Imaging of the Thyroid in

Benign and Malignant Disease

Charles M. Intenzo, MD,* Hung Q. Dam, MD,† Timothy A. Manzone, MD, JD,† and
Sung M. Kim, MD*

The thyroid gland was one of the first organs imaged in nuclear medicine, beginning in the
1940s. Thyroid scintigraphy is based on a specific phase or prelude to thyroid hormone
synthesis, namely trapping of iodide or iodide analogues (ie, Tc99m pertechnetate), and in
the case of radioactive iodine, eventual incorporation into thyroid hormone synthesis within
the thyroid follicle. Moreover, thyroid scintigraphy is a reflection of the functional state of
the gland, as well as the physiological state of any structure (ie, nodule) within the gland.
Scintigraphy, therefore, provides information that anatomical imaging (ie, ultrasound, com-
puted tomography [CT], magnetic resonance imaging) lacks. Thyroid scintigraphy plays an
essential role in the management of patients with benign or malignant thyroid disease. In
the former, the structure or architecture of the gland is best demonstrated by anatomical or
cross-sectional imaging, such as ultrasound, CT, or even magnetic resonance imaging. The
role of scintigraphy, however, is to display the functional state of the thyroid gland or that
of a clinically palpable nodule within the gland. Such information is most useful in (1)
patients with thyrotoxicosis, and (2) those patients whose thyroid nodules would not
require tissue sampling if their nodules are hyperfunctioning. In neoplastic thyroid disease,
thyroid scintigraphy is often standard of care for postthyroidectomy remnant evaluation and
in subsequent thyroid cancer surveillance. Planar radioiodine imaging, in the form of the
whole-body scan (WBS) and posttherapy scan (PTS), is a fundamental tool in differentiated
thyroid cancer management. Continued controversy remains over the utility of WBS in a
variety of patient risk groups and clinical scenarios. Proponents on both sides of the
arguments compare WBS with PTS, thyroglobulin, and other imaging modalities with
differing results. The paucity of large, randomized, prospective studies results in depen-
dence on consensus expert opinion and retrospective analysis with inherent bias. With a
growing trend not to ablate low-risk patients, so that a PTS cannot be performed, some
thyroid carcinoma patients may never have radioiodine imaging. In routine clinical practice,
however, imaging plays a critical role in patient management both before and after treat-
ment. Moreover, as evidenced by the robust flow of publications concerning WBS and PTS,
planar imaging of thyroid carcinoma remains a topic of great interest in this modern age of
rapidly advancing cross sectional and hybrid imaging with single-photon emission com-
puted tomography, single-photon emission computed tomography/CT, and positron emis-
sion tomography/CT.
Semin Nucl Med 42:49-61 © 2012 Published by Elsevier Inc.

Benign Thyroid Disease

*Division of Nuclear Medicine, Department of Radiology, Thomas Jefferson
University, Philadelphia, PA.
†Division of Nuclear Medicine, Department of Medicine, Christiana Care
Health System, Helen F. Graham Cancer Center, Newark, DE.
Address reprint requests to Charles M. Intenzo, MD, Division of Nuclear
Medicine, Department of Radiology, Thomas Jefferson University, 1020
Walnut Street, Philadelphia, PA 19107. E-mail: charles.intenzo@
jefferson.edu
Radiopharmaceuticals and
Scintigraphic Imaging Technique
In our laboratory, thyroid scintigraphy is performed primar-
ily with technetium-99m (Tc99m) pertechnetate (Fig. 1).
Ten millicuries (370 MBq) are injected intravenously, and
imaging begins at approximately 15 minutes after injection.
On a pinhole collimator with a 3.5-mm aperture, the gamma
camera energy setting is placed on the 140 keV photopeak for

