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Thyroid

What You Need to


Know in Nuclear
Medicine

Eliot Siegel, MD
Outline
Thyroid anatomy, histology and physiology
Thyroid function studies
Thyroid radiopharmaceuticals
Radiation dose
Thyroiditis
Thyroid nodules
Cold nodules
What are the Major
Functions of Thyroid
Hormone?
Physiologic Effects of
Thyroid Hormones
Thyroid hormones have two major
physiologic effects:
Increase protein synthesis in virtually every
body tissue. (T3 and T4 enter cells, where T3,
binds to discrete nuclear receptors and
influences the formation of mRNA
T3 increases O2 consumption by increasing the
activity of the Na+, K+-ATPase (Na pump)
This occurs primarily in tissues responsible for basal
O2 consumption (ie, liver, kidney, heart, and skeletal
muscle)
T3 is believed to be the active thyroid
hormone, although T4 itself may be biologically
active.
How Often Do You Perform A Physicial
Exam of Your Patients Thyroid In the
Nuc Med Department?
Physical Examination
of the Thyroid Gland
Inspect the neck looking for the thyroid
gland. Note whether it is visible and
symmetrical. A visibly enlarged thyroid gland
is called a goiter.
Move to a position behind the patient.
Identify the cricoid cartilage with the
fingers of both hands.
Move downward two or three tracheal rings
while palpating for the isthmus.
Move laterally from the midline while
palpating for the lobes of the thyroid.
Note the size, symmetry, and position of the
lobes, as well as the presence of any nodules
The normal gland is often not palpable.
Anatomy
The thyroid is situated on the
front side of the neck, at the
level of C5 to T1 vertebral
bodies, just below the
laryngeal prominence
It is butterfly-shaped: the
wings correspond to the lobes
and the body to the isthmus
of the thyroid.
The thyroid is one of the
larger endocrine glands how
much does it weigh in adults?
Anatomy
The thyroid is situated on the
front side of the neck, at the level
of C5 to T1 vertebral bodies, just
below the laryngeal prominence
It is butterfly-shaped: the wings
correspond to the lobes and the
body to the isthmus of the thyroid.
The thyroid is one of the larger
endocrine glands and weighs
about 15-25 grams in adults
Blood Supply

The thyroid gland is supplied by two pairs


of arteries: the superior and inferior
thyroid arteries of each side
The superior thyroid artery is the first
branch of the external carotid, and
supplies mostly the upper half of the
thyroid gland
Inferior thyroid artery is the major
branch of the thyrocervical trunk,
which comes off of the subclavian
artery
Lymph drainage follows the arterial
supply.
There are three main veins that drain the
thyroid
Superior, middle and inferior thyroid
veins.
In 10% of people, there is an additional
thyroid artery, What is it called and
from where does it arise?
Blood Supply

The thyroid gland is supplied by two pairs of arteries:


the superior and inferior thyroid arteries of each
side
The superior thyroid artery is the first branch of the
external carotid, and supplies mostly the upper half of the
thyroid gland
Inferior thyroid artery is the major branch of the
thyrocervical trunk, which comes off of the subclavian
artery
Lymph drainage follows the arterial supply.
There are three main veins that drain the thyroid
Superior, middle and inferior thyroid veins.
In 10% of people, there is an additional thyroid artery, the
thyreoidea ima, that arises from the brachiocephalic trunk
or the arch of the aorta
Histology
Follicles are spherical and selectively absorb
iodine (as iodide ions, I-) from the blood and
for production of thyroid hormones
Twenty-five percent of all the bodys Iodine
is in the thyroid gland
The follicles are made of a single layer of
thyroid epithelial cells, which secrete T3 and
T4
Inside the follicles is a colloid which is rich in
a protein called thyroglobulin
The colloidal material serves as a reservoir of
materials for thyroid hormone production
and, to a lesser extent, a reservoir of the
hormones themselves
Scattered among follicular cells and in
spaces between the spherical follicles are
another type of thyroid cell
What are they and what do they excrete?
Histology

