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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
Hashimotos Thyroiditis
Silent, Painless Thyroiditis and Postpartum
Thyroiditis
De Quervains Thyroiditis (Subacute
Granulomatous Thyroiditis)
Acute Suppurative Thyroiditis
Riedels Thyroiditis (Struma)
Thyroid Goiter
Nodular Thyroid Disease
NEOPLASMS OF THE THYROID GLAND
Adenomas
Malignant Neoplasms
Papillary Carcinoma

SECTION ONE

THE THYROID GLAND


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

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

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 scintigraphy reveals functional information about the thyroid gland,

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Thyroid and Parathyroid Glands: Anatomy and Pathology

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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 lymphadenopathy, 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, metabolic, 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).

ANATOMY OF THE THYROID GLAND


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
left lobes of the thyroid gland are on either side of the
trachea, and each lobe has a superior and an inferior pole.
The 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
cm in width. The thyroid is anterior to the prevertebral

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,
10% to 30%).

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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 retropharyngeal 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 attachment 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 parathyroid 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 defined 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 sufficiently, 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 first 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 fibers descend from the
ganglia of the sympathetic trunk, while the parasympathetic
fibers course along with the vagus nerve. This autonomic
innervation is believed to strongly influence 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.

ENDOCRINOLOGY OF THE THYROID


GLAND
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. Ultimately, 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 first 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, organification, 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 organification usually results from enzymatic defects that interfere

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Chapter 40

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 approximately 70% of T3 and T4, thyroxine-binding preglobulin carries about 5% of T3 and 25% of T4, and albumin
carries the remaining hormones. The active form of T3 and
T4 is the free or unbound form, representing only 0.3% of
T3 and 0.03% of T4. T3 is approximately three to four times
more active physiologically than T4. T4 is synthesized
entirely within the thyroid, while 80% to 95% of T3 is
synthesized by peripheral conversion of T4.
Temporary interference with the organification of iodide
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).

CLINICAL MANIFESTATIONS OF THYROID


DISEASE
Thyrotoxicosis refers to a clinical syndrome that develops 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 flushing
reflecting peripheral vasodilatation, increased heat loss,
weight loss, myopathy, and increased appetite. Patients,
especially children, may be hyperactive. Cardiac manifestations are more common in older patients and include
tachycardia, palpitations, arrhythmias, and cardiomegaly.
Thyrotoxicosis associated with hyperthyroidism is most
frequently seen with Graves disease but may also be seen
with toxic multinodular goiter or a hyperfunctioning
adenoma. Toxic multinodular goiter associated with hyperthyroidism (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 inflammatory thyroid disease or ectopic thyroid
tissue (ovarian strumii), or it may be factitious (exogenous
hormone use or Munchausen syndrome) (Table 40-2).

Thyroid and Parathyroid Glands: Anatomy and Pathology

2137

Table 40-2
EVALUATION OF THE HYPERTHYROID PATIENT

TFTs
elevated

RAIU
(Normal)

RAIU
(Low)

RAIU
(High)

Plummers
disease

Thyroiditis
De Quervains thyroiditis

Graves
disease

Subacute lymphocytic
disease
Struma ovarii
Factitious disease
RAIU, 24-hour radioactive iodine uptake (normal, 10% to 30%); TFTs, thyroid
function tests.

Thyroid storm characterized by hypertension, tachycardia, and fever may present as a clinical emergency in
patients with unrecognized or inadequately treated thyrotoxicosis. 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
Gravesdisease and hyperthyroidism, thyroid ophthalmopathy may occur in euthyroid and even hypothyroid patients.
The most common patterns of extraocular muscle involvement 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 infiltration,
as well as due to an increase in the volume of the extraocular
muscles. Although most commonly symmetric, exophthalmos (proptosis) may be asymmetric or even unilateral.4
Clinical signs and symptoms include proptosis, lid retraction, 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

Table 40-1
COMMON MEDICATIONS THAT MAY
DECREASE THYROID IODIDE UPTAKE
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


Graves disease. Coronal CT scan shows bilaterally symmetric enlargement of the bellies of the extraocular muscles, with relative sparing of the
lateral rectus muscles (arrows).