0001-2998/12/$-see front matter © 2012 Published by Elsevier Inc. 49

doi:10.1053/j.semnuclmed.2011.07.004
50
Figure 1 Normal Tc99m pertechnetate thyroid scan.
Tc99m pertechnetate, with a 10% window. Four images are
then acquired each for 100,000 counts. These include ante-
rior as well as left and right anterior oblique images, all of
which are acquired with the pinhole aperture as close to the
patient’s extended neck as possible. The fourth image is then
obtained with the collimator positioned 10 cm above the
patient’s neck, which is extended anteriorly. A 2-cm lead
marker is placed at the sternal notch to assess the size of the
thyroid gland as well as the size of thyroid nodules, if present.
The field of view for this distant anterior projection extends
from the sternal notch to the salivary glands. Radioactive
iodine uptake (RAIU) measurements are obtained with the
use of a thyroid probe 24 hours after the oral administration
Figure 2 Discordant I-123/Tc99m pertechnetate thyroid nodule: Tc99m pertechnetate thyroid image (left) reveals a
hyperfunctioning nodule in the right thyroid lobe. 123I image in same patient (right) shows a congruent cold nodule.
Final pathology was papillary thyroid cancer (courtesy of Dr Leonard M. Freeman).
C.M. Intenzo et al
of a capsule consisting of 5 ␮Ci of 0.19 MBq of iodine-131
(131I).
Radiologists in many centers prefer iodine-123 (123I) for
thyroid scintigraphy over Tc99m pertechnetate because it is
trapped and organified, similar to stable iodine, and is theo-
retically an ideal thyroid tracer. The RAIU is obtained 24
hours after the patient orally ingests a capsule consisting of
200-400 ␮Ci (7.33-14.77 MBq) of 123I. Images are subse-
quently obtained in a similar fashion as those involving
Tc99m pertechnetate; however, the energy setting is on the
159 keV photopeak for 123I. We prefer using Tc99m pertech-
netate over 123I for several reasons. First, the count rate when
Tc99m pertechnetate is used is significantly faster than that
of 123I because of the significantly greater allowable dose of
Tc99m pertechnetate (370 MBq) compared with 123I
(7.33-14 MBq). For the same number of counts, an image
obtained from 123I takes substantially longer as opposed to
that obtained with Tc99m pertechnetate; consequently, a
smaller number of counts are acquired with 123I because of
the much lower count rate that allows a reasonable acquisi-
tion time. A greater count rate for Tc99m pertechnetate pro-
vides a better-quality image. Second, there is a logistical ad-
vantage of Tc99m pertechnetate over 123I. The former is
readily available either from molybdenum generators in hos-
pital nuclear laboratories or in bulk unit doses delivered
daily. Such easy access facilitates scheduling. 123I capsules, by
contrast, are cyclotron-produced and must be ordered in
advance from the distributor. Third, a dose of Tc99m
pertechnetate is significantly less expensive than an 123I cap-
sule, an important consideration in this era of health care cost
containment.
123I has a distinct advantage over Tc99m pertechnetate in
the evaluation of a particular thyroid nodule that appears
“warm” on a Tc99m pertechnetate scan but cold on an 123I
scan (Fig. 2). Such a “discordant” 123I/Tc99m pertechnetate
nodule traps Tc99m pertechnetate but does not organify io-
Imaging of the thyroid in benign and malignant disease 51

ule, and the scan should be repeated with 123I. Those who
prefer using 123I routinely claim that the need for a second
examination is avoided by using 123I at the start. However, a
discordant nodule is an uncommon occurrence and ⬍5% of
thyroid carcinomas present as a discordant nodule.1 Because
this scenario is encountered so infrequently, those who favor
Tc99m pertechnetate argue the routine use of 123I is not war-
ranted. At our institution, we only use 123I to exclude a dis-
cordant nodule (an uncommon occurrence), or if it is specif-
ically requested by the referring physician.
Another advantage of 123I over Tc-99 is for localization of
ectopic thyroid tissue because there is little to no background
activity on an 123I image compared with a Tc99m pertechne-
tate image, both in the head and neck (Fig. 3), and in the
pelvis (Fig. 4).

Figure 3 Lingual thyroid: 123I scan demonstrates oropharyngeal ac-
tivity (at tope of image) that conceivably could be obscured by
background activity from salivary gland secretion on a Tc99m
pertechnetate scan.
dine and is therefore a true cold nodule that requires further
work-up, possibly fine-needle aspiration, depending on the
patient’s risk factors for malignancy. Consequently, a solitary
nodule that appears warm (ie, increased activity) on Tc99m
pertechnetate could conceivably represent a discordant nod-
Thyrotoxicosis
Attributable to Hyperthyroidism
Graves’ Disease
Also termed diffuse toxic goiter, Graves’ disease is the most
common cause of hyperthyroidism. It is an autoimmune dis-
order involving autoantibodies to the thyroid-stimulating-
hormone (TSH) receptors on the follicle cell surface.2 These
TSH receptor antibodies result in hyperplasia of the follicles
with excess thyroid hormone production, with subsequent
TSH suppression. The RAIU is elevated at 24 hours, although
occasionally it is normal at 24 hours but elevated at 4 or 6
hours, referred to as Graves’ disease with rapid iodine turn-
over.3 The thyroid scan demonstrates a (usually) enlarged
gland with increased target-to-background activity (Fig. 5).

