Cap 77 Thyroid Gland

Ovid: Greenfield's Surgery: SCIENTIFIC PRINCIPLES AND PRACTICE
Copyright ©2006 Lippincott Williams & Wilkins

Mulholland, Michael W., Lillemoe, Keith D., Doherty, Gerard M., Maier, Ronald V., Upchurch,
Gilbert R.
Greenfield's Surgery: SCIENTIFIC PRINCIPLES AND PRACTICE, 4th Edition
Chapter 77
Thyroid Gland
Paul G. Gauger
Largely as a function of disease prevalence, surgical treatment of thyroid disorders is relatively

common. Excellent patient outcomes require a through understanding of embryology, anatomy,
physiology, and relevant pharmacology. Delicate and deliberate surgical technique and careful
attention to detail are required to prevent common complications of thyroid resections.
EMBRYOLOGY AND SURGICAL IMPLICATIONS
Developmental Embryology
As the first endocrine gland to develop, the thyroid is mostly of endodermal origin and originates
from the ventral embryologic digestive tract. A midline diverticulum arises in the area of the
foramen cecum at the base of the tongue at approximately 4 weeks of gestational age. The
rudimentary thyroid tissue descends as the median thyroid component (or anlage), which
ultimately becomes the isthmus (overlying the upper tracheal rings) and most of each lateral
lobe. It reaches its final position by gestational week 7 and undergoes histologic differentiation
into recognizable follicles between week 8 and 11.1 The embryology of the median component is
fairly well understood. Its initial appearance in evolution seems to be the endostyle, a groove in
the pharyngeal floor of the ammocaete larva of sea urchins, which takes up iodine in a fashion
similar to the human thyroid.2 The portion associated with the foramen cecum ruptures and
resorbs during week 6 of gestational age leaving behind a regressive fibrous tract, which becomes
the thyroglossal duct tract (including the portion associated with the central hyoid bone). The
distal end associated with the isthmus persists as a pyramidal thyroid lobe in about 30% to 50%
of individuals. The lateral thyroid component
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(also known as the ultimobranchial body in some vertebrates) develops on each side from the
caudal pharyngeal endoderm (with the contribution of the fourth and fifth branchial pouches).1,3,4
They arise later in development than the median component. These fuse with the posterior
portion of the median component on each side and, with this process, C cells (from neural crest
origin) migrate into the superolateral portion of the lobes and eventually secrete calcitonin. The
median and lateral thyroid components unite by a complicated mechanism in which the lateral
components move anteriorly and cranially and the median component migrates posteriorly and
cranially.5 Only after this point does the unified thyroid begin to differentiate into thyroid follicles.
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Basic glandular function begins on a cellular level by the third month of gestation when iodine
trapping occurs and thyroid hormones are first secreted. The control of descent and fusion of
thyroid tissue appears to be influenced by multiple transcription factors such as TTF-1, TTF-2, and
Pax-8.6 The lateral components become increasingly removed from the pharynx leaving a
tapering connection on each side, which eventually detaches and is replaced by mesenchyme.7
The residual posterolateral projection from the lateral thyroid component toward the pharynx,
when present, is known as the tubercle of Zuckerkandl [attributed to Viennese anatomist Emil
Zuckerkandl (1849–1910)]. Because of its branchial pouch origin, the lateral thyroid component is
closely associated with the superior parathyroid anlage (from fourth pouch).
Congenital Abnormalities
An uncommon developmental malformation is the lingual thyroid gland, which is most often
associated with agenesis of thyroid tissue in the standard position. It represents a failure of the
median thyroid component to descend from the region of the foramen cecum. The size of a lingual
thyroid can often be decreased by using exogenous thyroid hormone to suppress thyroid-
stimulating hormone (TSH) or, in some cases, by 131I ablation. Surgical excision may be required
if airway obstruction, obstructive dysphagia, or hemorrhage occurs. Ectopic thyroid tissue can be
found in other areas of the central cervical compartment and the mediastinum. These can be
sequestered nodules associated with multinodular goiters or they may be embryologic rests of
thyroid tissue. Although the concept of lateral aberrant thyroid tissue was originally used to
describe the findings of follicular tissue in the carotid sheath or the lateral compartments of the
neck, it is now generally agreed that this cannot occur as an embryologic abnormality. If thyroid
tissue is found in these areas, it most likely represents a regional nodal metastasis of an occult
thyroid cancer—typically a follicular variant of papillary thyroid cancer, which may have follicular
architecture that is similar to normal thyroid tissue.
Thyroglossal duct cysts occur in the midline of the neck along the path of descent of the median
thyroid component. They may occur from the base of the tongue to the low central neck, although
most are located just inferior to the hyoid bone. Although they are often discovered during infancy
and childhood, it is not uncommon for them not to be evident until adulthood—discovered either
because of complaints of mass or evidence of infection. Because the posterior wall of the cyst
abuts the flexible anterior pharynx, enlargement of the cyst can cause dysphagia and choking.
When examining the patient, elevation of the mass with protrusion of the tongue is very
suggestive of a thyroglossal duct cyst. Resection of a thyroglossal duct cyst involves excision of
the entire thyroglossal duct on either side of the cyst. The tract is often intimately associated with
the central portion of the hyoid bone and, for that reason, excision of this segment of bone is
critical to prevent recurrence (known as the Sistrunk procedure). The epithelial lining usually
contains some thyroid cells and, thus, thyroid carcinomas (usually of papillary type) can arise
primarily in thyroglossal duct cysts. Excision of the cyst and the thyroglossal duct may be
sufficient for small, limited carcinomas, but if regional nodal metastases are present or if the
tumor is of sufficient size, total thyroidectomy should be included to facilitate subsequent 131I
scanning and therapy.
ANATOMY AND SURGICAL IMPLICATIONS

A normal thyroid gland (especially in patients from iodine-sufficient regions) weighs between 15

and 20 g. The normal color is a dark shade of burgundy. Conditions such as chronic thyroiditis
may change the color to a pink–gray, whereas nodular disease often adds a brown or tan
discoloration. Fluid-filled cysts typically have a blue appearance. If the patient has previously
been prescribed minocycline (often for acne), the thyroid adopts permanent black coloration.8 The
upper portion of the isthmus typically crosses at or below the level of the cricoid cartilage and
overlies the second and third tracheal rings. The isthmus itself is approximately 1 to 2 cm in
transverse and vertical dimensions and the lower margin of the lobe is normally near the fourth or
fifth tracheal ring. The lateral lobes lie adjacent to the thyroid cartilage and cricothyroideus
muscles as well as the lateral trachea and a portion of the lateral esophagus on each side. The
two lateral lobes are roughly conical, approximately 5 cm long and 2 to 3 cm in transverse and
anteroposterior dimensions. The pyramidal lobe may attach to the center of the isthmus but often
is found on a slightly lateral aspect (often the left). It may be situated in front of the potential
space that exists between the superior thyroid pole and the cricothyroideus muscle. In that case,
it will need to be mobilized and divided to facilitate development of the cricothyroid space and,
thus, safe mobilization of the superior pole during thyroidectomy. Occasionally the pyramidal lobe
is accompanied by a small group of skeletal muscle fibers, which has been termed the “levator
glandulae superioris.”9
Muscular, Fascial, and Airway Relationships

The thyroid lies in the central compartment of the neck bordered by the contents of the carotid
sheath on each side. The anterolateral surface is covered by the sternothyroid muscles, which do
not completely meet in the midline above the level of the isthmus. The oblique upper muscular
insertion into the thyroid cartilage is the limiting factor preventing the lobes from encroaching
further toward the midline and onto the underlying thyrohyoid muscle. Superficial to that are the
paired sternohyoid muscles that meet in the midline raphe marking the most common plane of
dissection used to expose the thyroid gland. These muscles are innervated by the ansa cervicalis
(ansa hypoglossi) formed from the descendens hypoglossi (containing fibers of C1), and the
descendens cervicalis (containing fibers of C2 and C3) and contributory branches can be seen on
the lateral aspects. The thyroid is invested in a thin layer of connective tissue that is an expansion
of the pretracheal fascia (often called the “thyroid sheath”). The plane defined by this layer is
usually easy to develop as the thyroid is mobilized away from surrounding structures. Especially
near the superior portion of the thyroid, the sheath defines a coronal plane that, when opened,
exposes the potential space between the pharynx and esophagus and the cervical vertebral
bodies. The superior parathyroid gland may be found between the sheath and the
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thyroid capsule, within the sheath, or posterior to the sheath. The sheath is not to be confused
with the thyroid capsule, which is more integral to the gland itself. The sheath is condensed as the
anterior suspensory ligament above the isthmus. The sheath also suspends the inner surface of
the thyroid gland to the trachea rings and cricoid cartilage. It is condensed posteromedially into
the ligament of Berry on each side. The ligament of Berry is often a very firm attachment to the
trachea near the cricothyroid interval, which means that it is often intimately associated with the
recurrent laryngeal nerve (RLN). It is in the course of dividing these attachments that the RLN is
most vulnerable to iatrogenic injury.

Vascular Relationships
The thyroid gland has a very high blood flow index per tissue mass and receives its arterial supply
from a paired system of superior thyroid arteries (originating from the external carotid arteries)
and the inferior thyroid arteries (originating from the thyrocervical trunks). The superior artery
courses along the inferior pharyngeal constrictor muscle group and branches near the tip of the
superior pole of the thyroid, usually into at least the anterior and posterior branch. The inferior
thyroid artery (ITA) courses upward behind the carotid artery and then crosses medially and often
in a slightly downward course to serve the thyroid lobe. The ITA has multiple branches that
course in a plane between the sheath and the capsule of the gland. The relationship of the ITA to
the RLN is an important landmark. There is always an intersection (except in the case of a direct
laryngeal nerve), but the specific relationship may be variable. Occasionally, the lowest thyroid
artery (arteria thyroidea ima) arises from the aorta or innominate artery and directly serves the
inferior portion of the thyroid gland. Venous drainage is by a widely anastomotic system that
condenses into three main trunks: The superior thyroid veins course adjacent to the superior
thyroid arteries but empty into the internal jugular vein at the level of the carotid bifurcation. The
inferior thyroid veins form nearly all of the vascular connections found at the inferior poles of the
thyroid lobes. The number and configuration of these veins can be quite variable, but in general
they descend along the course of the thyrothymic tract to drain into the ipsilateral innominate or
brachiocephalic veins. Middle thyroid veins are present in approximately half of patients. The
number and course are highly variable as they drain laterally to the internal jugular vein. These
veins are divided in the course of mobilizing the thyroid lobe. If a vessel is seen passing from the
region of the carotid sheath to the thyroid and it is not immediately apparent whether it is ITA or
middle thyroid vein, its identity can be confirmed by tracing it laterally. If it passes anterior to the
carotid artery, it is a middle thyroid vein while if it passes deep to the carotid, it is the ITA.
Neurologic Relationships
Two nerves have critical importance during thyroidectomy: the RLN (also known as the inferior
laryngeal nerve) and the external branch of the superior laryngeal nerve. The right recurrent
laryngeal nerve arises from the vagus at the level of the subclavian artery and passes (recurs)
around the posterior aspect of the artery before ascending into the central compartment. The
nerve takes an oblique course in the central neck and may be 1 to 2 cm lateral to the trachea low
in the central neck before traveling toward its entry into the larynx. The left RLN arises from the
vagus nerve as it crosses the aortic arch. It passes inferior and medial to the arch and ascends to
the larynx in the tracheoesophageal groove along a course that is typically linear and more
vertical. The RLN often lays immediately posterolateral to the ligament of Berry, but it is not
infrequent that it can be embedded in the fibrous connections of the ligament itself, especially the
anterior branch if the nerve bifurcates outside the larynx. Although it may be tempting to describe
this as the nerve “running through thyroid tissue,” that cannot actually occur. Pelizzo has recently
described the tubercle of Zuckerkandl as a constant anatomic landmark to facilitate identification
of the recurrent laryngeal nerve during thyroid resection.10 In the standard anatomic relationship,
the tubercle of Zuckerkandl is lateral to the RLN (Fig. 77.1). An uncommon, but high-risk
anatomic arrangement occurs when the RLN is lateral to the tubercle of Zuckerkandl (Fig. 77.2).
As the thyroid lobe is retracted anteromedially during thyroidectomy, the RLN may seem to be
anterolateral to the tubercle. If the surgeon is unaware of this possibility (which often exists when
the tubercle has undergone nodular enlargement), the nerve is subject to iatrogenic injury. The

nerve usually bifurcates extralaryngeally but often at a point less than 0.5 cm from the cricoid
cartilage. Up to 58% of recurrent laryngeal nerves will bifurcate proximal to inferior border of the
cricoid cartilage.11 Extralaryngeal trifurcations exist in approximately 1% of RLNs.
FIGURE 77.1 The standard anatomic relationship whereby the recurrent laryngeal nerve (RLN)
passes medial to the tubercle of Zuckerkandl before its insertion into the cricothyroid interval.
It is critical to be aware of the occasional “direct” laryngeal nerve (also called the “nonrecurrent
laryngeal nerve”). This anomaly results from abnormal embryonic development of the aortic arch.
The anomaly is more common on the right (approximately 0.5% to 0.7%) than on the left
(approximately 0.04%).12 On the right, a direct nerve is the consequence of the formation of the
arteria lusoria vascular abnormality, in which the innominate artery is absent and the right
common carotid and right subclavian arteries originate directly from the arch. The subclavian
artery takes a retroesophageal course. A “false” nonrecurrent inferior laryngeal nerve has been
described as a communicating branch between the cervical sympathetic system and the RLN,
which can mimic a nerve that appears to
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emerge from the region of the vagus nerve as would be seen with a direct nerve.13 To have a
direct nerve on the left side, a number of other anomalies must exist. Specifically, the aortic arch
must be right sided (as occurs in situs inversus viscerum), the origin of the left subclavian artery
must be abnormally sited on the aortic arch, and the ligamentum arteriosum must be displaced to
the right.