Follicles are spherical and selectively absorb iodine (as


iodide ions, I-) from the blood and for production of thyroid
hormones
Twenty-five percent of all the bodys Iodine is in the thyroid
gland
The follicles have a single layer of thyroid epithelial cells, which
secrete T3 and T4
Inside the follicles is a colloid which is rich in a protein called
thyroglobulin
The colloidal material serves as a reservoir of materials for
thyroid hormone production and, to a lesser extent, a reservoir
of the hormones themselves
Scattered among follicular cells and in spaces between the
spherical follicles are another type of thyroid cell,
parafollicular cells or C cells, which secrete calcitonin.
Physiology
The primary function of the thyroid is
production of the hormones thyroxine
(T4), triiodothyronine (T3), and calcitonin
(reduces blood calcium)
Up to 40% of the T4 is converted to T3 by
peripheral organs such as the liver, kidney
and spleen
T3 is about ten times more active than T4
T3 and T4
Thyroxine (T4) is synthesized by the follicular
cells from the tyrosine residues of
thyroglobulin (TG)
Iodine, captured with the "iodine trap" is
activated by the enzyme thyroid peroxidase and
linked to the tyrosine residues on TG
Upon stimulation by TSH the follicular cells
reabsorb TG and proteolytically cleave the
iodinated tyrosines from TG, forming T4 and T3
(in T3, one iodine is absent compared to T4),
and release them into the blood
What percentage of thyroid hormone is T3 vs.
T4?
T3 and T4
Thyroxine is synthesised by the follicular cells
from the tyrosine residues of thyroglobulin
(TG)
Iodine, captured with the "iodine trap" is
activated by the enzyme thyroid peroxidase
(TPO) and linked to the 3' and 5' sites of the
benzene ring of the tyrosine residues on TG
Upon stimulation by TSH the follicular cells
reabsorb TG and proteolytically cleave the
iodinated tyrosines from TG, forming T4 and T3
(in T3, one iodine is absent compared to T4),
and release them into the blood
Thyroid hormone that is secreted from the
gland is about 90% T4 and about 10% T3
T3 and T4
In the blood, T4 and T3 are partially
bound to thyroxine-binding globulin,
transthyretin and albumin.
Only a very small fraction of the
circulating hormone is free (unbound) -
T4 0.03% and T3 0.3%
T3 and T4 Regulation
The production of thyroxine is
regulated by thyroid-
stimulating hormone (TSH),
released by the pituitary
The thyroid and thyrotropes
(cells in anterior pituitary
which produce TSH) form a
negative feedback loop
TSH production is suppressed
when the T4 levels are high,
and vice versa
What modulates TSH
production?
T3 and T4 Regulation
The production of thyroxine is
regulated by thyroid-stimulating
hormone (TSH), released by the
pituitary. The thyroid and
thyrotropes form a negative feedback
loop
TSH production is suppressed when
the T4 levels are high, and vice versa
The TSH production itself is
modulated by thyrotropin-releasing
hormone (TRH)
Produced by the hypothalamus and
secreted at an increased rate in
situations such as cold (in which an
accelerated metabolism would
generate more heat)
TSH production is blunted by
somatostatin (SRIH).
Calcitonin
Parafollicular cells produce calcitonin in response
to hypercalcemia (not TSH, which stimulates
thyroxine production)
Calcitonin plays a role in the calcium metabolism;
it is the functional opposite of parathyroid
hormone, and exerts its influence mainly on bone
Its relatively small role is signified by the fact
that after removal of the thyroid, calcium levels
typically remain stable.
Iodine