Figure 4 Ectopic thyroid in the pelvis: thyrotoxicosis and a pelvis mass on ultrasound prompted a CT of the pelvis (A)
in an 81-year-old woman, confirming the mass within the left ovary (arrow). Scintigraphy of the neck and pelvis (B)
demonstrates overall suppressed Tc99m pertechnetate activity in the thyroid (arrow, top left image) with a 24-hour
RAIU of 3%. An image of the pelvis was then obtained (top right), showing the pelvic mass (arrowhead) displacing the
bladder (arrow) to the right. A follow-up 123I scan of the pelvis (bottom left) postvoid confirms the pelvic mass (arrow).
Surgical removal of the mass subsequently led to the diagnosis of struma ovarii containing thyroid tissue. Two months
later, thyroid f unction normalized; the 24-hour RAIU was 16% and the Tc99m pertechnetate thyroid scan then
demonstrated normal tracer concentration. The 123I pelvic image clearly is superior to the Tc99m pertechnetate image,
whose bladder activity added to background.
52
Figure 5 Graves’ disease: The thyroid gland is enlarged with a
“dumbbell” or “bat-wing” shape, with elevated target-to-back-
ground activity.
Not uncommonly, a patient with Graves’ disease can be
found to have one or more TSH-dependent cold thyroid nod-
ules in addition to the diffuse toxic goiter, the so-called Ma-
rine-Lenhart Syndrome.4 This eponym is rarely used, and
this variation of Graves’ disease is usually referred to as nod-
Figure 6 Marine-Lenhart syndrome: as with Graves’ disease, the
gland is enlarged with increased target-to-background, however the
presence of cold nodules in both lobes (arrows) indicate Graves’
disease superimposed on a multinodular goiter.
C.M. Intenzo et al
Figure 7 Toxic autonomous nodule: Tc99m pertechnetate thyroid
scan in this thyrotoxic patient shows a hyperfunctioning nodule in
the left thyroid lobe entirely suppressing the remainder of the gland.
ular Graves’ disease or Graves’ disease coexistent with a
multinodular goiter (Fig. 6).
Toxic Autonomous Nodule
When one or more hot nodules in the thyroid produce excessive
amounts of thyroid hormone released into the systemic circula-
tion with consequent thyrotoxicosis, this is referred to as toxic
autonomous nodule(s), toxic adenoma, or the eponym Plum-
mer disease. The etiology is presumed to be a somatic mutation
in the TSH receptor gene within a thyroid adenoma, altering its
control by TSH, resulting in uninhibited production of thyroid
hormone.5 In scintigraphy, the toxic nodule appears hot,
whereas the extranodular (normal) thyroid tissue demonstrates
either faint or no activity because there is no stimulation by the
suppressed TSH (Fig. 7). The RAIU is either mildly elevated or
in the normal or upper-normal range.
Toxic Multinodular Goiter
This term is best described as a large, heterogeneous thyroid
gland with several nodules, both hyperfunctioning and non-
functioning, in the presence of hyperthyroidism. The exact
etiology is unclear; repeated follicle cell divisions eventually
form areas of hyperplasia, which eventually develop into au-
tonomous thyroid nodules unresponsive to TSH which co-
exist with the nonfunctioning (cold) nodules.6 In most indi-
viduals with multinodular goiter (MNG), any excess thyroid
hormone produced by the autonomous thyroid nodules is
balanced by decreased production by the cold nodules re-
sulting in a euthyroid state. In toxic MNG, however, this
homeostasis is offset by a net overproduction of thyroid hor-
mone, resulting in hyperthyroidism, which is usually mild.
Toxic MNG usually occurs in elderly patients; the RAIU is
usually either normal or slightly elevated. On scintigraphy,
Imaging of the thyroid in benign and malignant disease 53

Figure 8 Toxic multinodular goiter: both hot and cold nodules are Figure 9 Subacute thyroiditis: activity in the thyroid gland on this
scattered throughout the thyroid of a thyrotoxic patient. distant anterior image is virtually absent in this thyrotoxic patient
with palpable neck tenderness. The 24-hour RAIU was ⬍1%.

the thyroid gland is enlarged with multiple nodular areas, both

cold and hot, with an overall heterogeneous pattern (Fig. 8). period is called postpartum thyroiditis. The hyperthyroidism
occurs 2-6 months after delivery and usually last 2-6 weeks.
Thyrotoxicosis Attributable Silent thyroiditis has the same scintigraphic appearance as
to Thyroid Inflammation subacute thyroiditis for the same reason, ie, poor tracer concen-
Subacute Thyroiditis tration by the thyroid gland by the disrupted follicles (Fig. 10),
A viral infection of the thyroid gland, subacute thyroiditis
often follows an upper respiratory tract infection. There is
subsequent infiltration of giant cells and neutrophils into
the thyroid follicles, which swell and eventually disrupt. The
follicle swelling causes neck pain and tenderness, and the
follicle disruption causes excess release of thyroid hormone
in the circulation, with subsequent thyrotoxicosis. The TSH
level is then suppressed, and the RAIU is very low because the
damaged follicle cannot transport iodine.7 This inability to
transport iodine and anions similar to iodine (ie, Tc99m
pertechnetate) across the cell membrane inhibits radiophar-
maceutical concentration within the thyroid on scintigraphy
(Fig. 9). The hyperthyroidism generally subsides during a
period of weeks, followed by a hypothyroid phase, with
eventual recovery into the euthyroid state.
Silent Thyroiditis
Also referred to as painless thyroiditis or subacute lympho-
cytic thyroiditis, silent thyroiditis is caused by an infiltration
of lymphocytes into the thyroid follicles because of an auto-
immune response. This causes follicle disruption and subse-
quent thyrotoxicosis, similar to that seen in subacute thyroid-
itis.8 Unlike subacute thyroiditis, however, there is no Figure 10 Silent thyroiditis: there is markedly decreased activity in the
swelling of the follicles from giant cell infiltration, so there is thyroid compared with the submandibular gland at the top of the image
no neck tenderness on palpation. A period of transient hypo- in this thyrotoxic patient without any history of neck tenderness, nor
thyroidism eventually develops, followed by euthyroid re- thyroid hormone ingestion, nor intravenous contrast administration.
covery. Approximately 10% of patients will redevelop this The 24-hour RAIU was 4%. The thyroid peroxidase antibody levels
disorder.9 Silent thyroiditis occurring during the postpartum were elevated, indicating an autoimmune etiology.
54 C.M. Intenzo et al