FIGURE 77.2 The uncommon, but high-risk anatomic variation where the recurrent laryngeal
nerve (RLN) courses lateral to the tubercle of Zuckerkandl, which is often enlarged. The nerve is
encountered much earlier in the dissection required for thyroidectomy and is at risk of being
misidentified as a vascular structure.
FIGURE 77.3 Cernea classification of the anatomic relationships between the external branch of
the superior laryngeal nerve (EBSLN), the superior pole of the thyroid, and the superior thyroid
artery. With type 1 anatomy, the nerve crosses the superior thyroid vessels 1 cm or more above
the superior thyroid pole. With type 2 anatomy, the nerve crosses the vessels less than 1 cm
above (type 2a) or even below (type 2b) the superior pole. Type 2 variants are the most
vulnerable to iatrogenic injury.
The superior laryngeal nerve arises from the vagus at the nodose ganglion near the base of the

skull and descends with along the course of the internal carotid artery. At the level of the hyoid
bone, it divides into the internal branch (which enters the larynx at the thyrohyoid membrane to
provide sensory innervation to the superior larynx) and the external branch (which provides
motor innervation to the cricothyroideus muscle). It has a variable course in relation to the
inferior pharyngeal constrictor muscle and the branches of the superior thyroid artery. It is this
fact that makes the external branch of the superior laryngeal nerve (EBSLN) vulnerable to
iatrogenic injury. One classification of the anatomic variations is depicted in Figure 77.3.
Lymphatic Relationships
The thyroid gland has intracapsular lymph channels, which provide some communication from
lobe to lobe across the isthmus. A rich plexus of lymphatics surrounds the region of the thyroid
and, consequently, lymph flows in multiple directions from the gland. These factors are important
to understand for treatment of thyroid malignancies. Within the anterior suspensory ligament is a
small group of midline lymph nodes known as the Delphian nodes. Along with the pretracheal and
paratracheal nodes and those along the recurrent laryngeal nerves, these central compartment
lymph nodes are classified as level VI. The upper jugular (level II), midjugular (level III), and
lower jugular (level IV) lymph nodes divide the central compartment from the lateral
compartment of the neck, whereas the posterior triangle lymph nodes are level V (Fig. 77.4). The
superior mediastinal lymph nodes (level VII) may also be involved by thyroid cancer. Thyroid
cancers with regional lymph node metastases tend to involve level VI lymph node metastases
before sequentially involving level III and level IV and ultimately level V. Level II and level VII
involvement is less common but does occur. Level I involvement is rare. Rare documented cases
of “skip” metastases directly to the lateral compartment with no level VI involvement have been
reported.14

FIGURE 77.4 Classification scheme for regional lymph node basins in the neck.
Parathyroid Relationships
Parathyroid glands in normal or typical location are encountered during thyroidectomy by virtue of
their association with the thyroid gland. Parathyroid glands that develop in ectopic locations will
typically not be encountered during thyroidectomy and are not discussed here. The superior
parathyroid gland is typically located in a relatively constant area largely because of the
embryologic association between the lateral thyroid component and the superior parathyroid
anlage (both associated with branchial pouch IV). The tubercle of Zuckerkandl was noted by
Gilmour to be anatomically associated with the position of the ipsilateral superior parathyroid
gland as well as the recurrent laryngeal nerve.15 In relation to the point at which the RLN
intersects the inferior thyroid artery, a 2-cm circumscribed area on the cranial aspect will often
contain the superior parathyroid gland. It may also be found tucked posterior to the inferior
thyroid artery or even posteromedial to the superior thyroid pole. Superior parathyroid glands are
nearly never found within the thyroid capsule. If a superior parathyroid gland is found on one
side, the chance of the contralateral gland being in a similar position is approximately 80%.
The location of the normal inferior parathyroid gland may be more variable. It may be found on
the anterior aspect of the inferior thyroid pole (especially with Hashimoto's disease or large
multinodular goiter) but is often on the inferolateral aspect. It may also be in the triangular region
caudal to the inferior thyroid artery and anterior to the RLN. If it is not in these locations, it is

often embedded in fat and thymic tissue within

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the thyrothymic tract. It may also be located under the thyroid capsule in an intrathyroidal
position. The symmetry of inferior parathyroid glands from side to side is approximately 70%.
THYROID PHYSIOLOGY
Production of Thyroid Hormones

The thyroid gland produces thyroxine (T4), triiodothyronine (T3), and calcitonin under complicated
regulatory mechanisms. The regulation of thyroid hormone secretion is well understood, but it can
be affected by many physiologic and pharmacologic factors. Approximately 100 to 150 µg of
dietary iodide is required for normal thyroid hormone synthesis to occur. Daily intake from iodine-
containing foods is usually far in excess of that in most developed regions of the world. The
kidneys excrete the excess iodide not utilized by the thyroid. The availability of thyroid hormones
to all tissues is conceptually divided into the process of hormone production within the thyroid
gland (specifically within the follicular cells) and the delivery and metabolism of the hormones in
peripheral tissues. The integration of these systems to maintain a euthyroid state is ultimately
orchestrated by the anterior pituitary gland through its secretion of thyrotropin (TSH). The active
uptake of iodide in the thyroid occurs on the basolateral aspect of the follicular cells and is
performed by a Na+/K+ adenosine triphosphatase (ATPase)- mediated pump. This symporter
system is influenced by both TSH and the circulating concentration of iodide. TSH secretion is
increased in response to decreased circulating T3 levels. TSH acts within the thyroid gland to
regulate the synthesis of thyroglobulin (Tg), the active uptake of iodide, its incorporation with
tyrosine (an oxidative reaction catalyzed by thyroid peroxidase [TPO]), and the subsequent
production of T4 and T3 (and their storage bound to Tg in the colloid component of the gland),
and ultimately the release of both T4 and T3 into the circulation. Hormone release is again an
active process of micropinocytosis that involves resorption of the bound Tg into the follicular cell
where enzymatic degradation releases the T4 and T3, which is released from the basal portion of
the cell into the circulation. T4 is produced in preference to T3 in the thyroid gland by a ratio of
approximately 13:1. This ratio can be altered to increase the relative fraction of T3 in situations of
iodine deficiency or by TSH hyperstimulation. T4 has a relatively weak biologic action so a
peripheral conversion to the more active T3 hormone is required. Most of this takes place in the
plasma and liver by type 1 deiodinase enzymes. All of the T4 in the circulation is derived from the
thyroid, whereas far less than 20% of T3 in the circulation is from the thyroid, the majority being
produced enzymatically from monodeiodination of T4 in nonthyroidal tissues. In circulation, most
thyroid hormone (>99% of both T4 and T3) is bound to proteins such as thyroxine-binding
globulin (TBG), albumin, and thyroxine-binding prealbumin. Protein-bound thyroid hormones are
considered biologically inert because they do not enter cells until they are released from proteins
to circulate in the very small free fraction. The half-life of T4 is approximately 7 days, whereas the
half-life of T3 is much shorter—on the order of 8 to 12 hours.

Action of Thyroid Hormones

Thyroid hormones have many broad effects on various body tissues. The peripheral conversion
from T4 to T3 increases the binding affinity of thyroid hormone for the nuclear thyroid receptor
protein at least tenfold. Specific T3 receptors are present on the cell membrane to assist in
transport into the cell. Triiodothyronine acts within the nucleus of peripheral tissues via the
thyroid hormone receptor to activate T3-regulated gene transcription. Four T3 nuclear receptor
subtypes have been identified with slightly different downstream actions. Ultimately, the
physiologic actions of thyroid hormone relate to growth, differentiation, calorigenesis, and TSH
suppression.
Calcitonin is physiologically effective in many other species, but in humans it is apparently less
important. Although exogenous calcitonin may have a therapeutic effect, endogenous calcitonin
secretion rarely results in an impact on serum calcium levels.
RELEVANT LABORATORY TESTS

An understanding of the normal relationship between free T4 (FT4) levels and TSH levels is critical
for appropriate interpretation of thyroid function tests. Thyroid dysfunction can be determined
directly, by measuring FT4 levels or, indirectly, by measuring TSH. If TSH is to be used as the
primary indicator of thyroid dysfunction, an intact hypothalamic—pituitary axis is required.
Normally, a log/linear inverse relationship between TSH and FT4 is defined by the negative
feedback inhibition of TSH secretion by circulating thyroxine levels. Therefore, high TSH and low
FT4 levels are indicative of hypothyroidism and, conversely, low TSH and high FT4 levels are
characteristic of hyperthyroidism. It is likely that each individual has a genetically determined FT4
set point. Early subtle deviation from that set point (via in situ conversion to FT3 in the pituitary)
will cause amplified changes in the TSH value, thus making TSH a very sensitive early indicator of
incipient thyroid dysfunction.
Calcitonin
Calcitonin is a 32–amino acid polypeptide, which is currently measured by immunometric
techniques using monoclonal antibodies (one each to C-terminal and N-terminal region).
Calcitonin levels are generally less than 10 pg/mL for normal healthy people and for nearly all
patients with thyroid disease, other than medullary thyroid carcinoma (MTC). Therefore, calcitonin
serves as a very specific tumor marker for MTC. Basal calcitonin levels are useful for diagnosis
and observation of these patients.
Free Thyroxine (FT4) and Free Triiodothyronine (FT3)

Technically, it is easier to measure the total (free + protein-bound) hormone levels (measured at
nanomolar levels) as compared to the very small free hormone concentrations (measured at
picomolar ranges). Because T4 is more tightly protein bound than T3, it is less bioavailable and,

consequently, very difficult to measure directly. Measurement of free hormone levels in clinical
laboratories involves index methods (requiring two separate tests), single-test ligand assays, or
physical separation methods to isolate the free fraction before direct measurement. Ligand assays
performed on automated immunoassay analyzers are fairly common in clinical use and are
standardized against known hormone concentrations. Because this method does not rely on
physical separation of the free and protein-bound hormone fractions, it is more accurately
considered a free hormone estimate. The only reason to
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measure FT4 or FT3 in preference to total thyroxine (T4) or total triiodothyronine (TT3) is to
improve the ability to detect thyroid dysfunction in the presence of thyroid hormone-binding
abnormalities, which are relatively common. For example, some common drugs such as
phenytoin, carbamazepine, furosemide, and aspirin may compete with thyroid hormone for
binding to serum proteins.
Thyroglobulin
Serum thyroglobulin is reflective of three factors: the mass of thyroid tissue present, the presence
of injury or inflammation of the gland, which allows leakage of Tg, and the degree of stimulation
of the TSH receptor. The primary clinical use of Tg measurement is as a tumor marker, which
serves as an index of the amount of differentiated thyroid cancer present (assuming that total
thyroidectomy has been performed). Tg is measured in the serum by radioimmunoassay methods
or increasingly, by immunometric assays. The latter is more susceptible to competitive
interference by thyroglobulin autoantibodies (TgAb), which cause an artifactual decrease in the
measured levels. The particular assay utilized must be very sensitive to detect Tg levels at the
lower end of the reference range (1 to 3 µg/L) to be useful in monitoring for recurrence of
differentiated thyroid carcinoma (DTC). It is critical to understand that the TSH level is a major
influence on the level of Tg and, consequently, interpretation of any level requires an
understanding of whether the patient was hypothyroid or not at the time of measurement.
Thyroid Autoantibodies
Thyroid peroxidase autoantibodies (TPOAb) were initially described as antimicrosomal antibodies
because they were found to react with crude preparations of thyroid cell membranes. Currently,
competitive and noncompetitive immunoassay methods are used to quantify TPOAb, but there is
wide variability in the sensitivity and specificity of the available quantitative assays. It is the most
sensitive test for detecting autoimmune thyroid disease and TPOAb is often the first abnormality
to appear in Hashimoto's disease because hypothyroidism develops (present in >95% of such
patients). A significant fraction (up to 12%) of people with no apparent thyroid disorder, however,
may also have positive TPOAb titers.
During thyroid hormone synthesis and release, thyroglobulin is polymerized and degraded,
creating a complex structure that consequently leads to the equally complex immunologic
structure of thyroglobulin autoantibodies (TgAb). TgAb are measured by competitive and
noncompetitive immunoassays. They may be present in approximately 3% to 10% of the general
population and are even more common (20%) in patients with differentiated thyroid carcinoma.

In fact, sensitive quantitative TgAb determination is a critical accompaniment to serum Tg

measurement, which is common during management of thyroid carcinoma. TgAb measurements,
however, are not as useful as TPOAb in evaluation of autoimmune thyroid disease.
Thyroid-stimulating hormone receptor autoantibodies (TRAb) are heterogeneous and may mimic
the action of TSH to cause hyperthyroidism as seen in Graves' disease or, conversely, may block
the action of TSH and cause hypothyroidism as seen in neonates of a mother with thyroid
autoantibodies. The specific different types include thyroid-stimulating antibodies (TSAb), TSH
receptor blocking antibodies (TBAb), Thyroid growth simulating antibodies (TGI), thyroid binding
inhibiting immunoglobulins (TBII).
Thyroid-Stimulating Hormone (Thyrotropin)

Now that the sensitivity and specificity of TSH assays are very high, the indirect approach of
measuring TSH levels is the most sensitive method for detecting thyroid dysfunction. The inverse
relationship between TSH and FT4 also dictates that small alterations in FT4 will lead to a larger
response in TSH, thus adding further support to this strategy. For many years, assays have easily
detected the elevated TSH levels, which indicated hypothyroidism, but until the assays became
ultrasensitive (thus able to detect very low TSH levels), the ability to diagnose hyperthyroidism by
a TSH level alone was very limited. Modern methods are generally based on nonisotopic
immunometric assays and are able to achieve a sensitivity of 0.02 mIU/L or less. At present, the
upper limit of the normal range is considered to be approximately 5 mIU/L, but this is likely to be
redefined at approximately 2.5 mIU/L in the future as it becomes more clear that many patients
in the interval between these values progress to develop hypothyroidism, especially if thyroid
autoantibodies are present. It is this range of 0.5 to 2.0 mIU/L that is generally considered the
target range for TSH when patients are treated with levothyroxine (LT4) for hypothyroidism
because, consequently, most patients then have FT4 levels in the upper third of the normal
reference range.
Total Thyroxine (TT4) and Total Triiodothyronine (TT3)

Currently, TT4 and TT3 hormones are measured by competitive immunoassay methods (with
enzymes, fluorescence, or chemiluminescence used for signaling). Total hormone assays require
an inhibitor to block or displace the hormone from its binding proteins. This factor, along with
large sample dilution, allows binding of the hormone to the antibody reagent. Because of the
tenfold lower concentrations of T3 in the serum, the TT3 assay requires even greater sensitivity
and precision. Because of variability in the quantity and the binding capacity of serum proteins,
however, abnormal TT4 and TT3 measurements are more commonly caused by these factors
instead of true thyroid dysfunction. Older free hormone indices (FT4I or FT3I) are basically derived
from the mathematical relationship between the measured total hormone concentration and an
“uptake” test (also called thyroid hormone binding ratio tests).
RELEVANT PHARMACOLOGY

Thionamide
The common antithyroid drugs propothiouracil (PTU), methimazole (Tapazole), and carbimazole
(commonly used in the United Kingdom, but not in the United States) are examples of the
thionamide drug class. PTU prevents oxidation iodide to iodine and the incorporation of iodine and
tyrosine by inhibiting TPO. PTU also inhibits peripheral conversion of T4 to T3, whereas
methimazole does not. For this reason, PTU is the preferred thionamide during treatment of
thyroid storm. Because the half-life is only 2 to 3 hours, it requires multiple doses per day,
whereas methimazole can be given just once or twice daily. Both drugs have significant side effect
profiles. The most common is skin rash (3% with PTU, 7% with methimazole), whereas the most
serious is agranulocytosis (0.44% with PTU, 0.12% with methimazole).16 These drugs are
effective in pregnancy but the minimal necessary dose should be used because the placental
passage which will decrease thyroid hormone production in the fetus.
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Ionic Inhibitor
Iodine, usually supplied in a preparation such as Lugol's iodine (KI), can function as a short-term
antithyroid medication by inhibiting thyroglobulin proteolysis as well as blocking organification and
inhibition of thyroid hormone release. When used in preparation for an operation to ameliorate
hyperthyroidism, it can also decrease the vascularity of the gland as well, which can be beneficial.
Its effect only lasts 10 to 14 days, after which an escape phenomenon can occur.
T3 Production Inhibitors
Although PTU, glucocorticoids, and iopanoic acid (Telpaque) act to inhibit the peripheral
conversion of T4 to T3, this is the major role for β-adrenergic blocking agents such as propranolol
or metoprolol. Many hyperthyroid patients are prepared for operation using these drugs alone if
the severity of symptoms is moderate.
Inhibitors of Peripheral Thyroid Action

β-Blockers also serve to ameliorate the peripheral effects of hyperthyroidism, such as palpitations,
diaphoresis, nervousness, and tremor. These drugs will have an impact on symptoms within a
couple of days when administered orally or even within hours if administered intravenously.
Radioactive Iodine
Radioiodine is usually administered in the form of 131I. It is trapped by follicular cells,
incorporated into the iodine–tyrosine complex, and deposited into colloid. Once accumulated
within the cells, 131I undergoes beta decay, releasing high-energy electrons for a short distance
into the surrounding tissues. This cytotoxicity is focused (and essentially limited to tissues that
possess the ability to concentrate iodine) and generally thought to affect tissues only within a 2-
mm radius. Gamma rays are also released that allow for the use of the radioisotope for scanning
procedures (usually requiring only a low dose). In moderate doses, it can be used to treat

hyperthyroidism and, in higher doses, it is used to destroy differentiated thyroid carcinoma.
THYROID IMAGING TECHNIQUES