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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 fibrosis of the extraocular muscles
may lead to abnormal eye movements (see Chapter 9).
Hypothyroidism refers to decreased thyroid hormone
synthesis (serum TSH is high, while T3 and T4 levels are
low). Primary hypothyroidism may be secondary to structural 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 (131I) treatment. In children it may be related
to enzyme deficiencies, defects in organification, or congenital anomalies such as lingual thyroid or thyroid agenesis.5 Central hypothyroidism refers to decreased thyroid
stimulation by TSH related to pituitary disease (secondary
hypothyroidism) or hypothalamic TRH deficiency (tertiary hypothyroidism). Unless readily identified and managed, hypothyroidism occurring prenatally or during infancy will result in cretinism. Hypothyroidism occurring in
older children and adults is termed myxedema. Clinical
manifestations are extremely variable, ranging from fatigue
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 enlargement of the thyroid gland, most commonly multinodular
goiters, but also neoplastic and inflammatory 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

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 findings
highly suggestive of a thyroid malignancy.

THYROID IMAGING
Nuclear scintigraphy and ultrasonography are frequently
the first imaging modalities used to assess patients with
suspected thyroid disorders. CT and MR imaging are
frequently utilized to address specific 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.

Nuclear Scintigraphy
Nuclear scintigraphy provides excellent functional information 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 scintigraphy 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 obtained from the chin to the sternal notch in multiple views
including anterior, posterior, and bilateral oblique projec-

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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 administration, doses, and some physical properties of these agents are
reviewed in Table 40-3. Imaging is performed approximately 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 reflects the
percentage of the dose given to the patient that is
accumulated within the thyroid gland, corrected for radioactive decay. Normal 24-hour uptake ranges from 10% to
30%. Several medications such as propylthiouracil, methimazole, and iodine-containing contrast agents used for
imaging may temporarily interfere with the organification 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 underlying thyroid disease, temporary changes in thyroid function 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 function should be withdrawn for adequate periods of time prior
to nuclear scanning. In general, if CT contrast is administered, 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

2139

More recently, fluorodeoxyglucose positron emission


tomography (18FDG-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 thyroglobulin 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. Specifically, 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 perpendicular 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 approximately100 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

Table 40-3
RADIONUCLIDES COMMONLY USED IN IMAGING THE THYROID GLAND
Radionuclide
Tc-99m
I-123
I-131 (diagnostic)
I-131 (whole body)*
I-123 (whole body)*
I-131 (treatment)
I-131 (treatment)

Administration

Dose

Half-life

Energy

Intravenous
Oral
Oral
Oral
Oral
Oral
Oral

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

6.02 hr
13.6 hr
8.05 days

140 keV
159 keV
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).

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FIGURE 40-5 Recurrent thyroid cancer in a 64-year-old woman following thyroidectomy for papillary
carcinoma, tall cell variant. A, 18FDG-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), confirmed 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 defined mass originating in the right thyroid lobe with extracapsular extension and direct
invasion of the jugular vein, which is filled with tumor (arrows). J, Left jugular vein with normal flow void; N,
metastatic disease. B, Unenhanced axial T1-weighted MR image superior to A shows tumor in the right jugular vein.

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Chapter 40

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 organification by the thyroid. Another
advantage of MR imaging is that it readily identifies 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 highquality 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 images, as well as axial fast spin-echo T2-weighted images
with the application of fat saturation. Following intravenous contrast administration, axial T1-weighted images
with the application of fat saturation are usually acquired. 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
neck musculature (Fig. 40-1). Following contrast administration, the normal gland enhances diffusely and homogeneously.

Thyroid and Parathyroid Glands: Anatomy and Pathology

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,
Ultrasound Division, University of Pennsylvania Medical Center.)

PATHOLOGY OF THE THYROID GLAND


Congenital Anomalies

Ultrasonography
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
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
is normally uniformly hyperechoic.17 The more hypoechoic
a focal lesion is relative to the normal thyroid gland, the
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 calcifications are present, they appear as
foci of increase echogenicity with distal acoustic shadowing. Calcifications are nonspecific and may be seen in
benign as well as malignant lesions.18 Ultrasound may also
be used to guide fine needle aspiration of nodular
disease within the thyroid or to guide aspiration of suspicious 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-filled structures.