with a very low RAIU. After the later period of hypothyroidism, 131I therapy can range from the same day to several days later,

however, the RAIU increases and the tracer concentration
within the thyroid gland is relatively increased above normal,
representing a “rebound” phenomenon.10
Malignant Thyroid Disease
The Radioiodine Whole-Body Scan (WBS)
Planar nuclear medicine imaging has traditionally played a
leading role in the management of patients with differenti-
ated thyroid cancer. After total or near-total thyroidectomy, a
diagnostic radioiodine WBS is typically performed. Because
functioning thyroid tissue concentrates radioiodine, the WBS
has several purposes: (1) to assess the amount of remnant
thyroid tissue from thyroidectomy, (2) to evaluate for func-
tioning metastases, (3) to guide the selection of therapeutic
131I dose, and (4) to reveal altered biodistribution (Fig. 11).
Commonly, the findings on a WBS are used to tailor the
therapeutic dose of 131I in conjunction with clinical, surgical,
and pathologic history. The interval between the WBS and
provided the patient remains hypothyroid until treatment.
In preparation for a WBS, the patient’s TSH is allowed to
increase greater than 30 mIU/L after thyroidectomy to opti-
mize the thyroid tissue avidity for radioiodine.11,12 Elevation
of TSH is also required for follow-up testing for the detection
of recurrent/residual thyroid carcinoma. TSH elevation can
be accomplished by either thyroid hormone withdrawal or
by administration of recombinant human TSH (rhTSH; Thy-
rogen; Genyzme, Cambridge, MA). This latter approach in-
volves daily intramuscular injections of 0.9 mg of rhTSH for
2 days. The patient is then administered a diagnostic dose of
131I or 123I on the third day. Imaging is performed on the
fourth day with 123I, and on the fifth day for 131I. Quantitative
serum thyroglobulin (Tg) level and anti-Tg antibodies
(TgAbs) are also drawn on day 5 to provide a “stimulated” Tg
measurement. WBS performed with rhTSH has diagnostic
accuracy comparable with the use of hormone with-
drawal.13,14 To maximize the sensitivity of the WBS, patients
should be encouraged to follow a low-iodine diet for 7-21

