Sei sulla pagina 1di 39
40 Thyroid and Parathyroid Glands: Anatomy and Pathology Laurie A. Loevner SECTION ONE: THE THYROID


Thyroid and Parathyroid Glands:

Anatomy and Pathology

Laurie A. Loevner

SECTION ONE: THE THYROID GLAND ANATOMY OF THE THYROID GLAND ENDOCRINOLOGY OF THE THYROID GLAND CLINICAL MANIFESTATIONS OF THYROID DISEASE THYROID IMAGING Nuclear Scintigraphy Cross-Sectional Imaging Ultrasonography PATHOLOGY OF THE THYROID GLAND Congenital Anomalies Autoimmune Disease and Thyroiditis Graves’ Disease Hashimoto’s Thyroiditis Silent, Painless Thyroiditis and Postpartum Thyroiditis De Quervain’s Thyroiditis (Subacute Granulomatous Thyroiditis) Acute Suppurative Thyroiditis Riedel’s Thyroiditis (Struma) Thyroid Goiter Nodular Thyroid Disease NEOPLASMS OF THE THYROID GLAND Adenomas Malignant Neoplasms Papillary Carcinoma

Follicular Carcinoma Hurthle Cell Tumors Medullary Carcinoma Anaplastic Carcinoma Primary Lymphoma Rare Malignancies Metastatic Disease SECTION TWO: THE PARATHYROID GLANDS ANATOMY OF THE PARATHYROID GLANDS ENDOCRINOLOGY OF THE PARATHYROID GLANDS CLINICAL MANIFESTATIONS OF PARATHYROID DISEASE Hyperparathyroidism Hypoparathyroidism IMAGING OF PATHOLOGY OF THE PARATHYROID GLANDS Parathyroid Adenoma Ultrasonography Cross-Sectional Imaging Nuclear Scintigraphy Reoperation for Hyperparathyroidism Parathyroid Hyperplasia Parathyroid Carcinoma Parathyroid Cyst



The thyroid gland plays a critical role in the regulation of several metabolic functions including cardiac rate and output, lipid catabolism, and skeletal growth, as well as oxygen and heat production. As a result, patients with


hormonally active thyroid abnormalities (hypothyroidism or hyperthyroidism) present with a wide range of symptoms. The evaluation of such patients requires an understanding of the hormonal functions carried out by the thyroid gland. In addition to the pathophysiology resulting from abnormal thyroid function, cross-sectional imaging to assess the morphologic features of the thyroid gland may be necessary for comprehensive patient care. Nuclear scintigra- phy reveals functional information about the thyroid gland,


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology


Thyroid and Parathyroid Glands: Anatomy and Pathology 2135     FIGURE 40-1 Normal thyroid gland on

FIGURE 40-1 Normal thyroid gland on MR imaging. A, Unenhanced axial T1-weighted MR image shows the normal appearance of the thyroid gland (T ), which is homogeneously hyperintense to the neck musculature (m). The normal anatomic relationship of the gland to the jugular vein (J ), carotid artery (c), esophagus (e), and musculature


(m) is shown. B, Axial T2-weighted image at the same level as A shows the normal gland to be hyperintense relative to the neck musculature.


while imaging including ultrasound, computed tomography (CT), and magnetic resonance (MR) imaging provide important adjunctive anatomic information. In addition to evaluating the intrinsic structure of the thyroid gland, these modalities provide important information about the related structures in the neck, including the presence of lymphade- nopathy, and extension of disease into adjacent soft tissues of the neck such as the mediastinum, trachea, and carotid sheath. The anatomy and physiology of the thyroid gland will be reviewed. Congenital, autoimmune, inflammatory, meta- bolic, and neoplastic diseases of the thyroid will then be discussed, and the diagnostic utility of radiologic imaging to evaluate each of these thyroid abnormalities will be addressed.

(longus colli) and paraspinal musculature and posterior (deep) to the sternothyroid and sternohyoid muscles (Fig. 40-1). Usually, the entire thyroid gland is in the neck above the level of the clavicles; however, substernal extension into the superior mediastinum may occur. An accessory lobe, referred to as the pyramidal lobe, may be present in 50% to 70% of people. It usually arises from the isthmus of the gland and extends superiorly along the course of the distal thyroglossal duct. 1 The pyramidal lobe may be attached to the hyoid bone or, uncommonly, it may arise from the medial aspect of the right or left thyroid lobe. A pyramidal lobe is most commonly recognized in patients with Graves’ disease because it is enlarged and readily identified on nuclear scintigraphy (Fig. 40-2).




The thyroid gland is shield-shaped in the majority of


patients. It consists of right and left lobes that are usually joined by the isthmus, though occasionally the isthmus may be absent. The thyroid isthmus is anterior to the trachea, usually overlying the first through third tracheal rings. Uncommonly, it may be more cranial, positioned at or just caudal to the anterior cricoid cartilage arch. The right and



lobes of the thyroid gland are on either side of the


trachea, and each lobe has a superior and an inferior pole.



normal thyroid gland is situated with its upper margin


near the oblique line on the thyroid cartilage and its lower


margin at the level of the fourth or fifth tracheal cartilage; a region referred to as the thyroid bed. The normal thyroid gland weighs between 15 and 35 grams and in males the average thyroid volume is 19.6 ml, while in females it is 18.6 ml. The gland size varies with patient weight, age, and


gender and the thyroid gland is enlarged in females during


menstruation and pregnancy. The average thyroid lobe measures 3 cm in greatest anteroposterior dimension and 2

FIGURE 40-2 Iodine-131 scan in a patient with Graves’ disease. There is diffuse enlargement and uptake of I-131 by the thyroid gland. A pyramidal lobe is noted (arrows). The 24-hour uptake was 48% (normal,



in width. The thyroid is anterior to the prevertebral

10% to 30%).




As discussed in Chapter 34, the pharynx and cervical esophagus are surrounded posteriorly and along their lateral margins by the retrovisceral space. At the level of the pharynx, this space is often referred to as the retropharyn- geal space, while at the level of the cervical esophagus, this same space is usually referred to as the retroesophageal space. At the level of the thyroid cartilage and the attach- ment of the inferior pharyngeal constrictor muscles to this cartilage, the retrovisceral space has an anterior projection that extends around the sides of the cervical esophagus to encompass the larynx, trachea, thyroid gland, and parathy- roid glands. This ventral extension is often referred to as the visceral compartment. This fascia thus attaches the thyroid gland to the larynx and trachea. As a result, the thyroid gland moves with the larynx during swallowing. The thyroid gland is encapsulated, and from this capsule septae extend into the substance of the gland. Projecting up into the lower aspect of this visceral compartment is a fold of fascia containing the inferior thyroid artery. As a result, this fascial fold divides the lower visceral compartment into anterior and posterior sections. The anterior section, or pretracheal space, extends down behind the sternum to the level of the innominate vessels (sternoclavicular joint) in the anterior mediastinum. The posterior section of the visceral compartment is the retroesophageal space, which extends behind the esophagus down into the posterior mediastinum to approximately the level of the carina. Thus, the entire visceral space is a single, somewhat complex-shaped common space that contains in its anterior portion the larynx, trachea, thyroid gland, and parathyroid glands and surrounds the cervical esophagus and pharyngeal constrictor muscles. The superior mediastinum is dened as being separated from inferior mediastinum by a plane connecting the joint between the manubrium and the body of the sternum (second costal cartilage) and the lower border of the fourth thoracic vertebra. The inferior mediastinum is further subdivided into anterior (in front of pericardium), middle (pericardium and heart and roots of the great vessels), and posterior (behind the pericardium) compartments. The anterior mediastinum is continuous with the pretracheal space while, as mentioned, the posterior mediastinum is continuous with the retropharyngeal space and the spaces lateral to the esophagus and trachea, between the carotid sheaths. 3 If a thyroid gland enlarges sufciently, it will extend outside the normal volume of the thyroid bed. Direct caudal growth is downward into the pretracheal space. As such, the thyroid extension lies in the retrosternal region, anterior to the common carotid arteries and the internal jugular veins. In this location, the thyroid enlargement is usually referred to as a retrosternal or substernal goiter. These goiters are usually resected via a cervical approach, without the need for a sternotomy. If the caudal thyroid gland enlargement is posteriorly directed, the goiter can grow along the sides of the esophagus and eventually extend behind the esophagus. Once behind the esophagus, the goiter can project either down into the posterior mediastinum or up behind the pharynx. If the thyroid growth is into the posterior mediastinum, the goiter is referred to as a mediastinal goiter and it lies dorsal to the great vessels. In this location, many surgeons prefer to resect the goiter via a sternectomy

approach. Cranial extension behind the pharynx is resected via a cervical approach. The thyroid gland has a rich vascular supply. There are paired superior and inferior thyroidal arteries. The right and left superior thyroidal arteries are the rst branches off of the respective external carotid arteries, and travel inferiorly from their origin to the thyroid gland. The thyrocervical trunks, which originate from the subclavian arteries, each give rise to an inferior thyroidal artery. The thyroidea ima is an inconstant vessel that, when present, arises directly from the aortic arch and helps supply the inferior thyroid gland. The venous drainage of the thyroid gland is via the superior and middle thyroidal veins, which empty into the internal jugular vein, and an inferior vein, which drains into the innominate vein. The thyroid gland is innervated by the tenth cranial (vagus) nerve and the cervical sympathetic neural plexus. The sympathetic bers descend from the ganglia of the sympathetic trunk, while the parasympathetic bers course along with the vagus nerve. This autonomic innervation is believed to strongly inuence thyroid gland perfusion. The thyroid gland contains multiple lobules, each of which is composed of multiple follicles. Thyroglobulin is stored within colloid in these follicles, and the follicular cells secrete thyroid hormones. Parafollicular (C) cells are also dispersed throughout the stroma of the gland and secrete thyrocalcitonin.


The primary function of the thyroid gland is to synthesize hormones that play a vital role in the regulation of a variety of metabolic functions. Two hormones, triiodothyronine (T3) and thyroxine (T4), are synthesized within the thyroid. They are released from the thyroid in response to a feedback mechanism with the pituitary-hypothalamic axis. Ulti- mately, the secretion of thyroid hormones is mediated by thyrotropin-stimulating hormone (TSH) secreted by the anterior lobe of the pituitary gland. Pituitary secretion of TSH is in turn regulated by thyrotropin-releasing hormone (TRH) secreted by the hypothalamus. The synthesis of hormones within the thyroid is a regulated, systematic process. The rst step involves trapping of iodide, in which iodide from the circulating plasma is actively transported into the thyroid gland and concentrated within follicular cells. This active transport mechanism traps iodine to a concentration of approximately 100 times more than that in the serum. Iodide is then oxidized by thyroid peroxidase into its chemically active form. Subsequently, organication, a process in which tyrosine residues on thyroglobulin molecules are iodinated to form monoiodotyrosine (MIT) and diiodotyrosine (DIT), occurs. The coupling of MIT and DIT forms T3, and the coupling of two molecules of DIT forms T4. Next, T3 and T4 are released from thyroglobulin and secreted into the circulation in free and bound forms. 2 Simultaneously, deiodination of free MIT and DIT occurs for iodide salvage and recycling within the thyroid gland. Aberrant organica- tion usually results from enzymatic defects that interfere


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology


with the oxidation of iodide or the iodination of tyrosine. Rarely, there may be failure of iodide trapping. In the circulation, several carrier proteins transport









thyroid hormones. Thyroxine-binding globulin carries ap- proximately 70% of T3 and T4, thyroxine-binding preglobu-







lin carries about 5% of T3 and 25% of T4, and albumin






carries the remaining hormones. The active form of T3 and



De Quervains thyroiditis



T4 is the free or unbound form, representing only 0.3% of


Subacute lymphocytic


T3 and 0.03% of T4. T3 is approximately three to four times




more active physiologically than T4. T4 is synthesized


Struma ovarii


entirely within the thyroid, while 80% to 95% of T3 is


Factitious disease


synthesized by peripheral conversion of T4. Temporary interference with the organication of iodide

RAIU, 24-hour radioactive iodine uptake (normal, 10% to 30%); TFTs, thyroid function tests.


may occur with several medications and with the iodinated contrast materials that are frequently used in CT studies (Table 40-1). The result is altered (decreased) radioactive iodine uptake measurements. Hence, these medications and contrast CT studies should be discontinued prior to nuclear scintigraphy (see below).


Thyroid storm characterized by hypertension, tachycar- dia, and fever may present as a clinical emergency in patients with unrecognized or inadequately treated thyrotox- icosis. If unrecognized, it may result in death. Thyroid ophthalmopathy, more common in women, is characterized by proptosis usually secondary to enlargement of the extraocular muscle bellies, with sparing of their tendinous insertions. Although most commonly seen in


Thyrotoxicosis refers to a clinical syndrome that devel- ops when circulating levels of T4 and T3 are increased (TSH is usually suppressed). Hyperthyroidism refers to sustained thyroid hyperfunction with increased thyroid hormone synthesis and release. Thyrotoxicosis is manifested by a variety of symptoms including warmth and ushing reecting peripheral vasodilatation, increased heat loss, weight loss, myopathy, and increased appetite. Patients, especially children, may be hyperactive. Cardiac manifesta- tions are more common in older patients and include tachycardia, palpitations, arrhythmias, and cardiomegaly. Thyrotoxicosis associated with hyperthyroidism is most frequently seen with Gravesdisease but may also be seen with toxic multinodular goiter or a hyperfunctioning adenoma. Toxic multinodular goiter associated with hyper- thyroidism (Plummers disease) commonly develops in patients over the age of 50 years and is related to a hyperfunctioning thyroid nodule. 3 Rarely, thyrotoxicosis may be associated with a TSH-secreting pituitary adenoma or thyroid neoplasms. Thyrotoxicosis not associated with hyperthyroidism (low radioactive iodine uptake) may be related to inammatory thyroid disease or ectopic thyroid tissue (ovarian strumii), or it may be factitious (exogenous hormone use or Munchausen syndrome) (Table 40-2).

Gravesdisease and hyperthyroidism, thyroid ophthalmopa- thy may occur in euthyroid and even hypothyroid patients. The most common patterns of extraocular muscle involve- ment are enlargement of the inferior rectus muscle, enlargement of both the inferior and medial rectus muscles, and enlargement of all of the muscles (Fig. 40-3). 4 There usually is relative sparing of the lateral rectus muscles, and isolated involvement of this muscle should raise the suspicion of a different disease process such as myositis or pseudotumor. Proptosis may also be related to an increase in orbital fat secondary to edema and lymphocytic inltration, as well as due to an increase in the volume of the extraocular muscles. Although most commonly symmetric, exophthal- mos (proptosis) may be asymmetric or even unilateral. 4 Clinical signs and symptoms include proptosis, lid retrac- tion, decreased ocular range of motion, and corneal exposure caused by eyelid retraction. Extraocular muscle enlargement may result in compression of the optic nerve at the orbital




Iodine-containing contrast agents Oral cholecystographic agents Thyroxine (Synthroid) Cytomel (T3)


Antithyroid medications (propylthiouracil)


Iodide preparations Antibiotics Antihistamines

FIGURE 40-3 Thyroid ophthalmopathy in a 43-year-old woman with Gravesdisease. Coronal CT scan shows bilaterally symmetric enlarge- ment of the bellies of the extraocular muscles, with relative sparing of the lateral rectus muscles (arrows).




2138 NECK   FIGURE 40-4 Enhanced CT scan of a multinodular goiter with substernal extension and

FIGURE 40-4 Enhanced CT scan of a multinodular goiter with substernal extension and compression of the trachea and esophagus. A, Axial CT scan at the level of the upper trachea shows diffuse nodular enlargement of the thyroid gland that is heterogeneous in density. There is marked displacement of the trachea (T ) and esophagus (e) from left to right. B, There is extension of goiter (arrows) behind the trachea into the middle mediastinum.


apex, resulting in visual loss. Surgical decompression of the orbit is frequently necessary to preserve vision. Late in the disease, contractures and brosis of the extraocular muscles may lead to abnormal eye movements (see Chapter 9).

presence of a thyroid mass, violation of the thyroid gland capsules integrity, or direct extension of a thyroid lesion into the trachea or carotid sheath structures are ndings highly suggestive of a thyroid malignancy.