It is common for patients to present to the surgeon after having undergone multiple imaging
tests. In general, only ultrasonography is routinely useful in evaluation of the patient with a
thyroid nodule. In other specific circumstances, various other tests may be useful.
Nuclear Medicine Imaging

Radionuclide imaging provides functional imaging of the thyroid gland with limited anatomic
detail. Therefore, it is unique when compared with other thyroid imaging techniques in that the
image provided depends on the specific functional characteristics of the thyroid tissue.
Technetium Pertechnetate Tc Scintigraphy

99m
99mTcis the radionuclide most commonly available for thyroid imaging. The 99mTc pertechnetate
component is actively trapped by functional thyroid cells in a manner similar to iodine but is not
organified or stored in the thyroid. The isotope emits gamma (γ) radiation (the mechanism of
scintigraphic imaging) and very small amounts of other types of radiation. Because the thyroid
rapidly absorbs the injected 99mTc pertechnetate, imaging can occur early after administration
and an entire study may take only an hour. A normal result demonstrates equal distribution
bilaterally. Abnormal results include either concentration of the tracer in the region of a known
nodule indicating an area of hyperfunction or, conversely, an area of photopenia (the “cold
nodule”) indicating a region of hypofunction. Before the era of fine-needle aspiration (FNA)
biopsy, this finding elevated the concern for potential malignancy.
123 Iodine Scintigraphy

Because 123I is trapped and organified by the thyroid gland, it can better indicate the functional
characteristics of thyroid tissue. It is produced in a cyclotron and has a short half-life (about 13
hours). These factors are responsible for the substantial cost associated with this test. 123I emits
x-rays, some β particles and γ rays. After administration of an oral dose, the thyroid absorbs
sufficient isotope to allow imaging by 4 hours. Images are also obtained at 24 hours, and the total
fraction of dose retained by the thyroid can then be calculated as the 24-hour radioactive iodine
uptake (RAIU).
131 Iodine Scintigraphy

131I concentrates in the thyroid by the same mechanism as 123I, but it has a much longer half-life
(about 8 days) and emits much more β radiation along with β radiation at a range that is
suboptimal for clear image creation. Because of its long half-life and thorough clearance from
background tissues, however, it remains the isotope of choice for imaging of patients with
differentiated thyroid carcinoma. Ultimately, treatment or ablation of residual or metastatic
carcinoma (largely by the effect of the β irradiation) is accomplished with higher doses of the
isotope than required for imaging.

Positron Emission Tomography

18F fluorodeoxyglucose positron emission tomography (PET) scanning with 3-dimensional
tomographic reconstruction can be very helpful in imaging thyroid carcinomas. Because of the
expense and the inconsistent insurance coverage, usage is currently limited to unusual
circumstances such as recurrent thyroid malignancy which is otherwise occult (Fig. 77.5). The
sensitivity in thyroid carcinomas is approximately 60% to 70% and false-positive findings are very
rare.17 PET scanning is so frequently used in the evaluation of other solid malignancies that occult
thyroid carcinomas are occasionally discovered.18 All thyroid incidentalomas discovered by PET
scanning are not malignant, however. In one series, just over 25% of such tumors were thyroid
cancers and elevated standard uptake values (SUV) were often suggestive of this compared with
those tumors ultimately proved to be benign.19
99m Tc SestaMIBI Scintigraphy

Although 99mTc-SestaMIBI scintigraphy is commonly used in localization of parathyroid tumors, it
has incidentally been noted to concentrate in follicular tumors, most notably those with Hürthle
cell cytology. For this reason, it may have a role in localizing persistent disease in patients with
Hürthle cell carcinoma. In contrast to radioactive iodine, however, it does not have therapeutic
potential in ablating tissue. If a thyroid nodule is incidentally imaged on SestaMIBI scanning,
there is no capability to predict whether it is a benign or malignant tumor.20

FIGURE 77.5 18F fluorodeoxyglucose (FDG) PET scan of a patient with late recurrence of
differentiated thyroid carcinoma in the mediastinum. The tumor is the intensely FDG-avid mass
superior to the cardiac activity.
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111 Indium-Octreotide Scintigraphy

Octreotide scanning (somatostatin receptor scintigraphy) has been occasionally useful in imaging
differentiated thyroid carcinoma, especially when radioiodine scintigraphy has failed to do so. Its
therapeutic potential is undefined.
Ultrasonography
Ultrasound of the thyroid requires a high-frequency “small parts” probe (generally 7.5 to 10 mHz
or higher). It is a very sensitive technique to determine the size, number, and distribution of
thyroid nodules. Ultrasound often detects very small, subtle nodules that are not otherwise
clinically evident. Studied prospectively, the prevalence of asymptomatic thyroid nodules (thyroid

incidentalomas) detected by ultrasonography is 67%.21 Because ultrasonography can detect

nodules at a preclinical stage, it follows that proper perspective about the significance or
insignificance of these nodules must be maintained. In practical terms, selective FNA biopsy
should be limited to those nodules greater than 1 cm or those that have increased in size under
serial ultrasound measurement. As with any imaging technique that depends on individual
performance of the test, a user-dependent sensitivity range exists. Also, the specific
measurement of the dimensions of the nodules can vary between examiners because of variable
placement of both the transducer and the measurement cursor. Despite these factors,
ultrasonography is a very valuable enhancement to the workup of the thyroid nodule or
multinodular goiter. It can be especially useful when employed by the surgeon who will be
performing the thyroid resection. Additionally, it has a rapidly developing role in the preoperative
staging and the postoperative follow-up of patients with differentiated thyroid carcinoma. In
experienced hands, it is a very sensitive technique for detecting abnormally enlarged lymph nodes
or recurrence within the thyroid bed. Its utility is even further enhanced by ultrasound guidance
of the subsequent FNA biopsy.22
Cross-sectional Imaging
Computed tomography (CT) scans and magnetic resonance imaging (MRI) scans are useful in
certain circumstances. In large nodules firmly fixed to contiguous structures or accompanied by
new vocal cord paralysis, the concern for an invasive thyroid cancer is raised. CT scan may
suggest invasion of the laryngeal or tracheal cartilages, which may modify the operative
approach. Large goiters that have an obvious substernal component on physical examination or
that are accompanied by an upper airway obstructive component may warrant preoperative CT
scan to define the extent of the goiter, not only to help plan the specific operative plan but also to
facilitate anesthetic evaluation for difficult airway management techniques such as fiberoptic
intubation (Fig. 77.6).

FIGURE 77.6 Example of a multinodular goiter with a large substernal component causing
tracheal displacement and compression.
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FUNCTIONAL DISORDERS AND GENERAL TREATMENT

CONSIDERATIONS
Hyperthyroidism
Hyperthyroidism can be caused by diverse pathophysiology, such as Graves' disease, toxic
multinodular goiter, and solitary toxic adenoma. Typical symptoms are heat intolerance, sweating,
palpitations, tremor, hyperphagia, thirst, and sleep disturbances. Elderly patients can present with
muscle wasting, atrial fibrillation, angina pectoris, or congestive heart failure. Regardless of
specific cause, the need to control hyperthyroidism before operation is critical to prevent thyroid
crisis (i.e., thyroid storm). Maximal safety is assured with thionamides combined with β-blockade,
but many studies suggest that propranolol or metoprolol used without thionamides are as safe
and effective.23,24 β-Blockade alone is not universally accepted because of the occasional
occurrence of postoperative thyroid crisis, tachycardia, hyperhydrosis, or anxiety.25 Doses of β-
blockers must continue until the morning of surgery and should not be stopped abruptly
postoperatively. Lugol's solution (iodine plus potassium iodide, 6 mg per drop) can be
administered as 5 to 10 drops three times daily for 2 weeks preoperatively to decrease
vascularity. Henry S. Plummer at the Mayo Clinic was the first physician to define the role of
iodine preoperatively in Graves' disease, which contributed to remarkable improvements in
perioperative mortality.
Graves' Disease
Graves' disease, which was described by Dr. Robert Graves in the 1830s as a toxic diffuse goiter
associated with exophthalmos and palpitations, is an autoimmune disorder with a genetic
predisposition and a female predominance (five to seven times higher than the incidence in
males). It is characterized by the presence of thyroid-stimulating antibodies (TSAb). These
antibodies bind to the TSH receptor on follicular cells and stimulate thyroid hormone release. The
autoimmune disease may also affect the eyes to cause exophthalmos and pretibial regions to
cause myxedema. Graves' ophthalmopathy may be the first manifestation of disease, and it
covers a wide spectrum from very mild changes in acuity or ocular dryness to obvious proptosis.
It may be clinically so severe as to require aggressive ophthalmologic treatment in approximately
5% of patients. The pathophysiology is not entirely understood, but the ophthalmopathy appears
to have some relationship to inflammation of the periorbital fibroblasts. Aside from the
ophthalmopathic findings of proptosis and lid lag on physical examination, patients with Graves'
disease have a diffuse goiter, which may be smooth or occasionally irregular. The gland is by
nature very vascular and may occasionally have an audible bruit overlying it. T4 and T3 levels are
increased and TSH levels are suppressed. The uptake of 131I generally shows a symmetrically
enlarged gland with increased 24-hour RAIU measurements.

Three main treatment modalities for Graves' disease are medical therapy, radioactive iodine
treatment, and thyroidectomy. Selection of therapy depends on age, disease severity, goiter size,
and patient preference. Practice patterns differ dramatically across the world, especially regarding
the use of radioiodine (it is less common in Europe and especially Japan compared to the United
States). The most common initial treatment involves thionamides and often β-blockade. In a small
fraction of patients, antithyroid drugs may be the only therapy necessary, but in general, this
strategy is considered an impermanent solution. Although the drugs may theoretically be used
long term, they are associated with a small, but real risk of life-threatening agranulocytosis.
Additionally, a number of less severe side effects make tolerance difficult for many, and the
recurrence of thyrotoxicosis can be unpredictable. Ultimately, most patients pursue a permanent,
or “ablative” therapy such as radioactive iodine (RAI) or surgery. Treatment with RAI is very
effective and has not been associated with secondary risk of development of a new malignancy,
yet there is still a practical hesitance to use this treatment in young children. RAI takes a full 1 to
2 months to provide definitive results and thus antithyroid medications must continue during this
period. Although euthyroidism is the most common result of therapy, the effects are slowly
progressive such that over 95% of patients become hypothyroid within 10 years following
treatment. RAI therapy has been occasionally associated with exacerbation of Graves'
ophthalmopathy, although the effect is ameliorated by corticosteroids and the early addition of
LT4 posttreatment.26,27,28 Because of this concern, patients with severe ophthalmopathy should
consider total thyroidectomy instead of RAI to prevent such an exacerbation; however, ultimate
resolution of ophthalmopathy is no more likely with operation.
Surgery for Graves' disease has the advantage of rapid correction of the hyperthyroid state. The
specific operation has typically been either bilateral subtotal thyroidectomy or total
thyroidectomy. Subtotal thyroidectomy intends to remove enough tissue to resolve the
hyperthyroidism but leave enough to maintain euthyroidism. Graves' disease is dynamic and,
thus, remissions and exacerbations are common. This factor makes the determination of exactly
how much tissue to leave as a remnant very challenging (typically estimated between 4 and 8 g
of thyroid tissue). For these reasons, total thyroidectomy is becoming the preferred operation for
treatment of Graves' disease with the intention of obviating the chance of recurrence but
accepting hypothyroidism requiring LT4 therapy. The transient hypocalcemia that can occur after
total thyroidectomy (from the effect on the parathyroid glands) may be greatly worsened in the
patient with Graves' disease because of the increased bone turnover observed with
hyperthyroidism. With proper supportive treatment, however, recovery is common and the
incidence of permanent hypoparathyroidism should be no higher than in other patients.
Toxic Multinodular Goiter

The term toxic multinodular goiter (MNG) refers to thyrotoxicosis that is caused by a multinodular
goiter that may be of endemic or nonendemic etiology. H. S. Plummer first distinguished toxic
adenomatous goiter from Graves' disease. Although the eponym “Plummer disease” now more
commonly refers to the patient with a solitary toxic nodule (see below), many clinicians still
include toxic MNG under that historical blanket. Thyrotoxicosis may occur as a progression from
euthyroid multinodular goiter that was originally TSH dependent, which then progressed to a state
of autonomy whereby it is not suppressible with LT4. After that, it may progress to a toxic state in

which distinct nodular areas are overproducing T4 and T3 with resultant TSH suppression.
Although the cause is clearly distinct, it is possible that some patients included in this diagnostic
category actually have Graves' disease with nodular degeneration of their diffuse goiter. Patients
with toxic MNG, however, are often easily distinguished from those with Graves' disease. The
typical patient is female and more than 50 years old with a previous history of multinodular
goiter. Thyrotoxicosis may be precipitated in a MNG with or without areas of autonomy when an
iodide load is provided (the Jod-Basedow phenomenon). Historically, this has been seen over a
period of years following public health efforts to iodinate salt or flour in an iodine-deficient
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population. This is still seen after exposure to iodinated radiographic contrast media,
expectorants, or iodide-containing drugs such as amiodarone.
Hyperthyroidism present in a patient with MNG can involve a wide spectrum of severity such that
it is not uncommon for a patient having indications for thyroidectomy, for reasons such as
continued nodular growth or substernal extension, to have a suppressed TSH in the absence of
major functional symptoms. This subclinical thyrotoxicosis is another potential indication for
thyroidectomy because it rarely resolves spontaneously and prolonged hyperthyroidism, even
when mild, may have deleterious health effects. Thyroidectomy is a relatively common treatment
for toxic MNG, with radioiodine treatment representing a less-common alternative because it often
requires high doses or repeated treatments because of the large goiter size and low radioiodine
uptake. Long-term remissions from antithyroid drug treatment are even less common or
predictable than seen in treatment of Graves' disease.29
Solitary Toxic Adenoma

Patients with thyrotoxicosis and a new dominant thyroid nodule may have a toxic adenoma.
Nodules must usually grow to at least 2 cm in size before hyperthyroidism is clinically evident. As
expected, T3or T4, or both are elevated and TSH is suppressed. Thyroid scintigraphy will
demonstrate a single “hot” area corresponding to the known nodule with suppression of the
remainder of the thyroid substance. FNA is rarely helpful and the incidence of malignancy within
these nodules is negligible. Treatment options include 131I RAI therapy or resection. RAI is
effective in controlling the hyperthyroidism, but depending on nodule size, may leave behind a
palpable abnormality. In particular, younger patients with sizable nodules may choose operation.
The resection is typically a hemithyroidectomy and isthmusectomy. The contralateral lobe is often
normal and will maintain normal thyroid hormone production after the hyperthyroidism is
remedied.
Hypothyroidism
Primary hypothyroidism can arise from intrinsic thyroid disease, iatrogenic thyroid removal or
destruction, and antithyroid drug effects. Secondary hypothyroidism can also occur from failure of
thyrotropic function (via TSH) of the pituitary gland because of disease, removal, or destruction of
that gland as well. Rarely, tertiary hypothyroidism can occur with destructive disorders of the
hypothalamus via decreased production of thyrotropin-releasing hormone. The most common
cause of primary hypothyroidism in adult patients is Hashimoto's thyroiditis. In large part,

hypothyroidism is straightforward to address with exogenous LT4 therapy, with the exception of
the patient with thyroid hormone resistance. As defined by hypothyroidism itself, the role for
surgical therapy is limited. The structural thyroid disorder causing the hypothyroidism, however,
may be an indication for thyroidectomy (e.g. goiter).
Thyroiditis
A summary of conditions causing a painful neck mass is delineated in Table 77.1. Inflammatory
conditions of the thyroid are a disparate family of conditions that require surgical therapy in the
minority of situations. However, they can be quite prevalent in patients undergoing evaluation for
thyroid surgery and a thorough understanding is required to avoid diagnostic and therapeutic
misadventures. The different types of thyroiditis are presented in descending order of clinical
frequency.
TABLE 77.1 DIAGNOSIS: DIFFERENTIAL DIAGNOSIS OF THE PAINFUL NECK MASS