Figure 11 Anterior and posterior 123I diagnostic whole body scan on a 53-year-old female patient with a history of a
1.5-cm Hürthle cell carcinoma with capsular invasion. A large thyroid remnant is present as well as 2 discrete foci of
activity in the mediastinum representing lymph node metastases.
Imaging of the thyroid in benign and malignant disease
days, avoid exposure to iodinated contrast for radiologic
studies, and if possible, suspend known iodine-rich medica-
tions, such as amiodarone.11,12
Traditionally, a WBS has been acquired after an oral admin-
istration of a small dose of 131I several weeks after a thyroidec-
tomy. However, 123I has gained in popularity as its availability
has increased in recent years. Choosing which of these 2 radio-
isotopes to use for imaging requires careful consideration of the
differences in their physical characteristics. Because 123I has a
short half-life of 13.3 hours, imaging is performed at 24 hours
with a typical dose of 37-74 mBq (1-2 mCi). In contrast, 131I has
a much longer half-life of 8.02 days. Therefore, 131I scans are
acquired at a later time frame ranging from 24 to 72 hours.
Because of the differences in half-life, the radiation exposure
from 123I is much less than from 131I.15 By contrast, the short-half
of 123I necessitates imaging at 24 hours, at which time target-to-
background ratio may be suboptimal. Metastatic thyroid carci-
noma with slow radioiodine metabolism may not be able to
concentrate radioiodine in adequate amounts to be detected by
123I with its short half-life.15,16 Some authors have proposed
using greater doses of 111-185 mBq (3-5 mCi) of 123I, allowing
for delayed imaging at 48 hours, which may improve the detec-
tion rate of weakly avid thyroid remnant or metastatic dis-
ease.17-19
131I is a less than optimal diagnostic imaging agent because
of its high energy gamma energy of 364 keV. The lower
gamma energy of 123I (159 keV) makes it make more suitable
for imaging with conventional gamma cameras. Moreover,
the low-photon energy of 123I allows for imaging with single-
photon emission computed tomography. For nuclear medi-
cine departments on tight budgets, 131I may be the preferred
radiopharmaceutical because it is much more affordable than
123I, which is cyclotron-produced and therefore relatively
costly. The authors of many studies have shown that the use
of 131I or 123I has comparable effectiveness in detecting thy-
roid remnant tissue after thyroidectomy.19-24
The choice between 123I and 131I for the WBS also relates to
the controversial concept of thyroid stunning. Stunning refers to
reduced uptake of a therapeutic dose of 131I because of damage
to thyroid cells because of the beta emission from a WBS per-
formed with 131I.25 Because 123I is a pure gamma emitter, stun-
ning theoretically should not occur with this isotope.17,21 Silber-
stein26 demonstrated no significant difference in outcomes in
nonmetastatic thyroid cancer patients who had WBS with either
14.8 MBq (0.4 mCi) of 123I or 74 MBq (2 mCi) of 131I before
ablation with 3.7 GBq (100 mCi) of 131I. His data suggest that
even if stunning occurs with 131I, it does not affect ablation rates.
The concept of stunning is beyond the scope of this article, and
the reader is referred to the excellent recent review of this subject
by McDougall in this journal.27
Concern about stunning is one reason, along with the in-
creased availability of 123I, why many institutions no longer
use 131I for WBS. The same concerns underlie the great vari-
ation in doses of 131I used for WBS. Greater doses of up to 370
mBq (10 mCi) of 131I have been shown to have no additional
value compared with lower doses.28 Because the possibility of
stunning is in the minds of many practitioners, almost all use
much lower doses.29 Overall, the dose of 131I used for WBS
55
has gradually declined over the years. Current guidelines
recommend the use of 37-185 MBq (1-5 mCi) of 131I with
scanning performed 2-3 days later.11-12,30
WBS performed with 123I and 131I also require different cam-
era systems and collimators. High-energy, parallel hole collima-
tors are preferred for imaging the high energy 131I gamma pho-
tons. However, not all departments have a dedicated high
energy collimator, and some centers use more versatile medium
energy collimators for this purpose. Camera systems with
thicker crystals of up to 5/8-inch thickness are also preferred for
131I scans. In contrast, either an all-purpose or high-resolution
low energy collimator, which is available at all institutions, is
used to image 123I, with its lower energy photon.
When scanning thyroid cancer patients after radioiodine
administration, some institutions use anterior and posterior
whole-body sweeps from head-to-toe and whereas others
acquire multiple spot images of the head, neck, chest, abdo-
men, pelvis, and proximal lower extremities. Several authors
have cited the superiority of pinholes images of the neck and
have incorporated pinhole imaging into their protocols.31,32
Imaging with markers to define the location of the anatomic
landmarks, such as the sternal notch can be useful in problem
solving indeterminate sites of increased activity. Physicians
should review the images before the patient leaving the de-
partment to assess the need for additional views, such as
lateral or oblique projections.
The Posttherapy Scan (PTS)
A PTS is routinely obtained after 131I ablation to confirm
localization in remnant thyroid tissue. Both American and
European guidelines recommend routinely obtaining
PTS.11,30 The time frame in which the PTS is obtained after
131I therapy can vary from 3 to 8 days, with later imaging
providing greater target-to-background ratio. Although
the optimal time for performing the PTS remains contro-
versial, recent data surprising suggests that earlier imaging
at 72-96 hours may be preferred for the detection of met-
astatic disease.33 Because the therapeutic dose of 131I is
much greater than the low dose of 131I use for the WBS, the
PTS can reveal additional unexpected sites of uptake (Fig.
12), such as pulmonary or skeletal lesions, which may
alter staging and prognosis in some patients.29,34 As a re-
sult, the PTS can change patient management by leading to
immediate additional imaging studies, prompting an ear-
lier follow-up time frame, or altering plans for subsequent
WBS and additional 131I therapy. PTS can be more sensi-
tive than the WBS for detection of thyroid remnant and
metastatic disease because it is typically acquired several
days after therapy, compared with 48-72 hours for 131I
WBS. This difference provides a greater target-to-back-
ground ratio on the PTS. By contrast, dominant activity in
the thyroid bed on a PTS can mask smaller, less iodine-
avid locoregional metastases.18,35,36 The PTS can also be
helpful in patients with normal WBS but elevated stimu-
lated Tg levels. This scenario is an indication for 18F-fluo-
rodeoxyglucose positron emission tomography (PET)
scanning. However, if the PET scan is normal, then empiric 131I
56 C.M. Intenzo et al

Figure 12 (A) Anterior and posterior 123I diagnostic WBS on a 5-year-old boy with a history of papillary thyroid
carcinoma with multifocal lymphovascular invasion and positive surgical margins. Two intense lesions are present in
the thyroid bed suggesting thyroid remnant tissue. Subtle activity in the right lower neck is also noted. The patient was
subsequently treated with 1.9 GBq (52 mCi) of 131I. (B) PTS performed 7 days later revealed unexpected diffuse
pulmonary activity suggesting pulmonary metastases. The thyroid bed tissue is again identified and 2 definite lymph
node metastases are now present in the right neck.

