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ENDOCRINE SURGERY
50
Ultrasound waves pass easily through fluids and
soft tissues, making the procedure especially
useful for examining the thyroid. In contrast,
ultrasound waves are unable to penetrate bone
or gas, so ultrasound is of limited use for examining regions surrounded by bone, or areas that
contain gas or air.
For ultrasound examination of the thyroid,
the patient is positioned lying face up with the
neck extended and a small pillow behind the
upper back. A clear gel is applied to the area of
the body being studied to help the transducer
make secure contact with the body and eliminate air pockets between the transducer and the
skin. The ultrasonographer then presses the
transducer firmly against the skin and sweeps
it back and forth over the area of interest.
Set up of office-Based Ultrasound
Office-based ultrasound is rapidly becoming an
important tool for all endocrine surgeons and
endocrinologists and is being currently used by
at least 30% or more of all practicing endocrinologists in the office setting. Prior to proceeding with installing ultrasound technology in
your office it is wise to follow these simple steps:
1. Assess the need for ultrasound in your parti-
cular office:
Surgeons are in general highly motivated
to provide best treatment for their
patients and this technology has been
shown to aid in the diagnosis and treatment of patients with thyroid disease.
Considerable literature on using ultrasound as an extension of the physical exam.
Convenience to you and your patients.
2. Put aside time for training and credentialing
such that reimbursement from insurance
companies is a viable option:
Courses are offered through the American
Association of Endocrine Surgeons, American Thyroid Association (ATA), American
College of Surgeons, American Association
of Clinical Endocrinologists, Head and
Neck Society, Endocrine Society, American
Institute of Ultrasound in Medicine.
Document your competence, clinical correlation for first 50–200 cases.
Work closely with radiology colleagues.
3. Look at a broad range of equipment available
for purchase and test 2–4 of them in your
office with your patient population:
Consider image quality, cost, size, ease of
use, portability, ability to use different
kinds of probes, durability, reliability of
service, warranties, resale value.
4. Make a clear plan for documenting your
exam and reporting it to the referring
physicians:
Save digital images and hard copies.
5. Lay out a plan for continued training and
updating of equipment on an ongoing basis.
Reporting and Communication
of Thyroid Ultrasound
One of the limitations of USS is the high interobserver variability [5], thus making detailed
and consistent communication one of the most
important aspects of thyroid ultrasound. Communication channels must be open both
ways. While we strongly advocate for surgeonperformed ultrasound in all patients with
thyroid diseases, we also urge all endocrine surgeons to establish a long-term collegial relationship with radiologists who have a focused
interest in thyroid imaging and have knowledge
about patients with thyroid diseases. We believe
that while first pass images can be obtained by
an ultrasound technologist, all but the simplest
of patients require a thorough second pass evaluation by a dedicated radiologist. This helps
increase experience in different diseases of the
thyroid, and allows for improved diagnostic
yields eventually benefiting the patient. Detailed
reviewing of the images and reporting of course
can be done after the patient has left the radiology unit based on saved images. If possible
images obtained by the radiologist should be
accessible to the endocrine surgeon both in the
short and in the long term. Standardized reporting by both radiologist and surgeons makes
long-term care of patients with thyroid disease
easier and more accurate.
Standard Evaluation of the Thyroid by Ultrasound
USS is often the first imaging modality used to
investigate a thyroid mass in the euthyroid
51
THYROID IMAGING
Table 4.1. Possible applications of ultrasound in patients
with thyroid diseases
Diagnosis of thyroid aplasia or hypoplasia
Identification of ectopic thyroid tissue
In utero investigation of the fetal thyroid gland
Determination of thyroid size and morphology:
Volume
Thyroid morphology: diffuse goiter, multinodular
goiter, thyroid nodule
Echogenicity: hypoechoic, isoechoic, or hyperechoic
Blood flow determination
Evaluation of regional lymph nodes
Diagnostic fine needle aspiration biopsy
Treatment: cyst aspiration, ethanol injection, laser
photocoagulation
patient (Table 4.1) [6, 7]. USS is advantageous
because it is accessible, inexpensive, noninvasive, and avoids ionizing radiation. Ultrasound
scanning of the neck is performed by high-frequency transducers (7–13 MHz). Images are
obtained in the transverse (axial) and longitudinal (sagittal) planes (Figs. 4.1 and 4.2). Often a
sweeping and a painting motion of the wrist is
used to obtain images without undue pressure
on the neck of the patient. The trachea is often
used as the central orienting structure for most
ultrasonographers. Lateral and anterior to the
trachea lies the thyroid gland on transverse
images. Normal thyroid lobes show a homogenous echogenicity, whereas the echogenicity of
the sternocleidomastoid and strap muscles
(sternohyoid and sternothyroid) are lower [8].