The thyroid gland develops in the first trimester of


pregnancy, beginning around the fifth 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 fifth gestational week and gives rise to follicular thyroid
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 fifth
branchial pharyngeal pouches at around the fifth week of
gestation. They give rise to the parafollicular C cells that are
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 final 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

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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
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 ventricular aspect of the interventricular septum, and none were
associated with abnormalities of thyroid function.30 Intratracheal 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 fibrous 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
Incomplete degeneration of the thyroglossal duct may
result in a persistent fistulous tract or in a thyroglossal duct
cyst along the path of migration of the thyroid gland from

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/floor 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
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 secondarily 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 finding of a thyroid origin is vertical motion of the
mass with swallowing or tongue protrusion. These larger

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).

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Chapter 40

Thyroid and Parathyroid Glands: Anatomy and Pathology

2143

resection of the cyst accompanied by total thyroidectomy


and/or radioiodide therapy.

Autoimmune Disease and Thyroiditis


Thyroiditis is infiltration of the thyroid gland with
inflammatory cells. This may be seen in a diverse group of
autoimmune, inflammatory, and infectious processes. Thyroiditis may be acute and self-limiting or chronic and
progressive.
Several autoimmune disorders may affect the thyroid
gland including Graves disease, Hashimotos thyroiditis,
and silent/postpartum thyroiditis. Each differs in pathophysiology and clinical presentation. Graves disease and silent
thyroiditis are usually associated with thyroid hyperfunction, 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.

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.

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

Graves Disease
Graves disease 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 Graves disease the thyrotropin
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 specific autoimmune
markers may be elevated, confirming 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

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.

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colloid. Vascularity is increased. Graves disease is associated with other autoimmune diseases of the thyroid
including Hashimotos thyroiditis.
Radionuclide scintigraphy may be useful in evaluating a
patient with suspected Graves disease as well as in
differentiating it from acute thyroiditis. Typically in Graves
disease, the thyroid gland is diffusely enlarged with intense
radiotracer uptake, often as high as 80% in 24 hours (Fig.
40-13).
The differential diagnosis includes thyroiditis, toxic
multinodular goiter, and toxic adenoma. In contrast to
Graves disease, 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 Graves disease and subacute
thyroiditis is important for appropriate patient management,
as patients with Graves disease 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/floor 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.

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Thyroid and Parathyroid Glands: Anatomy and Pathology

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

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
Graves disease, and the overall uptake is not as avid as that
in Graves disease. 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 findings in Graves
disease are nonspecific. 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, reflecting 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
Hashimotos Thyroiditis
Hashimotos thyroiditis (chronic lymphocytic thyroiditis)
is the prototype autoimmune thyroiditis. Pathologically, the
thyroid gland is enlarged and demonstrates lymphocytic and
plasma cell infiltration, follicular cell atrophy, and interlob-

ular fibrosis.40 Additionally, the normal follicular epithelial


cells may be altered, being replaced with pink oxyphilic
epithelium (Hurthle or Askanazy cells).41 It is usually
associated with a goiter. The pathogenesis of Hashimotos
thyroiditis involves both cellular and humoral mechanisms.
Autoantibodies have been identified against thyroglobulin,
thyroperoxidase, and TSH receptors. In reported cases,
when TSH receptor-blocking antibodies disappeared, normal thyroid function returned.42 Hashimotos thyroiditis is

FIGURE 40-15

Toxic multinodular goiter. Technetium-99m pertechnetate scans show enlargement of the thyroid gland with regions of
increased and decreased uptake.

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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,


Graves disease, and pernicious anemia.
Hashimotos thyroiditis occurs predominantly in women,
most commonly presenting in the fourth and fifth 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
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
findings are nonspecific, imaging can be useful, especially in
patient follow-up and monitoring of disease.
On scintigraphy, there is no typical pattern in Hashimotos 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 defined, hypoechoic regions
separated by fibrous 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 fibrotic, resulting in a heterogeneous echotexture.
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 fibrosis have been described.16
Following contrast administration, there may be regions that
enhance more than the remainder of the gland (Fig. 40-17).
Ultrasound may be used to follow patients with
Hashimotos thyroiditis to detect occult malignancy because

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 hypoechoic lesions or diffuse disease that may be difficult 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
Silent, Painless Thyroiditis and Postpartum Thyroiditis
Silent, painless thyroiditis and postpartum thyroiditis
are two different types of subacute lymphocytic thyroiditis, which are usually self-limited. When this inflammatory 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 infiltration, follicular disruption with hormone release usually causes patients
to present with thyrotoxicosis. As the disease progresses, patients may be hypothyroid transiently before returning to a
euthyroid state.51 Patients may or may not have glandular

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.