therapy can be used followed by a PTS in an attempt to localize
the origin of the high Tg level. Either focal uptake on the PTS, or
low-level liver uptake from metabolism of radioactive Tg suggest
successful targeting of thyroid tissue. A follow-up WBS 6-12
months following 131I therapy is important to determine
whether the treatment was successful or not, along with repeat
measurement of the stimulated Tg level.
Utility of the Diagnostic
WBS in the Preablation Setting
Much controversy currently exists over the need to obtain a
diagnostic WBS before 131I ablation. European guidelines do
not recommend routine use of initial preablation WBS.11 The
American Thyroid Association (ATA) currently recommends,
based on expert opinion only, a WBS before 131I ablation only
when the neck ultrasound or surgical report cannot ade-
quately define the extent of residual thyroid remnant or when
the WBS may alter the therapy dose or the decision to treat at
all.30 However, several authors remain strong proponents of
the continued use of WBS and cite many advantages of the
WBS scan.26,31,37 One such advantage is ability to assess the
size of the thyroid remnant. In a majority of patients,
the surgeon is unable to remove the entire thyroid gland
because of surgical experience and risk of damaging the re-
current laryngeal nerve. As a result, considerable remnant
thyroid tissue may remain following surgery which can be
readily detected on a WBS by either 131I or 123I. A large thy-
roid remnant is problematic for several reasons. First, the
patients are at a greater risk for the development of radiation
thyroiditis after 131I therapy resulting in significant neck pain
and swelling. These patients may need to be pretreated with
corticosteroids to reduce the inflammatory response.30 Sec-
ond, a sizeable thyroid remnant may absorb the bulk of the
therapeutic 131I dose, limiting the amount available to treat
metastatic foci. Therefore, some surgeons may elect to per-
form additional thyroidectomy based on the results of the
WBS before 131I ablation.35 Alternatively, some institutions
use a 2-step approach when dealing with patients who have
both a large thyroid remnant and metastatic disease.27 In this
regimen, a smaller dose of 131I is first given to ablate the large
thyroid remnant. This is later followed by a larger dose of 131I
to treat the metastases.
Proponents of not acquiring WBS note that the sensitivity
of the WBS scan to detect locoregional disease may be com-
promised by the often significant activity within the thyroid
remnant which can mask adjacent metastatic disease.38 Fur-
thermore, operative and histologic reports may also already
reveal advanced disease. Occasionally, a WBS may identify
patients in whom the surgeon performed a true total thyroid-
ectomy, leaving no remnant in the neck. Absence of any
thyroid bed or neck activity has been reported in up to 6% of
Imaging of the thyroid in benign and malignant disease 57

patients.31 In these cases, 131I therapy may be deferred en-
tirely by the WBS. Assessment of a thyroid remnant is not
limited to a WBS. Neck ultrasound also has the capability to
determine the extent of a thyroid remnant, and a detailed
operative report by the surgeon can also provide information
on the extent of the thyroidectomy; however, the WBS re-
mains widely used to assess for extent of iodine-avid tissue.
The diagnostic WBS is often used to plan ablation treat-
ment. One of 3 therapeutic approaches is usually used to
treat post-thyroidectomy patients: low fixed dose, high fixed
dose, or dosimetry.39 Many experts encourage the use of a
WBS because the results can help accurately stage the disease
and may alter treatment choice. A greater therapeutic dose of
131I is typically given for patients with evidence of local met-

Figure 13 (A) A 71-year-old man with a history of follicular thyroid carcinoma metastatic to subcutaneous neck nodules.
123I anterior and posterior diagnostic WBS shows activity in the thyroid bed and superior mediastinum. Additional foci

of abnormal activity are present in the right skull, left posterior chest, and right pelvis all representing unexpected bone
metastases. (B) A T2-weighted axial magnetic resonance imaging of the pelvis with gadolinium demonstrates an
enhancing lesion in the right anterior iliac wing compatible with a skeletal metastasis.
58 C.M. Intenzo et al

Figure 14 A 17-year-old female patient with a history of bilateral multifocal papillary thyroid carcinomas with extra-
capsular invasion and a single cervical lymph node metastasis. She was previously treated with 3.7 GBq (100 mCi) of
131I at another institution 1 year previously. Anterior and posterior 123I images demonstrate a large thyroid remnant and

mild, diffuse symmetric activity in the breasts bilaterally.