Hypothyroidism refers to decreased thyroid hormone synthesis (serum TSH is high, while T3 and T4 levels are low). Primary hypothyroidism may be secondary to struc-



tural or functional derangements of the thyroid gland, and in adults it most often results from processes that destroy thyroid tissue such as autoimmune disease or iodine-131 ( 131 I) treatment. In children it may be related to enzyme deciencies, defects in organication, or congen- ital anomalies such as lingual thyroid or thyroid agene- sis. 5 Central hypothyroidism refers to decreased thyroid stimulation by TSH related to pituitary disease (secondary hypothyroidism) or hypothalamic TRH deciency (ter- tiary hypothyroidism). Unless readily identied and man- aged, hypothyroidism occurring prenatally or during in-

Nuclear scintigraphy and ultrasonography are frequently the rst imaging modalities used to assess patients with suspected thyroid disorders. CT and MR imaging are frequently utilized to address specic issues regarding thyroid disease such as the extent of thyroid goiter or extension of neoplasm outside the thyroid capsule and into adjacent structures in the neck. They are used in assessing for regional nodal metastases in the setting of thyroid cancer and in the evaluation of recurrent disease following treatment for thyroid cancer.


fancy will result in cretinism. Hypothyroidism occurring in older children and adults is termed myxedema. Clinical manifestations are extremely variable, ranging from fatigue

Nuclear Scintigraphy


to coma. Many of the secondary manifestations of thyroid disease are frequently responsible for the clinical presentation of such patients. Any condition that causes marked enlarge- ment of the thyroid gland, most commonly multinodular goiters, but also neoplastic and inammatory processes, may compress the adjacent esophagus and trachea, causing dysphagia and respiratory distress, respectively (Fig. 40-4). Similarly, there may be compression and displacement of the jugular vein and carotid artery. Because the recurrent laryngeal nerve travels in the tracheoesophageal groove, thyroid lesions that extend to this area may present with vocal cord paralysis. Cervical lymphadenopathy in the

Nuclear scintigraphy provides excellent functional infor- mation about the thyroid because the radionuclides used to image the gland do so by utilizing some step of hormone synthesis within the thyroid. The primary role of scintigra- phy in the evaluation of a focal thyroid mass is to determine whether a lesion is ‘‘hot’’ (low incidence of malignancy) or ‘‘cold’’ (higher incidence of malignancy). 6, 7 Nuclear imaging of the thyroid gland is performed with a gamma scintillation camera. The patient is usually placed in a hyperextended supine position. Images are typically ob- tained from the chin to the sternal notch in multiple views including anterior, posterior, and bilateral oblique projec-


Chapter 40

tions. Findings on imaging are correlated with those on palpation of the gland. Currently, morphologic detail of the thyroid gland is obtained using technetium (Tc-99m) pertechnetate, iodine 123 (I-123), and iodine 131 (I-131). Routes of administra- tion, doses, and some physical properties of these agents are reviewed in Table 40-3. Imaging is performed approxi- mately 20 minutes following administration of Tc-99m pertechnetate, 4 to 24 hours following oral ingestion of I-123, and 24 to 72 hours following administration of I-131. The normal thyroid gland shows homogeneous radionuclide uptake and distribution. The isthmus of the thyroid gland may demonstrate slightly less activity than the right and left thyroid lobes. I-131 is used for determining 24-hour thyroid iodine uptake, measured with a dedicated probe centered 1 inch above the sternal notch. Thyroid uptake reects the percentage of the dose given to the patient that is accumulated within the thyroid gland, corrected for radioac- tive decay. Normal 24-hour uptake ranges from 10% to 30%. Several medications such as propylthiouracil, methi- mazole, and iodine-containing contrast agents used for imaging may temporarily interfere with the organication of iodide, altering radioactive iodine uptake measurements for as long as 6 weeks (Table 40-1). 811 The uptake of I-131 may be reduced by as much as one half 1 week following injection of iodinated agents for CT examination. 810 Furthermore, in over one third of patients with underly- ing thyroid disease, temporary changes in thyroid func- tion may occur following injection of iodinated contrast material. 8 Therefore, if CT imaging is believed to be necessary in a patient who will also be studied with nuclear scans using iodinated radionuclides, it should be performed without contrast administration. If contrast is desired, then CT should be performed after nuclear scintigraphy. Medications that interfere with thyroid func- tion should be withdrawn for adequate periods of time prior to nuclear scanning. In general, if CT contrast is adminis- tered, one should wait at least 6 weeks before performing nuclear scintigraphy. I-131 is used in both the evaluation and treatment of patients with thyroid cancers that concentrate iodine. It is particularly useful in the follow-up of patients after thyroidectomy to evaluate for residual thyroid tissue in the operative bed as well as to assess for distant metastatic disease (see Neoplasms of the Thyroid Gland).

Thyroid and Parathyroid Glands: Anatomy and Pathology


More recently, uorodeoxyglucose positron emission tomography ( 18 FDG-PET) has played an increasingly important role in the follow-up of patients with thyroid cancer due to increased glucose metabolism by malignant tumors. It may be particularly useful in assessing metastatic thyroid tumors that do not concentrate radioiodine 12, 13 . It is frequently used in evaluating patients with rising thyroglob- ulin levels following thyroidectomy. 14 Whole body scans are obtained to identify regions of FDG uptake (Fig. 40-5). Potential pitfalls include indolent or well-differentiated thyroid tumors that take up FDG poorly and FDG uptake in areas that are not related to metastatic thyroid cancer.

Cross-Sectional Imaging

While scintigraphy provides functional information about the thyroid, CT and MR imaging provide important adjunctive anatomic information that is superior to that of nuclear imaging. These modalities not only provide better delineation of lesions within the thyroid, but also play a critical role in the detection of lymph node metastases, as well as extension of thyroid disease to adjacent tissues in the neck. Specically, invasion of the paraspinal musculature, esophagus, trachea, and carotid sheath structures may be assessed 15 (Fig. 40-6). The detailed anatomic information provided by CT and MR imaging is also valuable in guiding the surgical approach. For CT and MR examinations, patients are typically scanned in the supine position with the neck mildly hyperextended so that the hard palate is roughly perpendicu- lar to the tabletop. When possible, the patient is scanned with quiet breathing and swallowing suspended. Contiguous 3 mm thick axial sections are obtained from the level of the cavernous sinuses (upper level of the external auditory canal) to the superior mediastinum, including the aortic arch. In cases where small lesions are being evaluated, thinner sections (1 to 2 mm) may be obtained. The normal thyroid gland (due to its iodide content) has a density of approximately 80 to 100 HU on CT. That is, since the thyroid gland normally concentrates iodine approxi- mately100 times over the iodine concentration in the serum, and since iodine is the basis of the CT contrast agents, the radiodensity of the thyroid gland on noncontrast CT images correlates well with thyroid function. Thus, a well-seen thyroid gland usually indicates a normally functioning









210 mCi 200400 µ Ci 30100 µ Ci 25 mCi 12.5 mCi 100 mCi 100200 mCi

6.02 hr

140 keV



13.6 hr

159 keV

I-131 (diagnostic) I-131 (whole body)* I-123 (whole body)* I-131 (treatment)I-131 (treatment)


8.05 days

364 keV






*Diagnostic whole body scan following thyroidectomy to evaluate for residual thyroid tissue in the thyroid bed or to detect distant metastases; to detect ectopic thyroid tissue such as struma ovarii; in hyperthyroid patients with no demonstrable iodine uptake in the thyroid. Cancer treatment following thyroidectomy with the goal of ablating residual thyroid tissue (may require hospital admission, depending on the dose). Cancer treatment with the goal of ablating thyroid metastases (may require hospital admission, depending on the dose).




2140 NECK   FIGURE 40-5 Recurrent thyroid cancer in a 64-year-old woman following thyroidectomy for papillary

FIGURE 40-5 Recurrent thyroid cancer in a 64-year-old woman following thyroidectomy for papillary carcinoma, tall cell variant. A, 18 FDG-PET image shows a region of intense radiotracer uptake (arrow) in the base of the right neck. B, Unenhanced axial T1-weighted MR image shows a corresponding soft-tissue mass in the right tracheoesophageal groove (arrows), conrmed to be recurrent tumor at surgery.


thyroid. Conversely, a poorly seen gland, or portion of a gland, correlates with poor thyroid function. The injection of iodinated contrast material intravenously usually increases the density of the gland diffusely. While iodinated contrast material may provide additional information about lesions

within the thyroid, as mentioned, such contrast will alter radioactive iodine uptake measurements for up to 6 weeks following the study. Therefore, in patients in whom nuclear scintigraphy will also be performed, either contrast should not be administered for the CT study or the nuclear imaging


FIGURE 40-6 A 68-year-old man presented with a rapidly enlarging right neck mass and facial swelling. MR imaging revealed a right thyroid tumor with extension to the jugular vein. A, Unenhanced axial T1-weighted MR image shows a poorly dened mass originating in the right thyroid lobe with extracapsular extension and direct invasion of the jugular vein, which is lled with tumor (arrows). J, Left jugular vein with normal ow void; N,


metastatic disease. B, Unenhanced axial T1-weighted MR image superior to A shows tumor in the right jugular vein.


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology


should be performed prior to CT. Alternatively, MR with contrast material (gadolinium) may be used in conjunction with scintigraphy, as this contrast agent does not interfere with iodide uptake or organication by the thyroid. Another advantage of MR imaging is that it readily identies blood vessels (signal voids) that on CT may be confused with lymph nodes. MR imaging is performed with an anterior neck coil centered over the thyroid gland, which provides high- quality images with a high signal-to-noise ratio and the best soft-tissue resolution. Nodules as small as 4 mm may be detected. 16 Multiple pulse sequences should be obtained including noncontrast sagittal and axial T1-weighted im- ages, as well as axial fast spin-echo T2-weighted images with the application of fat saturation. Following intra- venous contrast administration, axial T1-weighted images with the application of fat saturation are usually ac-


quired. On T1-weighted images, the normal thyroid gland shows homogeneous signal intensity slightly greater than that of the musculature in the neck. On T2-weighted images, the thyroid gland is hyperintense relative to the

FIGURE 40-7 Ultrasonography in a patient previously treated for thyroid cancer shows a metastatic cervical lymph node (denoted by markers). (Courtesy of Dr. Jill Langer, Department of Radiology,

neck musculature (Fig. 40-1). Following contrast admin-

Ultrasound Division, University of Pennsylvania Medical Center.)

istration, the normal gland enhances diffusely and homoge- neously.





Real-time ultrasound of the thyroid gland is usually performed with high-resolution linear array transducers ranging from 7.5 to 10 MHz. 17 The neck is mildly hyperextended, and the thyroid gland is imaged in its entirety in both the transverse and longitudinal planes. The

The thyroid gland develops in the rst trimester of pregnancy, beginning around the fth week of gestation, and its development is completed by the tenth week of gestation. It develops from median and paired lateral anlages. The median anlage arises in the midline oropharynx at the fourth to fth gestational week and gives rise to follicular thyroid


carotid arteries and jugular veins are posterior and lateral to the thyroid lobes, respectively, and provide excellent anatomic markers during the examination. The thyroid gland

tissue, which will ultimately secrete hormones. 22 The lateral anlages are believed to arise from the ultimobranchial bodies, which in turn are derived from the fourth and fth



normally uniformly hyperechoic. 17 The more hypoechoic

branchial pharyngeal pouches at around the fth week of



focal lesion is relative to the normal thyroid gland, the

gestation. They give rise to the parafollicular C cells that are


higher the likelihood of malignancy. 18 The advantages of ultrasound are three: it is accessible, inexpensive, and noninvasive. It is a quick and highly sensitive modality for distinguishing cystic from solid lesions. Focal lesions meeting all of the criteria for a simple cyst (thin wall with smooth margins, anechoic, distinct back wall, and enhanced through transmission) are usually benign. However, any complicated cyst may represent a carcinoma. When calcications are present, they appear as foci of increase echogenicity with distal acoustic shadow- ing. Calcications are nonspecic and may be seen in benign as well as malignant lesions. 18 Ultrasound may also be used to guide ne needle aspiration of nodular disease within the thyroid or to guide aspiration of suspi- cious cervical lymph nodes in the setting of thyroid cancer (Fig. 40-7). 1921 Drawbacks of ultrasound are that the quality of the images as well as their interpretation are dependent on the expertise of the examiner. Another limitation is that ultrasound is not as good as cross-sectional imaging techniques in identifying lymphadenopathy or in evaluating for extension of thyroid disease into the soft tissues of the neck, chest, or air-lled structures.

thought to derive from the neural crest. 22 The parafollicular cells ultimately secrete calcitonin. By the tenth week in utero, the right and left lateral anlages fuse with the median anlage, resulting in the bilobed thyroid gland (see also Chapter 33). 22, 23 During fetal development, the thyroid gland must descend from its place of origin, the foramen cecum, located at the anterior, midline base of the tongue, to its nal adult destination in the lower neck both anterior and lateral to the trachea. The thyroid is attached to the tongue base by the thyroglossal duct, which is lined by squamous epithelium. During the caudal descent of the gland, this duct elongates and subsequently degenerates and atrophies. Abnormal development or aberrant caudal descent of the thyroid gland results in a variety of congenital anomalies. Arrest of descent can occur anywhere from the tongue down to the lower neck. Ectopic thyroid has rarely been reported in the submandibular and lateral neck regions. 24 In these cases, these ectopias may be misinterpreted as metastatic disease. Failure of descent of the median thyroid anlage, or complete failure of descent of the thyroid, results in a lingual thyroid gland at the base of the tongue, the most common type of functioning ectopic thyroid tissue (Fig. 40-8). In





the foramen cecum at the tongue base to the anterior lower neck. Thyroglossal duct cysts most often are anterior midline neck masses, although they may be located in a paramedian location especially when infrahyoid. Over half of these cysts have normal thyroid follicular tissue in their walls. 35 Approximately 65% of thyroglossal duct cysts are infrahyoid in location and are encased by the thyroid strap muscles (Fig. 40-9). Cysts may also occur in the suprahyoid region (20%) at the tongue base/oor of the mouth (Fig. 40-10) or in the hyoid region (15%) above the strap muscles. On cross-sectional imaging, uncomplicated thyroglossal duct cysts are usually well demarcated. On CT, they most often are isodense to water; however, they may be hyperdense when there is high protein content. On MR imaging, they typically have low T1-weighted and high


FIGURE 40-8 Lingual thyroid. Lateral I-123 scintigraphy showing increased radiotracer uptake at the base of the tongue region consistent with lingual thyroid (arrow). (Courtesy of Dr. Joseph Sam, Department of

T2-weighted signal intensities. However, when the contents of the cyst are proteinaceous, the cysts may be hyperintense on T1-weighted images (Fig. 40-11) and usually remain intermediate to hyperintense on T2-weighted images. Thick peripheral enhancement is unusual unless a cyst is secondar-


Radiology, Nuclear Medicine Division, University of Pennsylvania Medical Center.)

such cases, up to 75% of patients may have no functioning thyroid tissue in the neck. 2527 As a result, if tissue at the base of the tongue is not recognized as thyroid and is resected, the patient may become acutely and severely hypothyroid. 28 Nuclear imaging plays the major role in establishing the diagnosis of a lingual thyroid gland as well as in determining whether there is normal functioning thyroid tissue in the neck. On noncontrast CT, lingual thyroid is hyperdense due to its iodine content, and on MR imaging it has high signal intensity on T1-weighted and T2-weighted images compared to the tongue musculature. Avid enhancement is seen following contrast administration. Overdescent of the thyroid may result in ectopic normal thyroid in the lower neck or mediastinum. On rare occasions, thyroid tissue may be found in remote locations, such as within the heart and within ovarian teratomas (struma ovarii). 29, 30 In the handful of reported cases of intracardiac thyroid tissue, all arose from the right ventricu- lar aspect of the interventricular septum, and none were associated with abnormalities of thyroid function. 30 Intratra- cheal thyroid ectopia may also occur, with aberrant thyroid tissue most often located at or just below the cricoid cartilage. 31 The overwhelming majority of patients with this condition are female, and most present with respiratory distress that may be acute or chronic. The intratracheal thyroid tissue may be contiguous with the thyroid lobe by a bridge of tissue or a thin brous strand. 31 Any pathology that may arise within normally located thyroid may also arise in ectopic tissue. Though extremely rare, carcinoma has been described in ectopic tissue. 27, 32 Scintigraphy using Tc-99m pertechnetate or I-131 should be performed when ectopic thyroid is suspected. 33 Other developmental anomalies of the thyroid gland include agenesis or hemiagenesis of one lobe, with normal formation of the contralateral lobe and isthmus. 6, 33, 34

ily infected. On sonography, these lesions have typical features of a cyst. They may also demonstrate internal echoes when proteinaceous or infected, similar to other complicated cysts. Nuclear scintigraphy is usually not necessary in the evaluation of thyroglossal duct cysts. The one exception is a cyst in a child without a palpable thyroid gland; in this case, nuclear scintigraphy may be necessary to determine if the cyst contains the patients only functional thyroid tissue. When large, these cysts are clinically detected as palpable midline or near-midline neck masses. A highly suggestive clinical nding of a thyroid origin is vertical motion of the mass with swallowing or tongue protrusion. These larger


Incomplete degeneration of the thyroglossal duct may result in a persistent stulous tract or in a thyroglossal duct cyst along the path of migration of the thyroid gland from

FIGURE 40-9 Infrahyoid thyroglossal duct cyst. Enhanced axial CT scan shows a thyroglossal duct cyst (C) in a right paramedian location. Note the small portion of the cyst extending into the superior thyroid notch and bowing the thyrohyoid membrane backward (arrow).