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Chapter 40

enlargement. Radioactive iodine uptake is low, and the pattern on scintigraphy varies from no tracer uptake to diffuse
or heterogeneous uptake.34 Nuclear scans may return to normal 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.
De Quervains Thyroiditis (Subacute Granulomatous
Thyroiditis)
De Quervains thyroiditis is a self-limited inflammatory
process that usually occurs following a viral upper
respiratory tract infection.2, 22 The viral infections that have
been associated with subacute thyroiditis include coxsackievirus and the mumps.53 The peak incidence is in the
second to fifth decades of life, with an occurrence three
times more frequent in women. Early in the inflammatory
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 inflamed 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. Scintigraphy 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
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 fistula (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
Riedels Thyroiditis (Struma)
Riedels thyroiditis (struma) is a rare form of chronic
thyroiditis characterized by a fibrosing reaction similar to
that seen in retroperitoneal fibrosis, which destroys the
thyroid and extends into the adjacent soft tissues of the neck.
Within the fibrosing tissue is a lymphocytic and plasma cell
infiltration 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
usually occurs in the fourth to seventh decades of life. On

Thyroid and Parathyroid Glands: Anatomy and Pathology

palpation, the thyroid is frequently firm, 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 fibrosis, as well as infiltration of adjacent
soft tissues in the neck.57 Riedels thyroiditis may be
associated with mediastinal or retroperitoneal fibrosis as
well as sclerosing cholangitis.

Thyroid Goiter
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 compensatory 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 enlargement of the thyroid associated with a euthyroid state. There
are two stages in its development. The first 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 iodinedeficient 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 calcifications, cyst formation, and scarring. Glandular enlargement may be asymmetric, involving

FIGURE 40-18 Riedels thyroiditis (struma). An axial CT scan shows


slight enlargement of the thyroid gland with multiple areas of poorly
defined hypodensity. Note the associated narrowing of the subglottic
airway (A), as well as obliteration of the fat in the right tracheoesophageal
groove (arrow).

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

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 identified with nuclear scintigraphy (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

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 multinodular goiter was less likely to be malignant than a solitary
cold nodule in a normal gland, recent studies have demonstrated 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 diffuse 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 reflecting
regions of hemorrhage, cyst formation, or necrosis (Fig.
40-20). More focal regions of hyperdensity are common,
reflecting calcifications present in over one half of patients,
hemorrhage, or colloid (Fig. 40-21). On MR imaging,
multinodular goiter may show a wide spectrum of appearances.62 On T1-weighted images, multiple foci of high
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.
Enhancement is usually inhomogeneous. Unlike CT, calcifications may be difficult 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 secondary 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.

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Thyroid and Parathyroid Glands: Anatomy and Pathology

2149

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 calcifications are also noted.

show continuity between a cervical and a mediastinal


goiter. When symptoms related to compression of the
aerodigestive tract or vessels occur in elderly patients,
nonsurgical candidates, or those refusing surgery, therapy with I-131 may be effective in reducing thyroid
volume.63
Specifically 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 percentage 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.

Nodular Thyroid Disease


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 involution. 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 difficult to distinguish benign from malignant
nodules. Findings on ultrasound, CT, and MR imaging are
nonspecific. A sonolucent halo around a thyroid nodule
or a solid, hyperechoic lesion favors a benign process (Fig.
40-22).18 The presence of calcification is nonspecific, 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, ipsilateral 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-

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

FIGURE 40-23

FIGURE 40-24 A 60-year-old woman presented with hyperthyroidism. 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
gland consistent with an autonomous nodule. (Courtesy of Dr. Joseph Sam,
Department of Radiology, Ultrasound Division, University of Pennsylvania 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 reflect
benign conditions, most commonly adenomas or hyperplasia.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 (adenomas, cysts, inflammation), 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 fine needle aspiration
is nondiagnostic, repeat aspiration or surgical excision may
be necessary.70

NEOPLASMS OF THE THYROID GLAND

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

Adenomas
Thyroid adenomas are true benign neoplasms distinctly
separate from the adjacent thyroid tissue and encased by a