astatic disease to cervical lymph nodes. However, greater
doses may be required to adequate treat distant metastases to
bone, lungs, or liver. Van Nostrand and colleagues31 showed
that WBS, which included pinhole imaging on all patients,
revealed activity in the neck outside of the thyroid in 14% of
their population suggesting lymph node metastases. This
same study demonstrated that distant metastases are detected
by WBS in up to 4% of patients. In some circumstances, large
lymph node metastases identified on a WBS may prompt
surgical excision before 131I therapy.
A WBS may also be beneficial by revealing activity in un-
expected locations (Fig. 13). Prominent activity in the sali-
vary glands may place patients at a higher risk for the devel-
opment of sialoadenitis and xerostomia. In a retrospective
study, Van Nostrand et al31 showed that 3% of their patients
had marked salivary gland activity. Activity in the breasts in
women on a WBS can result in a postponement of the 131I
therapy because breast tissue is radiosensitive and ablation
when the breast is iodine-avid may place the patient at a
greater risk for breast carcinoma (Fig. 14). Breast activity has
been reported in up to 6% of patients.31 Patients with central
nervous system metastases may warrant treatment with cor-
ticosteroids before radioiodine therapy to limit radiation-in-
duced swelling and mass effect.
Overall, the information obtained from a WBS before 131I
therapy can drastically change decisions regarding the care of
thyroid carcinoma patients. Van Nostrand et al showed that
WBS can alter management in 29% of patients when (1) no
uptake was identified in the thyroid bed, (2) multiple foci of
activity were present in the neck or thyroid bed, (3) more
than 1 lesion outside the thyroid bed, (4) presence of distant
metastases, or (5) breast uptake.31 Patients with unexpected
disease identified in cervical lymph nodes or outside the thy-
roid bed in the neck on WBS are defined as intermediate risk
and those with distant metastases are defined as high risk by
the ATA guidelines.30 Together with other staging guidelines,
Imaging of the thyroid in benign and malignant disease
such as the tumor-nodes-metastases (ie, TNM) classification
by the American Joint Committee on Cancer, extrathyroidal
findings on WBS provides the practitioner with additional
information on prognosis, thereby affecting disease manage-
ment and future treatment strategies.40 The contrarian view
also argues that WBS is not needed in most patients because
the patient will be treated with 131I anyway. However, not all
patients require 131I therapy, including those with no detect-
able thyroid remnant.
Are There Any
Disadvantages to Diagnostic WBS?
Is there any harm to the patient from, including a WBS before
131I therapy? A WBS will add an upfront extra expense. How-
ever, the wealth of information disclosed by a WBS has the
potential to change treatment and can result in less patient
morbidity and downstream cost in the future. The findings
on a WBS may possibly prevent additional unnecessary and
more expensive advanced imaging. Quality of life can also be
improved by preventing initial undertreatment of disease,
leading to additional 131I therapy that could have been pre-
vented. Morbidity associated with multiple 131I treatments
can also be avoided if additional surgery is indicated before
the first 131I therapy. Although the WBS scan requires 2 ap-
pointments, one for the isotope administration and another
for the scan itself, the additional visits do not seem inconve-
nient to patients, many of whom expect a scan before treat-
ment. In our experience, the WBS appointments allow pa-
tients to familiarize themselves with our laboratory,
personnel, and overall treatment strategy. In particular, a
consultation with a nuclear medicine physician after a WBS
offers an opportunity to involve patients in their own care,
answer their questions, and put them at ease about the up-
coming therapy. This approach can reduce the surprises
which can occur when patients show up for 131I therapy sight
unseen.
Are Surveillance
Diagnostic WBS Still Needed?
By omitting a WBS, the possibility of stunning is completely
removed. Another argument against regularly performing
surveillance WBS is that the information regarding locore-
gional and distant metastases gained from a WBS can be
equally found by other modalities, such as neck ultrasound,
chest x-ray, magnetic resonance image, and CT scans of the
chest. Neck ultrasound performed by experienced operators
is considered the most sensitive modality for the detection of
nonpalpable lymph node metastases.11,41 However, because
postoperative changes in the soft tissues of the neck may lead
to a suboptimal ultrasound examination, it is recommended
to wait at least 3 months after thyroidectomy to perform neck
ultrasonography.35,42 Long-term prospective studies show
that in patients with normal neck ultrasound in combination
with an undetectable stimulated Tg, the risk of recurrence is
⬍0.5%.34,43 Similarly, some authors advocate not ablating
postoperative patients with undetectable stimulated Tg and
normal neck ultrasounds.42 If these patients are not treated,
59
there will be no PTS, so the WBS is the only chance to acquire
any imaging information on these patients.
One of the major points against using WBS for surveillance
is that stimulated Tg detects or excludes most recurrences
regardless of the WBS results. In heterogenous patient pop-
ulations with mixed risk subjects, many authors have shown
that WBS does not provide any additional benefit compared
to stimulated Tg.34,43,44 However, Robbins et al45 studied 131I