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology



resection of the cyst accompanied by total thyroidectomy and/or radioiodide therapy.


Autoimmune Disease and Thyroiditis


Thyroiditis is inltration of the thyroid gland with inammatory cells. This may be seen in a diverse group of autoimmune, inammatory, and infectious processes. Thy- roiditis may be acute and self-limiting or chronic and progressive. Several autoimmune disorders may affect the thyroid gland including Gravesdisease, Hashimotos thyroiditis, and silent/postpartum thyroiditis. Each differs in pathophys- iology and clinical presentation. Gravesdisease and silent thyroiditis are usually associated with thyroid hyperfunc- tion, while Hashimotos disease (chronic lymphocytic thyroiditis) is typically associated with hypofunction. As will be discussed later, the term goiter simply refers to a clinically evident enlargement of the thyroid gland.


Graves’ Disease Gravesdisease is the most common of the autoimmune disorders, occurring in approximately 0.4% of the U.S. population. 2 The peak incidence is in the third to fourth decades of life, with a female predominance. There is a familial predisposition. In Gravesdisease the thyrotropin


FIGURE 40-10 Suprahyoid thyroglossal duct cyst. T2-weighted MR image shows the cyst (C) in the region of the foramen cecum at the base of the tongue.

receptor on the follicular cells is the target for thyroid autoantibodies, which bind to these receptors, stimulating them as though TSH triggered the receptor. This results in constant autonomous function of the thyroid resulting in hyperthyroidism. Serologic tests for specic autoimmune


cysts may have multiple septations on imaging (Fig. 40-12). Small thyroglossal duct cysts are usually clinically occult and may be recognized only if they become secondarily infected or traumatized, or if they are incidentally noted on imaging studies of the neck being performed for unrelated reasons. Rarely, thyroglossal duct cysts may undergo malignant degeneration, usually into papillary carcinoma. This should be suspected when a soft-tissue component or nodule exists within or around the cyst or if the cyst has calcications. 36 Thyroglossal duct cysts may be excised for a variety of indications including secondary infection, a mass effect resulting in pain or dysphagia, or for cosmesis. Acutely infected cysts should be treated with a full course of antibiotics prior to surgical excision. In cases where a cyst is associated with a sinus tract, excision of the entire tract is necessary. The general operation for a thyroglossal duct cyst is the Sistrunk procedure. Sistrunk proposed that the body of the hyoid bone should be removed during surgical resection of a thyroglossal duct cyst. In so doing, recurrences were reduced from nearly 50% to less than 4%. In cases of small thyroglossal duct cysts with carcinoma, surgical resection alone may be considered adequate therapy when there is no evidence of angio-invasion, the surgical margins are clear, the remainder of the thyroid gland is normal on ultrasound, and the patient is young and has no

markers may be elevated, conrming the diagnosis. Marked enlargement of the thyroid gland without focal nodules referred to as diffuse toxic goiter results. There may be prominent enlargement of a pyramidal lobe (Fig. 40-2). Pathologically, in the thyroid gland there is diffuse hyperplasia of the follicular epithelial cells and depletion of


signicant risk factors. Otherwise, in a patient of advanced age, or with unfavorable pathologic ndings or nodularity in the thyroid gland, management may require surgical

FIGURE 40-11 Thyroglossal duct cyst containing proteinaceous material. Unenhanced axial T1-weighted image shows a midline cyst that is hyperintense due to its proteinaceous contents.




colloid. Vascularity is increased. Gravesdisease is associ- ated with other autoimmune diseases of the thyroid including Hashimotos thyroiditis. Radionuclide scintigraphy may be useful in evaluating a patient with suspected Gravesdisease as well as in differentiating it from acute thyroiditis. Typically in Gravesdisease, the thyroid gland is diffusely enlarged with intense radiotracer uptake, often as high as 80% in 24 hours (Fig.


The differential diagnosis includes thyroiditis, toxic multinodular goiter, and toxic adenoma. In contrast to Gravesdisease, where there is concordance between the

clinical presentation of thyrotoxicosis and the radionuclide uptake, in the acute phase of thyroiditis when the patient is clinically hyperthyroid, the gland may be so impaired that there is little observable radionuclide uptake (Fig. 40-14), which is usually less than 10% (normal, 10% to 30%). On scintigraphy, tracer uptake is often inhomogeneous and reduced. During the subacute phase of thyroiditis, the radiotracer uptake usually returns to normal if the gland recovers and the patient reverts to a euthyroid state. Differentiation between Gravesdisease and subacute thyroiditis is important for appropriate patient management, as patients with Gravesdisease often require medication to


FIGURE 40-12 A 27-year-old male with a thyroglossal duct cyst that moved with tongue excursions. A, Midline sagittal T2-weighted image shows a complex septated cystic neck mass involving the base of the tongue/oor of the mouth (C ) and


foramen cecum (white arrow) and extending down to the infrahyoid neck. Note the internal septations (black arrows). B, Axial T2-weighted image showing the left paramedian portion of the cyst with internal septations (black arrows). Note that the cyst is deep to the strap muscles (white arrows), a location characteristic of these lesions. C, Enhanced axial CT image at the same level as B shows the thyroglossal duct cyst. Note that the internal septations are not as well seen as on the MR image due to differences in soft-tissue resolution between the two imaging modalities. S, Strap muscles.


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology



FIGURE 40-14 Thyroiditis. I-123 scintigraphy in a 50-year-old woman who presented with hyperthyroidism. Note that the gland is so impaired that there is little observable radionuclide uptake, which was 7.3% at 24 hours (normal, 10% to 30%). Sternal notch (arrow). (Courtesy


of Dr. Joseph Sam, Department of Radiology, Nuclear Medicine Division, University of Pennsylvania Medical Center.)


FIGURE 40-13 Gravesdisease. I-131 scintigraphy shows diffuse increased radiotracer uptake throughout the thyroid gland. The 2 hour uptake was 25.5% and the 24 hour uptake was 57%, with the upper limits of normal being 10% and 30%, respectively. (Courtesy of Dr. Joseph Sam,

ular brosis. 40 Additionally, the normal follicular epithelial cells may be altered, being replaced with pink oxyphilic


Department of Radiology, Nuclear Medicine Division, University of Pennsylvania Medical Center.)

epithelium (Hurthle or Askanazy cells). 41 It is usually


treat the secondary manifestations of hyperthyroidism (beta blockers for tachycardia) as well as thyroid medication, radioiodine ablation of the thyroid gland, or surgery when required. Subacute thyroiditis is treated conservatively. In toxic multinodular goiter, there are areas of both increased and decreased uptake within an enlarged gland (Fig. 40-15) distinct from the homogeneous uptake seen in Gravesdisease, and the overall uptake is not as avid as that in Gravesdisease. In toxic adenoma, there is focal uptake in a single nodule. If the nodule is autonomous, suppression of the normal glandular tissue may be observed. On cross-sectional imaging, the ndings in Gravesdisease are nonspecic. The thyroid is enlarged. On ultrasound, the gland is often diffusely hyperechoic, without discrete nodules. A characteristic increase in thyroid vascularity is observed on color Doppler studies in both systole and diastole, particularly in patients with active hyperthyroidism. 37, 38 On CT and MR imaging, the enlarged thyroid demonstrates avid enhancement. The noncontrast CT density is actually decreased, reecting a decrease in iodine concentration even though there is an overall increase in the iodine content of the gland. Even after treatment, density values may not return to normal. 39

associated with a goiter. The pathogenesis of Hashimotos thyroiditis involves both cellular and humoral mechanisms. Autoantibodies have been identied against thyroglobulin, thyroperoxidase, and TSH receptors. In reported cases, when TSH receptor-blocking antibodies disappeared, nor- mal thyroid function returned. 42 Hashimotos thyroiditis is


Hashimoto’s Thyroiditis


Hashimotos thyroiditis (chronic lymphocytic thyroiditis)


is the prototype autoimmune thyroiditis. Pathologically, the thyroid gland is enlarged and demonstrates lymphocytic and plasma cell inltration, follicular cell atrophy, and interlob-

FIGURE 40-15 Toxic multinodular goiter. Technetium-99m pertech- netate scans show enlargement of the thyroid gland with regions of increased and decreased uptake.




2146 NECK   FIGURE 40-16 Hashimoto ’ s thyroiditis. A , Transverse ultrasound image showing heterogeneity

FIGURE 40-16 Hashimotos thyroiditis. A, Transverse ultrasound image showing heterogeneity in the echotexture of the right lobe of the thyroid gland with a more focal region of decreased echogenicity posteriorly (arrows). V, Jugular vein; C, carotid; T, trachea. B, Corresponding enhanced axial CT scan shows a focal region of hypodensity (arrows) corresponding to the abnormality seen on ultrasound.


associated with other autoimmune disorders including lupus, Gravesdisease, and pernicious anemia. Hashimotos thyroiditis occurs predominantly in women, most commonly presenting in the fourth and fth decades of life. It may also present in children, in whom it is the most common thyroiditis. 43 The clinical presentation is frequently that of hypothyroidism. 44 Antibody titers are markedly elevated during the acute phase. In the acute phase of

there is a well-known increase in the incidence of non-Hodgkins lymphoma in this setting. 4649 Thyroid lymphoma may produce solitary or multiple focal hypo- echoic lesions or diffuse disease that may be difcult to distinguish from Hashimotos thyroiditis. 46, 47 The presence of cervical lymphadenopathy raises the suspicion of lymphoma. Primary thyroid carcinoma is unusual but has been reported. 50


glandular destruction and hormone release, symptoms of hyperthyroidism may be evident. However, ultimately, hypothyroidism usually prevails. The diagnosis of thyroiditis in general is based on the clinical presentation, and laboratory analysis of thyroid function and imaging is not a critical component of the initial workup of these patients. Although the radiologic ndings are nonspecic, imaging can be useful, especially in patient follow-up and monitoring of disease. On scintigraphy, there is no typical pattern in Hashi- motos thyroiditis. Uptake of radioiodine or Tc-99m pertechnetate is most commonly heterogeneous and patchy, and may be uniformly increased or mildly to severely decreased. 41, 45 In children, a homogeneous distribution of tracer is more common. 43 Ultrasonography demonstrates a variety of patterns. The thyroid may be normal or enlarged in size and is diffusely abnormal, with heterogeneous echogenicity (Fig. 40-16). There may be numerous poorly dened, hypoechoic regions separated by brous strands. 19 Large nodules within the gland raise the possibility of superimposed non-Hodgkins lymphoma. In end-stage disease, the thyroid gland may be atrophied and brotic, resulting in a heterogeneous echotex- ture. On CT, there is an inhomogeneous distribution of iodine. With MR imaging, T2-weighted images may show areas of increased signal intensity. Linear, septated, low-intensity bands thought to represent brosis have been described. 16 Following contrast administration, there may be regions that enhance more than the remainder of the gland (Fig. 40-17).

Silent, Painless Thyroiditis and Postpartum Thyroiditis Silent, painless thyroiditis and postpartum thyroiditis are two different types of subacute lymphocytic thyroid- itis, which are usually self-limited. When this inamma- tory process occurs in the absence of pregnancy, it is termed painless thyroiditis. Low-titer antithyroid antibodies may be present, and the disorders are thought to be autoimmune. During the early phase of lymphocytic inltration, follic- ular disruption with hormone release usually causes patients to present with thyrotoxicosis. As the disease progresses, pa- tients may be hypothyroid transiently before returning to a euthyroid state. 51 Patients may or may not have glandular


Ultrasound may be used to follow patients with Hashimotos thyroiditis to detect occult malignancy because

FIGURE 40-17 Hashimotos thyroiditis. Enhanced axial T1-weighted MR image shows two nodules (arrows) in the right lobe of the thyroid gland that enhance more than the remainder of the gland.


Chapter 40

enlargement. Radioactive iodine uptake is low, and the pat- tern on scintigraphy varies from no tracer uptake to diffuse or heterogeneous uptake. 34 Nuclear scans may return to nor- mal in conjunction with resolution of the process. Postpartum thyroiditis typically occurs 4 to 6 weeks following delivery. It occurs in up to 5% of postpartum women and may recur with subsequent pregnancy. 52 As with silent thyroiditis, women may present with goiter, thyrotoxicosis, and antithyroid antibodies. The process usually resolves after transient hypothyroidism; however, some patients progress to chronic lymphocytic thyroiditis.

Thyroid and Parathyroid Glands: Anatomy and Pathology


palpation, the thyroid is frequently rm, which may be confused with a malignancy. 57 One-third of patients will develop hypothyroidism. On ultrasound the thyroid may be hypoechoic, and on CT the involved thyroid may be hypodense compared to normal thyroid (Fig. 40-18). 17, 58 The characteristic MR appearance includes decreased signal intensity on T1-weighted and T2-weighted images believed to correspond to brosis, as well as inltration of adjacent soft tissues in the neck. 57 Riedels thyroiditis may be associated with mediastinal or retroperitoneal brosis as well as sclerosing cholangitis.

De Quervain’s Thyroiditis (Subacute Granulomatous Thyroiditis)

Acute Suppurative Thyroiditis

Thyroid Goiter


De Quervains thyroiditis is a self-limited inammatory process that usually occurs following a viral upper respiratory tract infection. 2, 22 The viral infections that have been associated with subacute thyroiditis include coxsack- ievirus and the mumps. 53 The peak incidence is in the second to fth decades of life, with an occurrence three times more frequent in women. Early in the inammatory process, follicles may be replaced with neutrophils forming microabscesses. Later, macrophages and multinucleated giant cells surround the damaged follicles, stimulating a granulomatous process. 2 Viral inclusions have not been found in the inamed gland. With healing, there is regeneration of the follicles. The clinical presentation may include painful enlargement of the thyroid gland, fever, and thyrotoxicosis with low radioactive iodine uptake. Scintigra- phy shows a variable pattern that usually reverts to normal as the patient returns to a euthyroid state. 6 On non-contrast CT, the gland is slightly enlarged and has a lower than normal attenuation.