In areas of the world where iodine


- essential for the production of
thyroxine, which contains four
iodine atoms - is lacking in the
diet, the thyroid gland can be
considerably enlarged, resulting in
the swollen necks of endemic
goiter
Cretinism
Congenital hypothyroidism can be endemic,
genetic, or sporadic.
If untreated, it results in mild to severe
impairment of both physical and mental
growth and development.
Poor length growth is apparent as early as
the first year of life
Adult stature without treatment ranges from
1 to 1.6 meters, depending on severity, sex
and other genetic factors
Bone maturation and puberty are severely
delayed
Ovulation is impeded and infertility common.
Cretinism
Neurological impairment may be mild, with
reduced muscle tone and coordination, or so
severe that the person cannot stand or walk
Cognitive impairment may also range from mild to
so severe that the person is nonverbal and
dependent on others for basic care
Thought and reflexes are slower.
Other signs may include thickened skin and a
protruding abdomen
Sporadic and Genetic
Cretinism
Results from abnormal development
or function of the fetal thyroid gland
Has been almost completely
eliminated in developed countries by
early diagnosis by newborn screening
programs followed by lifelong
treatment with thyroxine
Endemic Cretinism
Arises from a diet deficient in iodine and has
affected far more people worldwide and continues
to be a major public health problem in many
countries
Iodized salt is a cheap and easy way of adding
iodine to the diet
This has eliminated endemic cretinism in most
developed countries, and some governments have
made the iodination of flour mandatory
What Can Be
Done to Minimize
the Adverse
Effects
Associated with
Accidental I-131
Exposure (e.g.
Nuclear Reactor
Accident)?
In the event of large accidental releases of such
material into the environment, the uptake of
radioactive iodine isotopes by the thyroid can be
blocked by saturating the uptake mechanism with
a large surplus of non-radioactive iodine, taken in
the form of potassium iodide tablets
One possibly preventable consequence of the
Chernobyl disaster was an increase in thyroid
cancers in children in the years following the
accident
Symptoms of Hyper and
Hypothyroidism?
Hyper- and
Hypothyroidism
Causes of
Hypothyroidism
Hashimoto's thyroiditis /
thyroiditis
Ord's thyroiditis (atrophic form
common in Europe)
Postoperative hypothyroidism
Postpartum thyroiditis
Silent thyroiditis
Acute thyroiditis
Iatrogenic hypothyroidism
Causes Hyperthyroidism
Thyroid storm
Graves-Basedow disease
Toxic thyroid nodule
Toxic nodular struma (Plummer's disease)
Hashitoxicosis
Iatrogenic hyperthyroidism
De Quervain thyroiditis (inflammation starting as
hyperthyroidism, can end as hypothyroidism)
TSH
The development of sensitive
immunoradiometric (IRMA) assays to
measure serum thyroid hormone (TSH,
thyrotropin) has been a valuable tool in
the diagnosis and management of
thyroid diseases
The expected normal range for TSH is
0.4-4.0 mU/L (milli international units
per liter) but anything higher than 2.5
mU/L is considered at risk
TSH
Serum TSH has become the screening
test of choice for thyroid disease
Primary hypothyroidism produces
elevated TSH levels whereas patients
with primary hyperthyroidism (i.e.
Graves) should have undetectable TSH
values
Patients who present with a normal or
detectable TSH level and elevated
thyroid hormone concentrations
require further evaluation to exclude
central causes of hyperthyroidism
Name a couple of causes of central
hyperthyroidism
(Pituitary TSHomas or PRTH
(pituitary resistance to thyroid
hormone)
Fetal and Neonatal
Thyroid Function
When does the fetal thyroid begin to
concentrate iodine?
Do TSH, T4 and T3 cross the
placenta?
How about Thionamides
(propylthiouracil, methimazole,
carbamizole for treatment of
Graves disease), and TRH?
Fetal and Neonatal
Thyroid Function
The fetal thyroid does not concentrate
iodine during the first 12 weeks of
gestation; beyond this point, iodine uptake
increases progressively until term
There is probably only minimal transfer of
maternal TSH, T4 and T3 across the
placenta
Iodine and Technetium both cross the
placenta and will be concentrated in the
fetal thyroid
Thionamides, and TRH can cross the
placenta without difficulty.
Breast Feeding After Tc and
Diagnostic and Therapeutic I-131