Posterolaterally, the thyroid is bordered by the
sonolucent common carotid artery and internal
jugular vein and medially by trachea (Fig. 4.1A).
The esophagus with its echogenic mucosa can
usually be seen behind and to the left of the
trachea (Fig. 4.1B). Lymph nodes can be seen
medial or lateral to the major neck vessels;
lymph nodes in the level VI (pretracheal) compartment are more difficult to see because of
shadowing by the tracheal air column.
Ultrasound Evaluation of Thyroid
Nodules
Thyroid nodules are very common and may be
observed at USS in 50% of the adult population.
Many are not palpable, and the incidence of
thyroid cancer in incidentally identified or nonpalpable thyroid nodules is the same as that in
patients with palpable nodules [9]. Thyroid
malignancy is relatively rare and is diagnosed
in approximately 25,000 patients per year in the
USA [9]. The most common cause of benign
thyroid nodules is nodular hyperplasia [9].
Although less than 7% of thyroid nodules are
malignant [10], it is critical that they be accurately identified. Ultrasound can accurately
determine the size and location of thyroid
nodules
in two planes (longitudinal and transverse) to
be considered a true nodule (Fig. 4.2). Size measurements include transverse diameter (width),
antero-posterior diameter (AP diameter or
10
. All thyroid nodules need to be seen
ab
Fig. 4.1. Normal thyroid anatomy seen on transverse ultrasound images (A) Normal right with doppler. Trachea is seen as a
midline structure (TR), and carotid artery (C) and internal jugular vein (IJ) are seen bilaterally (B) Normal left. The esophagus is seen
on the left posteriorly.
52
ENDOCRINE SURGERY
ab
Fig. 4.2. Transverse and longitudinal images of the thyroid with measurement of nodule size in each. (A) Transverse image;
(B) longitudinal image.
depth), and longitudinal dimension (length).
USS can detect lesions as small as 2–3 mm
[2, 11]. Nodules found ‘‘incidentally’’ within a
clinically normal thyroid gland are referred to
as an ‘‘incidental thyroid nodule’’ or ‘‘thyroid
incidentaloma’’ [12]. Their frequency is higher
in women, increases with age, and varies
between countries [13], but generally there is a
high incidence in the population. The diffuse
use and high sensitivity of USS is helping the
incidental discovery of small and nonpalpable
thyroid nodules during carotid, parathyroid, or
other ultrasonographic examinations of the
neck. Moreover, USS shows one or more additional nodules in about 50% of patients with
clinically palpable solitary nodules [12].
The echogenicity of the nodules can vary
from hyper- to iso- to hypo-echoic, often even
in the same patient. USS examination should
search for additional, unsuspected nodules;
measure number of nodules and size; record
sonographic appearances to assess risk of
malignancy and select lesions that require
USS-guided FNAB [14, 15]. Several studies
have been performed to establish whether specific findings in a thyroid USS alone can differentiate benign from malignant thyroid nodules.
While these signs are useful and widely used by
those experienced in thyroid USS, ultrasound
alone cannot reliably distinguish benign and
malignant nodules [16, 17]. Although individual
USS features may be of limited value, when
multiple signs of thyroid malignancy appear in
combination it is at least possible to make some
accurate predictions. FNAB and cytological
examination have higher sensitivity and specificity, and are considered the best single test in
all patients with thyroid nodules; better than
thyroid USS alone [18]. Most benign thyroid
nodules are hypoechoic. USS patterns predicting thyroid malignancy include hypoechogenicity of the nodule, microcalcifications, central
(intranodular) increased vascularity and
absence of a halo sign (Table 4.2)(Fig. 4.3).