Acute suppurative thyroiditis is uncommon and typically occurs due to seeding of the thyroid gland by bacterial, and occasionally fungal, organisms in immunocompromised or debilitated patients. 22 It may be associated with a fourth branchial cleft abnormality, and one of the roles of imaging is to exclude a stula (from the pyriform sinus apex) as an etiology of the thyroiditis. 54 On cross-sectional imaging, the affected portion of the gland (lobe[s] and/or isthmus) will be enlarged and heterogeneous in CT density and MR signal intensity. With disease progression, focal abscesses may develop and there may be obliteration of the adjacent soft tissues in the neck resulting from associated myositis and cellulitis. 55

As mentioned, the term goiter refers to any clinical enlargement of the thyroid gland. A goiter develops because as the thyroid gland compensates for inadequate thyroid hormone output, the follicular epithelium undergoes com- pensatory hypertrophy to achieve a euthyroid state. As a result, either hypothyroidism or hyperthyroidism may develop. Although initially the goitrous enlargement is diffuse, with time it usually becomes nodular. If the impediment to thyroid hormone output abates, the thyroid gland may revert to normal during the diffuse state. Diffuse nontoxic goiter is a diffuse nonnodular enlarge- ment of the thyroid associated with a euthyroid state. There are two stages in its development. The rst stage is hyperplasia (follicular cell growth) characterized by diffuse glandular enlargement and hyperemia. The second stage is colloid involution, which occurs when a euthyroid state is maintained. Endemic goiters are prevalent in iodine- decient areas. In simple sporadic goiter, there is a female predominance and a peak incidence at puberty. 2 With time, most simple goiters progress to multinodular goiters that may remain nontoxic or may induce thyrotoxicosis. Multinodular goiter is characterized by nodularity, focal hemorrhage, focal calcications, cyst formation, and scar- ring. Glandular enlargement may be asymmetric, involving


Riedel’s Thyroiditis (Struma) Riedels thyroiditis (struma) is a rare form of chronic thyroiditis characterized by a brosing reaction similar to that seen in retroperitoneal brosis, which destroys the thyroid and extends into the adjacent soft tissues of the neck. Within the brosing tissue is a lymphocytic and plasma cell inltration and a vasculitis (phlebitis). 56 As a result, stridor, dysphagia, and vocal cord paralysis may result from


recurrent laryngeal nerve involvement. In fact, Reidels


thyroiditis is one of the few nonmalignant thyroid causes of recurrent laryngeal nerve paralysis. The cause of Reidels thyroiditis is unknown. It is more common in women and

FIGURE 40-18 Riedels thyroiditis (struma). An axial CT scan shows slight enlargement of the thyroid gland with multiple areas of poorly dened hypodensity. Note the associated narrowing of the subglottic

usually occurs in the fourth to seventh decades of life. On

airway (A), as well as obliteration of the fat in the right tracheoesophageal groove (arrow).





nodules may demonstrate autonomous function. In patients with thyrotoxicosis, therapeutic doses of I-131 may be required to reduce thyroid function. Although it was previously thought that a solitary cold nodule in a multi- nodular goiter was less likely to be malignant than a solitary cold nodule in a normal gland, recent studies have demon- strated similar rates of malignancy. 5860 A dominant or enlarging mass within a goitrous thyroid should be biopsied (Fig. 40-19). 61 On ultrasonography, a simple goiter demonstrates dif- fuse glandular enlargement with uniform or irregular echogenicity that may be increased or decreased. A multinodular goiter is often irregular, showing diffuse inhomogeneous echogenicity or multiple focal hypoechoic nodules. On CT evaluation of multinodular goiter, the gland is asymmetric, with multiple low-density areas reecting regions of hemorrhage, cyst formation, or necrosis (Fig. 40-20). More focal regions of hyperdensity are common, reecting calcications present in over one half of patients, hemorrhage, or colloid (Fig. 40-21). On MR imaging, multinodular goiter may show a wide spectrum of appear- ances. 62 On T1-weighted images, multiple foci of high

FIGURE 40-19 Papillary carcinoma developing within a goitrous gland. Axial T2-weighted MR image shows multiple demarcated solid and cystic nodules/masses diffusely within the thyroid gland. The large predominately solid nodule replacing the left gland (arrows) and the

signal intensity may represent cysts containing colloid or hemorrhage (methemoglobin). On T2-weighted images, diffuse heterogeneity may be present, 62 and nodules as small as 3 to 5 mm can be visualized. 16 Alternatively, multiple large, heterogeneous nodules may be present.


dominant nodule in the right lobe (curved arrows) represented papillary carcinoma at pathology.

Enhancement is usually inhomogeneous. Unlike CT, calci-


one lobe more than the other and/or involving the isthmus. Thyroid goiters may extend substernally and into the anterior mediastinum. Multiple patterns may be identied with nuclear scin- tigraphy (Fig. 40-15). Radioactive iodine or Tc-99m pertechnetate may accumulate in multiple foci throughout the gland or, less typically, in only a few nodules. Some

cations may be difcult to detect and, when visualized, may appear as low-intensity foci on T1- and T2-weighted sequences. CT and MR imaging are useful in evaluating second- ary manifestations of goiter including compression and displacement of the trachea, esophagus, and adjacent vessels (Fig. 40-4). Importantly, substernal and mediastinal extension is readily detected (Figs. 40-4 and 40-21). In contrast, nuclear scintigraphy and ultrasound may fail to


FIGURE 40-20

Multinodular goiter. A, Enhanced axial CT image shows asymmetry in the thyroid gland. Both


lobes are enlarged (the right greater than the left), with multiple focal regions of low density consistent with goiter. B, Enhanced axial CT image superior to A shows nodular enlargement with a focal area of hypoattenuation within the isthmus of the gland. The patient has an orotracheal tube in place.


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology


Thyroid and Parathyroid Glands: Anatomy and Pathology 2149   FIGURE 40-21 Multinodular goiter with substernal

FIGURE 40-21 Multinodular goiter with substernal extension. A, Enhanced axial CT scan reveals extensive enlargement of the thyroid gland with diffuse heterogeneous hypodensity. The patient has an orotracheal tube in place. B, There was substernal extension of the thyroid goiter. Multiple calcications are also noted.


show continuity between a cervical and a mediastinal

Nodular Thyroid Disease


goiter. When symptoms related to compression of the aerodigestive tract or vessels occur in elderly patients, nonsurgical candidates, or those refusing surgery, ther- apy with I-131 may be effective in reducing thyroid volume. 63 Specically on CT and MR reports, the radiologist must mention any shift in the axis of the trachea, the location of any tracheal narrowing, the degree of this narrowing, and the length of the stenotic segment. The location of the tracheal narrowing should be given with reference to the bottom of the cricoid cartilage, as this is an easily recognizable endoscopic landmark. The length of the segment in centimeters should then be mentioned. Finally, the percent- age of the tracheal cross-sectional area reduction should be estimated. If the patient has normal pulmonary function, a 50% reduction in tracheal cross-sectional area usually is associated with dyspnea at rest. In addition, the greatest dimension of the enlarged thyroid gland and the most cranial and caudal levels of the gland should be noted. Thus, a typical report might mention that ‘‘there is a large multinodular goiter of 9 cm in greatest dimension. The most cranial level of the gland is at the level of the true vocal cords, and the most caudal level is 1 cm below the level of the top of the manubrium. The tracheal axis is shifted to the right, and starting 2 cm below the level of the cricoid cartilage and extending over a 3 cm length of trachea, there is an approximately 30% narrowing of the cross-sectional tracheal area.’’ Such a report provides all of the necessary information to the clinicians in order for them to make an appropriate treatment decision. The extension of a goiter outside of the normal thyroid bed occurs into the substernal area in 5.7% 20% of the cases. Extension into the posterior mediastinum occurs in 9.8%12% of cases, and this always occurs in conjunction with extension into the anterior mediastinum. There are also (7.4%) of goiters that extend up behind or along the side of the pharynx.

Palpable nodules in the thyroid gland are common, occurring in approximately 4% to 7% of the population, or an estimated 10 to 18 million people in the United States. 64 Furthermore, on CT and MR imaging studies of the neck performed for other reasons, as many as 14.5% of patients may be found to have incidental thyroid nodules. 65 Most represent follicular nodules that develop in adenomatous goiters following cycles of hyperplasia and colloid involu- tion. However, since any nodule could represent a thyroid carcinoma, the challenge lies in identifying those lesions that are malignant in the most cost-effective, noninvasive manner. It is difcult to distinguish benign from malignant nodules. Findings on ultrasound, CT, and MR imaging are nonspecic. A sonolucent halo around a thyroid nodule or a solid, hyperechoic lesion favors a benign process (Fig. 40-22). 18 The presence of calcication is nonspecic, seen in 10% to 15% of all benign and malignant lesions. 18 Similarly, malignant and benign lesions may be cystic, solid, or mixed. 18 Clinical factors that increase the likelihood of a nodules representing a carcinoma include age (less than 20 or more than 60 years), male gender, low-dose irradiation during childhood for benign conditions, a family history of thyroid carcinoma or multiple endocrine neoplasia, ipsilat- eral lymph nodes, and longstanding goiter. 6, 66 However, most thyroid nodules occur sporadically and are not associated with these conditions. Radionuclide scintigraphy plays an important role in distinguishing cold nodules (those that do not demonstrate radioactive iodine uptake relative to the normal gland) from hot or hyperfunctioning nodules (those that demonstrate increased uptake compared to the surrounding thyroid). Cold nodules have a higher incidence of malignancy (Fig. 40-23). The risk of cancer in cold nodules is approximately 20%, compared to less than 5% in hot nodules. 6, 67 The dy-





FIGURE 40-24 A 60-year-old woman presented with hyperthyroid- ism. The 24 hour uptake was 46% (upper limit of normal is 30%), and scintigraphy showed a hot nodule with suppression of the remainder of the

FIGURE 40-22 Ultrasonogrpahy of the thyroid gland in a patient with a palpable nodule. Note the homogeneous, echogenic nodule with a ‘‘sonolucent halo’’ suggestive of a benign thyroid lesion. At pathology this

gland consistent with an autonomous nodule. (Courtesy of Dr. Joseph Sam, Department of Radiology, Ultrasound Division, University of Pennsylva- nia Medical Center.)


was shown to be a follicular adenoma. (Courtesy of Dr. Jill Langer, Department of Radiology, Ultrasound Division, University of Pennsylva- nia Medical Center.)

namic phase in Tc-99m pertechnetate thyroid imaging may be useful in evaluating cold nodules, with studies suggesting that malignant nodules have a perfusion equal to or greater than that of the surrounding normal thyroid gland. 68 Functioning or hot nodules in over 90% of cases reect benign conditions, most commonly adenomas or hyperpla- sia. 6 If the adjacent normal thyroid tissue is suppressed on scintigraphy, and if, in turn, the nodule cannot be suppressed with exogenous thyroid hormone, it is considered to have autonomous function (Fig. 40-24). Because the incidence of carcinoma in hot nodules is low, these lesions are frequently managed conservatively with close follow-up. While the majority of cold nodules are benign (adeno- mas, cysts, inammation), because of their higher incidence of malignancy, they usually require biopsy or surgical removal. 7 Fine needle aspiration with palpation, CT or ultrasound guidance that ensures positioning of the needle within the lesion has gained wide acceptance as an accurate diagnostic method for evaluating thyroid nodules. 18, 69, 70 Specimens may be obtained with 22- to 25-gauge needles. Typically, on average, three separate passes are made to ensure the most adequate specimen possible. Interpretation requires a skilled cytopathologist. Benign nodules may be followed, and malignant or suspicious nodules are usually surgically resected. In instances where ne needle aspiration is nondiagnostic, repeat aspiration or surgical excision may be necessary. 70




FIGURE 40-23 A 39-year-old male with a palpable thyroid nodule in the left thyroid gland. Nuclear scintigraphy shows a cold nodule (arrow) in



the lateral aspect of the left lobe of the thyroid. Subsequent biopsy revealed follicular carcinoma. (Courtesy of Dr. Joseph Sam, Department of

Thyroid adenomas are true benign neoplasms distinctly


Radiology, Nuclear Medicine Division, University of Pennsylvania Medical Center.)

separate from the adjacent thyroid tissue and encased by a


Chapter 40

brous capsule. They are usually solitary and nonfunction- ing, most commonly detected in young and middle-aged adults. Autonomously functioning adenomas are not usually associated with hyperthyroidism. 71 Toxicity is most com- monly seen with large lesions and advanced age. Follicular adenomas slowly increase in size, usually not exceeding 4 cm. 2 Sudden enlargement of a follicular adenoma is usually related to spontaneous hemorrhage within the lesion. 72 Spontaneous degeneration of an adenoma may occur, and in fact, most thyroid cysts represent degeneration of adenomas. The presence of carcinoma within an adenoma is rare. 72 Hurthle cell adenomas are rare neoplasms composed of granular cells and pink-staining cytoplasm. Unlike follicular adenomas, these are not well circumscribed, and some believe they are malignant. If an adenoma is autonomous (independent of TSH), ablation with I-131 may be performed, as the short-acting beta radiation will deposit preferentially in the nodule. Alternatively, the nodule may be surgically removed. In either case, the risk of postprocedural hypothyroidism is small. The previously suppressed normal thyroid tissue resumes normal function following treatment. Recent reports describe successful treatment of auto- nomous thyroid and parathyroid adenomas with 95% ethanol injection. Results vary but generally show resolu- tion of the hyperthyroid state without development of hypothyroidism. 7378 A potential complication is inadver- tent injection of ethanol into the recurrent laryngeal nerve at the level of the tracheoesophageal groove, which may result in vocal cord paralysis. 79

Malignant Neoplasms

The incidence of thyroid cancer in men and women increased up to 1975. This increase was believed to reect the use of low-dose radiation to treat the head and neck, particularly in children for benign diseases such as thymic enlargement and adenoidal hypertrophy. 80 There is a linear dose-response relationship between 100 and 2000 rads. 6, 81 Approximately 15% to 30% of patients who received radiation in this dose range will develop a thyroid nodule, and 6% to 8% will develop thyroid cancer. Long-term follow-up is necessary, as the latent period for the development of cancer may be as long as 30 years. Early detection is essential since carcinoma in this population is more aggressive and may require extensive surgical management to achieve a cure rate equivalent to that of nonirradiated patients. 66 Thyroid carcinoma following high- dose irradiation (greater than 2000 rads) is rare, likely because irradiation at these doses destroys thyroid tissue. 6 Individuals at increased risk (low-dose radiation exposure, genetic predisposition) of developing thyroid cancer may be screened and followed by obtaining serum calcitonin levels, as calcitonin serves as a sensitive marker for tumor development. Approximately 12,000 new cases of thyroid carci- noma are diagnosed in the United States each year, and the annual death rate is approximately 1000. 82 Of inter- est, the prevalence of incidental thyroid carcinomas identi- ed at autopsy is 3.9% 83 and at surgery it is 10.5%. 84 Differentiated thyroid carcinomas including papillary and

Thyroid and Parathyroid Glands: Anatomy and Pathology


follicular subtypes are most common and have a favorable prognosis. Thyroid carcinoma arises from both follicular and parafollicular C cells. Malignant potential and behavior ranges from low-grade (papillary carcinoma) to aggressive (anaplastic carcinoma) and is reected by mortality rates:

papillary carcinoma 8% to 11%, follicular carcinoma 24% to 33%, medullary carcinoma 50%, and anaplastic carcinoma 75% to 90%. 66 The prognosis is dependent upon the biological behavior, the tumor size, and the tendency for hematogenous or lymphatic metastases. The major histo- logic classication of thyroid carcinoma includes papillary, follicular, medullary, and anaplastic types. The majority of carcinomas (60% to 80%) are papillary, while follicular, medullary, and anaplastic types each account for approxi- mately 5% to 20% of thyroid cancers. 6, 85 The major role of scintigraphy in assessing a domi- nant, palpable thyroid mass is to determine whether the lesion is hot or cold (Figs. 40-23 and 40-24). The risk

of cancer in a cold nodule is four times that of a hot nodule. 6, 67 Ultrasonography, because of its availability, is frequently the rst imaging modality used to assess a thyroid mass. It is useful in distinguishing solid from cystic lesions. Ultrasound also plays a signicant role in the follow-up of patients treated for papillary carcinoma. Its main utility in this regard is in identifying cervical lymph nodes suspicious for regional metastases that can

be biopsied with ultrasound guidance (Fig. 40-22). It should

be remembered that the main role of cross-sectional imaging (ultrasound, CT, and MR) is not in the character- ization of an intrathyroidal lesion, as there are no imaging ndings that are histologically specic. The role of the radiologist is to assess the ndings related to a thyroid mass, including invasion through the thyroid capsule and inltration of adjacent tissues and structures in the neck, and to identify the presence of cervical lymph node metastases.