Both Iodine and Technetium are secreted


in the breast milk of lactating women, so
nursing should be delayed for 48-72 hours
following Tc99m, and for longer following
I-123 imaging
Women who are breast feeding should
permanently discontinue breast feeding if
they are to undergo I-131 therapy
Radionuclides Used in
Thyroid Imaging
Iodine-123
What is the half-life, energy, and
dose, and imaging time after the
dose is given?
Iodine-123
Physical Characteristics and Dose
I-123 decays by electron capture, has a physical half-
life of 13.6 hours, and a gamma energy of 159 keV
It is produced in a cyclotron by either one of two
methods
Dose
200-400 uCi
Imaging Time After Administration of I-123
The maximal count rate in the thyroid occurs
approximately 6 hours following the oral administration
of the agent
Images are typically acquired 4 hours following
administration of the tracer, and uptake values are
determined at 4 and 24 hours
Indications

I-123 is the agent of choice when


evaluating substernal goiters because
there is usually substantial
mediastinal blood pool activity
associated with Tc-pertechnetate
What is the half life, energy, and
dose for I-131?
I-131
Physical Characteristics
I-131 has a physical half-life of 8.05
days and emits a high energy gamma
(364 keV) and particulate emissions
Beta particles with average energy =
192 keV, max energy = 607 keV are
emitted and deposit the majority of
their energy within 2.2 mm of their
site of origin
Diagnostic Dose
Diagnostic: 2-5 mCi p.o. for whole body
iodine scans for following a patient with
thyroid carcinoma.
Thyroid hormone should be discontinued
for several (2-6) weeks in advance of study
or treatment
A serum TSH level is very helpful to gauge
the adequacy of thyroid hormonal
withdrawal
Unless the TSH level is increased, the
validity of an I-131 body scan, especially if
it is normal, should be questioned
Indications
The long half-life, high energy gamma, and beta
emissions described above limit the usefulness of
I-131 for imaging purposes
Its administration results in a very high radiation
dose to the thyroid, 90% of which is the result of
beta decay
I-131 is not the tracer of choice for imaging
applications, except in the case of delayed imaging
for thyroid carcinoma metastases or mediastinal
masses, where the higher energy gamma and
improved target-to-background ratio following
washout are useful
Technetium-99m
Pertechnetate
What is the dose and when is the
best time to image?
Pharmacology
Pertechnetate (TcO4-) is a monovalent anion
trapped by the thyroid gland in the same manner
as iodine (an active transport mechanism)
After trapping pertechnetate slowly "washes"
from the gland- it does NOT undergo
organification
Peak thyroid activity occurs between 20 and 40
minutes after injection
Only 2-4% of the administered dose is trapped in
the thyroid
Pertechnetate is secreted in human milk
(discontinue breast feeding for 48 hours after
dosing) and also crosses the placenta to
accumulate in the fetus
Technique
The typical dose used for thyroid imaging
is 3 mCi intravenously
A rough estimate of thyroid uptake can be
obtained from the Tc-pertechnetate exam
Hypofunctioning gland will appear less intense
than the salivary glands
Normal gland equal to the salivary glands
Hyperfunctioning thyroid hotter than the
salivary glands
How To Tell If Its
Technetium or I-123
In comparison to I-123 studies, more
background activity is usually present
on pertechnetate images
Is it The Pyramidal
Lobe?
Linear esophageal activity, due to tracer
secreted by the salivary glands which is
swallowed, may be seen
This can be cleared from the esophagus by
drinking water
A pinhole collimator is used for enhanced
resolution and also facilitates oblique
views.
What is the Size of the Smallest
Nodules That Can be Detected on a Tc
Pertechnetate Scan?
What is the Size of the Smallest
Nodules That Can be Detected on
a Tc Pertechnetate Scan?
The size of nodules that can be detected by
pertechnetate imaging depends upon the nodules
function and size
Hot nodules may be seen even if they are very
small, but a hypofunctioning nodule less than 0.8
to 1.0 cm in size lying within the gland may not be
discernible