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fibrous capsule. They are usually solitary and nonfunctioning, most commonly detected in young and middle-aged
adults. Autonomously functioning adenomas are not usually
associated with hyperthyroidism.71 Toxicity is most commonly 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 autonomous thyroid and parathyroid adenomas with 95%
ethanol injection. Results vary but generally show resolution of the hyperthyroid state without development of
hypothyroidism.7378 A potential complication is inadvertent 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 reflect
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 highdose 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 carcinoma are diagnosed in the United States each year, and
the annual death rate is approximately 1000.82 Of interest, the prevalence of incidental thyroid carcinomas identified 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 reflected 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 histologic classification 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 approximately 5% to 20% of thyroid cancers.6, 85
The major role of scintigraphy in assessing a dominant, 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 first imaging modality used to assess a
thyroid mass. It is useful in distinguishing solid from
cystic lesions. Ultrasound also plays a significant 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 characterization of an intrathyroidal lesion, as there are no
imaging findings that are histologically specific. The role
of the radiologist is to assess the findings related to a
thyroid mass, including invasion through the thyroid
capsule and infiltration of adjacent tissues and structures in
the neck, and to identify the presence of cervical lymph
node metastases.
Papillary Carcinoma
Papillary carcinoma is a low-grade malignancy occurring 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 thyroid carcinoma, it constitutes only about 1% of all
malignancies diagnosed in the United States. Histologically, papillary carcinoma may have a spectrum of
findings 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 clinically, it behaves like these tumors.23, 89 Frequently, papillary 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 papillary cancer are also common, including occult cancers
(less than 1.5 cm), intrathyroidal encapsulated, and extrathyroidal 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

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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
thyroid carcinoma. However, an increase in the incidence
of papillary carcinomas in these same regions has been
noted.
At gross pathology these tumors are firm, and they may
have calcium, hemorrhage, necrosis, and/or cysts. Histologically, papillary cancer is characterized by the presence of
papillae (epithelial cells encasing a fibrovascular core) and
clear nuclei.87, 88 Psammoma bodies (microscopic calcified
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 infiltration of the
gland that is manifest as heterogeneous hypodensity, or
a normal-appearing gland on CT (Fig. 40-27). Thus,
although not commonly reported, infiltrative papillary
carcinoma may not be detected in the thyroid gland on
imaging (Fig. 40-28). Papillary carcinoma has the highest 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 calcified (Fig. 40-29), cystic, hemorrhagic, or may contain colloid.93 Cystic nodal metastases are characterized by a thin or imperceptible wall
(Fig. 40-30), and they can be mistaken for benign cysts.

Cystic nodes are different from the necrotic nodes frequently seen with metastatic squamous cell carcinoma that
have central low density but retain a thick rind of residual lymphatic tissue. Hemorrhagic or colloid-containing
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
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

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
cervical lymph node metastases (arrows).

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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 infiltrative
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 calcified right cervical nodal metastasis (arrows).

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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),
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
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

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).

addition, tumor size and the number of structures adherent to


the gland are predictors.
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
deficiency. They are slightly more aggressive than papillary
carcinomas. On gross evaluation, they are either encapsulated 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 approximately 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 specific criteria including
that of an isolated thyroid mass composed predominantly of
Hurthle cells in the absence of inflammatory 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 hematogenous dissemination may occur.

FIGURE 40-31 Colloid-containing metastatic cervical lymph node.


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

Medullary Carcinoma
Medullary carcinoma arises from parafollicular C cells
that are believed to be derived from neural crest tissue in the
ultimobranchial bodies. It is relatively uncommon and has a

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FIGURE 40-33

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


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

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).

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 commonly 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 specific 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 infiltrative
on gross pathology.99, 100 Well-described patterns of medullary carcinoma include amyloid-containing, classic, trabecular, 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 immunostaining of resected tumor, may help predict the tumors
behavior.102
Unlike papillary and follicular subtypes, medullary
carcinoma does not concentrate radioiodine. However,
radionuclides specific for neuroendocrine tissue such as
I-131 meta-iodobenzylguanidine (MIBG) and the somato-

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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 calcifications and necrosis are frequently present.107

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
(arrows).

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.
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 anaplastic. They commonly occur in patients with long-standing

Primary Lymphoma
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
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 secondarily by lymphoma.
Imaging, including MR imaging, cannot reliably distinguish lymphoma from thyroiditis in patients with Hashimotos 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
Usually it is hypoechoic on ultrasound17, 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 calcification 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 infiltrative 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, esophageal lumen). B, Inferior image shows a necrotic metastatic lymph node (N ). C, Carotid; J, jugular vein.