THYROIDAL CAUSES
Acute thyroiditis
Subacute thyroiditis
Acute thyroid cyst (hemorrhage into cyst or nodule)
Rapidly enlarging thyroid carcinoma
Painful Hashimoto's thyroiditis
Radiation thyroiditis
NONTHYROIDAL CAUSES
Infected thyroglossal duct cyst
Infected branchial cleft cyst
Infected cystic hygroma
Cervical adenitis
Globus hystericus (no mass palpable)
(Adapted from Farwall AP, Braverman LE. Thyroiditis. In Randolph GW, ed. Surgery of the
thyroid and parathyroid glands. Philadelphia: WB Saunders, 2003, p. 49.)
Hashimoto's Thyroiditis
Also known as chronic thyroiditis, autoimmune thyroiditis, and lymphocytic thyroiditis, this
condition was described by Hashimoto in 1912 as struma lymphomatosa based on the histologic
findings. It affects perhaps up to 10% of the general population and is the most common cause of
both goiter and hypothyroidism in the United States. Although it can occur at nearly any age, the
peak is from age 30 to 60. Female to male preponderance is as high as 9:1. It is clearly an
autoimmune condition and there is a moderate genetic predisposition, associated with HLA-DR3, -
DR5, and -B8. The disease prevalence is increased in iodine-sufficient regions and this may be
because immunogenicity of the thyroglobulin molecule increases with the degree of iodination.
The histologic changes are characterized by lymphocytic infiltration with fibrosis and germinal
centers. Some follicular cells may undergo metaplasia to Hürthle cells. The typical presentation is
that of a painless diffuse goiter in a young woman discovered on physical examination or

associated with hypothyroidism. Patients often note a sense of fullness in, or awareness of, the
region of the thyroid. When the associated goiter is large, compressive symptoms of dysphagia or
dyspnea may occur. The goiter is typically firm and rubbery and slightly “bumpy” with prominent
lateral lobes. Nodular disease can and does occur in a gland affected by Hashimoto's disease and
needs to be investigated with FNA to rule out coexisting malignancy, typically papillary cancer or,
rarely, thyroid lymphoma. Thyroid autoantibody titers are elevated, primarily TPOAb and
secondarily, TgAb, and erythrocyte sedimentation rate (ESR) is normal. A 24-hour RAIU is
variable and can be elevated, normal, or often depressed. Patients are often hypothyroid but may
be euthyroid at the time of presentation. If patients are euthyroid, approximately 5% per year will
progress to hypothyroidism.30 In approximately 5% of patients, a transient phase of
hyperthyroidism, termed “Hashitoxicosis,” may be seen at the onset of disease and, in fact, the
subsequent pattern in thyroid function changes are nearly indistinguishable from that of silent
thyroiditis. For the majority of patients, treatment of Hashimoto's thyroiditis is limited to LT4
therapy in those with hypothyroidism, which is dosed for the goal of a TSH level in the lower
portion of the normal range. Surgery is indicated in patients
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with large goiters, significant compressive symptoms, local symptoms refractory to LT4 therapy,
or the inability to rule out malignancy (typically in the nodular subtype).
Painless or Postpartum Thyroiditis

Sporadic silent (painless) thyroiditis and postpartum thyroiditis are known as destruction-induced
thyroiditities and are probably variants of the same process, distinguished only by the relationship
to pregnancy.31 Along with subacute thyroiditis, these conditions are characterized by the onset of
thyrotoxicosis, a goiter, and low 24-hour RAIU. Even excluding postpartum cases, there is a
female predominance by 2:1 and the age range of affected patients is broad. The cause appears
to be autoimmune, but the genetic predisposition is low. There is no fever or malaise and the
goiter is painless, but persistent. Thyroid autoantibodies titers are often high, and the ESR is
usually normal. Thyroid function is dynamic and follows a pattern similar to that of subacute
thyroiditis with the abrupt onset of thyrotoxicosis followed by a period of euthyroidism, then
hypothyroidism. Permanent hypothyroidism is fairly common, especially if the disease course was
characterized by very limited hyperthyroidism with evident progressive hypothyroidism. A 24-hour
RAIU is very low (usually <5%), consistent with leakage of preformed thyroid hormones from a
thyroid gland that is damaged on the cellular level. At the histologic level, lymphocytic infiltration
is seen along with destruction of follicular cells. If it is pregnancy associated, it is likely to relapse
with future pregnancies. If symptoms of thyrotoxicosis are significant, β-adrenergic blocking drugs
may be used, but antithyroid drugs are not appropriate because the gland is not hyperfunctioning
at the follicular cell level. Rarely, severe thyrotoxicosis may be impacted by iopanoic acid, which
markedly inhibits peripheral conversion of T4 to T3. If LT4 therapy is instituted during the
hypothyroid phase for symptomatic relief, it can be withdrawn after 6 to 9 months to determine if
recovery has occurred.
Subacute Thyroiditis
Subacute thyroiditis is a common form of thyroiditis that affects women more often than men by

a 5:1 ratio and often in the age group of 20 to 60. There are a number of synonymous terms,
such as de Quervain's thyroiditis, giant cell thyroiditis, pseudogranulomatous thyroiditis, subacute
painful thyroiditis, and subacute granulomatous thyroiditis. The cause is not entirely certain, but it
appears to be virally related or mediated. There may be moderate genetic predisposition. A
prodrome consistent with an upper respiratory viral infection is very common. The patient often
has fever and malaise and an exquisitely painful and firm goiter that is also transient. The goiter
is usually unilaterally dominant, and the patient may have pain that radiates to the ipsilateral ear.
At a histologic level, giant cells (which may also be seen on FNA, thus supporting the diagnosis)
and granulomas often infiltrate the thyroid. It is common to see a dynamic picture of thyroid
function with subclinical or obvious thyrotoxicosis followed by hypothyroidism, which may
occasionally be permanent. Consistent with follicular cell destruction, serum Tg levels may be
elevated. Antithyroid antibodies may be present in low titers and the ESR is often high. A 24-hour
RAIU is usually quite low (<5%). Management is similar to painless thyroiditis in that β-blockers
may be used, but antithyroid medications are not useful. Salicylates or nonsteroidal
antiinflammatory drugs (NSAIDs) are adequate to control pain in most cases, with the occasional
need for oral glucocorticoids. Although the course of disease can be protracted for weeks or
months, relapse is rare and management is usually limited to management of symptoms.
Amiodarone-Induced Thyrotoxicosis or Thyroiditis

Although the significance of amiodarone-induced thyrotoxicosis or thyroiditis is usually related to
the thyrotoxicosis induced by the Jod-Basedow mechanism, increased understanding of the
condition has led to the realization that it often includes a component of destructive thyroiditis as
well, especially when background iodine deficiency is not a factor.32 The antiarrhythmic drug
amiodarone is 37% iodine by weight and the iodine load can induce thyrotoxicosis. Amiodarone
therapy results in thyrotoxicosis in 3% of patients in iodine-sufficient regions and up to 10% of
patients in iodine-deficient regions.33 In addition, the drug inhibits 5′ deiodinase. Secondary
medical treatment of the hyperthyroidism is difficult because of both the long half-life of the drug
and the decompensation in cardiac function related to underlying heart disease. Amiodarone-
induced destructive thyroiditis is very common in the United States. Two types of amiodarone-
induced hyperthyroidism can occur, but distinction between the types can be clinically difficult.
Type I is iodine-induced and is more common in iodine-deficient areas (type Ia is often associated
with preexisting multinodular goiter). In general, amiodarone should be stopped and thionamides
may be variably effective. A 24-hour RAIU may be normal or elevated in iodine-deficient areas
(opening that therapeutic possibility) but in iodine-sufficient areas (type Ib is often associated
with Graves' disease), 24-hour RAIU is decreased. Type II, defined primarily by destructive
thyroiditis, is usually seen in iodine- sufficient areas and can be self-limited. Decreased thyroid
parenchymal blood flow on color flow Doppler imaging is typical. A 24-hour RAIU is typically very
low and serum interleukin-6 may be elevated. Corticosteroids are used therapeutically and, if
tolerated, β-blockers as well. If hyperthyroidism is severe in either type I or II, thyroidectomy
may be required to resolve the thyrotoxicosis and allow continuation of amiodarone. Some
recommend iopanoic acid before thyroidectomy. Because of the cardiac decompensation,
thyroidectomy may need to be done under local anesthesia and sedation to avoid the risks of
general anesthesia.

Acute Thyroiditis
Acute thyroiditis refers to a rare suppurative condition caused by bacterial organisms. It may
occur in children or young adults (approximately age 20 to 40 years) with equal sex predisposition
and no evidence of genetic predisposition. Patients with acquired immunodeficiency syndrome
(AIDS) may be at risk for this condition. A clinical prodrome, usually a viral or bacterial upper
respiratory infection, may occur and the patient is often affected by a significant fever and
malaise and may have radiating pain to the region of the ipsilateral ear. Staphylococcus aureus
and Streptococcus pyogenes are the most common pathogens, but many other possibilities exist.
A painful, but ultimately transient goiter may be evident, which often is a thyroidal or
perithyroidal abscess. The patient usually remains euthyroid and antithyroid antibody titers are
normal. ESR may be elevated. If a 24-hour RAIU scan is performed, it is often normal but uptake
may be focally decreased in the region of active infection. Bacterial infection of the thyroid may
occur via hematologic spread from a distant site or local infiltration from other head and neck
infections. If acute thyroiditis is related to a fistulous communication with the pyriform sinus, the
condition may recur repeatedly. It is the potential for abscess formation or pyriform sinus fistula
that makes this a disease that occasionally requires surgical intervention even if FNA is able to
determine the causative organism and if appropriate parenteral antibiotics are instituted. In
general, this condition is still associated with some risk of mortality and these patients should be
admitted to the hospital for appropriately aggressive management.
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Riedel's Thyroiditis
Also known as Riedel's struma or invasive fibrous thyroiditis, this rare disorder affects mainly
women (by a ratio of 4:1) and usually occurs between the ages of 30 and 60. The cause is
unknown and a genetic predisposition is not apparent. There is no prodrome and no fever or
malaise. The patient presents with a painless but persistent, and often progressive, goiter.
Patients are usually euthyroid at presentation but may eventually become hypothyroid. They may
have detectable antithyroid antibody titers and a normal ESR. If obtained, the 24-hour RAIU is
often normal or somewhat decreased. Physical examination reveals an exceptionally firm goiter
often described as “woody.” Most commonly, this is a diffuse, bilobar process. Histologically, the
disease is characterized by extensive fibrosis, which may progress to a point of compression of
adjacent structures such as the trachea and esophagus. Riedel's thyroiditis is often accompanied
by other equally mysterious focally sclerotic conditions such as retroperitoneal fibrosis,
mediastinal fibrosis, retroorbital fibrosis, and sclerosing cholangitis.34 Because of its infiltrative
nature, it is important to differentiate Riedel's thyroiditis from thyroid carcinoma. FNA is often
inadequate and open biopsy may be required. If substantial compression exists, surgery is often
required to relieve these symptoms. Extensive resection is often unsafe or impossible, and wedge
resections, especially of the isthmus, may be very effective in relieving symptoms. Medical
therapy, including corticosteroids, methotrexate, or tamoxifen, may have a positive impact in the
chronic setting.35
NODULAR THYROID DISEASE AND GENERAL TREATMENT

CONSIDERATIONS
Nontoxic Multinodular Goiter

From a world health perspective, endemic goiter is still a significant issue affecting up to 12% of
the world's population. Endemic goiters are caused by dietary iodine deficiency, which ultimately
is also responsible for endemic cretinism—another major world health issue. Goitrogenic
substances found in diets may also be contributory. Iodine deficiency in a region is addressed
over time by iodination of dietary components (e.g., salt, bread flour, or vegetable oil).
In endemic goiter, T4 levels may be normal or decreased, whereas T3 levels are normal or often
increased. This reflects an adaptive regulatory mechanism by which the thyroid preferentially
shifts production to the more biologically potent T3. Exogenous thyroxine therapy will induce a
decrease in goiter size in roughly 80% of patients treated. Resection may be indicated for large
size, increase in size while on T4, or compression of the trachea, esophagus, or superior vena
cava.
In most developed countries, the term goiter generically refers to a group of diseases causing
thyroid enlargement in patients not affected by iodine deficiency. Specifically, it can refer to
conditions such as Graves' disease, nodular goiter, chronic lymphocytic thyroiditis, subacute
thyroiditis, and Reidel's thyroiditis. In common usage, goiter typically refers to patients with
nodular goiter, which may be uninodular or multinodular. Asymptomatic, multinodular goiter is
common and if reasonable assurance that the goiter is not harboring a malignancy can be
obtained by FNA, thyroidectomy is not usually indicated. Sometimes, because of the number of
nodules if significant size (>1 cm), repeated FNA during longitudinal observation becomes
impractical. Patients may grow frustrated with the prospects of multiple FNAs and elect
thyroidectomy to simplify management. Compressive symptoms involving the airway or
esophagus are also an indication for thyroidectomy. A multinodular goiter causing subclinical or
obvious thyrotoxicosis (toxic multinodular goiter) should also be removed (see later). Options for
removal include subtotal thyroidectomy or total thyroidectomy. Total thyroidectomy is the
preferred option because of the significant chance for recurrent nodular degeneration of the
thyroid remnant after subtotal thyroidectomy. If a goiter develops a substernal portion,
thyroidectomy is warranted because of the inability to monitor continuing growth in the
mediastinum. If tracheal compression develops gradually, it may be largely asymptomatic. The
natural history of that situation is the unpredictable possibility of sudden respiratory obstructive
crisis usually exacerbated by an upper respiratory infection. Because all of the important
attachments to the thyroid parenchyma remain in the neck, even very large substernal goiters
can be removed through a cervical incision. Less than 5% to 10% will require partial sternotomy
for full removal.
Solitary or Dominant Thyroid Nodule