In general, Tc-pertechnetate 5-mm pinhole
imaging has a sensitivity of 80 to 95% for cold
nodules between 8 to 18 mm, but nearly 0% for
nodules less than 5 mm
What is a Discordant
Nodule?
Discordant Nodule
A subset of thyroid carcinomas that are capable
of trapping but not organifying iodine
Therefore, it is possible to have a warm or hot
nodule on a Tc-99m scan that would be cold on I-
123
Therefore, any patient with a non cold nodule on a
Tc-99m scan should be repeated with I-123 to
avoid this disparity
Cold nodules with Tc-99m scan will inevitably be
cold with an I-123 scan
Tc-Pertechnetate:
Indications
Pertechnetate is the preferred imaging agent
when:
Patient has been taking thyroid blocking agents
(Propylthiouracil)
Thiouracil blocks oxidation and organification of iodide
following its uptake by the thyroid gland, but will not
interfere with trapping of pertechnetate.
Patient is unable to take medication orally
The study must be completed in < 2 hrs
Relative Radiation dose to the Thyroid,
by Agent
Which Gives Greatest and Least Dose?
Radiation Dose by Thyroid
Imaging Radiopharmaceutical
Assuming normal sized adult gland (20 gm) with
normal RAIU (15%):
* I-131: 800-1000 rad/mCi; 16,000 rad/mCi in the
neonate
Radiation to thyroid per adult dose for cancer diagnosis is
around 5,000 rads
I-123: 7.5 rad/mCi (adult); 160 rad/mCi (neonate)
Radiation per adult dose is 2.5 rad
99mTc-O4: 0.13 rad/mCi (adult); 3.4 rad/mCi (neonate)
Radiation per adult dose is 0.39 rad
Normal Thyroid with Asymmetry
of Thyroid Simulating Right
Thyroid Nodule
Accessory Thyroid
Tissue
Pyramidal Lobe
Not esophageal activity
Can distinguish by having patient drink a
cup of water
Which of the following dietary
supplement will affect thyroid
uptake?
A. Vitamin A
B. Vitamin B
C. St. Johns wort
D. Kelp tablets
E. lactobacillus
Which of the following dietary
supplement will affect thyroid
uptake?
A. Vitamin A
B. Vitamin B
C. St. Johns wort
D. Kelp tablets
Kelp tablets contain iodine and
therefore may affect measured values
of thyroid uptake
E. lactobacillus
Which of the following will
not affect thyroid uptake?
a. Iodinated contrast media
b. Propylthiouracil
c. Thyroid hormones
d. Beta blockers
Which of the following will
not affect thyroid uptake?
a. Iodinated contrast media
b. Propylthiouracil
c. Thyroid hormones
d. Beta blockers do not
Thyrotropin is also known
as:
TRH
TSH
Secreted by anterior pituitary and
causes thyroid to release thyroxine (T4)
T3
T4
Thyrotropin is also known
as:
TRH
TSH
Secreted by anterior pituitary and
causes thyroid to release thyroxine (T4)
T3
T4
Which of the following
statements is not true?
a. TRH stimulates the release of TSH by
the anterior pituitary
b. Release of T3 is inhibited by elevation of
T4
c. T3 and T4 are both hormones which are
manufactured and released by the
thyroid
d. TRH is synthesized in the hypothalmus
Which of the following
statements is not true?
a. TRH stimulates the release of TSH by
the anterior pituitary
b. Release of T3 is inhibited by elevation of
T4
c. T3 and T4 are both hormones which are
manufactured and released by the
thyroid
d. TRH is synthesized in the hypothalmus
Most people have four
parathyroid glands
True
False
Most people have four
parathyroid glands
True
Small percentage have more or less
False
Which of the following are
used to image the parathyroid?
A. 99mTc pertechnetate
B. 99mTc sestamibi
C. 201Tl chloride
D. A and B
E. B and C
Which of the following are
used to image the parathyroid?
A. 99mTc pertechnetate
B. 99mTc sestamibi
C. 201Tl chloride
D. A and B
E. B and C
The collimator attached to
a thyroid uptake probe is:
a) Converging
b) Diverging
c) Pinhole
d) Flat field
e) Low energy all purpose
The collimator attached to
a thyroid uptake probe is:
a) Converging
b) Diverging
c) Pinhole
d) Flat field
1. provide for the highest possible efficiency (quantified results) ... that way counting time decreases if CR is
better, as well, can balance counting time and dose

2. limit the area seen by the crystal so that it excludes most radioactivity outside the region of interest (only
from ROI)... you still want to attenuate and only desire the counts that will accurately represent the
radionuclide distribution