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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 confirmed pathologically.

FIGURE 40-37 Anaplastic carcinoma. Sagittal sonographic image


shows a large, hypoechoic mass in the thyroid gland.

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 findings 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, fibrosarcomas, leiomyosarcomas, chondrosarcomas, 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
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 thyroglobulin 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.

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

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

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3. Plummer HS. The clinical and pathologic relationship of simple and


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5. Takashima S, Nomura N, Tanaka H, et al. Congenital hypothyroidism: assessment with ultrasound. AJNR 1995;16:11171123.
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28. Neinas FW, Gorman CA, Devine KD, et al. Lingual thyroid. Clinical
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30. Fujioka S, Takatsu Y, Tankawa H, Yamanaka K, Ando F.


Intracardiac ectopic thyroid mass. Chest 1996;110:13661368.
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32. Dominguez-Malagon H, Guerrero-Medrano J, Suster S. Ectopic
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33. Takashima S, Nomura N, Tanaka H, et al. Congenital hypothyroidism: assessment with ultrasound. AJNR 1995;16(5):1117
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34. Shibutani Y, Inoue D, Koshiyama H. Thyroid hemiagenesis with
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35. Pollice L, Caneso G. Struma cordis. Arch Pathol Lab Med
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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 flow Doppler
sonography in Graves disease: thyroid inferno. AJR 1988;150:
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38. Castagnone D, Rivolta R, Rescalli S, et al. Color Doppler sonography
in Graves disease: 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
1994;19(3):177180.
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:
513518.
43. Alos N, Huot C, Lambert R, et al. Thyroid scintigraphy in children
and adolescents with Hashimotos disease. J Pediatr 1995;127(6):
951953.
44. Doniach D, Bottazzo GF, Russell RCG. Goitrous autoimmune
thyroiditis (Hashimotos disease). Clin Endocrinol Metab 1979;8:
6380.
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 lymphoproliferative 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
1980;140:6571.
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:
423431.
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:
836843.
54. Hatabu H, Kasagi K, Yamamoto K, et al. Acute suppurative
thyroiditis associated with pyriform sinus fistula: sonographic
findings. 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
1994;8(2):159162.
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
1993;17:324325.

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58. Belfiore 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):
523543.
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):
757762.
64. Dworkin HJ, Meier DA, Kaplan M. Advances in the management of patients with thyroid disease. Semin Nucl Med 1995;25:
205220.
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 Scientific
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:
699710.
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 autonomously functioning thyroid nodules. Clin Endocrinol Metab
1980;50:10891093.
72. Ross DS. Evaluation of the thyroid nodule. J Nucl Med
1991;32:21812192.
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:
871876.
76. Papini E, Panunzi C, Pacella CM, et al. Percutaneous ultrasoundguided ethanol injection: a new treatment of toxic autonomously functioning thyroid nodules. J Clin Endocrinol Metab
1993;76:411416.
77. Livraghi T, Paracchi A, Ferrari C, et al. Treatment of autonomous
thyroid nodules with percutaneous ethanol injection: 4-year experience. Radiology 1994;190:529533.
78. Ozdemir H, Ilgit ET, Yucel C, et al. Treatment of autonomous
thyroid nodules: safety and efficacy 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
1988;72:11771211.
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
1977;1:123130.
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:
809817.
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:
805828.
89. Chen KTK, Rosai J. Follicular variant of thyroid papillary carcinoma:
a clinicopathologic study of six cases. Am J Surg Pathol
1977;1:123130.
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 findings.
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
1981;194:677680.
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
1971;285:11151120.
99. Steiner AL, Goodman AD, Powers SR. Study of a kindred with
pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism, 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
1984;53:278285.
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
1993;27:4855.
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):
11961198.
109. Haugen BR, Nawaz S, Cohn A, et al. Secondary malignancy of the
thyroid gland: a case report and review of the literature. Thyroid
1994;4(3):297300.
110. Czech JM, Lichtor TR, Carney JA, van Heerden JA. Neoplasms
metastatic to the thyroid gland. Surg Gynecol Obstet 1982;155:
503505.

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SECTION TWO

THE PARATHYROID GLANDS


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 hyperparathyroidism. A second focus is the detection of an unrecognized 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 parathyroid 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.