PapillaryCarcinoma Papillary carcinoma is a low-grade malignancy occur- ring most commonly in female adolescents and young adults. It comprises up to 80% to 90% of all thyroid cancers. However, despite being the most common thy- roid carcinoma, it constitutes only about 1% of all malignancies diagnosed in the United States. Histologi- cally, papillary carcinoma may have a spectrum of ndings and may be purely papillary, mixed papillary and follicular, or completely follicular. 8688 The mixed papillary subtype behaves like papillary carcinoma. 86 The completely follicular variant is also included under papillary carcinomas because, both biologically and clini- cally, it behaves like these tumors. 23, 89 Frequently, papil- lary carcinoma is multifocal and microscopic in the thyroid gland. This condition is believed to represent intraglandular lymphatic spread rather than multiple synchronous tumors. However, other patterns of papil- lary cancer are also common, including occult cancers

(less than 1.5 cm), intrathyroidal encapsulated, and ex- trathyroidal cancers. 90, 91 In goiter belt areas of the world, not only is there a prevalence of goiter, but there is also

a higher than average rate of anaplastic carcinoma. In

the regions of the world that have introduced iodine into




2152 NECK     FIGURE 40-25 Papillary thyroid carcinoma in two different patients. A , Enhanced

FIGURE 40-25 Papillary thyroid carcinoma in two different patients. A, Enhanced axial CT scan shows a dominant hypodense mass (M ) replacing the right lobe of the thyroid gland. Also note the pathologic ipsilateral cervical lymph node (N ). B, A sagittal sonogram of the right lobe of the thyroid shows a dominant nodule with

heterogeneous echogenicity. There are both cystic and frond-like solid components. (Courtesy of Dr. Jill Langer,


Department of Radiology, Ultrasound Division, University of Pennsylvania Medical Center.)


the diet to decrease the incidence of goiter, there has also been a decrease in the frequency of anaplastic

Cystic nodes are different from the necrotic nodes fre- quently seen with metastatic squamous cell carcinoma that


thyroid carcinoma. However, an increase in the incidence

have central low density but retain a thick rind of resid-



papillary carcinomas in these same regions has been

ual lymphatic tissue. Hemorrhagic or colloid-containing


noted. At gross pathology these tumors are rm, and they may have calcium, hemorrhage, necrosis, and/or cysts. Histolog-

nodes may be hyperintense on unenhanced T1-weighted MR images (Fig. 40-31). Although in the vast majority of cases regional nodal metastases from thyroid cancer occur


ically, papillary cancer is characterized by the presence of papillae (epithelial cells encasing a brovascular core) and clear nuclei. 87, 88 Psammoma bodies (microscopic calcied remnants of papillae) are present in over one third of papillary cancers. Uncommon histologic subtypes of papillary cancer have been noted to behave more aggressively, including tall cell and columnar cell variants. 92 The tall cell variant is composed of oxyphilic (pink) cells. 92 At presentation these malignancies are frequently extrathyroidal, with vascular invasion, and they have a poorer prognosis than other papillary carcinomas. The imaging appearance of papillary carcinoma is variable and may include a dominant nodule (Fig. 40-25), multifocal nodules (Fig. 40-26), diffuse inltration of the gland that is manifest as heterogeneous hypodensity, or

in the anterior and posterior cervical lymph chains, occasionally (2%) metastases occur in retropharyngeal nodes (Fig. 40-32). Any lymph node seen in a patient with papillary carcinoma should raise the suspicion of metastatic disease because of the high rate of lymphatic spread. This is



normal-appearing gland on CT (Fig. 40-27). Thus,


although not commonly reported, inltrative papillary carcinoma may not be detected in the thyroid gland on imaging (Fig. 40-28). Papillary carcinoma has the high- est incidence of the thyroid malignancies for cervical lymph node spread, seen in up to 50% of cases. Metastatic


lymph nodes are not uncommonly normal in size (Fig.


40-27) and may be calcied (Fig. 40-29), cystic, hemor- rhagic, or may contain colloid. 93 Cystic nodal metas- tases are characterized by a thin or imperceptible wall

FIGURE 40-26 Papillary carcinoma presenting with multiple nodules. Enhanced axial CT scan shows a focal nodule (N ) in the left thyroid lobe, as well as a focal nodule in the isthmus on the right (N ). Both were found to be papillary carcinoma at histologic evaluation. Also note the bilateral


(Fig. 40-30), and they can be mistaken for benign cysts.

cervical lymph node metastases (arrows).


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology



FIGURE 40-27 A 41-year-old woman presented with a palpable neck mass found to represent metastatic papillary carcinoma in a lymph node. A, Enhanced axial CT scan shows a low-density pathologic


cervical lymph node (arrows). B, CT image obtained at the level of the thyroid gland shows no dominant mass; however, there is diffuse heterogeneous low density of the gland that represented inltrative papillary carcinoma at pathology. Note the pathologic but normal-sized node (arrow). C, Image obtained just below the thyroid gland demonstrates central compartment nodal disease (arrows).


FIGURE 40-28 A 25-year-old woman who presented with a cervical

nodal metastasis (arrow). In spite of the fact that no lesion could be


detected in the thyroid gland, diffuse papillary carcinoma was found at histologic evaluation.

FIGURE 40-29 Metastatic papillary carcinoma. Enhanced axial CT image shows a calcied right cervical nodal metastasis (arrows).





FIGURE 40-30 Metastatic papillary carcinoma. Enhanced axial CT image shows a cystic lymph node (arrows).


especially true if the node enhances, as these tumors are highly vascular. Hematogenous spread to the lungs, bones (Fig. 40-33),

FIGURE 40-32 Metastatic papillary carcinoma in a retropharyngeal node. Enhanced fat-suppressed axial T1-weighted MR image shows a metastatic retropharyngeal lymph node (arrow).


and central nervous system may occur; however, this is less common (approximately 5%), especially in the absence of nodal disease. Since papillary carcinomas concentrate radioiodine, scanning with I-131 following thyroidectomy

addition, tumor size and the number of structures adherent to the gland are predictors.


may be valuable in identifying recurrent/residual thyroid disease in the operative bed of the neck as well as in detecting distant metastases (Fig. 40-34). Subsequently, treatment with I-131 may be performed (Table 40-3). The prognosis for papillary thyroid carcinoma is excellent, with a 20-year survival rate of over 90%. 87, 88, 90, 91 The most important prognostic factors appear to be (1) age, as patients older than 50 years have a poorer prognosis than younger patients; (2) tumor size; (3) extrathyroidal extension (violation of the thyroid capsule); and (4) histologic subtype. In males, the age at presentation and the absence of gross nodal metastasis are predictors of survival. In females, in

Follicular Carcinoma True follicular carcinomas of the thyroid gland constitute only 5% of all thyroid cancers. Follicular carcinomas are well-differentiated, relatively low-grade malignancies that are reportedly more common in the setting of iodine deciency. They are slightly more aggressive than papillary carcinomas. On gross evaluation, they are either encapsu- lated or invasive. Pathologically, they are characterized by capsular and vascular invasion and are usually solitary lesions. Distant metastases to the lung and bone related to hematogenous seeding are more common than lymph node spread; the latter is seen in less than 8% of cases. 94 The 5-year survival rate for encapsulated variants is approxi- mately 90%; however, invasive variants have a poorer prognosis. Like papillary carcinoma, follicular cancers concentrate iodine, and I-131 imaging may be useful in the follow-up of these patients.


Hurthle Cell Tumors Hurthle cells are derived from follicular epithelium. 95 A Hurthle cell neoplasm must meet specic criteria including that of an isolated thyroid mass composed predominantly of Hurthle cells in the absence of inammatory cells. 95, 96 These tumors are diagnosed according to the criterion of malignancy used for follicular neoplasms of the thyroid gland. Regional nodal metastases in addition to hematoge- nous dissemination may occur.


FIGURE 40-31

Colloid-containing metastatic cervical lymph node.

MedullaryCarcinoma Medullary carcinoma arises from parafollicular C cells


Unenhanced axial T1-weighted MR image shows a hyperintense nodal mass (N ).

that are believed to be derived from neural crest tissue in the ultimobranchial bodies. It is relatively uncommon and has a


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology


Thyroid and Parathyroid Glands: Anatomy and Pathology 2155   FIGURE 40-33 Metastatic papillary thyroid

FIGURE 40-33

Metastatic papillary thyroid carcinoma. A, Unenhanced sagittal T1-weighted MR image shows


a hypervascular (note the ow voids) metastasis to the clivus. B, Axial fast spin-echo T2-weighted MR image shows the clival mass with prominent ow voids (arrows).


higher mortality rate than well-differentiated papillary and follicular malignancies. Medullary carcinomas are usually solitary lesions. They may invade locally (Fig. 40-35), may spread to regional cervical lymph nodes, 97 and may result in hematogenous seeding with distant metastases most com- monly to the lungs, bones, and liver. Because of their origin from parafollicular C cells that secrete calcitonin (up to 90% of medullary carcinomas secrete calcitonin), calcitonin provides a specic hormonal marker for following these patients. 48, 98 Medullary carcinoma occurs sporadically, but may also be inherited as an autosomal dominant trait (approximately 15% of cases are familial) and comprises a component of the multiple endocrine neoplasia (MEN) syndromes, types IIA and IIB, which include medullary thyroid carcinoma and adrenal pheochromocytomas. 99, 100 Hyperparathyroidism is common in MEN type IIA (Sipples syndrome) due to hyperplasia of the parathyroid glands. 99, 100 Medullary carcinomas may be encapsulated or inltrative on gross pathology. 99, 100 Well-described patterns of medul- lary carcinoma include amyloid-containing, classic, trabecu- lar, and epithelial types. 100 There is a broad spectrum of histologic and biochemical subtypes. The prognosis for medullary thyroid cancer is variable. Patients with thyroid cancer in the setting of MEN type IIB tend to have very aggressive, often fatal tumors that frequently occur at a young age, while those in association with MEN type IIA have favorable outcomes. 101 Sporadic tumors may behave in an indolent manner or may be aggressive. 101 Serum levels of calcitonin and carcinoembryonic antigen, as well as immu- nostaining of resected tumor, may help predict the tumors behavior. 102

FIGURE 40-34 I-131 scintigraphy following thyroidectomy for papillary carcinoma. Whole body images obtained 72 hours after the administration of I-131 shows radiotracer uptake in diffuse lung metastases (arrows).

Unlike papillary and follicular subtypes, medullary carcinoma does not concentrate radioiodine. However, radionuclides specic for neuroendocrine tissue such as I-131 meta-iodobenzylguanidine (MIBG) and the somato-





goiter. Anaplastic carcinoma actually comprises a group of high-grade thyroid neoplasms that are characterized by undifferentiated histology and a highly aggressive course. Other terms include undifferentiated, dedifferentiated, and sarcomatoid carcinoma. These cancers grow rapidly, and typically compress and invade the aerodigestive tract and vessels (Fig. 40-36). Lymphatic metastases occur in the majority of patients and are necrotic in approximately one half of cases (Fig. 40-36). 48, 107 These neoplasms do not concentrate radioiodine. On ultrasound they are frequently hypoechoic (Fig. 40-37). 17, 18, 97 On CT, punctate calcica- tions and necrosis are frequently present. 107


PrimaryLymphoma Primary lymphoma of the thyroid gland is uncommon, representing less than 5% of all lymphomas arising in extranodal sites and approximately 1% to 3% of all thyroid malignancies. It usually presents in elderly women with a long history of goiter. In addition, patients with Hashimotos

FIGURE 40-35 Medullary thyroid carcinoma with direct extension into the vertebral compartment. Axial T2-weighted MR image shows a large, heterogeneous mass (M ) in the left lobe of the thyroid gland. There is direct invasion of the longus colli muscle complex and the spine

thyroiditis have an increased incidence of developing lymphoma of the thyroid, usually the non-Hodgkins type. 46, 47 The thyroid gland may also be involved secondar- ily by lymphoma. Imaging, including MR imaging, cannot reliably distin-




statin analog I-111 pentetreotide have been used with some success to evaluate primary as well as metastatic medullary thyroid carcinoma. 103106 These neoplasms may also take up gallium or thallium.

guish lymphoma from thyroiditis in patients with Hashi- motos thyroiditis. 1, 108 Patients usually present with a rapidly enlarging thyroid mass and symptoms of obstruction related to compression of the aerodigestive tract. 1, 46 Thyroid lymphoma may present as multiple nodules, but more commonly (80%) it presents as a solitary mass. 1, 46


Anaplastic Carcinoma Anaplastic carcinoma usually presents in elderly women (over the age of 60 years), and is highly aggressive and rapidly fatal. Life expectancy is measured in months. Approximately 10% of all thyroid malignancies are anaplas- tic. They commonly occur in patients with long-standing

Usually it is hypoechoic on ultrasound 17, 18 and hypodense on CT. 46 While lymphoma is typically cold on iodine and technetium nuclear scintigraphy, it may show increased uptake on gallium scans. Necrosis and calcication are uncommon. 46 On MR imaging, lymphoma is usually hyperintense on T2-weighted images and isointense to normal thyroid on T1-weighted images. 1, 108


FIGURE 40-36 Anaplastic thyroid carcinoma. A, Unenhanced axial CT scan shows an inltrative mass in the left lobe of the thyroid gland Extension outside the thyroid capsule is suggested by soft-tissue stranding in the adjacent neck fat (arrow). There is also obliteration of the fat plane between the thyroid and the esophagus (long arrow, esoph- ageal lumen). B, Inferior image shows a necrotic metastatic lymph node (N ). C, Carotid; J, jugular vein.


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology



FIGURE 40-39 Metastatic renal cell carcinoma to the thyroid gland. Enhanced axial CT scan shows diffuse enlargement of the thyroid gland with multiple hypodense nodules (arrows) consistent with metastatic renal cell carcinoma conrmed pathologically.


Rare Malignancies Primary squamous cell carcinoma of the thyroid gland is rare and may result from squamous metaplasia of epithelial cells. Similarly, rare sporadic cases of mucoepidermoid carcinoma may occur (Fig. 40-38). These are typically seen in patients with a long history of goiter and have a poor prognosis. There are no diagnostic imaging ndings to distinguish these from other neoplasms. Primary sarcomas of the thyroid gland are extremely rare, can be radiation induced, and have a poor prognosis. Such lesions include liposarcomas, brosarcomas, leiomyosarcomas, chondro- sarcomas, osteosarcomas, and angiosarcomas. Teratomas in infants, and rarely in adults, may involve the thyroid gland. Thymus-related lesions may also rarely occur. About 1.5% of thyroid glands contain thymic tissue, and intrathyroidal thymomas can occur. Similarly, spindle


FIGURE 40-37 Anaplastic carcinoma. Sagittal sonographic image shows a large, hypoechoic mass in the thyroid gland.

and epithelial thymus-like tumors (SETTLE) and carcinoma with thymus-like features (CASTLE) have been reported. Even a very rare intrathyroidal paraganglioma has been reported.


Metastatic Disease Metastatic disease to the thyroid gland is uncommon. Lung and breast carcinomas are the most common causes of thyroid metastases found at autopsy, while renal carcinoma is the most common metastasis detected clinically. 109 Metastatic melanoma and colon carcinoma metastatic to the thyroid gland have also been reported. 110 Multiple thyroid masses are usually present in the setting of metastatic disease (Fig. 40-39). When atypical histology of a resected thyroid mass is detected, metastatic disease should be considered. Testing to establish the presence of thyroglobu- lin and/or calcitonin supporting the belief that the neoplasm is thyroidal in origin may be extremely useful, and the absence of these markers favors metastatic disease.




FIGURE 40-38 Mucoepidermoid carcinoma of the thyroid gland in a 76-year-old woman with a long-standing history of goiter. Axial fat-suppressed T2-weighted image shows diffuse goiter. A 1 cm hyperin-

1. Shibata T, Noma S, Nakano Y, et al. Primary thyroid lymphoma: MR appearance. J Comput Assist Tomogr 1991;15(4):629633. 2. De Lellis RA. The endocrine system. In Cotram R, Kumar V,


tense nodule (N ) was biopsied and sdshown to be mucoepidermoid carcinoma.

