine if an adequate specimen has been obtained. If only blood is identified on the initial quick stains, then additional aspirates are required in order to achieve a diagnostic specimen. A high-rate of cellular aspirates can be obtained with this method and there are virtually no complications using ultrasound guidance.
  6. 6. Figures 1 Normal Thyroid. Transverse scan of the normal thyroid demonstrates a uniformly echogenic gland that is homogenous without focal lesions. 2 Complex Cyst Secondary to An Adenoma with Internal Hemorrhage. Note the predominantly cystic mass (calipers) with internal septae. Needle aspiration revealed blood from a degenerating adenoma. 3 Colloid Cyst. Note the predominantly anechoic lesion (calipers). There are tiny foci of high amplitude echoes within the cyst that represent crystalline debris. 4 Hashimoto’s Thyroiditis. This longitudinal image of the thyroid demonstrates a heterogeneous gland with an irregular predominantly hypoechoic parenchymal echogenicity. Color Doppler revealed marked increased flow related to chronic inflammation. 5 Papillary Carcinoma. Note the hypoechoic mass at the junction of the right lower lobe of the thyroid and isthmus. A tiny punctate area of calcification representing a psammoma body is seen within the superior portion of the mass. 6 Papillary Carcinoma. Note the dominant hypoechoic mass containing multiple punctate areas of high amplitude calcifications. References or Suggested Reading: 1. Ahuja AT, Metreweli C. Ultrasound of thyroid nodules. Ultrasound Quarterly 2000;16(3):111-121 2. Gooding GA. Sonography of the thyroid and parathyroid. Radiol Clin North Am. 1993 Sep;31(5):967-89 3. Watters DAK, Ahuja AT, Evans RM. Role of ultrasound in the management of thyroid nodules. Am J Surg. 1992 Dec;164(6):654-7 4. Simeone JF, Daniels GH, Mueller PR, Maloof F, et al.High-resolution real-time sonography of the thyroid. Radiology. 1982 Nov;145(2):431-5 5. Solbiati L, Livraghi T, Ballarati E, Ierace T, Crespi L. Thyroid Gland. In: Solbiati L, Rizzatto G, eds. Ultrasound of Superficial Structures. London: Churchill Livingstone, 1995:49-85 About the Author:
  7. 7. Dr. R. Brooke Jeffrey is currently a Professor of Radiology and is the Chief of Abdominal Imaging at Stanford University School of Medicine. He is active in clinical practice and is a member of various professional organizations, including the American College of Radiology. Dr. Jeffrey is a well-known speaker and he has lectured on many different ultrasound and radiology topics at numerous conferences around the country. He is active in research and has authored several publications in peer-review medical journals. Examination: 1. Which of the following statements is (are) true? A. The human thyroid gland develops in the fetus in the second trimester. B. The human thyroid gland develops in the fetus as an outgrowth of cells from the pharynx near the base of the tongue. C. The human thyroid gland (once it develops in the fetus) ascends or moves up to its final position in the anterior neck region. D. all of the above are true. E. only B & C are true. 2. The normal adult thyroid gland contains two lobes joined in the midline by an isthmus and its normal location is A. posterior and slightly caudad (or lower) to the cartilages of the larynx. B. anterior and slightly cephalad (or above) to the cartilages of the larynx. C. anterior and slightly caudad (or lower) to the cartilages of the larynx. D. posterior and slightly cephalad (or above) to the cartilages of the larynx. E. anterior and even with the cartilages of the larynx. 3. Which of the following statements is (are) true? A. The cells of the thyroid follicles produce the thyroid hormones called T4 and T3. B. When the cells of the thyroid follicles undergo malignant transformation, they lead to medullary carcinoma. C. The second set of cells in the thyroid gland are called A cells and they produce the hormone calcitonin. D. If the A cells undergo malignant transformation, they lead to papillary, follicular and aplastic carcinomas. E. all of the above are true. 4. Due to the superficial location of the thyroid, _________ frequency linear array transducers are preferred for scanning purposes. A. 2-3 MHz B. 3-5 MHz C. 5-7 MHz D. 7-10 MHz E. 10 MHz and higher
  8. 8. 5. Which of the following statements is (are) true? A. Parenchymal thyroid blood vessels can readily be detected by the use of current high-resolution power Doppler, but not the surface blood vessels. B. The use of Color Doppler is particularly valuable in assessing thyroid lesions that are predominantly solid. C. With high-resolution scanners, the presence of internal flow or avascular debris indicates a low likelihood of tumor. D. All of the above are true. E. None of the above are true. 6. The imaging approach to the management of patients with thyroid nodules varies from institution to institution. At many institutions, high-resolution ultrasound has largely replaced __________ as the imaging method of choice in evaluating the patient with the possible thyroid nodule. A. MRI B. CT C. scintigraphy D. arteriography E. routine xray imaging 7. In general, patients with nodules ___________ are not appropriate for biopsy unless the nodule has suspicious features or unless the patient is in a high-risk group for thyroid cancer. A. greater than 1 cm B. less than 1 cm C. greater than 1 inch D. less than 1 inch E. less than 2 cm 8. It is important to characterize the echogenicity of nodules because A. hypoechoic lesions tend to have a greater clinical likelihood for malignancy B. echogenic lesions tend to have a greater clinical likelihood for malignancy C. isoechoic lesions tend to have a greater clinical likelihood for malignancy D. B and C above. E. none of the above. 9. Which of the following statements is (are) true? A. Areas of cystic change within the nodule should be identified, as this indicates a lesion that is likely to be benign. B. Fine punctate areas of calcification often appear sonographically as high amplitude echoes without acoustic shadowing and are typical for malignant calcifications related to psammoma bodies. C. Color Doppler of thyroid nodules is highly specific in differentiating benign from malignant as malignant nodules primarily demonstrate prominent internal vascularity. D. A & B above are true. E. B & C above are true.