Thyroid nodular disease is very common, whereas thyroid malignancy is relatively rare. The
prevalence of thyroid nodules is approximately 4% to 7% in the general population and, in fact,
thyroid nodules are present in approximately 50% of autopsy specimens. In contrast, the
incidence of thyroid cancer (in the absence of significant risk factors) is 4 per 100,000 per year.
Therefore, a great deal of culling needs to occur to appropriately identify those patients who

require operation and to avoid operation for a large fraction of patients who do not.
When assessing a patient with a solitary thyroid nodule, first assess factors in the history that
may indicate the likelihood of benign or malignant disease. A new thyroid nodule that occurs at
the extremes of age is more likely to be malignant than one that occurs in the third through
seventh decade. The risk of a solitary thyroid nodule in a child under 14 being malignant may be
as high as 50%.36 Patient gender itself does not generally confer risk of malignancy, and the fact
that thyroid cancer occurs in a greater number of women than men is related more to the
increased prevalence of nodular thyroid disease in women. A new thyroid nodule that occurs after
the age of 60, however, is more likely to be malignant in a man than in a woman.
Many factors apparent on physical examination or imaging can also be used to assess the
potential for malignant disease in the patient with a thyroid nodule. The consideration that
nodular disease is uninodular (e.g., solitary) instead of multinodular has traditionally implied that
the former situation is more concerning for malignancy. Especially in the era of thyroid
ultrasound, this distinction is inappropriately overemphasized because at least half of nodules
considered solitary by clinical examination are actually just a dominant nodule in a multinodular
goiter. It is mostly a practical consideration that the dominant nodule (largest or most apparent)
of a multinodular gland is the one that dictates subsequent clinical decision-making. The physical
characteristics of a nodule (size, firmness, texture) have a limited ability to predict malignancy.
Significant fixation to surrounding tissues can greatly elevate the level of concern, but this is not
entirely reliable. Associated lymphadenopathy in the central or lateral cervical compartments is
certainly concerning for potential malignancy. Although many patients with benign thyroid disease
describe hoarseness or a change in voice, this is often largely subjective and is of limited concern
unless accompanied by objective hoarseness and ipsilateral recurrent laryngeal nerve paralysis.
Thyroid functional status can be important in two ways. First, if the nodule is truly solitary and the
patient is
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hyperthyroid, it may be a toxic autonomous nodule. If this is confirmed by nuclear scintigraphy,

the risk of malignancy in this nodule is negligible. If the patient is chronically hypothyroid (likely
from Hashimoto's disease), a firm, indistinct nodule raises the question of whether an extranodal
lymphoma may be present.
Several hereditary environmental factors and hereditary conditions can increase the risk of
developing thyroid cancer. A critical question in assessing any patient with a thyroid nodule is
whether any history of radiation exposure exists. At least 90% of radiation-associated thyroid
cancers are papillary thyroid carcinoma. Typical exposures have included external beam
irradiation treatment for acne, tinea capitis, external otitis, recurrent tonsillitis, or neonatal thymic
enlargement, treatments that were common in the 1940s and 1950s but that are no longer used.
In the current era, excessive diagnostic radiation or too high-dose therapeutic irradiation (e.g.,
treatment of lymphoma or head and neck malignancies) is responsible for relevant exposures.
The association is well documented and there appears to be a linear relationship between the
dose of radiation and the risk for thyroid cancer with even a higher risk among those exposed at a
young age.37 The typical latent period between exposure and clinically evident cancer appears to
be in the 3- to 8-year range. It is not clear, however, exactly when, if ever, the risk is no longer
present. Cases appear to increase for up to three decades after exposure and then begin to tail
off. Another source of radiation exposure to the thyroid gland is nuclear fallout, related to either

atomic weapons or nuclear power plant accidents, such as Chernobyl in 1986, which exposed 1.5
million people in southern Belarus and northern Ukraine. This acute γ radiation exposure is likely
the main risk factor, but longer term exposure to diverse radioisotopes of iodine that secondarily
contaminate the regional water and food supplies may also be contributory.
Another critical question to investigate is whether a family history of thyroid cancer or associated
conditions exists. The prototypical issue here is to uncover a family history of medullary thyroid
cancer, which suggests the potential for an inherited syndrome such as familial medullary thyroid
carcinoma or multiple endocrine neoplasia type 2. Papillary thyroid cancer, however, may have a
familial association as well, either independently or, more commonly, associated with Cowden's
syndrome or Gardner's syndrome (familial adenomatous polyposis).
In most situations, extensive thyroid function testing is not necessary and a TSH is all that is
required. After initial clinical assessment, thyroid nodular disease is often assessed by ultrasound
(USN). Relevant factors include the size of the nodule and other sonographic characteristics.
Hyperechoic nodules are often benign, whereas thyroid malignancies, regardless of cell type, are
often hypoechoic. Irregular margins between the nodule and surrounding tissues will raise the
concern for malignancy. A sonolucent dark rim around the nodule is referred to as a “halo” and is
much more likely to occur with a benign nodule, although it is occasionally seen with a
malignancy as well. Significant calcification with acoustic shadowing (e.g., “eggshell”) is usually
indicative of chronicity and is more likely associated with a benign nodule, whereas subtle
microcalcifications, which are too small to cause acoustic shadowing and which cause a “twinkling”
effect when the transducer is moved, are highly correlated with malignancy. Also important is
whether the nodule is truly solitary or whether there are additional nodules, especially in the
contralateral lobe, that may affect the specific surgical recommendations. Although it is still
common for patients to undergo thyroid scintigraphy, its utility is actually very limited and it
should not be a routine investigation for a thyroid nodule. The only helpful role is to determine the
specific nature of a nodule in a patient with hyperthyroidism. The additional diagnostic information
provided by knowing the nodule is “cold” or “photopenic” is very limited, especially in the era of
FNA, which can categorize the potential for malignancy to a much greater degree. Both USN and
FNA are able to confirm if the nodule is cystic in character. Although smaller cysts may resolve
with aspiration, recurrence is very likely if the cyst is 4 cm or greater and, consequently, these
patients should consider resection.
FNA is the cornerstone of diagnostic evaluation of the thyroid nodule. It can reliably identify
colloid nodules, benign nodular hyperplasia, thyroiditis, papillary thyroid carcinoma (PTC),
medullary thyroid carcinoma, and anaplastic thyroid carcinoma. FNA may suggest an extranodal
lymphoma. It can also classify nodules as follicular lesions or Hürthle cell lesions. These lesions
currently require at least partial thyroidectomy (e.g., lobectomy) to determine whether it is a
follicular (or Hürthle cell) adenoma or follicular (or Hürthle cell) carcinoma. That is because the
determination of malignancy can be made only by the demonstration of capsular or vascular
invasion. FNA should have a false-positive rate of 0 to 0.5% and a false-negative rate of 0 to 5%.
The potential for a nondiagnostic interpretation is directly related to the number of follicular cells
recovered for analysis. This is ultimately related to technique and the number of sampling needle
passes performed. Ultrasound guidance can help ensure that the biopsy results are representative
of the nodule of interest, but ultimately, it will not significantly change the possibility of a
nondiagnostic result if inadequate technique is employed.

Standard disposable needles from 23- to 27-gauge size range and 10-mL syringes are used. The
target nodule is fixed between two fingers on the nondominant hand while multiple passes
through portions of the nodule are made without requiring a separate skin puncture for each. An
average of three separate biopsy maneuvers is reasonable practice. The technique does not rely
heavily on aspiration or suction as the name might imply. The ideal sample remains mostly in the
needle hub and barrel before expelling it onto a slide or into fixative for cytologic preparation.
Current limitations require that decisions based on FNA are contingent on the cytologic
appearance. It is likely that in the near future, however, specific molecular markers or gene
expression data will be identified that will allow specific testing of FNA specimens to indicate risk
of malignancy.
THYROID MALIGNANCY AND GENERAL TREATMENT

CONSIDERATIONS
General Considerations
Thyroid cancers exhibit a wide spectrum of behavior, from the inconsequential, occult, well-
differentiated thyroid carcinomas to the nearly uniformly fatal course of undifferentiated
anaplastic cancers. Fortunately, at least 98% of thyroid cancers are well differentiated. Although
the general treatment strategy for thyroid carcinomas is familiar (surgical resection, staging of
disease, appropriate application of adjuvant treatments, and secondary screening or follow-up), a
number of unique points are emphasized below.
Tumor Classification
Differentiated thyroid cancers are of follicular cell origin (papillary thyroid carcinoma and its
variants, follicular thyroid carcinoma, and Hürthle cell carcinoma) or parafollicular (C-cell) origin
(medullary thyroid carcinoma). There is, then, a spectrum
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of dedifferentiation that exists between these tumors and undifferentiated cancers such as
anaplastic carcinoma. Tumors such as insular carcinoma exist along this spectrum. In a general
sense along this progression, prognosis is directly related to the degree of differentiation. A
number of classification systems exist. Although the original systems were based on architectural
characteristics noted during histopathologic analysis, most current systems include certain
cytologic and biologic behavioral attributes as well. The American Thyroid Association (ATA), the
Armed Forces Institute of Pathology (AFIP), and the World Health Organization (WHO) all consider
papillary thyroid cancers, including classic papillary carcinoma, mixed papillary-follicular variants,
and follicular variants, and follicular thyroid carcinomas (FTC) as DTC. Still some disagreement
exists about the classification of Hürthle cell carcinomas (HCC). In general, the ATA and WHO
consider HCC as a subtype of follicular thyroid carcinoma, although the AFIP does not. Support for
considering HCC as a subtype of follicular thyroid carcinoma includes the histologic demonstration
of the transition of follicular to Hürthle cells, in intact TSH receptor adenylate cyclase system in
Hürthle cells, and the ability of Hürthle cells to produce thyroglobulin and thus maintain Tg
positivity on immunohistochemical staining).38 Other characteristics, however, such as higher
oncogene expression in HCC than FTC and the general impression that HCC can display a more

aggressive clinical course than FTC cause some to classify HCC tumors outside the FTC family.39
Medullary thyroid carcinoma is also a differentiated thyroid carcinoma but is of parafollicular cell
origin.
Papillary Thyroid Carcinoma

Papillary thyroid carcinoma (PTC) accounts for approximately 80% of thyroid carcinomas.
Although it occurs across the spectrum of age from childhood to the elderly, the peak incidence
begins in the third and fourth decades of life. It is more common in females than males. It is
especially prevalent in iodine-sufficient regions of the world. Papillary carcinoma arises from the
follicular cells, is characterized by papillary architecture, and is often associated with calcifications,
psammoma bodies, squamous metaplasia, and fibrosis. Cytology is diagnostically important and
typical findings include large, overlapping nuclei, which are optically clear (known as Orphan
Annie nuclei), and intranuclear grooving. As a whole, the prognosis is excellent, especially in
those patients with tumors that define a low risk for recurrence. Greater than 30% of PTC is
multicentric throughout the thyroid. Although multifocality does not signify a worse prognosis, this
characteristic, in part, influences the rationale for total thyroidectomy discussed below. The
incidence of cervical lymph node metastases varies across series and is influenced by whether
lymphadenectomy is performed for prophylactic or therapeutic reasons. In general, it
approximates 30% to 40%. Distant metastases occur in 2% to 14% of patients with PTC.38 At
least 70% of PTC can take up radioiodine and thus, RAI scanning is an important part of the
treatment strategy.
Variants
A follicular variant of papillary thyroid carcinoma essentially combines the histologic and
architectural appearance of follicular tumors with the cytologic features of papillary carcinoma. In
terms of treatment and biologic behavior, this variant behaves in the same manner as classic PTC.
The dilemma caused by this variant is based on the fact that, in contrast to classic PTC, it is very
difficult to diagnose on frozen section analysis. It is often interpreted as a follicular lesion with the
final diagnosis deferred until formal histopathology when the cytologic features are more
apparent. More aggressive variants of papillary carcinoma include tall cell and columnar types,
which also exist on the spectrum of dedifferentiation toward anaplastic carcinoma.
Microcarcinoma.
PTC less than 1 cm in size are considered microcarcinomas (occult or incidental tumors). They
may be multifocal and are usually clinically unapparent until thyroidectomy is performed for
another indication. Although they are by definition malignant, this group of tumors requires a
different set of considerations based on “nonmalignant” biologic behavior and patient outcome.
Prognosis is exceptionally good, with a 0.4% cause-specific mortality rate.37 If such a
microcarcinoma is found after lobectomy, adequate treatment has already been rendered and
completion thyroidectomy or radioiodine scanning, or both, are not indicated. Somewhat in
contrast, if these microcarcinomas are diagnosed preoperatively, which is difficult because of their
size, thyroid resection is usually recommended. Some groups, however, have chosen to follow
these patients closely with ultrasound. Approximately 70% do not increase in size significantly.40

Nonetheless, these tumors cannot be completely discounted. It is not uncommon for PTC to be
diagnosed by biopsy of a lateral compartment lymph node even if the associated primary tumor is
not apparent. If these patients are treated with total thyroidectomy, very careful histologic
sectioning will be required to find the associated primary tumor, which may be as small as 1 mm.
Follicular Carcinoma
Follicular thyroid carcinoma (FTC) accounts for approximately 10% to 20% of all thyroid cancers.
Again there is a female-to-male predominance, and the incidence begins to increase in the 5th
decade of life. Determination that a follicular neoplasm is a carcinoma is not contingent only on
the specific cellular architecture, but instead is based on the findings of vascular invasion and
capsular invasion. This determination is rarely able to be made on frozen section and the
information is often not available until final histopathology results.41 FTC is often more advanced
at the time of diagnosis compared with PTC. For example, it is more common for FTC to be locally
infiltrative of muscles and perithyroidal vascular structures. Because of this difference in stage at
diagnosis, the overall 10-year survival for patients with FTC is slightly worse than for those with
PTC, but when patients are matched for age and stage with PTC, this difference largely
disappears.42 In contrast to PTC, follicular cancers are usually solitary. Approximately one third of
patients with FTC have distant metastases at the time of diagnosis and the pattern is consistent
with a mechanism of hematogenous spread, with lung and bone most often being involved.
Lymph node involvement is limited to only about 10% of patients. Importantly, at least 80% of
FTC will take up radioiodine, opening up this therapeutic possibility.
Minimally Invasive Follicular Carcinoma.

Follicular neoplasms with demonstrable capsular invasion but no vascular invasion are classified
as minimally invasive follicular cancers. These patients have an excellent prognosis, conceptually
equivalent to patients with incidental papillary microcarcinomas. If such a tumor is found after
hemithyroidectomy, there is no reason for the patient to undergo completion thyroidectomy and
radioiodine scanning as would be recommended for true FTC.43
Hürthle Cell Carcinoma.

Malignant Hürthle cell neoplasms account for approximately 5% of thyroid carcinomas and, in
general, occur in patients slightly older than those with PTC or FTC. Despite their relatively
uncommon nature, HCC enters diagnostic consideration frequently because Hürthle cells are
frequently seen on FNA cytology from thyroid nodules. Patients with Hashimoto's disease or
colloid nodules may demonstrate Hürthle cells. It is the nodule that contains almost entirely
Hürthle cells, however, that raises concern for HCC. If this is suggested on FNA, operation, which
at minimum is a
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thyroid lobectomy, is appropriate to establish the nature of the tumor. Hürthle cell adenomas
(neoplasms with no evidence of capsular or vascular invasion) certainly exist but, occasionally, a
tumor that is otherwise histologically compatible with a Hürthle cell adenoma is found to be
associated with lymph node or distant metastases. For these reasons and considering the

perspective that HCC may behave more aggressively, many surgeons advocate total
thyroidectomy for any Hürthle cell neoplasm.44 Again, HCC is more prevalent in women than men
and is more often associated with lymph node metastases and distant metastases than PTC and
FTC in general. Although it is a DTC likely of follicular cell origin, very few HCC tumors will take up
radioiodine (only approximately 10%). For this reason, and considering the concern of a more
unpredictably aggressive biologic behavior for HCC, aggressive and complete surgical resection is
especially important in this disease. Therefore, total thyroidectomy may often be combined with
central compartment lymphadenectomy and perhaps modified radical neck dissection if lymph
node involvement is evident.
Medullary Carcinoma
MTC arises from the parafollicular C cells and accounts for about 7% of all thyroid malignancies.
Approximately 75% occur in a sporadic fashion and 20% to 25% may be familial (multiple
endocrine neoplasia [MEN] types 2A and 2B, as well as familial medullary thyroid carcinoma).
These are autosomal-dominant inherited endocrinopathies related to a group of specific mutations
on chromosome 10q11.2 (RET proto-oncogene) (Table 77.2). The familial forms of MTC have
different degrees of aggressiveness related to the specific syndrome. Familial MTC has the most
indolent course, whereas MEN 2B has the most aggressive course, with MEN 2A intermediate to
these. Most sporadic MTC is relatively slow growing and may be quite indolent. These patients
typically do not present before approximately 30 years of age. A subset of patients with sporadic
MTC have a much more aggressive course. This variability in biologic behavior accounts for the
overall 10-year survival rate of approximately 50%. Overall, MTC is more aggressive than other
DTC and is more likely to metastasize, first to the level VI lymph nodes and then to the lateral
compartment nodes (e.g., level III, IV, and V). At least 50% to 75% of patients with sporadic
MTC have nodal metastases already present at the time of diagnosis. Distant metastases may
involve the liver, lungs, and bone. FNA can be diagnostic for medullary cancer, especially if the
specimen is stained for calcitonin. MTC is unique in that a very specific tumor marker is used for
diagnosis and to guide subsequent follow-up. Serum calcitonin is the most useful marker, but
most MTC also makes carcinoembryonic antigen (CEA) as well.
TABLE 77.2 DISEASE: PHENOTYPES RELATED TO MUTATION OF THE RET PROTO-

ONCOGENE
Phenotype Clinical features Prevalence (%)
MEN 2A (60%) Medullary thyroid carcinoma 100
Pheochromocytoma 10–60
Hyperparathyroidism 5–20
MEN 2B (5%) Medullary thyroid carcinoma 100
Pheochromocytoma 50
Marfanoid habitus 100
Mucosal neuromas (gut) and 100
ganglioneuromatosis
FMTC (35%) Medullary thyroid carcinoma 100
MEN 2A, multiple endocrine neoplasia type 2A; MEN 2B, multiple endocrine neoplasia
type 2B; FMTC, familial medullary thyroid carcinoma.