Robbins SL, eds. Robbins Pathologic Basis of Disease, 4th ed. Philadelphia: WB Saunders, 1989:12141242.




3. Plummer HS. The clinical and pathologic relationship of simple and exophthalmic goiter. Am J Med Sci 1913;146:790803.

4. Villadolid MC, Yokoyama N, Izumi M, et al. Untreated Gravesdisease patients without clinical ophthalmopathy demonstrate a high frequency of extraocular muscle (EOM) enlargement by magnetic resonance. J Clin Endocrinol Metab 1995;80(9):2830


5. Takashima S, Nomura N, Tanaka H, et al. Congenital hypothyroid- ism: assessment with ultrasound. AJNR 1995;16:11171123.

6. Price DC. Radioisotopic evaluation of the thyroid and parathyroids. Radiol Clin North Am 1993;31:9911015.

7. Sandler MP, Patton JA, Ossoff RH. Recent advances in thyroid imaging. Otolaryngol Clin North Am 1990;23:251270.

8. Nygaard B, Nygaard T, Jensen LI, et al. Iohexol: effects on uptake of radioactive iodine in the thyroid and on thyroid function. Acad Radiol


9. Laurie AJ, Lyons SG, Lassen EC. Contrast material iodides:

potential effects on radioactive thyroid uptake. J Nucl Med 1992;


10. Sternthall E, Lipworth L, Stanley B, Abreau C, Fang SL, Braverman LE. Suppression of thyroid radioiodine uptake by various doses of stable iodide. N Engl J Med 1980;303:10831088.

11. Lauberg P, Boye N. Inhibitory effect of various radiographic contrast agents on secretion of thyroxine by the dog thyroid and on peripheral and thyroidal deiodination of thyroxine to triiodothyronine. J Endocrinol 1987;112:387390.

12. Feine U, Lietzenmayer R, Hanke J, Wohrle H. Fluorine-18-FDG and iodine-131 uptake in thyroid cancer. J Nucl Med 1996;37:1468


13. Dietlein M, Scheidhauer K, Voth E, Theissen P, Schicha H. Fluorine-18 uorodeoxyglucose positron emission tomography and iodine-131 whole body scintigraphy in the follow-up of differentiated thyroid cancer. Eur J Nucl Med 1997;24:13421348.

14. Wang W, Larson SM, Fazzari M, et al. Prognostic value of [ 18 F] uorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab 2000;85:1107


15. Gotway MB, Higgins CB. MR imaging of the thyroid and parathyroid glands. Magn Reson Imaging 2000;8(1):163182.

16. Gefter W, Spritzer CE, LiVolsi VA, et al. Thyroid imaging with high-eld strength surface-coil MR. Radiology 1987;164:


17. Gooding GA. Sonography of the thyroid and parathyroid. Radiol Clin North Am 1993;31(5):967989.

18. Solbiati L, Volterrani L, Rizzatto G, et al. The thyroid gland with low uptake lesions: evaluation by ultrasound. Radiology 1985;155:


19. Hopkins CR, Reading CC. Thyroid and parathyroid imaging. Semin US, CT, MRI 1995;16(4):279295.

20. Quinn SF, Nelson HA, Demlow TA. Thyroid biopsies: ne-needle aspiration biopsy versus spring-activated core biopsy needle in 102 patients. J Vasc Intervent Radiol 1994;5(4):619623.

21. Sanchez RB, van Sonnenberg E, DAgostino HB, et al. Ultrasound guided biopsy of nonpalpable and difcult to palpate thyroid masses. J Am College Surgeons 1994;178(1):3337.

22. LiVolsi VA. The thyroid and parathyroid. In: Sternberg SS, ed. Diagnostic Surgical Pathology, 2nd ed. New York: Raven Press,


23. Pintar JE, Toran-Allerand CD. Normal development of the hypothalamic-pituitary-thyroid axis. In: Braverman LE, Utiger RD, eds. Werner and Ingbars, The Thyroid, 6th ed. Philadelphia: JB Lippincott, 1991;721.

24. Hammond RJ, Meakin K, Davies JE. Case report: lateral thyroid ectopiaCT and MRI ndings. Br J Radiol 1996;69:11781180.

25. Morgan NJ, Emberton P, Barton RP. The importance of thyroid scanning in neck lumpsa case report of ectopic tissue in the right submandibular region. J Laryngol Otol 1995;109(7):674676.

26. Guneri A, Ceryan K, Igci E, et al. Lingual thyroid: the diagnostic value of magnetic resonance imaging. J Laryngol Otol 1991;105(6):


27. Montgomery ML. Lingual thyroid: comprehensive review. West J Surg 1985;43:661671.

28. Neinas FW, Gorman CA, Devine KD, et al. Lingual thyroid. Clinical characteristics of 15 cases. Ann Intern Med 1973;79:205210.

29. Kantelip B, Lusson JR, DeRiberolles C, et al. Intracardiac ectopic thyroid. Hum Pathol 1986;17:12931296.

30. Fujioka S, Takatsu Y, Tankawa H, Yamanaka K, Ando F. Intracardiac ectopic thyroid mass. Chest 1996;110:13661368.

31. Brandwein M, Som P, Urken M. Benign intratracheal thyroid. Arch Otolaryngol Head Neck Surg 1998;124:12661269.

32. Dominguez-Malagon H, Guerrero-Medrano J, Suster S. Ectopic poorly differentiated (insular) carcinoma of the thyroid. Report of a case presenting as an anterior mediastinal mass. Am J Clin Pathol


33. Takashima S, Nomura N, Tanaka H, et al. Congenital hypo- thyroidism: assessment with ultrasound. AJNR 1995;16(5):1117


34. Shibutani Y, Inoue D, Koshiyama H. Thyroid hemiagenesis with subacute thyroiditis. Thyroid 1995;5(2):133135.

35. Pollice L, Caneso G. Struma cordis. Arch Pathol Lab Med


36. Hays LL, Marlow SF Jr. Papillary carcinoma arising in a thyroglossal duct cyst. Laryngoscope 1968;78:21892193.

37. Ralls PW, Matsumoto N, Fukui K, et al. Color ow Doppler sonography in Gravesdisease: thyroid inferno. AJR 1988;150:


38. Castagnone D, Rivolta R, Rescalli S, et al. Color Doppler sonography in Gravesdisease: value in assessing activity of disease and predicting outcome. AJR 1996;166(1):203207.

39. Kaneko T, Matsumoto N, Fukui K, et al. Clinical evaluation of thyroid: CT values in various thyroid conditions. J Comput Assist Tomogr 1979;3:14.

40. Volpe R. The pathology of thyroiditis. Hum Pathol 1978;9:429438.

41. Wang PW, Chen HY, Li CH, et al. Tc-99m pertechnetate trapping and thyroid function in Hashimotos thyroiditis. Clin Nucl Med


42. Takasu N, Yamada T, Takasu M, et al. Disappearance of thyrotropin-blocking antibodies and spontaneous recovery from hypothyroidism in autoimmune thyroiditis. N Engl J Med 1992;326:


43. Alos N, Huot C, Lambert R, et al. Thyroid scintigraphy in children and adolescents with Hashimotos disease. J Pediatr 1995;127(6):


44. Doniach D, Bottazzo GF, Russell RCG. Goitrous autoimmune thyroiditis (Hashimotos disease). Clin Endocrinol Metab 1979;8:


45. Intenzo CM, Park H, Kim SM, et al. Clinical, laboratory, and scintigraphic manifestations of subacute and chronic thyroiditis. Clin Nucl Med 1993;18:302306.

46. Takashima S, Ikezoe J, Morimoto S, et al. Primary thyroid lymphoma: evaluation with CT. Radiology 1988;168:765768.

47. Ott RA, Calandra DB, McCall A, et al. The incidence of thyroid carcinoma in patients with Hashimotos thyroiditis and solitary cold nodules. Surgery 1985;98:12021206.

48. Compagno J, Oertel JE. Malignant lymphoma and other lympho- proliferative disorders of the thyroid gland: clinicopathologic study of 245 cases. Am J Clin Pathol 1980;74:111.

49. Clark OH, Greenspan FS, Dunphy JE. Hashimotos thyroiditis and thyroid cancer: indications for operations. Am J Surg


50. Nordmeyer JP, Shafeh TA, Heckmann C. Thyroid sonography in autoimmune thyroiditis: a prospective study on 123 patients. Acta Endocrinol 1990;122:391395.

51. Mizukami Y, Michigishi T, Hashimoto T, et al. Silent thyroiditis: a histologic and immunohistochemical study. Hum Pathol 1988;19:


52. Hamburger JI. The various presentations of thyroiditis: diagnostic considerations. Ann Intern Med 1986;104:219224.

53. Hay ID. Thyroiditis: a clinical update. Mayo Clin Proc 1985;60:


54. Hatabu H, Kasagi K, Yamamoto K, et al. Acute suppurative thyroiditis associated with pyriform sinus stula: sonographic ndings. AJR 1990;155:845847.

55. Kawanaka M, Sugimoto Y, Suehiro M, et al. Thyroid imaging in a typical case of acute suppurative thyroiditis with abscess formation due to infection from a persistent thyroglossal duct. Ann Nucl Med


56. Malotte M, Chonkich GD, Zuppan CW. Riedels thyroiditis. Arch Otolaryngol Head Neck Surg 1991;117:214217.

57. Fontan JP, Carballido FC, Felipe FP, et al. Case report: Riedel thyroiditis: US, CT, and MR evaluation. J Comput Assist Tomogr



Chapter 40

58. Belore A, LaRose GL, LaPorta GA, et al. Cancer risks in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity. Am J Med 1992;93:363369.

59. Cerise EJ, Spears R, Ochsner A. Carcinoma of the thyroid and nontoxic nodular goiter. Surgery 1952;31:552561.

60. McCall A, Jarosz H, Lawrence AM, et al. The incidence of thyroid carcinoma in solitary cold nodules and in multinodular goiters. Surgery 1986;100:11281132.

61. Shulkin BL, Shapiro B. The role of imaging tests in the diagnosis of thyroid carcinoma. Endocrinol Metab Clin North Am 1990;19(3):


62. Noma S, Kanaoka M, Minami S, et al. Thyroid masses: MR imaging and pathologic correlation. Radiology 1988;168:759764.

63. Huysmans DA, Hermus AR, Corstens FH, et al. Large, compressive goiters treated with radioiodine. Ann Intern Med 1994;121(10):


64. Dworkin HJ, Meier DA, Kaplan M. Advances in the manage- ment of patients with thyroid disease. Semin Nucl Med 1995;25:


65. Huang T, Loevner LA, Yousem DM. Management of incidental thyroid lesions detected on CT and MR imaging of the neck performed for other purposes. Presented at the 30th Annual Scientic Conference, American Society of Head and Neck Radiology, Los Angeles, April 2428, 1996.

66. Harvey HK. Diagnosis and management of the thyroid nodule: an overview. Otolaryngol Clin North Am 1990;23:303337.

67. Shamma FN, Abrahams JJ. Imaging in endocrine disorders. J Reprod Med 1992;37:3945.

68. Klieger PS, Wilson GA, Greenspan BS. The usefulness of the dynamic phase in pertechnetate thyroid imaging for solitary hypofunctioning nodules. Clin Nucl Med 1992;17(8):617622.

69. Gharib H, Goellner JR, Johnson DA. FNA cytology of the thyroid: a 12 year experience with 11,000 biopsies. Clin Lab Med 1995;13:


70. Gharib H, Goellner JR. Fine needle aspiration of the thyroid: an appraisal. Ann Intern Med 1993;11:282289.

71. Hamberger JI. Evolution of toxicity in solitary nontoxic autono- mously functioning thyroid nodules. Clin Endocrinol Metab


72. Ross DS. Evaluation of the thyroid nodule. J Nucl Med


73. Livraghi T, Paracchi A, Ferrari, et al. Treatment of autonomous thyroid nodules with percutaneous ethanol injection: preliminary results. Radiology 1990;175:827829.

74. Monzani F, Goletti O, Caraccio N, et al. Percutaneous ethanol injection treatment of autonomous thyroid adenoma: hormonal and clinical evaluation. Clin Endocrinol 1992;36:491497.

75. Mazzeo S, Toni MG, DeGaudio C, et al. Percutaneous injection of ethanol to treat autonomous thyroid nodules. AJR 1993;161:


76. Papini E, Panunzi C, Pacella CM, et al. Percutaneous ultrasound- guided ethanol injection: a new treatment of toxic autono- mously functioning thyroid nodules. J Clin Endocrinol Metab


77. Livraghi T, Paracchi A, Ferrari C, et al. Treatment of autonomous thyroid nodules with percutaneous ethanol injection: 4-year experi- ence. Radiology 1994;190:529533.

78. Ozdemir H, Ilgit ET, Yucel C, et al. Treatment of autonomous thyroid nodules: safety and efcacy of sonographically guided percutaneous injection of ethanol. AJR 1994;163:929932.

79. Solbiati L, Pra LD, Ierace T, et al. High-resolution sonography of the recurrent laryngeal nerve: anatomic and pathologic considerations. AJR 1985;145:989993.

80. Duffy BJ Jr, Fitzgerald PJ. Cancer of the thyroid in children: a report of 28 cases. J Clin Endocrinol Metab 1950;10:12961311.

81. Favus MJ, Schneider AB, Stachura ME, et al. Thyroid cancer occurring as a late consequence of head-and-neck irradiation:

evaluation of 1,056 patients. N Engl J Med 1976;294:10191025.

82. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med 1993;328:553559.

83. Mazzaferri EL, de los Santos ET, Rofagha-Keyhani S. Solitary thyroid nodules: diagnosis and management. Med Clin North Am


84. Pelizzo MR, Piotto A, Rubello D, et al. High prevalence of occult papillary thyroid carcinoma in a surgical series for benign thyroid disease. Tumori 1990;76:255257.

Thyroid and Parathyroid Glands: Anatomy and Pathology


85. Sutton RT, Reading CC, Charboneau JW, et al. US-guided biopsy of neck masses in postoperative management of patients with thyroid cancer. Radiology 1988;168:769772.

86. Chen KTK, Rosai J. Follicular variant of thyroid papillary carcinoma.

A clinicopathologic study of 6 cases. Am J Surg Pathol


87. Rosai J, Zampi G, Carcangiu ML. Papillary carcinoma of the thyroid.

A discussion of its several morphologic expressions, with particular

emphasis on the follicular variant. Am J Surg Pathol 1983;7:


88. Carcangiu ML, Zampi G, Pupi A, Castagnoli A, Rosai J. Papillary carcinoma of the thyroid. A clinicopathologic study of 244 cases treated at the University of Florence, Italy. Cancer 1985;55:


89. Chen KTK, Rosai J. Follicular variant of thyroid papillary carcinoma:

a clinicopathologic study of six cases. Am J Surg Pathol


90. Vickery AL. Thyroid papillary carcinoma. Pathological and

philosophical controversies. Am J Surg Pathol 1983;7:797807.

91. Hay ID. Papillary thyroid carcinoma. Endocrinol Metab Clin North

Am 1990;19:545576.

92. Hawk WA, Hazard JB. The many appearances of papillary carcinoma

of the thyroid. Cleve Clin Q 1976;43:207216.

93. Som PM, Brandwein M, Lidov M, et al. The varied appearance of papillary carcinoma cervical nodal disease: CT and MR ndings. AJNR 1994;15:11291138.

94. Franssila KO, Ackerman LV, Brown CL, Hedinger CE. Follicular carcinoma. Semin Diagn Pathol 1985;2:101102.

95. Roediger WEW. The oxyphil and C cells of the human thyroid gland. Cancer 1975;36:17581770.

96. Bondeson L, Bondeson AG, Ljungberg O, Tibblin S. Oxyphil tumors

of the thyroid. Follow-up of 42 surgical cases. Ann Surg


97. Gorman B, Charboneau JW, James EM, et al. Medullary thyroid carcinoma: role of high-resolution US. Radiology 1987;162:147150.

98. Melvin KEW, Miller HH, Tashjian AH. Early diagnosis of medullary carcinoma of the thyroid by means of calcitonin assay. N Engl J Med


99. Steiner AL, Goodman AD, Powers SR. Study of a kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroid- ism, and Cushings disease: multiple endocrine neoplasia type 2. Medicine 1968;47:371409.