The risk of malignancy in thyroid nodules
occurring within a multinodular goiter (MNG)
has not been completely clarified, but some
authors find a similar frequency in uni- and
Table 4.2. Ultrasound characteristics of more commonly
associated with benign and malignant nodules
Features Benign Malignant
Echogenecity Hyperechoic Hypoechoic or
heterogeneous
Margins Smooth
border or
complete
halo
Colloid Comet tail
sign
Calcifications Peripheral
(eggshell)
Vascularity Peripheral Intranodular/central
Shape Flattened Rounded
Lymphadenopathy Absent Present
Cyst Thin walled Thick walled
Irregular border or
invasion into
adjacent tissue
–
Microcalcifications
53
THYROID IMAGING
a
b
Table 4.3. Biopsy recommendations for patients with
multiple thyroid nodules using ultrasound
Guidelines Recommendation
62
AACE
63
ATA
80
SRU
AACE: American Association of Clinical Endocrinologists; ATA: American Thyroid Association; SRU: Society of Radiologists in Ultrasound;
US: ultrasonographic.
In multinodular thyroid glands, the cytologic
sampling should be focused on lesions
characterized by suspicious US features
rather than on larger nodules
If two or more thyroid nodules >1–1.5 cm
are present, those who have a suspicious
US appearance should be aspirated
preferentially
In patients who have multiple discrete
nodules, the selection should be based
primarily on US characteristics rather than
nodule size
FNAB providing a decrease in nondiagnostic
rates from 15% to between 3.5 and 7% [19, 20].
In addition, it has been also recommended that
nodules less than 10 mm, detected incidentally,
do not require an FNAB. However, thyroid
malignancy was found in 6% of nonpalpable
lesions of 8–15 mm in size in MNGs and in 9%
in solitary thyroid nodules and the risk was
similar in nodules smaller or greater than
10 mm [10, 21]. Biopsy recommendations for
c
patients with multiple nodules seen on an USS
survey is presented in Table 4.3 [14].
Fig. 4.3. Transverse (A) and longitudinal (B) thyroid ultra-
sound images of a suspicious thyroid nodule. This nodule is
irregular, hypoechoic, has microcalcifications, and increased
intranodular vascularity on Doppler imaging (C).
MNGs. The possibility of thyroid malignancy
should be considered in all patients with
MNGs, and the use of USS guidance has been
shown to enhance the diagnostic efficacy of
Ultrasound Evaluation for Thyroid
Goiter
The diagnosis of goiter is based on physical
examination, though accurate measurements
are difficult without the aid of ultrasound [22].
Using this technique thyroid volume (in normal
adults subjects) ranges from 5 to 20 ml and is
related to age and body weight in both sexes
[23]. Thyroid ultrasound is not able to completely characterize intrathoracic extensions of the
thyroid [24, 25,]. Patients with goiter often have
them followed by ultrasound, sometimes many
times during their lifetime, though generally
decision making about surgical intervention is
often based on clinical grounds. Thyroid
volume is measured by real-time USS and
ENDOCRINE SURGERY
54
length width thickness of the thyroid lobe
multiplied by factor p/6, correspond to a rotation ellipsoid, while the best calculated volume
of the lobe is obtained by multiplying with the
optimized correction factor f ¼ 0.479; average
error of this method is 16%.
Multinodular goiter: Clinical evaluation of
patients with MNG is inaccurate and up to 50%
of subjects with a solitary palpable nodule or a
diffusely enlarged gland actually have multiple
nodules when investigated by USS [21]. It has
been recommended that all patients who have a
nodular thyroid, with a palpable solitary nodule
or a MNG should be evaluated by USS [26, 27].
The echogenicity of the nodules can vary from
hyper- to iso- to hypo-echoic, often even in the
same patient. USS examination should search for
additional, unsuspected nodules; measure
nodule, number, and size; record sonographic
appearances to assess risk of malignancy and
select lesions that require USS-guided FNAB [14].
Ultrasound Evaluation of Diffuse
Diseases of the Thyroid
Nonautoimmune nontoxic diffuse goiter appears
on USS as diffusely enlarged thyroid lobes with a
uniform or slightly irregular echogenicity. A diffuse reduction of thyroid echogenicity has been
seen in autoimmune thyroid disease (AITD),
which includes chronic lymphocytic thyroiditis
(Hashimoto’s thyroiditis), Graves’ disease, and
subacute thyroiditis [28, 29].