  9. 9. 10. Benign lesions of the thyroid include A. colloid cysts B. lymphoma C. hyperplastic or adenomatous nodules D. A & C above E. all of the above 11. Which of the following statements is (are) true? A. In general, benign lesions are isoechoic or echogenic compared to normal background echogenicity of the thyroid. B. Hyperplastic and adenomatous nodules often have a thick, incomplete or irregular halo on the periphery of the lesion. C. Color Doppler will reveal vascular flow within the nodules that have undergone hemorrhagic degeneration. D. Calcification is relatively common with benign nodules, it is frequently curvilinear and peripheral, and is often referred to as “eggshell” calcification. E. All of the above statements are true. 12. True cystic lesions of the thyroid are most often colloid cysts. They are predominantly A. hyperechoic but may have the presence of tiny high amplitude echoes casting reverberation artifacts known as comet-tails. B. anechoic but may have the presence of tiny high amplitude echoes casting reverberation artifacts known as comet-tails. C. anechoic and usually have the presence of curvilinear calcifications known as “egg-shell” calcifications. D. hyperechoic and usually have the presence of curvilinear calcifications known as “egg-shell” calcifications. E. isoechoic with no other specific findings. 13. A benign inflammatory condition of the thyroid is known as Hashimoto’s Thyroiditis. In more chronic cases of Hashimoto’s Thyroiditis, the typical sonographic features include A. a diffusely enlarged gland demonstrating hypoechoic areas with a very disorganized and heterogeneous pattern B. a predominantly anechoic appearance but may have the presence of tiny high amplitude echoes casting reverberation artifacts known as comet-tails. C. Due to the chronic inflammation, color Doppler may demonstrate prominent vascularity within areas of Hashimoto’s Thyroiditis. D. A & C above. E. All of the above. 14. ________ carcinoma is the most common thyroid malignancy. A. Follicular B. Medullary C. Papillary D. Aplastic
  10. 10. E. Lymphoma 15. Although uncommon, metastases to the thyroid gland may occur with A. lung cancer B. breast cancer C. colon cancer D. all of the above. E. none of the above 16. Sonographic features suggesting a malignant thyroid nodule include A. Increased internal flow on color Doppler is often seen and this is a specific finding because it is not encountered with benign nodules. B. a poorly defined margin, hypoechoicity and punctate calcifications (psammomatous calcification). C. well-defined, thin halos seen on the periphery D. A & B above E. all of the above 17. Nearly _________ of the population has sonographically demonstrable thyroid nodules. A. 15% B. 25% C. 40% D. 50% E. 30% 18. The clinical factors that might suggest an increased risk for thyroid cancer include A. prior-neck radiation B. MEN-II Syndrome C. known prior thyroid cancer D. a positive neck node E. all of the above 19. Which of the following statements is (are) true? A. In patients with a possible malignant lesion discovered on sonography, careful examination should be formed of the cervical lymph nodes along the trachea. B. Lymphadenopathy may demonstrate abnormal flow patterns on color Doppler sonography and may have fine punctate calcifications typical for papillary carcinoma. C. Although primary thyroid cancers are rarely cystic, metastases to lymph nodes may produce complex cystic masses that should not be mistaken for benign lesions such as a branchial cleft cyst or thyroglossal duct cyst. D. All of the above are true. E. Only B & C above are true. 20. One of the most useful aspects of ultrasound of the thyroid is to guide percutaneous biopsy. With fine needle aspiration,
  11. 11. A. it is not uncommon to perform 4 to 6 aspirations of a thyroid nodule to obtain an adequate sample. B. because most malignant nodules contain a hemorrhagic component, it is diagnostic if only blood is obtained. C. if after the first 4 aspirates are performed, it is determined that only blood has been obtained on the initial quick stains, then you should stop because more than 4 attempts greatly increases the risk for complications. D. B & C above E. none of the above.

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