Approximately 20% of patients thought to have sporadic MTC may in fact be index cases of
familial MTC. Therefore, any patient with a new diagnosis of MTC should have direct genetic
testing for the genetic abnormalities associated with MEN 2A (RET protooncogene analysis).
Appropriate screening for pheochromocytoma (which would be treated before the cervical
operation) and hyperparathyroidism are required.
The treatment strategy for MTC is distinct to that of DTC of follicular cell origin. Because of the
high likelihood of lymph node metastases and the fact that there is no effective adjuvant therapy
(MTC does not take up radioiodine), a more extensive initial surgical resection is warranted. The
appropriate operation for MTC is a total thyroidectomy with central compartment
lymphadenectomy (level VI nodes). Because intraoperative assessment of lymph node
involvement is relatively inaccurate, consideration should be given to ipsilateral modified radical
neck dissection as well. Some advocate bilateral modified radical neck dissection initially and
others advocate very extensive “microdissection” designed to completely remove any lymph node-
bearing tissue in these areas and more durably render the patient normocalcemic.45 Because of
technical issues and an unclear influence on prognosis, this approach has not met with
widespread acceptance.
It is common for patients to have persistent hypercalcitoninemia even after an extensive initial
operation. Most patients have a subsequent indolent course, although some patients will progress
more rapidly. Experience with remedial neck dissections in an attempt to render the patient
normocalcemic has generally been disappointing and requires an appropriate search for distant
metastases. This may include extensive imaging tests such as CT scanning, ultrasound, octreotide
scanning, selective venous sampling for calcitonin levels, and laparoscopy to investigate for
hepatic metastases. For most patients, the strategy of observation by clinical examination,
biochemical markers, and imaging tests is adopted with interval reassessment for resectable
regional and metastatic disease. When this is detected, especially if it is in a location whereby
ongoing growth could cause significant morbidity (e.g., tracheoesophageal groove), resection can
be offered. Hepatic resections for diffuse metastatic disease are inappropriate, whereas such an
operation may be considered for isolated bulky metastatic deposits. Chemotherapy has largely
been ineffective, although trials with tyrosine kinase-inhibiting drugs are ongoing. External beam
radiotherapy may be useful for locoregional tumor control, especially in those patients with
evidence of locally aggressive tumor behavior. This should not be employed, however, until
appropriate surgical options are exhausted.
Provocative testing (e.g., pentagastrin or calcium stimulated calcitonin levels) was until recently a
standard screening maneuver to identify patients with heritable forms of MTC. Now, these familial
forms of MTC, or at least the risk of developing the manifestations, may be diagnosed with the aid
of genetic testing for mutations in the RET proto-oncogene. The best use of such testing is to
identify the specific mutation in affected family members, which then guides testing of the
progeny. When other kindred members with the mutation are identified, thyroidectomy may be
performed before malignancy develops. In the setting of MEN 2A, MTC typically does not develop
before 12 years of age but is nearly always present by age 30. Accordingly, children with MEN 2A
should undergo total thyroidectomy, usually with central neck lymphadenectomy, at
approximately 6 years of age. The thyroid resection must be absolutely complete because the
region of
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thyroid that remains after a near total or subtotal thyroidectomy is the region that is most densely
populated with C-cells. If hyperparathyroidism is present and enlarged parathyroid glands are
encountered at operation, they should be removed as well. A subtotal parathyroidectomy or total
parathyroidectomy and autotransplantation (similar to that which would be considered for MEN 1)
are excessive options for the parathyroid disease encountered in MEN 2A and, instead, resection
may be guided by morphologic changes in the parathyroid glands. Children identified to have MEN
2B should undergo thyroidectomy and central neck lymphadenectomy as soon as the diagnosis is
made, preferably by 2 years of age.46 If MTC is already evident at the time of diagnosis (as
opposed to only C-cell hyperplasia), patients should undergo ipsilateral neck dissection as well.
There is no consensus about at which age patients confirmed to have the FMTC mutation should
undergo thyroidectomy, although this decision may be guided by the specifics of the family
history.
Anaplastic Carcinoma.
Although it formerly accounted for a larger fraction of thyroid malignancies, undifferentiated or
anaplastic cancer now accounts for just 1% to 2% of thyroid cancers. Most commonly, this occurs
in elderly patients who have a long-standing goiter. There is significant evidence to infer that
most anaplastic thyroid cancers of the spindle cell or giant cell type arise from transformation of
DTC, especially follicular and papillary carcinoma. Because of the improved outcome of lymphoma
compared with anaplastic cancer (see later), it is critical to further investigate a tumor classified
as a small cell anaplastic carcinoma. Appropriate studies must determine if the tumor is actually a
lymphoma or a poorly differentiated MTC. Anaplastic thyroid carcinoma is one of the most
aggressive and rapidly lethal malignancies known. Nearly all are too far advanced at the time of
diagnosis to be adequately treated by currently available therapies. The diagnosis may be made
by appropriate clinical suspicion (rapidly growing firm thyroid mass) and needle biopsy (FNA or
core). If not, excisional biopsy at operation may be required. If airway compromise is present or
impending, operation may include debulking and tracheostomy. Occasionally, a small anaplastic
cancer is found that is confined to the thyroid or is minimally extensive to surrounding tissues (e.
g., trachea). Especially in a young patient, aggressive resection may be legitimately considered.
The long-term prognosis for these patients, however, is usually limited by metastatic disease,
which may not be apparent at diagnosis. Adjuvant or primary palliative therapy consisting of
chemotherapy and external beam radiotherapy is still frequently employed. It is common to see a
measurable response early in therapy, but eventual tumor progression is typical. Unfortunately,
the overall impact is often very limited, so no single regimen has become a standardized
approach. Although doxorubican, taxol, and other drugs have been tried, doxorubicin and cisplatin
are more frequently used. Radiation therapy is often given in combination by using a
hyperfractionated routine such as two daily fractions, 5 days per week, until a total of 40 Gy is
delivered to the cervical compartments and superior mediastinum.47 Most often, chemotherapy
and radiotherapy follow an operation performed for diagnosis or airway control, but such a
regimen may also be used occasionally as neoadjuvant therapy before an attempt at resection is
undertaken.
Thyroid Lymphoma.
Primary thyroid lymphomas are rare tumors that account for less than 5% of thyroid

malignancies. The majority are classified as non-Hodgkin's lymphomas of B-cell origin. Nearly all
arise within from a background of Hashimoto's thyroiditis. Thyroid lymphoma usually affects
patients between 50 and 80 years of age and is more common in women than men. Most patients
present with a rapidly enlarging thyroid mass with compressive symptoms (e.g., dyspnea,
dysphagia, choking, pain) and most have a history of hypothyroidism (from Hashimoto's
thyroiditis). The cornerstone of treatment is chemotherapy (e.g., cyclophosphamide, doxorubicin,
vincristine, prednisone), often combined with radiotherapy. The diagnosis, however, must be
firmly established. Modern immunophenotypic analysis often allows this to occur with a small
amount of tissue obtained by FNA or core needle sampling. Operation is still occasionally required,
however, to obtain adequate tissue samples for diagnosis. Substantial surgical resection is often
not required, but there is a subset of patients with significant compressive symptoms who benefit
from palliative total or subtotal thyroidectomy.48
Metastases to Thyroid Gland.

Isolated metastases from other primary cancers can occur in the thyroid gland, although they are
rare. The most common tumor type to do so is renal cell carcinoma, although it can occur from
lung and gastrointestinal carcinomas as well as melanoma and sarcoma.49
Staging of Thyroid Malignancy

A number of patient factors have been investigated to predict risk and prognosis for patients with
DTC, such as age, gender, tumor size, involvement of lymph nodes, extrathyroidal invasion,
tumor grade or histologic features, and completeness of surgical removal. Many of these factors
are included in the staging systems outlined later. Although there are differences in these
systems, in general, they agree that younger patients with smaller tumors have an excellent
prognosis with decreased risk of recurrence and death compared with older patients.
One early prognostic staging scheme proposed by investigators from the Mayo Clinic was the
AGES system (age, histologic grade, extrathyroidal disease [invasion and distant metastases],
and tumor size).50 Although useful, the scheme was later modified to exclude histologic tumor
grade because there was not uniform agreement on DTC grading by pathologists.
Another system from the Lahey Clinic is the AMES system (age, metastases, extrathyroidal
invasion, and tumor size), which was originally described for patients with DTC.51 The main
criticism of this scheme is that it was defined based on a patient population, which included both
papillary and follicular thyroid carcinomas, and that there was no accounting for those patients
with low-risk versus-high risk FTC (see previously).
Another useful prognostic system is the MACIS scoring system (metastases, age, completeness of
resection, extrathyroidal invasion and distant metastases, and tumor size). This system calculates
a composite score based on these factors, then stratifies prognosis in proportion to these scores
(<6.00 is very low risk and >8.00 represents greatly increased risk).52
The European Organization for Research on Treatment of Cancer (EORTC) based their prognostic
scoring system on a multivariate analysis of patients with all types of thyroid malignancies and
found that patients with scores of less than 50 had a 5-year survival rate of 95%, whereas those
with scores greater than 109 had a 5-year survival rate of 5%.53 This system has not been

universally adopted for use in DTC because the high-risk, poor prognostic group contained a large
fraction of patients with anaplastic thyroid cancer. Although medullary thyroid carcinoma is
considered a differentiated cancer, its biologic behavior differs sufficiently from DTC of follicular
cell origin that their inclusion in this staging system also confounds the prognostic ability
somewhat.
The familiar TNM system (tumor size, nodal status, distant metastases) is also used to provide
prognostic information for patients. When used for thyroid cancer, the TNM system has been
modified to account for the risk-reducing influence of low
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patient age (Table 77.3). This system can provide consistency when comparing patients across
different series. This system, like all prognostic scoring systems, still has limited utility in guiding
initial treatment decisions (e.g., extent of resection) because the important components are not
known preoperatively.
TABLE 77.3 STAGING: TUMOR, NODE, METASTASIS STAGING SYSTEM FOR

DIFFERENTIATED THYROID CARCINOMA (PAPILLARY AND FOLLICULAR TYPES)
Stage Age <45 years Age >45 years
I Tany Nany M0 T1 N0 M0
II Tany Nany M1 T2 N0 M0
T3 N0 M0
III T4 N0 M0
Tany N1 M0
IV Tany Nany M1
T1, ±1 cm; T2,>1 cm,±4 cm; T3, >4 cm; T4, extrathyroidal extension; N0, no nodal
involvement; N1, regional nodal metastases; M0, no distant metastases; M1, distant
metastases.
Selection of Surgical Procedure

Although thyroidectomy as a primary treatment for DTC is well accepted to be both effective and
safe, some controversy persists about the extent of thyroidectomy necessary, especially when the
controversial questions are applied to individual patients who are likely to have low-risk tumors
and an excellent prognosis regardless of the specifics of surgical treatment. The advantages of
total thyroidectomy for all DTC of follicular cell origin include: (a) radioiodine can be used to
localize and treat small amounts of residual normal thyroid tissue, and especially regional or
distant metastases; and (b) serum thyroglobulin may then be used as a sensitive marker of
persistent or recurrent disease. If only lobectomy is performed, radioiodine treatment is usually
not possible because of the avidity of normal thyroid tissue for RAI, and thyroglobulin
measurements also lose their utility. Total thyroidectomy also addresses multifocal tumors
(especially PTC) even if they are not obvious at the time of operation. After treatment with
lobectomy, recurrence develops in the contralateral lobe in about 7% of patients, and half go on
to die of thyroid cancer.38 The risk of recurrence is decreased somewhat in patients treated with

bilobar resections (e.g., total thyroidectomy) compared with patients undergoing only unilateral
lobectomy. Overall, the application of total thyroidectomy in patients with DTC also decreases the
likelihood of requiring reoperation in the central compartment of the neck in the future.
Radioiodine Therapy
Radioiodine may be used in two ways after thyroidectomy: low doses are used to demonstrate
remaining thyroid tissue or metastatic disease as part of a radioiodine thyroid scan, whereas
higher doses are used for ablation or therapy. The timing of the initial postoperative scan is
dictated by the physiology of T4 and the fact that remnant thyroid or DTC tissue must be
stimulated by elevated levels of TSH to take up RAI. Although no precise threshold has been
established, a general consensus is held that the TSH should be at least 30 mIU/mL. The TSH rise
is generally achieved by thyroxine withdrawal, although recombinant human TSH is available
(Thyrogen, currently approved for diagnostic scanning only). The half-life of thyroxine is
approximately 7 days, so TSH values are significantly elevated 4 to 5 weeks after total
thyroidectomy or withdrawal from thyroxine treatment. To minimize the duration of hypothyroid
symptoms, patients can be managed on T3 (triiodothyronine, Cytomel) for the first 4
postoperative weeks. Because of the much shorter half-life of T3 (8 to 12 hours), it is held for only
2 weeks before scanning. One shortcoming of this strategy is that the rise of TSH can be slightly
unpredictable and the specific RAI scanning schedule may need to be adjusted.
Radioiodine therapy is well suited to DTC because most tumor cells retain the ability to
concentrate radioiodine. Additionally, many studies have shown a decreased rate of recurrence
and increased disease-specific and overall survival when 131I is used. Mazzaferri54 reported in
1997 a threefold decrease in the incidence of distant metastatic disease and local tumor
recurrence in tumors treated with radioiodine.54 In another study, the risk of cancer death was
decreased by half (from 16% to 8%) when radioiodine was used after surgery compared with
hormone replacement or external radiation alone.55 Many clinicians agree that radioiodine is
beneficial and well tolerated, but certainly this is not a unanimous conclusion.
There are no prospective, randomized trials with subgroup analysis to shed light on the dilemma
of which patients should receive postoperative radioiodine. The argument is further complicated
by the fact that because of the multiple staging and prognostic systems are used, comparisons
across studies can be difficult. Postoperative RAI is commonly used, even for lower-risk cancers,
and thyroid remnant ablation is generally accepted as part of the postoperative treatment of
patients who have undergone total or near-total thyroid excision for DTC. It is also widely
recognized that this approach may not be the final answer, and it is not entirely evident that using
postoperative radioiodine to “clear” a whole-body scan will impact the patient's recurrence or
survival. Perhaps the most appropriate approach is to select patients for postoperative radioiodine
therapy based on individual risk assessment.
Several situations exist wherein it is generally agreed that 131I is not beneficial. If the cancer is
nondifferentiated and does not concentrate radioiodine, ablative or therapeutic efforts will be
futile. Lesions smaller than 1 cm without evidence of metastatic disease are not treated with
radioiodine because of their exceptionally low potential for local or distant recurrence. Finally, if
only a lobectomy is performed, the radioiodine ablation is possible only 25% of the time because
of the volume of residual tissue and its avidity for RAI.