In Hashimoto’s thyroiditis, the most common
of the chronic thyroiditides and the most common thyroiditis in children, several patterns are
described: the thyroid gland can be normal in
size or enlarged, showing heterogeneous echogenicity or multiple hypoechoic or hyperechoic
areas separated by fibrous strands. In end-stage
disease, the thyroid gland can become small and
fibrotic, resulting in heterogeneous echo structure
[6, 7, 28, 29]. USS cannot distinguish autoimmune
thyroiditis from non-Hodgkin’s lymphoma.
Thyroid lymphoma occurs almost exclusively
in the thyroid gland of patients with Hashimoto’s thyroiditis as a rapidly growing mass in the
thyroid gland. The most common clinical manifestations are characterized by an enlarging
goiter and compressive symptoms [30]. On
USS lymphoma has a characteristic asymmetrical pseudocystic pattern [30].
Graves’ thyrotoxicosis patients have an
abnormal thyroid USS pattern characterized
by a diffuse low echogenicity with variable
degrees of increased blood flow. Color Doppler
USS may be a useful, noninvasive, and rapid
method also for differentiating subacute thyroiditis from Graves’ disease [31]. During the acute
stage of subacute thyroiditis, color Doppler USS
shows low echogenicity without increased tissue
vascularity in the affected swollen thyroid [31].
In the recovery stage, color Doppler ultrasonography showed isoechogenicity with slightly
increased vascularization. Vascularization
becomes normal at 1-year follow-up time [31].
Conversely, marked vascularization was
observed in patients with untreated Graves’ disease [31]. Moreover, on USS subacute thyroiditis is characterized by an enlarged thyroid gland
with some hypoechoic areas [32]. Interestingly,
methimazole (MMI) treatment induces changes
in thyroid hypoechogenicity, mainly in patients
who subsequently go into remission. The
absence or a low grade of thyroid hypoechogenicity after MMI treatment seems to be a
favorable prognostic indicator of remission in
Graves’ disease. Therefore, the evaluation of
thyroid echographic pattern can be considered
a useful prognostic tool in patients with Graves’
thyrotoxicosis [33, 34]. Color flow Doppler USS
can distinguish nodular variants of Graves’ disease from nonautoimmune forms of toxic MNG
[35]. Nodular variants of Graves’ disease are
characterized by nodules with normal vascularity surrounded by diffuse parenchymal hypoechogenicity with increased color flow Doppler
signal and maximal peak systolic velocity;
whereas nonautoimmune toxic MNG shows an
increased intra- and perinodular color flow
Doppler signal and peak systolic velocity and a
normal extranodular vascularity has been
described [35]. Interestingly, it has been
reported that in patients with thyrotoxicosis
factitia, the thyroid gland shows a normal
volume and echogenicity at USS and absent
hypervascularity or minimal intrathyroidal vascular spots at color flow Doppler USS [36].
Amiodarone-induced thyrotoxicosis (AIT)
occurs both in abnormal thyroid glands (nodular goiter, latent Graves’ disease) (type I AIT) or
in apparently normal thyroid glands (type II
AIT). Distinguishing the two forms is very
important clinically, because type I AIT
responds to MMI and potassium perchlorate
55
THYROID IMAGING
combined treatment, whereas type II AIT is
managed by glucocorticoids [37]. Color
flow Doppler USS is a technique that shows
intrathyroidal blood flow and provides realtime informations on thyroid morphology
and hyperfunction, representing a valuable tool
for a quick differentiation between the two types
of AIT (hypervascularity in patients with AIT
type I and absent vascularity in patients
with AIT type II). Therefore, the application of
Color flow Doppler USS has been shown to be
useful in patients with AIT, permitting an appropriate treatment and so a rapid control of
thyrotoxicosis.
Ultrasound Evaluation of Thyroid
Cysts
Thyroid cysts are benign lesions, which on USS
show a low or no echogenicity or with few
echoes in the presence of debris or necrotic
tissue. By USS, 15–25% of solitary thyroid
nodules are cystic [21]. Some studies indicate a
lower frequency of malignancy in a cystic than
in a solid thyroid lesion [21], and most cysts
originate from benign thyroid tissue (Fig. 4.4A)
[21]. The treatment of choice is aspiration, but
the recurrence rate is 10–80% depending on the
number of aspirations and cyst volume [21].