ANATOMY OF THE PARATHYROID


GLANDS
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 hyperthyroidism. In addition, in patients having neck surgery for
other reasons such as thyroid disease, the parathyroid
gland(s) may accidentally be injured or removed.

ENDOCRINOLOGY OF THE PARATHYROID


GLANDS
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 fibrous 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 fluids.
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)D3 (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 hyperparathyroidism. In primary hyperparathyroidism, hypercalcemia is
the result of excessive secretion of PTH from one or more of
the parathyroid glands.

CLINICAL MANIFESTATIONS OF
PARATHYROID DISEASE
Hyperparathyroidism
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 hyperparathyroidism 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).

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Thyroid and Parathyroid Glands: Anatomy and Pathology

2161

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 film 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 identified prior to surgery.3, 1214 Importantly, preoperative 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 illness.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.

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NECK

There are also secondary and tertiary forms of hyperparathyroidism. Secondary hyperparathyroidism occurs in patients 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 hyperparathyroidism due to the autonomous secretion of PTH from
chronically overstimulated parathyroid glands.

Hypoparathyroidism
Hypoparathyroidism is mainly a functional clinical disorder characterized by hypocalcemia and hyperphosphatemia secondary to a deficiency 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,
infiltrative (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, brachydactyly), but lack the unresponsiveness to PTH (normal calcium
and phosphate levels). These patients are said to have
pseudopseudohypoparathyroidism.

IMAGING OF PATHOLOGY OF THE


PARATHYROID GLANDS
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 surgeons, 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 preoperative localization.1820 In addition, some investigators
argue that the cost of imaging outweighs its benefit.18, 21
However, more recently, many surgeons have reported that
imaging has resulted in reduced operative time, reduced
morbidity, and lower costs.14, 22 Specifically, 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 identified 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 detected14; (2) the identification of ectopic adenomas27;
(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. Specifically, 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-filled structures such as the trachea or
esophagus.
Ultrasonography identifies 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 specificity 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 parathyroid 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

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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 specificity 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

FIGURE 40-42 Parathyroid adenoma in the right perithyroidal region.


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

mediastinum. This method offers superior soft-tissue discrimination and is more sensitive than CT for identifying
parathyroid adenomas. MR imaging should be performed on
a high field 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 misinterpretation 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 (flow 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
thallium-201 (Tl-201)/Tc-99m pertechnetate subtraction
scanning, Tc-99m sestamibi subtraction imaging with I-123
(Fig. 40-45) or Tc-99m pertechnetate, or Tc-99m sestamibi

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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 fatsuppressed 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.

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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 radionuclides that are concentrated in the thyroid gland (technetium and iodine) to be subtracted from those that accumulate 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 higherenergy 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 pertechnetate images are coregistered, computer-based subtraction
techniques can remove the thyroid component, permitting
identification 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
field of view to assess for the possibility of ectopic
adenomas. After thyroid subtraction, a perithyroidal parathyroid adenoma appears as a focus of increased thallium
uptake (Fig. 40-45). The major limitation of this examina-

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tion is motion artifact that may degrade the images, making


superimposition of the images and subtraction unreliable
and interpretation difficult.
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 examinations may result secondary to inflammatory conditions,
lymphoma, and thyroid nodules. Lesion size is an important
factor in determining the sensitivity of subtraction scintigraphy. Specifically, 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 influences 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, lipidsoluble 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 flow 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 microscopy has shown increased mitochondrial density in oxyphilic cells.49 Uptake is also dependent on gland size as well
as on their functional state.48, 49 The intracellular distribution 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). Dualphase 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 112 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 difficult 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 identified as foci of increased
radiotracer uptake. SPECT can be combined with Tc-99m
sestamibi scintigraphy for more accurate adenoma localization. When SPECT is combined with sestamibi scintigraphy,
early (10 to 30 minutes) and delayed (2 to 4 hours) images
after 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
Tl-201/Tc-99m pertechnetate subtraction scintigraphy, with

the accuracy of sestamibi ranging from 80% to 100% and


with a consistently high specificity.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 specificity 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 undergoing repeat surgery.62 In a recent study that looked at the
utility of scintigraphy combined with cross-sectional imaging (CT, ultrasound, MR imaging), the combination of
scintigraphy and ultrasound had grater sensitivity, specificity, 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 summary, 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 attributed 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 scintigraphy 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
during the initial surgery.4, 20, 23 Parathyroid adenomas may
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
A consensus in the literature is that imaging prior to

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2167

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 preoperative imaging is performed, the success rate of surgery is
approximately 80% to 90% compared to 65% when imaging
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
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 difficult. As with
cross-sectional imaging at initial surgery, lymphadenopathy may be mistaken for an adenoma. Because the
incidence of false-positive examinations caused by lymphadenopathy 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 parathyroid 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

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 inflammation.