Proponents of 131I therapy advocate that all patients who meet the indications for total
thyroidectomy should undergo postoperative radioiodine therapy because it should not be
assumed that residual thyroid tissue in the neck is tumor-free. Importantly, less than 30% of well-
differentiated thyroid cancers will be multifocal, multicentric, or microscopic. In these settings,
postoperative remnant thyroid ablation after total thyroidectomy serves to destroy remaining
thyroid tissue that may harbor occult microscopic carcinoma. There are additional compelling
reasons to provide postoperative radioiodine ablation. In short, it is easier to manage and follow
the patient without remaining thyroid tissue. Without competing normal tissue, visualization of
local or distant recurrences on follow-up 131I scanning is possible. If large amounts of thyroid
tissue remained after the initial operation, the bright emission of 131I from the residual thyroid
will obscure any small areas of local recurrence. Additionally, remaining thyroid tissue will cause
TSH suppression, which can decrease the uptake of 131I during postoperative imaging. Finally,
thyroglobulin measurements are the most specific tests for recurrent cancer when no normal
thyroid tissue or Tg antibodies (Tg-Ab) are present and when Tg level is measured during a period
of hypothyroidism—none of which is feasible when a remnant remains. It follows, therefore, that
only patients with a small cancer (<1 cm) carrying
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an exceptionally low risk of recurrence should be routinely excluded from consideration of

treatment with postoperative radioiodine therapy.
External Beam Radiotherapy

If gross residual disease remains after surgical resection, external radiotherapy may be
considered to assist in local tumor control. This is most often a consideration with tumors that
invade the tracheoesophageal axis. This occurrence is frequent with poorly differentiated tumors,
but it certainly can complicate DTC as well. It has also been considered for patients with extensive
lymph node involvement that is characterized by extranodal invasion of metastatic tumor. Bone
metastases are rarely treated completely with 131I and, thus, external beam radiotherapy may be
effective.56 Complications include skin erythema and desquamation, and tracheoesophageal
mucositis.
Thyroid-Stimulating Hormone Suppression

Levothyroxine therapy to suppress TSH levels is commonly recommended for patients with
differentiated thyroid carcinoma because TSH is considered a trophic factor for these cancers. The
efficacy is inferred from uncontrolled retrospective studies. It is important to individualize the
degree of suppression in patients, balancing the risk of recurrence with the risks of subclinical
hyperthyroidism (e.g., osteoporosis, cardiac arrhythmias). Many physicians will suppress TSH to
undetectable levels (<0.01 mIU/L) in high-risk cancers and less severely (TSH 0.05 to 0.1 mIU/L)
in low-risk cancers. If a patient has no evidence of recurrence and has extremely low or
undetectable thyroglobulin levels 5 to 10 years after treatment, it may be appropriate to lessen
the degree of TSH suppression.
New Horizons and Future Directions

Adjunctive treatment of DTC is dependent on the uptake and concentration of radioiodine by

cancerous thyroid tissue. Problematically, it has been reported that as many as 30% of advanced
DTC will eventually de-differentiate, and a portion of these cancers will lose the ability to
concentrate radioiodine. This may result from decreased expression of the human sodium iodide
symporter (hNIS). Both in vivo and in vitro research has shown that follicular cancer cell lines
have greater iodine uptake when stably transfected with hNIS.57,58 Application of these gene
therapy techniques to human subjects is not a current reality, but remains an exciting area of
research. Certain therapies have been used in humans in effort to “re-differentiate” thyroid cancer
cells such that they would regain the ability to concentrate radioiodine. In early pilot studies,
retinoic acid has been shown to increase radioiodine uptake and decrease thyroglobulin levels in
advanced thyroid carcinomas, and further studies hold promise for the treatment of de-
differentiated tumors.59
There are no significantly effective medical therapies to offer patients with radioiodine-resistant
thyroid cancers. In addition to the dedifferentiation therapies mentioned earlier, the past two
decades of research into the molecular biology and genetics of thyroid cancer have identified
potential targets for alternate therapies. Clinical trials have been established for a variety of drugs
with wide-ranging targets and molecular mechanisms of actions, including drugs that target
intracellular signaling molecules (ras and raf inhibition), receptor tyrosine kinases (anti-VEGF, anti-
EGFR, anti Her2/neu, and VEGF/EGF receptor inhibitors), angiogenesis (thalidomide,
combretastatins), apoptotic pathways (TNF-related apoptosis-inducing ligand [TRAIL]), and the
effect of rapamycin on the mTOR gene (mammalian target of rapamycin). To ensure future
progress in the treatment of patients with thyroid malignancies, all patients with radioiodine-
resistant tumors should be considered as candidates for clinical trials.
THYROID SURGERY
The first recorded goiter excision was by Abdul Kasan Kelebis Abis in Baghdad in AD 500. The
patient survived despite massive hemorrhage. Wilhelm Fabricus performed the first thyroidectomy
using scalpels in 1646. The patient did not survive and the surgeon was subsequently imprisoned.
By the mid-nineteenth century, the mortality associated with thyroid surgery was still as high as
40%. Substantial improvements began with the discovery of anesthesia, antisepsis, and improved
hemostasis. It was with this background that Albert Theodor Billroth, Theodor Kocher, and William
Halsted were able to make substantial technical contributions in making thyroidectomy safe and
efficacious.
Technique
There is little if any place for odd thyroid resections (e.g., nodulectomy) and only an occasional
role for isthmusectomy. Total thyroid lobectomy is the total extracapsular removal of the lobe and
the isthmus while preserving both parathyroid glands, the recurrent laryngeal nerve, and the
external branch of the superior laryngeal nerve. Total thyroidectomy is a matter of performing a
total thyroid lobectomy on the contralateral side during the same operation. Near-total
thyroidectomy and subtotal thyroidectomy will not be discussed here. For most thyroid
procedures, the patient is placed in supine position or semi-Fowler position with the arms tucked
to the side. A support is placed transversely under the shoulders to aid in extending the neck.

This extension must not be too extreme or a significant amount of postoperative pain may occur
in the occipitocervical region. After skin preparation, a curvilinear incision is made approximately
one to two fingerbreadths above the clavicular heads and not any higher than the level of the
cricoid cartilage (Fig. 77.7). If possible, it should be disguised in an existing skin crease.
Subplatysmal skin flaps are
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raised with an electrocautery to the level of the thyroid cartilage above and the sternal notch
below. These are carried onto the sternocleidomastoid muscles laterally, taking care to avoid the
anterior jugular veins. The plane of the midline raphe is developed to expose the anterior trachea
and the isthmus. The sternohyoid is reflected off the sternothyroid and then the sternothyroid is
bluntly dissected from the thyroid lobe. It is this maneuver that leads to division of the thyroid
sheath layer as the paraesophageal space is entered. The middle thyroid veins are divided and
ligated. Instead of lateral retraction of the strap muscles, it is occasionally useful to divide the
strap muscles transversely, instead of in the midline raphe, in the case of exceptionally large
goiters. This greatly improves exposure of the superior pole vessels and allows easier blunt
mobilization of the enlarged lobes.
FIGURE 77.7 With the patient's neck extended, the line above indicates the appropriate site of
incision for thyroid resection. Camouflage within an existing skin crease is often possible.

If a pyramidal lobe is present, it is mobilized and divided from the fibrous tissue in any remaining
thyroglossal duct tract. The anterior suspensory ligament is divided to mobilize the superior
aspect of the isthmus.
These procedures should be performed in a logical orderly sequence as follows: (a) exposure of
the thyroid gland, (b) dissection of the superior pole of the thyroid with preservation of the
external branch of the superior laryngeal nerve, (c) dissection of the inferior pole of the thyroid
lobe with preservation of the inferior parathyroid gland, (d) dissection of the posterolateral aspect
of the thyroid gland with preservation of the superior parathyroid gland and the recurrent
laryngeal nerve, and (e) closure. Figure 77.8 indicates the plane of dissection relevant to tasks c
and d.
Dissection of the superior pole of the thyroid must take place in the plane directly adjacent to the
thyroid capsule after the largely avascular space between the pole and the cricothyroideus muscle
is seen. To do so more proximally along the superior pole vessels imperils the EBSLN. This nerve
is not always seen during thyroidectomy, but it can nearly always be preserved by utilizing the
technique. Unequivocal identification of the recurrent laryngeal nerve is mandatory. This is done
by many surgeons as direct dissection and exposure in the proximal portion of the RLN before its
intersection with the ITA and the ligament of Berry. The safety provided by this maneuver,
however, is contingent on continuing the exposure more distally along the nerve as it approaches
the cricothyroid interval, because it is at this point of genu that the nerve is most vulnerable to
iatrogenic injury. Another technique of nerve exposure is provided by the close capsular dissection
that takes place when the lobe is retracted anteromedially and as the terminal branches of the
ITA are divided. As the ligament of Berry is divided, the genu of the nerve is identified and
protected. Although visual identification of the RLN remains the gold standard, palpation can aid
in the process. The nerve is often easy to palpate because it is a slightly firm linear structure
(similar to the feel of the vas deferens encountered during pediatric hernia repair) as the lobe is
retracted anteromedially. Although helpful, this technique should not supplant visual confirmation.
FIGURE 77.8 The capsular dissection necessary to preserve well-vascularized parathyroid tissue
and a fully functional recurrent laryngeal nerve begins in the area outlined above.
The ability to routinely preserve well-vascularized parathyroid tissue during thyroidectomy is

mandatory for surgeons performing these operations. Normal parathyroid tissue is subtle and may

be difficult to identify. It can be distinguished from surrounding fat by slight color differences and
a fine capillary vascular pattern that is not present in the adjacent fat or thymus.
Complications
The risk of death or major disability during thyroidectomy should be diminutive. The key
outcomes by which to measure the quality of surgical care, especially relevant to total
thyroidectomy, include recurrent laryngeal nerve paralysis and hypoparathyroidism. Although
both complications can occur in a self-limited fashion, the persistence or permanence (defined at
6 months after operation) of these complications is a critical measure. The rate of unintended
permanent recurrent laryngeal nerve dysfunction should be no greater than 1% and the rate of
permanent hypoparathyroidism should be no greater than 1% to 2%.
Injury to a RLN results in paralysis of the vocal cord it innervates. Depending on the specific
branch or combination of branches injured, the cord may remain in a paramedian position (also
called cadaveric position) or may remain abducted. If the contralateral cord is able to adduct to
the midline or beyond, the patient may have a voice that is not particularly hoarse, but is weak. If
the cord is paralyzed in the abducted position, vocal quality is very poor because of the difficulty
in approximating the cords during speaking. The patient's cough also has a bovine quality where
there is a lack of a sharp, percussive initiation. If both vocal cords are paralyzed, the
consideration of the specific cord positions is even more critical. If both cords are paralyzed in the
abducted position, the patient may have essentially no ability to speak. In this situation, the
patient may gradually develop some degree of airway obstruction as the cords gradually migrate
toward the midline. If both cords are paralyzed in the paramedian position, the airway is critically
narrowed. In this situation, stridor is usually apparent very soon after extubation and an
emergent procedure (e.g., cricothyroidotomy or tracheostomy) may be required to establish the
airway.
Functional monitoring of EBSLN integrity is feasible, but somewhat cumbersome and is not
routinely employed. Recurrent laryngeal nerve monitoring has been much more evident in recent
thyroid surgery practice. Although the technology has improved to a point that the technique is
relatively easy to employ, large studies have failed to detect a major improvement in RLN injury
rates (largely related to the low incidence of this complication in the proper hands despite specific
technique employed).60 Even so, RLN monitoring can be very helpful in facilitating nerve
identification and protection during complex reoperations, or initial thyroidectomy for very large
goiter or malignancy, even if it will not materially change the chance of injury.61
Injury to the EBSLN is both more common and more difficult to detect than injury to the RLN.
Because of anatomic variations, the EBSLN is at risk for injury during thyroidectomy in 15% to
68% of cases.62 The symptoms of injury may be only slightly evident to the patient or can be
devastating in the case of the vocal professional. Symptoms typically include early vocal fatigue,
decreased pitch range, and decreased projection ability. Findings on laryngoscopy are subtle and
include bowing and inferior displacement of the affected
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vocal cord and rotation of the posterior glottis toward the injured side. Laryngeal
videostroboscopy or percutaneous electromyography of the cricothyroideus muscle may be
required to detect injury in subtle cases. Because there is no effective treatment for this

condition, prevention is extremely important, usually by careful surgical technique to ligate the
individual branches of the superior thyroid artery at the level of the thyroid capsule.
The parathyroid glands are at risk during thyroid resection by virtue of the fact that they are often
firmly invested within the thyroid sheath or occasionally even within the thyroid capsule.
Parathyroid glands are served by end arteries, most often only a single branch. Inferior
parathyroid glands are served ultimately by the inferior thyroid artery. Superior parathyroid
glands are often served by the inferior thyroid artery but may also have contributions from the
superior thyroid artery distribution as well. Ligation of the trunk of the ITA must be avoided to
preserve blood supply to the parathyroid glands. Every attempt should be made to mobilize the
parathyroid glands away from the thyroid tissue being resected while preserving the blood supply.
If at the end of mobilization, a parathyroid gland appears blue and congested, it may be to the
result of constriction of the venous outflow. The capsule of the gland may be incised carefully and
if mild arterial bleeding is seen and the congestion appears to resolve, the parathyroid gland can
be left in situ. If the gland appears pale and devascularized, the arterial supply is probably
compromised. Such a parathyroid gland is unlikely to survive after the operation and should be
immediately autotransplanted. This may be done by mincing the gland and inserting or injecting
the pieces into well-vascularized skeletal muscle (e.g., sternocleidomastoid or pectoralis).63 Even
during thyroid lobectomy, meticulous technique must be used to preserve parathyroid viability,
even though permanent, or even temporary, hypoparathyroidism is unlikely. With total
thyroidectomy, this is even more critical. Temporary hypoparathyroidism is relatively common
from relative mild devascularization of parathyroid glands during mobilization. Approximately 20%
to 40% of patients will have mild temporary hypocalcemia beginning about 12 to 36 hours after
operation. This may not even be symptomatic and is usually easy to control with oral calcium or
occasionally vitamin D supplements (calcitriol, Rocaltrol). Severe symptomatic hypocalcemia can
be treated with intravenous calcium gluconate (calcium chloride is not safely administered
through a peripheral intravenous site outside of emergency settings). Temporary
hypoparathyroidism complicating thyroidectomy usually resolves over days to weeks, although
occasionally it may take months to do so. Hypoparathyroidism that persists longer than 6 months
is usually, but not always, destined to be permanent. The rate of permanent hypoparathyroidism
after total thyroidectomy must be low (approximately 1% to 2%).
The central compartment of the neck contains level VI lymph nodes and is bordered by the hyoid
bone above, the innominate vein below, and the carotid sheaths laterally. Removal of the central
compartment lymph nodes is a critical component of an operation to treat medullary thyroid
carcinoma. It is a reasonable consideration in the treatment of HCC and PTC because lymph node
involvement is both common and difficult to treat with a remedial operation in the future. If
central neck dissection is to be added to the routine performance of total thyroidectomy to treat
low-risk PTC, however, it must be assured that the incidence of hypoparathyroidism is not
increased, because it can be technically difficult to maintain parathyroid vascularization with a
thorough level VI lymphadenectomy.
These complications can largely be avoided or ameliorated by delicate and deliberate surgical
technique. A thorough understanding of the function and anatomy, both normal and abnormal, of
the thyroid and of the rationale behind various treatment options are also critical to ensure the
best outcomes for our patients.