Some benign cystic nodules resolve spontaneously [21]. Indications for therapy are symptoms of compression. Smaller cysts (2–3 ml) are
generally best left untreated [21]. If larger, it is
possible to perform aspiration and FNAB of any
residual nodule.
Ultrasound-Guided Fine-Needle
Aspiration Biopsy
Ultrasound can also used to guide FNAB, which
aids in positioning of the needle within the
lesion. The needle tip can be followed ultrasonographically as it travels and then enters a nodule
or suspicious lesion in the thyroid. FNAB is safe,
simple, and accurate. It is done in an outpatient
setting, and repeated aspirations may be done
[38]. FNAB in general is highly accurate and
overall reduces the number of patients referred
for surgery. FNAB reliability may vary widely
from one group to another, with a sensitivity
ranging from 57 to 93% [39, 40]. Image-guided
FNAB has reported accuracy of more than 95%
[7]. USS-guided FNAB allows more material to
be obtained for sampling in order to exclude
thyroid cancer reducing potential false-negative
diagnoses to about 1–5% [38, 41]. Finally, ultrasound-guided FNAB improves the accuracy and
reduces the rate of nondiagnostic FNAB of smaller thyroid nodules [42], increasing diagnostic
precision and significantly affecting thyroid
practice. In addition, USS and USS-guided
FNAB can be used to [43] characterize and detect
clinically occult thyroid bed tumor recurrence
and lymph node metastases.
Ultrasound Evaluation of Thyroid
Cancer
Thyroid ultrasound is a mainstay diagnostic
tool before and after treatment for all patients
a
Fig. 4.4. (A) Anechoic right thyroid cyst. (B) Cystic right-side lymph node, lateral to right carotid, FNA showed papillary carcinoma.
b
ENDOCRINE SURGERY
56
with thyroid cancer. The incidence of differentiated thyroid cancer (DTC) has increased over
the past few decades possibly due to more people being diagnosed as a result of extensive
screening especially with ultrasound.
Screening for thyroid cancer with USS:
Because of the high prevalence of small, clinically inapparent thyroid nodules and the minimal aggressiveness of most thyroid cancers,
USS should be used as a screening test only if
well-known risk factors are present [14]. Sonographic examination should be ordered for all
patients who have a history of familial thyroid
cancer, multiple endocrine neoplasia type 2, or
childhood head/neck history irradiation, even if
the thyroid is normal by palpation [26, 44].
USS features of thyroid cancer: Ultrasound
features more commonly associated with thyroid cancer are summarized in Table 4.3. The
specificity of USS features for diagnosing thyroid carcinoma varies from 85 to 95% for microcalcifications (small intranodular punctate
hyperechoic spots, with scanty or no posterior
acoustic shadowing), from 80 to 87% for solid
hypoechoic appearance, from 83 to 85% for
irregular or indistinct nodule margins, and
about 81% for chaotic and increased intranodular vascularity [9, 10, 45, 46]. In addition, some
authors report that a nodule shape taller than
wide may be suggestive of malignancy [47]. The
predictive value of these USS features for cancer
is in part diminished by their low sensitivity
(29.0–59.2%, 55.1–77.5%, and 74.2%, respectively), and no USS sign by itself can reliably
predict malignancy. The association of hypoechoic appearance of the nodule with at least one
or more USS features suggestive of malignancy
effectively indicates a subset of nonpalpable
thyroid nodules at higher risk for malignancy
[10, 46]. The presence of at least two suspicious
sonographic criteria reliably identifies 85–93%
of thyroid gland neoplastic lesions, thus
decreasing the number of USS-FNAB procedures to about one third of the nonpalpable
nodules (Fig. 4.3) [10, 48, 49].
The finding of adenopathy, or presence of a
cystic mass on ultrasound in the anterior or
lateral neck compartments on USS examination
is suspicious for thyroid cancer, even if the
thyroid itself is otherwise normal, given the
well-described risk of nodal metastasis from an
otherwise unrecognized papillary microcarcinoma [14] (Fig. 4.4B).