Parathyroid Hyperplasia
Chief-cell parathyroid hyperplasia accounts for hyperparathyroidism in up to 15% of patients and may be
associated with familial hyperparathyroidism or MEN
syndromes.78, 79 MEN is a spectrum of hereditary (autosomal dominant) conditions characterized by two or more
hyperfunctioning endocrine tumors. MEN type I is associated 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 hyperparathyroidism 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, clearcell hyperplasia may occur. Clear cells are chief cells with
an abundant amount of cytoplasmic glycogen.1 Histologically, there are numerous chief cells, occasional oxyphil
cells, and sparse adipose tissue. Usually all of the
parathyroid glands are enlarged, although usually not to
significant degrees.26, 84 Infrequently, one gland is disproportionately enlarged, and as a result may be mistaken
intraoperatively for an adenoma.
Treatment of primary parathyroid hyperplasia is removal of most if not all parathyroid tissue, with or
without autotransplantation to the forearm.30, 78 Parathyroid
hyperplasia is difficult to evaluate with any imaging

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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 hyperparathyroidism. The reported sensitivity for the detection
of parathyroid hyperplasia is low, ranging from approximately 30% to 70% with cross-sectional imaging techniques.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

FIGURE 40-47 Parathyroid carcinoma invading the airway. Unenhanced axial T1-weighted MR image shows a poorly defined 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
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 dominant gland but fail to identify the other hyperplastic

Parathyroid carcinoma is an unusual cause of hyperparathyroidism, 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
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
are noted to have tumor cells with mitotic figures admixed
with fibrous 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

FIGURE 40-48

Parathyroid cyst. A, Unenhanced axial T1-weighted


MR image shows a unilocular 3 cm cyst (arrows) in the right
paratracheal region, just below the inferior pole of the right thyroid lobe.
B, Corresponding axial T2-weighted MR image shows the hyperintense
cyst. Note the small hemorrhage level (arrows) in the dependent portion
of the cyst, which was confirmed at pathology. C, Axial contrastenhanced CT scan on another patient shows a partially cystic mass
(arrows) in the posterior left thyroid region. Within the anterior aspect of
the cyst is an enhancing nodule (arrowhead ). This was a functioning
parathyroid cyst within a parathyroid adenoma.

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patients and distant metastases (liver, lung, bone) in


approximately 25% of patients. Parathyroid carcinomas may
also invade adjacent tissues including surrounding fat, the
cervical musculature, the aerodigestive tract, nerves, or the
thyroid gland (Fig. 40-47).87, 88 Only invasion of adjacent
tissues, or lymph node or distant metastases, may distinguish
a parathyroid carcinoma from an adenoma in the setting of
hyperparathyroidism. Some parathyroid carcinomas may
take up Tc-99m sestamibi.89

Parathyroid Cyst
Parathyroid cysts, like adenomas, most commonly arise
in the inferior parathyroid glands (65% of cases), and 95%
of these cysts occur below the level of the inferior thyroid
border. They are rare in children, more common in women,
and typically present in the fourth to fifth decades of life.1, 90
They are usually large (1 to 4 cm).
Parathyroid cysts represent only 0.6% of all thyroid and
parathyroid lesions. Nonfunctioning cysts account for the
majority of cases and present at a mean age of 43.3 years.
Functioning cysts account for 11.5% to 30% of the cases, are
more common in men, and occur at a mean age of 51.9
years.
The origin of parathyroid cysts is unclear. They may arise
from pharyngeal pouch remnants or they may be acquired.
Proposed acquired etiologies include degeneration of parathyroid adenomas into cysts and enlargement or coalescence
of parathyroid microcysts.
Similar to their appearance at gross pathology, on
imaging they are usually large and unilocular and have
variable MR imaging and CT characteristics, depending on
their protein content (Fig. 40-48).90 They may be difficult to
distinguish from cystic or necrotic lymph nodes or from
cysts derived from other sources such as solitary thyroid
cysts and cervical thymic cysts.

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