100. Wolfe HJ, DeLellis RA. Familial medullary thyroid carcinomaand C-cell hyperplasia. Clin Endocrinol Metab 1981;10:351365.

101. Kakudo K, Carney JA, Sizemore GW. Medullary carcinoma of thyroid: biologic behavior of the sporadic and familial neoplasm. Cancer 1985;55:28182821.

102. Busnardo B, Girelli ME, Simioni N, Nacamuilli D, Busetto E. Non-parallel patterns of calcitonin and carcinoembryonic antigen levels in the follow-up of medullary thyroid carcinoma. Cancer


103. Dorr U, Wurstlin S, Frank-Raue K, et al. Somatostatin receptor scintigraphy and magnetic resonance imaging in recurrent medullary thyroid carcinoma: a comparative study. Horm Metab Res Suppl


104. Lebouthillier G, Morais J, Picard M, et al. Tc-99m sestamibi and other agents in the detection of metastatic medullary carcinoma of the thyroid. Clin Nucl Med 1993;18(8):657661.

105. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111-In-DTPA-D-phe]- and [I-123-tyr]- octreotide: the Rotterdam experience with more than 1,000 patients.

Eur J Nucl Med 1993;20:716731.

106. Dorr U, Sautter-Bihl ML, Heiner B. The contribution of somatostatin receptor scintigraphy to the diagnosis of recurrent medullary carcinoma of the thyroid. Semin Oncol 1994;21:4245.

107. Takashima S, Morimoto S, Ikezoe J, et al. CT evaluation of anaplastic thyroid carcinoma. AJR 1990;154:10791085.

108. Ohnishi T, Noguchi S, Murakami N, et al. MR imaging in patients with primary thyroid lymphoma. Am J Neuroradiol 1992;13(4):


109. Haugen BR, Nawaz S, Cohn A, et al. Secondary malignancy of the thyroid gland: a case report and review of the literature. Thyroid


110. Czech JM, Lichtor TR, Carney JA, van Heerden JA. Neoplasms metastatic to the thyroid gland. Surg Gynecol Obstet 1982;155:







Primary hyperparathyroidism resulting in hypercalcemia is the most common presentation of parathyroid pathology and is usually related to a parathyroid adenoma, although less commonly it may be secondary to gland hyperplasia. Imaging of the parathyroid glands primarily focuses on the detection of adenomas in patients with primary hyperpara- thyroidism. A second focus is the detection of an unrecog- nized adenoma in a patient with persistent or recurrent hypercalcemia after prior surgery for hyperparathyroidism. The role of imaging (as well as which modality to use) for preoperative localization of the parathyroid glands continues to be a controversial issue, with practices differing from institution to institution. The anatomy, physiology, and pathology of the parathy- roid glands will be reviewed. The diagnostic utility of radiologic imaging including ultrasonography, CT, MR imaging, and nuclear scintigraphy will be discussed, particularly as it pertains to the evaluation of primary hyperparathyroidism.


The parathyroid glands arise from the third and fourth branchial pouches. The upper or superior parathyroid glands arise from the fourth branchial pouch along with the lateral anlages of the thyroid gland. Because the superior parathyroid glands are closely related to the thyroid gland and have minimal descent, their positions are relatively constant along the dorsal aspect of the upper thyroid. Less than 2% of the superior parathyroid glands are ectopic in location. The lower or inferior parathyroid glands and thymus are derived from the third branchial pouch, and in contrast to the upper glands, the lower parathyroid glands descend a variable distance with the thymic anlage. As a result, the position of the inferior parathyroid glands, is more variable than that of the superior parathyroid glands, and the inferior glands may descend into the anterior mediastinum as far as the pericardium. On either side of the neck, a branch of the superior thyroidal artery usually supplies the upper parathyroid gland, while the inferior thyroidal artery supplies the lower parathyroid gland. Drainage from the glands is usually to the thyroidal veins. The cervical sympathetic plexus innervates the parathyroid glands. The number of parathyroid glands ranges from 1 to 12, although most individuals (over 80%) have 4. 1 The most common anatomic location of the upper parathyroid glands is posterior to the middle one third of the thyroid gland (75% of the time). The majority of the remainder of the upper parathyroids are located behind the upper or lower one third of the thyroid, with approximately 7% found below the inferior thyroidal artery. 1 The upper glands may also be located behind the pharynx or esophagus. 2 The most common anatomic location of the lower parathyroid glands

is lateral to the lower pole of the thyroid gland (50% of the time). The next most common location encompasses an area 1 cm below the lower thyroid pole (15%). The position of the remaining one third is variable along the thyrothymic tract, extending anywhere from the angle of the mandible to the lower anterior mediastinum. Intrathyroidal parathyroid glands are uncommon, occurring in 2% of cases. It is not possible with current imaging techniques to distinguish an intrathyroidal parathyroid adenoma from a primary thyroid lesion. 35 The variability in number and location of the parathyroid glands can create problems for the surgeon exploring the neck for diseased glands in patients with primary hyperthy- roidism. In addition, in patients having neck surgery for other reasons such as thyroid disease, the parathyroid gland(s) may accidentally be injured or removed.


The normal parathyroid glands are each less than 9 mm in maximal dimension, and are composed of chief cells and oxyphil cells embedded within a brous capsule and intermixed with adipose tissue. 6 The role of the oxyphil cells is unknown. They appear at around puberty and increase with age. Chief cells secrete parathormone (PTH), which regulates the concentration of calcium in interstitial uids. Serum calcium levels in turn regulate the secretion of PTH. Parathormone acts predominantly in three regions: (1) the skeleton to mobilize calcium into the plasma, (2) the kidneys to reduce calcium excretion, and (3) the gastrointestinal tract to increase calcium absorption. 7 Parathormone enhances the synthesis of 1,25-(OH)D 3 (vitamin D), which promotes the absorption of calcium by the intestines. In patients with elevated serum calcium concentrations, PTH should be suppressed. When a normal PTH level is encountered in the setting of hypercalcemia, it is referred to as hyperparathy- roidism. In primary hyperparathyroidism, hypercalcemia is the result of excessive secretion of PTH from one or more of the parathyroid glands.



Primary hyperparathyroidism is common, more common in women, occurring in approximately 1 in 700 adults. 8 In most cases, patients are asymptomatic and the condition is detected by routine screening blood tests for serum calcium that individuals frequently have as part of their yearly checkup. It occurs secondary to hypersecretion of PTH, resulting in hypercalcemia. The causes of primary hyper- parathyroidism include a single 1 to 3 cm parathyroid adenoma (75% to 85% of cases), parathyroid hyperplasia (10% to 15%), multiple parathyroid adenomas (2% to 3%), and, rarely, parathyroid carcinomas (less than 1%). 3, 911 Solitary adenomas vary widely in size, being very small (less than 1 cm) as well as very large (several centimeters).


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology


Thyroid and Parathyroid Glands: Anatomy and Pathology 2161   FIGURE 40-40 Patient with recurrent primary

FIGURE 40-40 Patient with recurrent primary hyperparathyroidism. A, Enhanced axial CT scan shows a hypodense mass (arrows) just posterior to the inferior pole of the left lobe of the thyroid gland. At surgery this was found to be a parathyroid adenoma separate from the thyroid. A clip in the right tracheoesophageal groove is from

prior neck exploration. B, Bone scan showing markedly increased uptake in the calvarium and nonvisualization of


the kidneys that has been described in association with hyperparathyroidism. C, Lateral plain lm radiograph demonstrating the classic ‘‘salt and pepper’’ skull.


Hyperplasia typically involves multiple parathyroid glands. The classic clinical features of hypercalcemia include bone pain related to osseous demineralization, abdominal pain secondary to renal calculi, and occasional psychiatric disturbances (Fig. 40-40). Hypercalcemia left untreated can also result in pancreatitis, peptic ulcer disease, and musculoskeletal dysfunction. The treatment of primary hyperparathyroidism is surgical excision of the abnormal parathyroid gland(s). Surgeons continue to debate over the ideal operative approach to cure primary hyperparathyroidism while limiting morbidity and controlling costs. Most surgeons still perform bilateral neck explorations since very small lesions or hyperplasia may be overlooked with current imaging techniques. Although the need for preoperative imaging localization remains a topic of debate, many surgeons report fewer complications and shorter operating times when abnormal parathyroid glands

are identied prior to surgery. 3, 1214 Importantly, preopera- tive imaging in many cases has allowed the surgeon to treat hyperparathyroidism successfully with only a unilateral neck exploration. 14, 15 Nonetheless, there are clearly certain situations in which all would agree that imaging plays a very useful role. This includes high-risk surgery patients where imaging may permit the surgeon to resect the abnormal gland with only a unilateral neck exploration. Alternatively, percutaneous injection of absolute ethanol to ablate adenomas may be performed under ultrasound guidance in patients who are poor surgical candidates due to underlying medical ill- ness. 16, 17 The success of treatment is monitored with serum calcium levels, which are followed until levels approach near-normal values. Also, when hyperparathyroidism recurs following surgery, imaging is indicated, as ectopic glands are prevalent in this group of patients.




There are also secondary and tertiary forms of hyperpara- thyroidism. Secondary hyperparathyroidism occurs in pa- tients with long-standing renal failure leading to changes in calcium metabolism, which in turn results in enlargement of the parathyroid glands. In tertiary hyperparathyroidism, hypercalcemia occurs as a sequela of secondary hyperpara- thyroidism due to the autonomous secretion of PTH from chronically overstimulated parathyroid glands.


Hypoparathyroidism is mainly a functional clinical dis- order characterized by hypocalcemia and hyperphosphate- mia secondary to a deciency of PTH. The clinical manifestation may be subtle and include facial contractions brought on by tapping the facial nerve (Chvosteks sign), or carpal contractions initiated by applying a blood pressure cuff (Trousseaus sign). Hypoparathyroidism may be acute and transient, usually following parathyroid or thyroid surgery. Chronic hypoparathyroidism may be iatrogenic (surgery), developmental (agenesis is rare), autoimmune, inltrative (secondary to cancers, amyloid, etc.), or part of a group of disorders called pseudohypoparathyroidism in which there is a resistance in the kidneys and skeleton to the physiologic effects of PTH. There is a group of patients that exhibit the characteristic phenotypical appearance of pseudohypoparathyroidism (short, round facies, brachydac- tyly), but lack the unresponsiveness to PTH (normal calcium and phosphate levels). These patients are said to have pseudopseudohypoparathyroidism.


Parathyroid Adenoma

Indications for preoperative localization of parathyroid adenomas remain a topic of debate. In addition, the choice of the appropriate imaging modality is also debated in the literature. When imaging is utilized, the modality options include ultrasonography, CT, MR imaging, and nuclear scintigraphy. Conventional catheter and digital subtraction angiography, as well as selective parathyroid venography with sampling and measurement of PTH levels, are highly accurate in detecting parathyroid adenomas; however, their major drawback is that they are relatively invasive and expensive. At many institutions with experienced parathyroid sur- geons, preoperative localization of the glands with imaging is not performed, as some studies suggest that the morbidity, mortality, and operative time are not greatly affected by pre- operative localization. 1820 In addition, some investigators argue that the cost of imaging outweighs its benet. 18, 21 However, more recently, many surgeons have reported that imaging has resulted in reduced operative time, reduced morbidity, and lower costs. 14, 22 Specically, when the cost of preoperative imaging was compared to that of increased operative time, imaging was found to be cheaper. 14 The surgical technique includes exploration of the perithyroidal region bilaterally, with particular emphasis on the inferior poles of the thyroid glands, as this is where most

parathyroid adenomas occur. In the hands of skilled surgeons, this procedure may be performed with a success rate of over 90%. 3, 18, 2326 When a parathyroid adenoma is not identied in the perithyroidal location, the surgeon may explore the anterior mediastinum, the deep cervical space, and the carotid sheath regions. Successful surgery in these cases is lower (less than 70%), and the surgical complication rate is higher. 23 Arguments for performing preoperative imaging to localize the parathyroid glands include (1) the need for only unilateral perithyroidal neck exploration when an adenoma is detected 14 ; (2) the identication of ectopic adenomas 27 ; (3) the detection of other head and neck masses (such as thyroid lesions); and (4) a reduction in operating room time. 13, 25, 2830 In addition, the operative success rate improves from 90% to close to 100% when preoperative imaging is performed. 14, 31

Ultrasonography Ultrasonography of the parathyroid glands is typically performed with a high-resolution linear array transducer (7.5 to 10 MHz) and an experienced sonographer. The patient is imaged in the supine position with the neck mildly hyperextended. Examination includes evaluation of the perithyroidal areas and the region of the carotid sheaths extending from the angle of the mandible superiorly to the sternal notch inferiorly. The typical appearance of a parathyroid adenoma is that of a homogeneous, well demarcated mass with an echogenicity less than that of the thyroid gland (Fig. 40-41). 24, 32 Adenomas are encapsulated and are typically solid; however, they may have cystic and/or hemorrhagic components resulting in regions of decreased and increased echogenicity, respectively. In addition, adenomas may undergo cystic degeneration. Color Doppler may on occasion provide additional information that may help to distinguish thyroid from parathyroid lesions. Specically, thyroid lesions tend to have some vascularity, whereas small parathyroid lesions more often lack Doppler signal. On occasion, larger parathyroid lesions may be vascular. 33 For adenomas located in the perithyroidal region, ultrasonography is an excellent modality. Limitations of ultrasonography predominantly center on the fact that it is less accurate than other imaging modalities in identifying ectopic parathyroid adenomas, and evaluation of the anterior mediastinum is limited secondary to acoustic impedance by air and bone. In addition, scanning artifact may obscure adenomas close to air-lled structures such as the trachea or esophagus. Ultrasonography identies adenomas in 95% of glands weighing more than 1 g (individual normal parathyroid glands weigh 35 to 55 mg each). 1, 24 Investigators report sensitivity of 50% to 70%, and specicity of 90% to 95% for adenomas in hyperplastic glands. 9, 10, 14, 24, 32, 34, 35

Cross-Sectional Imaging Cross-sectional imaging (CT and MR imaging) provides evaluation of the neck from the skull base through the anterior mediastinum, allowing detection of ectopic parathy- roid adenomas (Fig. 40-42). CT images should include contiguous thin (3 mm) sections. Intravenous contrast must be used in CT both to distinguish blood vessels from adenomas and because up to 25% of parathyroid adenomas


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology


Thyroid and Parathyroid Glands: Anatomy and Pathology 2163     FIGURE 40-41 A pitfall in Tc-99m

FIGURE 40-41 A pitfall in Tc-99m sestamibi scintigraphy is that thyroid lesions may concentrate sestamibi similarly to parathyroid adenomas. A, Sestamibi scan shows increased activity in the right lobe of the thyroid gland. B, Transverse ultrasound image reveals a well-demarcated mass in the thyroid (curved white arrows) that at surgery

was found to be a thyroid adenoma, as well as a rounded mass hypoechoic to and posterior to the thyroid that was a


parathyroid adenoma (straight arrows). J, Jugular vein; C, carotid artery.


enhance. 32 Limitations of CT in detecting adenomas include scanning artifacts related to swallowing and breathing. Lymph nodes, tortuous vessels, and the esophagus may also be mistaken for adenomas. As mentioned earlier, a drawback to using CT is the uptake of contrast by the thyroid gland, necessitating a wait of 6 to 8 weeks before nuclear scintigraphy with iodinated agents may be accurately performed. 36 In general, investigators have found that both the sensitivity and specicity of high-resolution CT are improved over those of ultrasound, being approximately 70% and 90%, respectively. 32, 37 MR imaging, like CT, allows excellent evaluation of the

mediastinum. This method offers superior soft-tissue dis- crimination and is more sensitive than CT for identifying parathyroid adenomas. MR imaging should be performed on a high eld strength system. Accuracy may be improved and artifacts related to heart motion reduced by using cardiac gating. The imaging sequences utilized should include axial T1- and T2-weighted 4 to 5 mm thick images extending from the skull base through the mediastinum. 38 The administration of intravenous contrast material (gadolinium) can increase lesion conspicuity. The appearance of adenomas on MR imaging is variable. 39 Usually, adenomas are iso- to hypointense compared to the thyroid gland on T1-weighted images, and they are usually hyperintense on T2-weighted images. They may enhance avidly following intravenous gadolinium administration (Fig. 40-43). Some lesions with dense cellularity may be iso- to hyperintense compared to muscle on T1-weighted images and isointense on T2-weighted images (Fig. 40-44). It is uncommon for an adenoma to be hypointense on T2-weighted images. Pitfalls in detection of parathyroid adenomas on MR imaging include misinterpre- tation of enlarged cervical lymph nodes for adenomas, 38 large cervical ganglia, and a multiplicity of ectopic sites. 39 Distinction between abnormal gland and vessel is less of a problem with MR imaging due to its ability to readily identify vascular structures (ow voids). MR imaging has a reported accuracy of over 90%. 40


Nuclear Scintigraphy Nuclear scintigraphy to identify parathyroid adenomas

may be performed with several radionuclides including

FIGURE 40-42

Parathyroid adenoma in the right perithyroidal region.

thallium-201 (Tl-201)/Tc-99m pertechnetate subtraction

Axial CT image shows the adenoma (A) that was detected in the evaluation of this patient with hypercalcemia.

scanning, Tc-99m sestamibi subtraction imaging with I-123 (Fig. 40-45) or Tc-99m pertechnetate, or Tc-99m sestamibi





FIGURE 40-43 Primary hyperparathyroidism secondary to a parathyroid adenoma. A, Unenhanced axial T1-weighted image shows a hypointense adenoma (arrow) just posterior to the inferior pole of the


right thyroid lobe. B, Corresponding axial T2-weighted image shows marked hyperintensity of the adenoma. C, Enhanced axial fat- suppressed T1-weighted image shows homogeneous enhancement of the lesion.