Ultrasound Evaluation for Thyroid
Cancer Recurrence
In the last decade several advances have been
developed to aid in the early detection of recurrent thyroid cancer [50]. These include (1) sensitive, reliable, and reproducible thyroglobulin
(Tg) assay that biochemically detects the earliest
sign of cancer recurrence; (2) development of
recombinant human thyroid-stimulating hormone (rhTSH) that allows scanning and Tg stimulation without thyroid hormone withdrawal;
(3) high-resolution ultrasound of the postoperative neck to identify early lymph node
recurrence. Neck ultrasonography is useful in
the follow-up of patients with DTC and in many
centers have replaced diagnostic radioactive
iodine scanning as the modality of choice for
follow-up of patients [27, 51]. Sensitivity of US
for the diagnosis of neck recurrence ranges
from 70 to 100% [52, 53, 54]. Using these new
tools, especially Tg after rhTSH stimulation and
neck ultrasound combined with ultrasoundguided FNAB of suspicious lymph nodes, sensitivity of thyroid cancer surveillance has
improved. Since most thyroid cancer metastasizes to the neck, and it is rare for thyroid cancer
to spread elsewhere without neck lymph node
involvement, neck ultrasound has proven very
helpful in locating early recurrent disease
even before serum Tg is elevated. It is also
valuable in following patients with positive
anti-Tg antibodies (anti-TgAb) [50]. Identifying
and evaluating lymph nodes should be done
with high-resolution ultrasound using a 10- to
14-MHz transducer with Doppler capability to
assess vascularity [50], concentrating on the
thyroid bed and jugular lymph nodes, although
metastatic lymph nodes may occur anywhere in
the neck [50].
Metastatic lymph nodes tend to be large,
round, hypoechoic, hypervascularized with a
loss of hilar architecture. The short to long
axis ratio (S/L) is a useful way to detect lymph
node metastasis as opposed to the long axis
alone. In other words, the lymph node exceeding 10 mm in long axis and with S/L over 0.5
showed a much higher incidence of metastasis
than S/L under 0.5 [55, 56, 57]. In DTC, metastatic lymph nodes may also demonstrate specific features such as hyperechoic punctuations
or microcalcifications and cystic appearance
57
THYROID IMAGING
[58, 59, 60]. Confirmation of malignancy of suspicious lymph nodes found on USS is usually
recommended and consists of an FNAB for
cytology and Tg determination in the aspirate
fluid [61]. Cystic appearance, hyperechoic
punctuations, loss of hilum, and peripheral vascularization can be considered major ultrasound criteria of lymph node malignancy.
Lymph nodes with cystic appearance or hyperechoic punctuations are highly suspicious for
malignancy. Lymph nodes with a hyperechoic
hilum should be considered as benign. Round
shape, hypoechogenicity, and the loss of hilum
taken as single criteria are not specific enough
to suspect malignancy [62]. Those performing
ultrasound should make a map of the potentially affected lymph nodes to aid the surgeon
in identifying and excising the correct lymph
node basin. Surgeon performed ultrasound
may be of additional help.
Single Photon Nuclear Medicine
Imaging
Commonly Used Radionuclides
Thyroid scintigraphy provides a visual
display of functional thyroid tissue following
the administration of a radionuclide that
concentrates in thyroid tissue. It can provide
valuable information regarding both thyroid
anatomy and function and can play an integral
role in the diagnosis and management of thyroid disease. Iodine or its ionized form (Iodide or
–
I
) is an essential component of the triodothyronine (T3) and thyroxine (T4) and is accumulated in the thyroid, where it plays a critical role
in the physiology and pathophysiology of the
gland. The transport of iodide by the sodium/
iodide symporter (NIS) is the first event in thyroid hormogenesis. The NIS is a protein located
on the basolateral membrane of the thyroid
follicular cells by which the thyroid concentrates iodide and it has been cloned and characterized [63, 64]. Under physiological conditions the expression of NIS in thyroid cells is
mainly dependent on TSH [65]. Iodide transport by NIS also occurs in some extrathyroidal
tissues, such as breast, salivary gland, and gastric mucosa, though differently regulated [65].
NIS mediates the first and crucial step in the
process of supplying iodide to the thyroid gland
for thyroid hormone synthesis. After the step of
iodide transport into thyroid follicular cells
using the NIS, iodine is then passively translocated via an I
channel across the apical mem-
brane into the colloid.