follow-up WBS after rhTSH administration compared with
Tg and found metastatic thyroid carcinoma on WBS in 13.7%
in patients of all risk categories with stimulated Tg of 2 ␮g/L
or less. They hypothesized that this scenario may be due to
thyroid metastases that do not produce Tg or that small-
volume disease may not produce enough Tg to be detectable
using current assays. This same study demonstrated that in a
low risk subgroup with stimulated Tg of 2 ␮g/L or less, 7.8%
had metastases outside the thyroid bed on WBS. They con-
cluded that rhTSH-stimulated Tg was not sufficient to screen
all patients for recurrent disease but may be adequate in a
low-risk cohort only. Moreover, a minority of patients will
have positive TgAbs, which would render the Tg levels in-
valid. In this subset of patients, regardless of risk stratifica-
tion, WBS would still be useful for identifying sites of recur-
rence. In addition, in patients with stimulated Tg levels
greater than 2.0 ng/mL, WBS is still helpful to localize the site
of disease recurrence. This is meaningful because distant me-
tastases are treated more aggressively than locoregional dis-
ease. Furthermore, WBS remains the gatekeeper to more ad-
vanced imaging with 18F-fluorodeoxyglucose PET as most
insurance companies require both elevated Tg levels and a
negative WBS to reimburse PET scanning.
For follow-up, both ATA and European guidelines do not
recommend WBS for surveillance in low-risk patients, as de-
fined by undetectable Tg, negative TgAbs, and normal neck
ultrasound.11,30 In these patients, WBS has no added value
when compared to stimulated Tg.34,43 However, for interme-
diate risk patients, defined as perithyroidal tumor invasion at
initial surgery, cervical lymph node metastases or PTS show-
ing uptake outside the thyroid, aggressive tumor histology or
vascular invasion and high risk patients (macroscopic tumor
invasion, incomplete tumor resection, distant metastases,
and higher Tg than expected based on PTS), the ATA believes
that a stimulated WBS may be of value. The European guide-
lines also state that WBS is indicated for high risk individu-
als.11 In high-risk patients, Tachi et al46 showed that WBS
also has predictive value for efficacy of 131I treatment of pul-
monary metastases. Patients who had pulmonary activity on
WBS using 185 MBq (5 mCi) of 131I demonstrated a 72%
reduction in pulmonary metastases on chest CT compared to
only a 5% reduction in patients without WBS pulmonary
activity. A significant decrease in Tg compared to no change
in Tg was also shown between the lung-positive vs lung-
negative groups in their study. Park et al47 evaluated both
postoperative and surveillance patients with positive 131I
WBS, Tg, ⱕ2 ng mL⫺1, and negative TgAb and found than
PTS was positive in 6.3% of cases, mostly in cervical and
mediastinal lymph node metastases. Therefore, Tg levels
60
alone cannot be used to alone to determine whether 131I
therapy should be performed.
Diagnostic WBS and
PTS—Competitive or Complementary?
One of the arguments against the routine use of a WBS before
131I therapy is that a PTS is more sensitive in detecting func-
tioning thyroid tissue because of the much larger doses of
radioiodine used for therapy.11 In studies in which the au-
thors compare 131I WBS to PTS, new foci were found on PTS
not identified on 131I WBS in 10%-13% of patients resulting
in a change in management in 9-16% of patients.48-50 How-
ever, when 123I is used for WBS instead of 131I, the sensitivity
of WBS compares more favorably to PTS. In a population,
including newly diagnosed and recurrent thyroid carcinoma
patients, Urhan et al15 found that WBS with 50-111 MBq
(1.35-3.0 mCi) of 123I had an 87% (228 of 263 patients)
concordance rate with PTS. Of the 35 discordant patients, 22
would have not led to a change in treatment dose. Further-
more, they showed that 10 lesions in 8 patients detected only
by the WBS and were not visualized on the PTS secondary to
intense thyroid bed activity masking lesions in adjacent tis-
sues. In many smaller studies, other authors have also shown
similar concordance in detecting recurrent disease between
both 123I WBS and PTS.17,20,21,51
Two studies revealed less favorable results with 123I WBS
compared with PTS. Donahue and colleagues used varying
doses 74-185 mBq (1.5-5.0 mCi) of 123I for WBS for patients
with newly diagnosed differentiated thyroid carcinoma com-
pared to PTS obtained 7-8 days after 131I ablation.18 Their
results showed that the PTS revealed new foci outside of the
thyroid bed in 21/108 (19%) patients not detected on the
WBS resulting in upstaging of 11/108 (10%) patients. Larger
doses used for the 131I therapy trended to a greater amount of
discordance between the WBS and PTS in this study. Com-
paring site of activity between WBS using a low dose of only
37 MBq (1 mCi) of 123I to PTS, Iwano et al16 found that
concordance between the 2 scans was high for thyroid bed
(89%) and skeletal metastases (86%), but was lower for me-
tastases to lymph nodes (61%) and lung (39%). In this study,
no lesions found on WBS were not identified by the PTS.
Regardless of the concordance or discordance of WBS and
PTS, the most fundamental concern with relying on PTS
alone is that, by definition, the PTS is performed after the fact.
Regardless of what the PTS shows, there is no way to turn
back time and change patient management. Only a WBS can
reveal information before therapy is administered. The WBS
and the PTS must be considered complementary studies,
because they serve different functions roles and provide in-
formation at different points in the patient’s treatment.
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