FIGURE 40-44 Ectopic parathyroid adenoma in the paraesophageal/tracheoesophageal tract. A, Unenhanced axial T1-weighted image shows a mass (arrow) impinging on the esophagus (e). B, Corresponding axial T2-weighted image shows an isointense adenoma. At histologic evaluation following surgical resection, the adenoma was highly cellular.


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology


Thyroid and Parathyroid Glands: Anatomy and Pathology 2165   FIGURE 40-45 Parathyroid adenomas detected in two

FIGURE 40-45 Parathyroid adenomas detected in two different patients by Tl-201/Tc-99m pertechnetate subtraction imaging (A to C) and by Tc-99m sestamibi subtraction imaging with I-123 (D). A, Tc-99m pertechnetate concentrated within the thyroid gland. B, Tl-201 concentrated within thyroid and parathyroid glands. C, Computer

techniques allow technetium concentrated in the thyroid gland to be subtracted from thallium that accumulates


within both thyroid and parathyroid tissue. After thyroid subtraction, a parathyroid adenoma is noted as a focus of increased thallium uptake (arrows). D, Tc-99m sestamibi subtraction imaging with I-123 shows an adenoma below the inferior pole of the left lobe of the thyroid gland. (Courtesy of Dr. Joseph Sam, Department of Radiology, Nuclear Medicine Division, University of Pennsylvania Medical Center.)


alone. 4144 Because no radionuclides are taken up by the parathyroid glands alone, subtraction techniques allow ra- dionuclides that are concentrated in the thyroid gland (tech- netium and iodine) to be subtracted from those that accumu- late within both thyroid and parathyroid tissue (thallium and sestamibi). Tl-201 is a potassium analog that is taken up by the thyroid as well as concentrated in parathyroid adenomas due to changes in potassium turnover. As a sole imaging agent, it cannot distinguish a parathyroid adenoma from the thyroid gland. Thallium emits low-energy photons and washes out of adenomas rapidly. Technetium has higher- energy photons that better penetrate the anterior neck and

mediastinum. Tc-99m is trapped in the thyroid gland but not in parathyroid tissue. When Tl-201 and Tc-99m pertechne- tate images are coregistered, computer-based subtraction techniques can remove the thyroid component, permitting identication of abnormal parathyroid tissue. Typically, 2 to 5 mCi of each radiotracer is administered intravenously, and either sequential or dual isotope imaging is performed. The mediastinum should be included in the eld of view to assess for the possibility of ectopic adenomas. After thyroid subtraction, a perithyroidal para- thyroid adenoma appears as a focus of increased thallium uptake (Fig. 40-45). The major limitation of this examina-




tion is motion artifact that may degrade the images, making superimposition of the images and subtraction unreliable and interpretation difcult. The reported sensitivity and diagnostic accuracy of Tl-201/Tc-99m subtraction scintigraphy vary, but each is approximately 80% to 85%. 14, 45 False-positive examina- tions may result secondary to inammatory conditions, lymphoma, and thyroid nodules. Lesion size is an important factor in determining the sensitivity of subtraction scintigra- phy. Specically, lesions less than 0.5 g are rarely visualized

(the combined weight of all parathyroid glands in normal patients is usually less than 200 mg). 1 The histologic content of the adenoma also inuences sensitivity, with greater accuracy seen in lesions having a high concentration of mitochondria. 46 Tc-99m sestamibi scintigraphy was introduced in the late 1980s. 47 Tc-99m sestamibi is a positively charged, lipid- soluble myocardial perfusion tracer. The mechanism for sestamibi uptake is not completely understood, but it could correspond to cellular components (chief and oxyphil cells), mitochondrial density in oxyphil cells, blood ow within adenomas, and/or potassium turnover. 48, 49 However, it has

been suggested that the number of oxyphil cells does not

clearly affect the results of sestamibi imaging since it is small in most hyperfunctioning glands. 48 Electron micros- copy has shown increased mitochondrial density in oxy- philic cells. 49 Uptake is also dependent on gland size as well

as on their functional state. 48, 49 The intracellular distribu- tion is determined by the negative transmembrane potential of cellular and mitochondrial membranes. Therefore, cells

with high mitochondrial content are believed to retain more

of the positively charged tracer.

Tc-99m sestamibi scintigraphy offers several advantages

over subtraction imaging including dual-phase acquisition,

handling of a single radiotracer, and the capability for single photon emission computed tomography (SPECT). Dual- phase Tc-99m sestamibi used alone takes advantage of the rapid washout of the tracer from the thyroid gland, while

there is avid retention in parathyroid lesions. Delayed images are frequently all that are necessary for good localization. Immediately following injection (5 to 30 minutes) of 20 mCi of radiotracer, images are obtained of

the neck and chest. Delayed images are obtained in the same

sites approximately 1 1 2 to 4 hours following radiotracer

injection. 41, 50, 51 The addition of pinhole imaging in the

delayed phase may further increase the detection of adenomas. 52 In difcult cases where Tc-99m sestamibi

subtraction imaging with I-123 is being utilized, 200 to 300

mCi of I-123 is given orally and a pinhole image of the

thyroid is obtained at 60 to 90 minutes. Subsequently, 20

mCi of Tc-99m sestamibi is injected, and immediate as well

as 2 hour delayed images of the neck and chest are acquired. Parathyroid adenomas are identied as foci of increased radiotracer uptake. SPECT can be combined with Tc-99m sestamibi scintigraphy for more accurate adenoma localiza- tion. When SPECT is combined with sestamibi scintigraphy,

the accuracy of sestamibi ranging from 80% to 100% and with a consistently high specicity. 14, 15, 35, 51, 5459 The most recent data on sestamibi suggest that it surpasses all other imaging modalities, including ultrasound and CT, in

both sensitivity and accuracy. 14, 15, 35, 51, 5459 A few studies have been performed to compare the accuracy of sestamibi parathyroid scintigraphy with that of MR imaging. Most, but not all studies, suggest that sestamibi is slightly more accurate. 5962

In most studies assessing the accuracy of imaging in

detecting parathyroid lesions, one or two imaging modalities were evaluated, and were compared and contrasted with each other. However, a handful of studies assessed the value of combining functional imaging (nuclear scintigraphy) with anatomic imaging (cross-sectional imaging). One study suggested that the greater specicity and anatomic coverage of sestamibi scintigraphy coupled with the greater anatomic detail provided by MR imaging may justify the use of both techniques in high-risk surgical patients or patients undergo- ing repeat surgery. 62 In a recent study that looked at the utility of scintigraphy combined with cross-sectional imag- ing (CT, ultrasound, MR imaging), the combination of scintigraphy and ultrasound had grater sensitivity, specic- ity, and accuracy than any imaging modality alone or than scintigraphy in combination with CT or MR imaging in the preoperative assessment of parathyroid disease. 5 In sum- mary, sestamibi is a highly sensitive and accurate imaging tool for the preoperative localization of parathyroid disease. The addition of cross-sectional imaging in certain cases to provide anatomic detail is helpful, especially in patients with ectopic tissue or in patients who are high surgical risks where operative precision and short surgical times are paramount (Figs. 40-44 and 40-46). Potential pitfalls in Tc-99m sestamibi scintigraphy include the occasional adenoma with rapid washout attrib- uted to low mitochondrial content, 63 poor conspicuity of lesions near the heart, 15 and the occasional thyroid lesion or Hurthle cell tumor that may retain Tc-99m sestamibi. 38, 64 In addition, small lesions, especially those under 100 to 200 mg, may go undetected. 38, 49, 65 The high incidence of concomitant thyroid lesions (40% to 50%) in patients with parathyroid adenomas may lead to false-positive scintigra- phy results because thyroid lesions may concentrate sestamibi to the same degree as parathyroid adenomas (Fig. 40-41). 4, 24, 38, 57, 58, 66 In addition, sestamibi uptake in thyroid cancers, as well as in nodal and distant metastases, can occur, 67, 68 and sestamibi retention in reactive lymph node hyperplasia has been reported. 69

Reoperation for Hyperparathyroidism

In patients with recurrent hyperparathyroidism following

surgery, reoperation reveals abnormal parathyroid glands in the perithyroidal region in 30% to 75% of cases (Fig. 40-40), likely corresponding to parathyroid disease overlooked


(10 to 30 minutes) and delayed (2 to 4 hours) images

during the initial surgery. 4, 20, 23 Parathyroid adenomas may

injection are frequently acquired. Some studies suggest

that for Tc-99m sestamibi SPECT, early images are more accurate in the detection and localization of adenomas. 53 The accuracy of Tc-99m sestamibi is higher than that of


also be detected in the anterior mediastinum in 30% of cases (Fig. 40-46), and they may be intrathyroidal in less than 10% of cases. The remainder of adenomas at reoperation are located in the deep cervical region. 4, 20, 70

Tl-201/Tc-99m pertechnetate subtraction scintigraphy, with


consensus in the literature is that imaging prior to


Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology


Thyroid and Parathyroid Glands: Anatomy and Pathology 2167   FIGURE 40-46 Ectopic parathyroid adenoma. A ,

FIGURE 40-46

Ectopic parathyroid adenoma. A, Delayed image from a sestamibi scan shows increased uptake


in a surgically proven ectopic parathyroid adenoma in the superior mediastinum (arrow). B, Enhanced chest CT scan shows the corresponding adenoma in the anterior mediastinum (arrow).


reoperation is useful despite the cost. 11, 71 When preopera- tive imaging is performed, the success rate of surgery is approximately 80% to 90% compared to 65% when imaging

to at least 2 weeks. 77 This is done to avoid trapping of the radiotracer in the thyroid gland that may occur as a result of postoperative inammation.


is not performed prior to reoperation. 11 In reoperations, the sensitivity of ultrasonography, CT, MR imaging, and scintigraphy is quite variable. 4, 11, 32, 7274

Parathyroid Hyperplasia


One of the major differences in imaging the patient who has failed prior surgery for detection of a parathyroid adenoma is that scar tissue in the operative bed in the perithyroidal region makes image interpretation as well as anatomic detection at surgery more difcult. As with cross-sectional imaging at initial surgery, lymphadenopa- thy may be mistaken for an adenoma. Because the incidence of false-positive examinations caused by lymph- adenopathy is lowest with nuclear imaging, 4 sestamibi scintigraphy as a single study is probably the most accurate and cost-effective means to detect parathyroid adenomas. However, because of the increased surgical risk in cases of reoperation including vocal cord paralysis, 20 as well as the distortion of anatomic landmarks due to prior surgery, many surgeons believe that a functional scintigraphic study combined with an anatomic cross-sectional examination (MR imaging is less likely than CT and ultrasound to mistake a lymph node for an adenoma) 4 is warranted, as it provides the most accurate means of detecting parathyroid tissue despite the fact that it is not the most cost-effective approach. In general, MR imaging in combination with sestamibi scintigraphy allows accurate detection of parathy- roid tissue. 62, 74, 75 I-123 or Tc-99m pertechnetate and Tc-99m sestamibi subtraction images may increase the sensitivity of ectopic parathyroid adenoma detection in cases of failed initial neck explorations. 76 Finally, the sensitivity of sestamibi imaging in patients who require repeat surgery may be increased if the interval between initial surgery and imaging is extended

Chief-cell parathyroid hyperplasia accounts for hyper- parathyroidism in up to 15% of patients and may be associated with familial hyperparathyroidism or MEN syndromes. 78, 79 MEN is a spectrum of hereditary (autoso- mal dominant) conditions characterized by two or more hyperfunctioning endocrine tumors. MEN type I is associ- ated with primary hyperparathyroidism, pancreatic islet cell tumors, and anterior pituitary neoplasms. 8082 Primary hyperparathyroidism, which is usually multiglandular, is the most common clinical presentation. MEN type IIA is characterized by pheochromocytoma, medullary thyroid cancer, and hyperparathyroidism. 8083 The hyperparathy- roidism of MEN type IIA is also multiglandular but is less severe than that of MEN type I. Chief-cell hyperplasia accounts for the majority of cases of parathyroid hyperplasia, although uncommonly, clear- cell hyperplasia may occur. Clear cells are chief cells with an abundant amount of cytoplasmic glycogen. 1 Histologi- cally, there are numerous chief cells, occasional oxyphil cells, and sparse adipose tissue. Usually all of the parathyroid glands are enlarged, although usually not to signicant degrees. 26, 84 Infrequently, one gland is dispro- portionately enlarged, and as a result may be mistaken intraoperatively for an adenoma. Treatment of primary parathyroid hyperplasia is re- moval of most if not all parathyroid tissue, with or without autotransplantation to the forearm. 30, 78 Parathyroid hyperplasia is difcult to evaluate with any imaging





glands. 26 Furthermore, when there is a discrepancy in the size of the glands, the surgeon may conclude that a single parathyroid adenoma is responsible for the hyperpara- thyroidism. The reported sensitivity for the detection of parathyroid hyperplasia is low, ranging from approxi- mately 30% to 70% with cross-sectional imaging tech- niques. 911, 26, 32 More recently Tc99m sestamibi imaging has detected pararthyroid hyperplasia in 50% to 75% of


cases. 10, 11, 15, 26, 38, 57, 65, 85


Parathyroid Carcinoma


Parathyroid carcinoma is an unusual cause of hyperpara- thyroidism, accounting for less than 2% of all cases. However, hyperparathyroidism accounts for the clinical presentation of approximately 85% of all parathyroid carcinomas. 1 Patients usually have the typical symptoms


FIGURE 40-47 Parathyroid carcinoma invading the airway. Unen- hanced axial T1-weighted MR image shows a poorly dened soft-tissue mass (M ) just below the inferior pole of the left lobe of the thyroid gland. The fat plane between this mass and the esophagus (e) is obliterated, and

associated with hypercalcemia. In addition, because these tumors are frequently large, many patients may have a palpable neck mass at presentation. Grossly, parathyroid carcinomas tend to be large (over 10 g), and histologically


there is extension into the left lateral wall of the adjacent airway (A ).


modality due to the small size of the hyperplastic glands. Because there can be marked heterogeneity in gland size in parathyroid hyperplasia, imaging may detect the domi- nant gland but fail to identify the other hyperplastic

are noted to have tumor cells with mitotic gures admixed with brous tissue, as well as capsular and vascular invasion. 86 Parathyroid carcinomas have no characteristic imaging features and may not be distinguishable from adenomas or other soft-tissue masses. Regional cervical and mediastinal lymph node metastases may occur in up to one third of