There are different iodine radionuclides
(summarized in Table 4.4) but only iodine-123
Table 4.4. Common isotopes used in thyroid imaging
Radionuclide Half-life Emission Dose mCi (MBq) Clinical application
I-127 Nonradioactive None – Fluorescent scanning
I-123 13.2 h g 159 keV 0.1–0.4 (3.7–14.8) Routine thyroid scanning; Whole-body
scanning
I-131 8.09 days g 364 keV 1–5 (37–185) Whole-body scanning, therapy for benign and
I-124 4.2 days b
I-125 60 days g 25-35 keV In vitro applications
Tc-99m-Tc O
Tl-Tl-201 73 h g 135-167 keV 2–4 (74–148) Follow-up recurrent thyroid cancer
Tc-99m-
sestamibi
In-111-
pentreotide
6h g 140 keV 1–10 (37–370) Routine thyroid scanning
4
6h g 140 keV 15–20 (555–740) Diagnosis of thyroid cancer patients with
2.5 days g 172 keV
+
positron
emitter
g 247 keV
– Iodine PET-scanning therapy
3.3 (122) Noniodine concentrating thyroid cancer
malignant thyroid disorders
elevated thyroglobulin levels and negative
I-131 scan
scanning; Medullary thyroid cancer
scanning
ENDOCRINE SURGERY
58
(I-123) and iodine-131 (I-131) are used routinely for thyroid-imaging in nuclear medicine,
always administered by mouth [7]. Iodine-131
(half-life 8.1 days) was the first radionuclide to
be used for imaging. The 364-keV gamma emission of I-131 enables scintigraphic imaging, but
this energy is higher than is optimal for gamma
cameras resulting in poor spatial resolution of I131 scans performed even with high-energy collimators. Given the high radioactive burden,
principally due to its beta emissions, and the
poor spatial resolution of the images, I-131 is
unsuitable for routine diagnostic thyroid
nuclear scan of benign thyroid disorders [66].
I-131 is mainly applied in diagnostic and posttreatment whole-body scanning in patients with
thyroid cancer [67]. Conversely, Iodine-123 is a
gamma emitter with favorable characteristics
(physical half-life: 13.3 h; gamma energy:
159 keV), but because a cyclotron was required
for production, its availability used to be limited, though now it is routinely available for
everyday use [66]. Many nuclear medicine
departments now routinely use I-123 for routine
thyroid scanning and for diagnostic whole-body
scanning.
There are also noniodine radionuclides used
for thyroid imaging such as Technetium-99m
pertechnetate (Tc-99m), which has become a
tracer commonly used for thyroid scintigraphy.
Tc-99m compared with I-123 has the following
advantages: daily availability in every nuclear
medicine unit, a shorter physical half-life (6 h),
and a preferable favorable energy (140 keV) for
scintigraphic imaging. Intravenously administered Tc-99m is loosely bound to plasma proteins and rapidly moves out of the intravascular
compartment, is transported by the NIS into the
follicular thyroid cell but is not organified. The
thyroid uptake of Tc-99m increases within the
first 15 min after intravenous administration
(influx >efflux), showing a plateau phase
between 15 and 30 min and decreases after
30 min. In comparison with I-123, Tc-99m has
a lower radiation dose to the thyroid, but a
larger effective dose to the whole body. Iodine
is very heavily concentrated in the thyroid
whereas Tc-99m is not. Thus, the dose to the
thyroid is greater with I-123, but the effective
dose is higher with Tc-99m. The range of normal uptake of Tc-99m is 0.25–3% of the injected
dose and the peak is earlier in a hyperthyroid
gland [68].
Less Commonly Used Radionuclides
Other noniodine radionuclides are: Thallium201 (Tl-201) was historically used in follow-up
study of postoperative patients with thyroid
cancer [69]; Tc-methoxyisobutlylisonitrile-99m
(Tc-sestamibi-99m) shows optimal image resolution and was used in those patients with
abnormal thyroglobulin value and negative
I-131 nuclear scan [70]; In-pentreotide-111,a
radiolabeled somatostatin analog (an octreotide
analog), is occasionally useful in cases of thyroid cancers that do not have iodine uptake such
as medullary carcinoma or other noniodine avid
DTCs, such as some Hurthle cellneoplasms. Use
of both Tl-201 and Tc-methoxyisobutlylisonitrile-99m (Tc-sestamibi-99m) has been replaced
by PET/CT in follow-up of DTC patients with
iodine nonavid disease. [71]
Uptake and Thyroid Scintigraphy
Thyroid scintigraphy is used in the differential
diagnosis of hyperthyroidism, to distinguish
other causes of thyrotoxicosis from hyperthyroidism, to help calculate therapeutic dose of I131 and to detect intrathyroidal defects in organification. Prior to thyroid scanning patients
should avoid all thyroid hormones or antithyroid medications, excess of iodine ingestion, and
injection of radiographic contrast media [67].