KEY POINTS
The thyroid is mostly from endodermal origin and originates from the
ventral embryologic digestive tract.
●
The upper portion of the isthmus typically crosses the trachea at or below
the level of the cricoid cartilage and overlies the second and third tracheal
rings.
●
The thyroid gland produces thyroxine (T4), triiodothyronine (T3), and

calcitonin under complicated regulatory mechanisms.
●
Ultrasonography is a very valuable enhancement to the workup of the

thyroid nodule or multinodular goiter.
●
Hyperthyroidism can be caused by diverse pathophysiology such as

Graves' disease, toxic multinodular goiter, and solitary toxic adenoma, and
can be treated by medications, radioiodine or operation.
●
Differentiated thyroid cancers (DTC) are of follicular cell origin (papillary

thyroid carcinoma and its variants, follicular thyroid carcinoma, and
Hürthle cell carcinoma) or parafollicular (C-cell) origin (medullary thyroid
carcinoma).
●
The advantages of total thyroidectomy for all DTC of follicular cell origin
include the fact that radioiodine can be used to localize and treat small
amounts of residual normal thyroid tissue, and especially regional or
distant metastases, and that serum thyroglobulin can then be used as a
sensitive marker of persistent or recurrent disease.
●
Anaplastic thyroid carcinoma is one of the most aggressive and rapidly

lethal malignancies known.
References
1. Moore KL. The developing human: clinically oriented embryology, 4th ed. Philadelphia: WB
Saunders, 1993.

2. Brookes M, Zietman Z. Clinical embryology. A color atlas and text. Boca Raton, FL: CRC
Press, 1998.
3. Larsen WJ. Human embryology. New York: Churchill Livingstone, 1997.
4. Merida-Velasco JA, Garcia-Garcia JD, Espin-Ferra J, et al. Origin of the ultimobranchial body
and its colonizing cells in human embryos. Acta Anat. 1989;136:325–330.
5. Weller GL. Development of the thyroid, parathyroid, and thymus glands in man. Washington
DC: Carnegie Institute of Washington, 1933.
6. Sackett WR, Reeve TS, Barraclough B, et al. Thyrothymic thyroid rests: incidence and
relationship to the thyroid gland. J Am Coll Surg. 2002; 195:635–640.
7. Gauger PG, Delbridge LW, Thompson NW, et al. Incidence and importance of the tubercle of
Zuckerkandl in thyroid surgery. Eur J Surg. 2001;167:249–254.
8. Tarjan G, Nayar R. Black thyroid syndrome. Thyroid 2002;12:343–344.
9. Bliss RD, Gauger PG, Delbridge LW. Surgeon's approach to the thyroid gland: surgical
anatomy and the importance of technique. World J Surg. 2000;2:891–897
10. Pelizzo MR, Toniato A, Gemo G. Zuckerkandl's tuberculum: an arrow pointing to the
recurrent laryngeal nerve (constant anatomical landmark). J Am Coll Surg. 1998;187:333–336.
11. Katz AD. Extralaryngeal division of the recurrent laryngeal nerve. Am J Surg.
1986;152:407–410.
12. Henry JF, Audiffret J, Denizot A, et al. The nonrecurrent inferior laryngeal nerve: review of
33 cases, including two on the left side. Surgery 1988;104:977–984.
13. Raffaelli M, Iacobone M, Henry JF. The “false'' nonrecurrent inferior laryngeal nerve.
Surgery 2000;128:1082–1087.
14. Machens A, Holzhausen HJ, Dralle H. Skip metastases in thyroid cancer leaping the central
lymph node compartment. Arch Surg. 2004;139:43–45
15. Gilmour JR. The gross anatomy of the parathyroid glands. J Pathol. 1938;46:133.

16. Cooper DS, Goldminz D, Levin AA, et al. Agranulocytosis associated with antithyroid drugs.
Effects of patient age and drug dose. Ann Intern Med. 1983;98:26–29.
17. Scanga DR, Martin WH, Delbeke D. Value of FDG PET imaging in the management of
patients with thyroid, neuroendocrine, and neural crest tumors. Clin Nucl Med. 2004;29:86–90.
P.1309
18. Davis PW, Perrier ND, Adler L, et al. Incidental thyroid carcinoma identified by positron
emission tomography scanning obtained for metastatic evaluation. Am Surg. 2001;67:582–584.
19. Kang KW, Kim SK, Kang HS, et al. Prevalence and risk of cancer of focal thyroid
incidentaloma identified by 18F-fluorodeoxyglucose positron emission tomography for
metastasis evaluation and cancer screening in healthy subjects. J Clin Endocrinol Metab.
2003;88:4100–4104.
20. Boi F, Lai ML, Deias C, et al. The usefulness of 99mTc-SestaMIBI scan in the diagnostic
evaluation of thyroid nodules with oncocytic cytology. Eur J Endocrinol. 2003;149:493–498.
21. Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable

nodules discovered incidentally on thyroid imaging. Ann Intern Med. 1997;126:226–231.
22. Rausch P, Nowels K, Jeffrey RB Jr. Ultrasonographically guided thyroid biopsy: a review
with emphasis on technique. J Ultrasound Med. 2001;20:1261–1262
23. Lennquist S, Jortso E, Anderberg B, et al. Beta blockers compared with antithyroid drugs as
preoperative treatment in hyperthyroidism: drug tolerance, complications, and postoperative
thyroid function. Surgery 1985;98:1141–1146.
24. Alderberth A, Stenstrom G, Hasselgren P. The selective beta 1 blocking agent metoprolol
compared with antithyroid drug and thyroxine as preoperative treatment of patients with
hyperthyroidism. Results from a prospective randomized study. Ann Surg. 1987;205:182–188.
25. Eriksson M, Rubenfeld S, Garber A, et al. Propranolol does not prevent thyroid storm. N
Engl J Med. 1977;296:263–264.
26. Tallstedt L, Lundell G, Blomgren H, et al. Does early administration of thyroxine reduce the
development of Graves' ophthalmopathy after radioiodine treatment? Eur J Endocrinol.
1994;130:494–497.

27. Tallstedt L, Lundell G, Torring O, et al. Occurrence of ophthalmopathy after treatment for
Graves' hyperthyroidism. The Thyroid Study Group. N Engl J Med. 1992;326:1733–1738.
28. Bartalena L, Marcocci C, Bogazzi F, et al. Use of corticosteroids to prevent progression of

Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism. N Engl J Med.
1989;321:1349–1352.
29. van Soestbergen M, van der Vijver J, Graafland A. Recurrence of hyperthyroidism in

multinodular goiter after long-term drug therapy: a comparison with Graves' disease. J
Endocrinol Invest. 1992;15:797–800.
30. Tunbridge WM, Brewis M, French JM, et al. Natural history of autoimmune thyroiditis. Br
Med J Clin Res. 1981;282:258–262.
31. Smallridge RC, DeKeyser FM, VanHerle AJ, et al. Thyroid iodine content and serum
thyroglobulin: cues to the natural history of destruction-induced thyroiditis. J Clin Endocrinol
Metab. 1986;62:1213–1219.
32. Bartalena L, Grasso L, Brogioni S, et al. Serum interleukin-6 in amiodarone-induced

thyrotoxicosis. J Clin Endocrinol Metab. 1994;78:423–427.
33. Harjai KJ, Licata AA. Effects of amiodarone on thyroid function. Ann Intern Med.
1997;126:63–73.
34. Violaris NS, Windle-Taylor PC. Idiopathic fibrosis of the upper aero-digestive tract. J
Laryngol Otol. 1989;103:333–334.
35. Few J, Thompson NW, Angelos P, et al. Riedel's thyroiditis: treatment with tamoxifen.
Surgery 1996;120:998–999.
36. Harness JK, Thompson NW, Nishiyama RH. Childhood thyroid carcinoma. Arch Surg.
1971;102:278–284.
37. DeGroot LJ, Kaplan EL, McCormick M, et al. Natural history, treatment, and course of
papillary thyroid carcinoma. J Clin Endocrinol Metab. 1990;71:414–424.
38. Kebebew E, Clark OH. Differentiated thyroid cancer: “complete'' rational approach. World J
Surg. 2000;24:942–951

39. Jossart GH, Clark OH. Well-differentiated thyroid cancer. Curr Probl Surg. 1994;31:933–
1012.
40. Ito Y, Tomoda C, Uruno T, et al. Papillary microcarcinoma of the thyroid: how should it be
treated? World J Surg. 2004;28:1115–1121.
41. Chen H, Nicol TL, Udelsman R. Follicular lesions of the thyroid. Does frozen section
evaluation alter operative management? Ann Surg. 1995; 222:101–106.
42. Emerick GT, Duh QY, Siperstein AE, et al. Diagnosis, treatment, and outcome of follicular
thyroid carcinoma. Cancer 1993;72:3287–3295.
43. van Heerden JA, Hay ID, Goellner JR, et al. Follicular thyroid carcinoma with capsular
invasion alone: a non-threatening malignancy. Surgery 1992;112:1130–1138.
44. Thompson NW, Nishiyama RH, Harness JK. Thyroid carcinoma: current controversies. Curr
Probl Surg. 1978;15:1–67.
45. Tisell LE, Hansson G, Jansson S, et al. Reoperation in the treatment of asymptomatic
metastasizing medullary carcinoma of the thyroid. Surgery 1986;99:60–66
46. Skinner MA, DeBenedetti MK, Moley JR, et al. Medullary thyroid carcinoma in children with
multiple endocrine neoplasia types 2A and 2B. J Pediatr Surg. 1996;31:177–181.
47. Crevoisier RD, Baudin E, Bachelot A, et al. Combined treatment of anaplastic thyroid
carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external
radiotherapy. Int J Radiat Oncol Biol Phys. 2004;60:1137–1143.
48. Sippel RS, Gauger PG, Angelos P, et al. Palliative thyroidectomy for malignant lymphoma of
the thyroid. Ann Surg Oncol. 2002;9:907–911.
49. Mirallie E, Rigaud J, Mathonnet M, et al. Management and prognosis of metastases to the
thyroid gland. J Am Coll Surg. 2005;200:203–207.
50. Hay ID, Grant CS, Taylor WF, et al. Ipsilateral lobectomy versus bilateral lobar resection in
papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel
prognostic scoring system. Surgery 1987; 102:1088–1095.
51. Cady B, Rossi R. An expanded view of risk-group definition in differentiated thyroid

carcinoma. Surgery 1988;104:947–953.
52. Hay ID, Bergstralh EJ, Goellner JR, et al. Predicting outcome in papillary thyroid carcinoma:
development of a reliable prognostic scoring system in a cohort of 1779 patients surgically
treated at one institution during 1940 through 1989. Surgery 1993;114:1050–1057
53. Byar DP, Green SB, Dor P, et al. A prognostic index for thyroid carcinoma: a study of the E.
O.R.T.C. thyroid cancer cooperative group. Eur J Cancer 1979;15:1033–1041.
54. Mazzaferri EL. Thyroid remnant 131I ablation for papillary and follicular thyroid carcinoma.
Thyroid 1997;7:265–271.
55. Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on
papillary and follicular thyroid cancer. Am J Med. 1994;97: 418–428
56. Brierley JD, Tsang RW. External-beam radiation therapy in the treatment of differentiated
thyroid cancer. Semin Surg Oncol. 1999;16:42–49.
57. Smit JW, Shroder-van der Elst JP, Karperien M, et al. Reestablishment of in vitro and in vivo
iodide uptake by transfection of the human sodium iodide symporter (hNIS) in a hNIS defective
human thyroid carcinoma cell line. Thyroid 2000;10:939–943.
58. Spitzweg C, Morris JC. Gene therapy for thyroid cancer: current status and future
prospects. Thyroid 2004;14:424–434.
59. Haugen BR. Redifferentiation therapy in advanced thyroid cancer. Current drug targets.
Immune, Endocrine, & Metabolic Disorders 2004;4:175–180
60. Dralle H, Sekulla C, Haerting J, et al. Risk factors of paralysis and functional outcome after
recurrent laryngeal nerve monitoring in thyroid surgery. Surgery 2004;136:1310–1322.
61. Yarbrough DE, Thompson GB, Kasperbauer JL, et al. Intraoperative electromyographic
monitoring of the recurrent laryngeal nerve in reoperative thyroid and parathyroid surgery.
Surgery 2004;136:1107–1115.
62. Teitelbaum BJ, Wenig BL. Superior laryngeal nerve injury from thyroid surgery. Head Neck
1995;17:36–40.
63. Gauger PG, Reeve TS, Wilkinson M, et al. Routine parathyroid autotransplantation during

total thyroidectomy: the influence of technique. Eur J Surg 2000;166:605–609.

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Ovid: Greenfield's Surgery: SCIENTIFIC PRINCIPLES AND PRACTICE

Copyright ©2006 Lippincott Williams & Wilkins

Largely as a function of disease prevalence, surgical treatment of thyroid disorders is relatively

EMBRYOLOGY AND SURGICAL IMPLICATIONS

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ANATOMY AND SURGICAL IMPLICATIONS

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Muscular, Fascial, and Airway Relationships

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often embedded in fat and thymic tissue within

Production of Thyroid Hormones

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Action of Thyroid Hormones

RELEVANT LABORATORY TESTS

Free Thyroxine (FT4) and Free Triiodothyronine (FT3)

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In fact, sensitive quantitative TgAb determination is a critical accompaniment to serum Tg

Thyroid-Stimulating Hormone (Thyrotropin)

Total Thyroxine (TT4) and Total Triiodothyronine (TT3)

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Inhibitors of Peripheral Thyroid Action

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hyperthyroidism and, in higher doses, it is used to destroy differentiated thyroid carcinoma.

THYROID IMAGING TECHNIQUES

Nuclear Medicine Imaging

Technetium Pertechnetate Tc Scintigraphy

123 Iodine Scintigraphy

131 Iodine Scintigraphy

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Positron Emission Tomography

99m Tc SestaMIBI Scintigraphy

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111 Indium-Octreotide Scintigraphy

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incidentalomas) detected by ultrasonography is 67%.21 Because ultrasonography can detect

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FUNCTIONAL DISORDERS AND GENERAL TREATMENT

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Toxic Multinodular Goiter

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Solitary Toxic Adenoma

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TABLE 77.1 DIAGNOSIS: DIFFERENTIAL DIAGNOSIS OF THE PAINFUL NECK MASS

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Painless or Postpartum Thyroiditis

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Amiodarone-Induced Thyrotoxicosis or Thyroiditis

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NODULAR THYROID DISEASE AND GENERAL TREATMENT

Nontoxic Multinodular Goiter

Solitary or Dominant Thyroid Nodule

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hyperthyroid, it may be a toxic autonomous nodule. If this is confirmed by nuclear scintigraphy,

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THYROID MALIGNANCY AND GENERAL TREATMENT

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