Radioiodine uptake value may be measured
early at 4–6 h and/or late at 24 h; a higher uptake
is occasionally seen on the early measurements
in patients with severe hyperthyroidism [67]. It
is generally possible to predict 24-hour uptake
from 4- or 6-hour uptake values with a low
potential error [72].
Increased uptake is typical in hyperthyroidism, iodine deficiency, and pregnancy (nuclear
scan tests should generally not be performed in
pregnant women), although occasionally uptakes
are used by some endocrinologists during pregnancy to distinguish Graves’ from thyroiditis
recovery phase of thyroiditis, lymphocytic thyroiditis, rebound after suppression of thyrotropin,
rebound after withdrawal of antithyroid medication, lithium carbonate therapy, amiodarone,
nontrapping defects of thyroid hormonogenesis.
Causes of decreased uptake include primary
hypothyroidism, destructive thyroiditis (subacute thyroiditis, silent thyroiditis, postpartum
thyroiditis) thyroidectomy, I-131 treatment,
59
THYROID IMAGING
external neck radiation, central hypothyroidism, thyroid hormone, excess iodine, dietary
variations, dietary supplements, radiological
contrast, amiodarone, topical iodine, medications other than those containing iodine,
antithyroid drugs, perchlorate, thiocyanate, sulphonamides, sulphonylurea, and high-dose
glucocorticosteroids [67].
Generally scintigraphy is not used routinely
to evaluate thyroid nodules except in those with
a suppressed thyroid-stimulating hormone
level, in whom it is more likely to find a hyperfunctioning nodule. A particular thyroid nodule
by nuclear scan analysis can be described as
‘‘cold’’ (nonfunctioning) or ‘‘hot’’ (hyperfunctioning). A functioning ‘‘hot’’ thyroid nodule is
rarely malignant though there are rare cases of
patients harbouring malignancy in a ‘‘hot’’
nodule [73, 74, 75, 76, 77, 78]. A nonfunctioning
thyroid nodule at scintigraphy is commonly
considered to indicate an increased risk of thyroid malignancy; however, overall only 5% of
nonfunctioning ‘‘cold’’ nodules are malignant
[15]. Therefore, thyroid scintigraphy is only
useful when a ‘‘hot’’ nodule is detected.
Thyroid Scintigraphy in Patients
with Hyperthyroidism
Thyrotoxicosis is caused by an excess of circulating free T4 and T3. Since the three most
common causes of hyperthyroidism are well
distinguished by thyroid scanning, this remains
one of the most common reasons thyroid scanning is used. The causes of thyrotoxicosis on
nuclear scan imaging can be distinguished
based on the pattern of iodine uptake. Patients
with hyperthyroidism and diffuse high uptake
have Graves’ disease – rarely TSH-secreting
pituitary tumors, placental tumors (choriocarcinoma, hydatiform mole). Patients with
hyperthyroidism and focal high uptake are toxic
MNG and single autonomous nodule, – rarely
thyroid cancer (follicular cancer) and struma
ovarii. Hyperthyroid disorders with low uptake
are thyroiditides, factitious thyrotoxicosis, thyrotoxicosis medicamentosa, excess iodine exposure [67].
Graves’ disease (associated with uniform
high intake of iodine) is characterized on
nuclear scanning (Fig. 4.5A) by a diffusely
enlarged thyroid gland and both early and late
uptake are uniformly increased (often 50–80%
at 24 h). In patients with toxic multinodular
goiter, the hyperfunctioning nodule(s) show
somewhat lower 24 h radioiodine uptakes
which may be in the normal range (often
20–40% at 24 h). Due to the suppressed TSH,
normal tissue is not visible. Destructive (suba-
cute) thyroiditis shows a reduced uptake 2%
[67, 79]. In patients with a single toxic adenoma
(hyperfunctioning nodule)(Fig. 4.5B), a single
a
Fig. 4.5. Thyroid scan (I-123) in a patient with Graves’ disease (A) and a single autonomous nodule (B).
b