3. relatively uniform detection across FOV and throughout the thickness of the organ (isoresponse curve)

e) Low energy all purpose


Which of the following are
part of the prep for a thyroid
uptake?
a. NPO from midnight
b. Administer Lugols solution
c. Have patient void before
administration of
radiopharmaceutical
d. Withhold caffeine containing
beverages for 24 hours prior to
exam
e. None of the above
Which of the following are
part of the prep for a thyroid
uptake?
a. NPO from midnight
b. Administer Lugols solution
c. Have patient void before
administration of
radiopharmaceutical
d. Withhold caffeine containing
beverages for 24 hours prior to
exam
e. None of the above
While taking information from a patient scheduled for
thyroid uptake and scan with 123I sodium iodide, a tech
learns that he has been taking Cytomel that week. What
does that mean?

a. Nothing; thyroid uptake will not be affected by


Cytomel
b. Imaging may still be obtained using 201Tl chloride
c. Both the uptake and scan can be performed
using 131I
d. Study should be performed as ordered, but the
uptake will be inaccurate
e. None of the above
While taking information from a patient scheduled for
thyroid uptake and scan with 123I sodium iodide, a tech
learns that he has been taking Cytomel that week. What
does that mean?

a. Nothing; thyroid uptake will not be affected by


Cytomel
b. Imaging may still be obtained using 201Tl chloride
a. Cytomel is synthetic form of T3 and will affect iodine
uptake. Images can be obtained using thallium. Uptake
values would be falsely low. Cytomel should be stopped
at least 2 weeks before uptake and scanning using
radioiodine
c. Both the uptake and scan can be performed
using 131I
d. Study should be performed as ordered, but the
uptake will be inaccurate
e. None of the above
Imaging of the thyroid
takes place
a. Approximately 20 minutes after
injection of 99mTc pertechnetate
b. 6 hours after administration of an
123I sodium iodide capsule

c. 24 hours after administration of an


123I sodium iodide capsule

d. All of the above


Imaging of the thyroid
takes place
a. Approximately 20 minutes after
injection of 99mTc pertechnetate
b. 6 hours after administration of an
123I sodium iodide capsule

c. 24 hours after administration of an


123I sodium iodide capsule

a. Lower count rate but less background


so better images than 6 hours
d. All of the above
Which of the following will not
optimize images of the
thyroid?
a. Use of pinhole collimator
b. Having the patient avoid swallowing
during image acquisition
c. Hyperextending the neck
d. Placing a radioactive marker on the
xiphoid process
a. Xiphoid not in field of view
Which of the following will not
optimize images of the
thyroid?
a. Use of pinhole collimator
b. Having the patient avoid swallowing
during image acquisition
c. Hyperextending the neck
d. Placing a radioactive marker on the
xiphoid process
a. Xiphoid not in field of view
A linear area of activity in the
esophagus is seen on a thyroid image
taken using 99mTc pertechnetate. What
does it represent?
a. Sublingual thyroid
b. Parathyroid
c. Pertechnetate secreted by the
salivary glands and swallowed
d. Parotid gland
A linear area of activity in the
esophagus is seen on a thyroid image
taken using 99mTc pertechnetate. What
does it represent?
a. Sublingual thyroid
b. Parathyroid
c. Pertechnetate secreted by the
salivary glands and swallowed
d. Parotid gland
The use of 131I for
thyroid imaging
A. Is common if an uptake is also planned
B. Is typically only used when scanning the
whole body for metastatic thyroid
disease after thyroidectomy
C. Delivers a lower radiation dose to the
thyroid than 99mTc pertechnetate, since
only microcurie amounts are administered
D. All of the above
The use of 131I for
thyroid imaging
A. Is common if an uptake is also planned
B. Is typically only used when scanning the
whole body for metastatic thyroid
disease after thyroidectomy
C. Delivers a lower radiation dose to the
thyroid than 99mTc pertechnetate, since
only microcurie amounts are administered
D. All of the above
Patient receives both 3mCi of 201Tl chloride and 5 mCi
of 99mTc pertechnetate, and pinhole images of the neck
are taken after each administration. If pertechnetate
image is subtracted from 201Tl image, activity remaining
represents:

a. Thyroid
b. Parathyroid
c. Salivary glands
d. Hypothalmus
e. Non-functioning thyroid tissue
Patient receives both 3mCi of 201Tl chloride and 5 mCi
of 99mTc pertechnetate, and pinhole images of the neck
are taken after each administration. If pertechnetate
image is subtracted from 201Tl image, activity remaining
represents:

a. Thyroid
b. Parathyroid
c. Salivary glands
d. Hypothalmus
e. Non-functioning thyroid tissue
Salivary glands can be
imaged using
a. 3 mCi of 201Tl
b. 5 mCi of 99mTc sestamibi
c. 5 mCi of 99mTc pertechnetate
d. 200 microcuries of 123sodium iodide
Salivary glands can be
imaged using
a. 3 mCi of 201Tl
b. 5 mCi of 99mTc sestamibi
c. 5 mCi of 99mTc pertechnetate
d. 200 microcuries of 123sodium iodide
Which of the following describes
delayed images at 2-3 hours after
injection of 99m sestamibi?
a. Persistent activity in normal thyroid with
complete washing in parathyroid
b. Persistent activity in parathyroid adenomas and
decreased activity in thyroid relative to early
images
c. Persistent activity in hyperfunctioning thyroid
tissue and no activity in parathyroid or salavary
glands
d. Activity in salivary glands and normal
parathyroid tissue
Which of the following describes
delayed images at 2-3 hours after
injection of 99m sestamibi?
a. Persistent activity in normal thyroid with
complete washing in parathyroid
b. Persistent activity in parathyroid adenomas and
decreased activity in thyroid relative to early
images
c. Persistent activity in hyperfunctioning thyroid
tissue and no activity in parathyroid or salavary
glands
d. Activity in salivary glands and normal
parathyroid tissue
A Hot nodule on a thyroid
image is most likely to be
benign
a. True
b. False
A Hot nodule on a thyroid
image is most likely to be
benign
a. True
b. False
Which of the following are
symptoms of hyperthyroidism?
a. Exopthalmos
b. Bradycardia
c. Cold intolerance
d. All of the above
e. B and C
Which of the following are
symptoms of hyperthyroidism?
a. Exopthalmos
b. Bradycardia
c. Cold intolerance
d. All of the above
e. B and C
The highest doses of
therapeutic 131I are given to
patients with
a. Graves disease
b. Toxic multinodular goiter
c. Thyroid cancer
d. Chronic thyroiditis
The highest doses of
therapeutic 131I are given to
patients with
a. Graves disease
b. Toxic multinodular goiter
c. Thyroid cancer
d. Chronic thyroiditis
A patient with 45% uptake of 123I
sodium iodide at 24 hours is:
a. Euthyroid
b. Hyperthyroid
c. Hypothyroid
d. athyroid
A patient with 45% uptake of 123I
sodium iodide at 24 hours is:
a. Euthyroid
b. Hyperthyroid
c. Hypothyroid
d. athyroid
The part of the thyroid that lies
anterior to the trachea and is often not
seen on thyroid imaging is the
a. Right lobe
b. Left lobe
c. Isthmus
d. Parathyroid
e. Superior thyroid notch
The part of the thyroid that lies
anterior to the trachea and is often not
seen on thyroid imaging is the
a. Right lobe
b. Left lobe
c. Isthmus
d. Parathyroid
e. Superior thyroid notch
On thyroid images taken using 123I sodium
iodide, the right lobe appears to be larger
than the left. The explanation for this is:

a. Right hemigoiter
b. Hypofunctioning left lobe
c. Normal
d. Patients head was turned slightly to
the left
e. Patients head was turned slightly to
the right
On thyroid images taken using 123I sodium
iodide, the right lobe appears to be larger
than the left. The explanation for this is:

a. Right hemigoiter
b. Hypofunctioning left lobe
c. Normal
d. Patients head was turned slightly to
the left
e. Patients head was turned slightly to
the right
Iodine is needed for the
thyroid gland to synthesize
T3 and T4
a. True
b. False
Iodine is needed for the
thyroid gland to synthesize
T3 and T4
a. True
b. False
About 90% of the thyroid
hormone secreted into the
blood is in the form of:

a. Thyroxine
b. Triiodothyronine
c. Thyroglobulin
d. Thyrotropin
e. iodotyrosine
About 90% of the thyroid
hormone secreted into the
blood is in the form of:

a. Thyroxine
b. Triiodothyronine
c. Thyroglobulin
d. Thyrotropin
e. iodotyrosine
A patient with
hyperparathyroidism will have

a. Myxedema
b. Exophthalmos
c. Cold nodules in the thyroid
d. Increased fracture risk
e. More than 4 parathyroid glands
A patient with
hyperparathyroidism will have

a. Myxedema
b. Exophthalmos
c. Cold nodules in the thyroid
d. Increased fracture risk
a. Elevated PTH is associated with
decrease in bone calcium and can also
affect nervous system
e. More than 4 parathyroid glands
Why is a 6 hour thyroid
uptake obtained?
a. In case the patient does not show up
the following day for 24 hour uptake
b. To detect hyperthyroidism when the
turnover is so rapid that the 24
hour uptake may be normal
c. In case an error is made in the
calculation of the 24 hour uptake
d. So that the patient can resume
eating
Why is a 6 hour thyroid
uptake obtained?
a. In case the patient does not show up
the following day for 24 hour uptake
b. To detect hyperthyroidism when the
turnover is so rapid that the 24
hour uptake may be normal
c. In case an error is made in the
calculation of the 24 hour uptake
d. So that the patient can resume
eating
Which patient will have the longest wait
before an accurate thyroid uptake with
123I can be obtained in a patient who

had or was given:


a. Myelogram
b. Synthroid
c. IVP
d. Lugols solution
e. Kelp tablets
Which patient will have the longest wait
before an accurate thyroid uptake with
123I can be obtained in a patient who

had or was given:


a. Myelogram
a. Was more true with pantopaque,
SNM advices 2 week wait after
iodinated contrast agents
b. Synthroid
c. IVP
d. Lugols solution
e. Kelp tablets
To stimulate secretion during salivary
gland scintigraphy, which of the
following is often used?

a. 99mTc sestamibi
b. lemon juice
c. Lugols solution
d. Captopril
e. furosemide
To stimulate secretion during salivary gland
scintigraphy, which of the following is often used?

a. 99mTc sestamibi
b. lemon juice
c. Lugols solution
d. Captopril
e. furosemide
Ectopic thyroid tissue
may occur
a. In the pelvis
b. In the neck
c. In the mediastinum
d. At the base of the tongue
e. All of the above
Ectopic thyroid tissue
may occur
a. In the pelvis
b. In the neck
c. In the mediastinum
d. At the base of the tongue
e. All of the above
If the salivary glands are not seen on a
thyroid scan obtained with the use of
99mTc pertechnetate, it may mean

a. That the thyroid is hyperfunctioning, and


trapped the majority of the tracer
b. That the salivary gland function is compromised
c. That the salivary glands lie inferior to the
thyroid and cannot be seen on anterior images
d. A and B
e. B and C
If the salivary glands are not seen on a
thyroid scan obtained with the use of
99mTc pertechnetate, it may mean

a. That the thyroid is hyperfunctioning, and


trapped the majority of the tracer
b. That the salivary gland function is compromised
c. That the salivary glands lie inferior to the
thyroid and cannot be seen on anterior images
d. A and B
e. B and C
When would a low energy all purpose collimator
be used for thyroid examinations?

a. During uptake counting


b. When searching for ectopic thyroid with 131I
sodium iodide
c. When performing whole body with 131I sodium
iodide scanning after thyroidectomy
d. When obtaining a blood pool image of the thyroid
with 99mTc pertechnetate to differentiate cystic
and solid masses
e. All except A.
When would a low energy all purpose collimator
be used for thyroid examinations?

a. During uptake counting


a. Flat field
b. When searching for ectopic thyroid with 131I
sodium iodide
a. Medium energy
c. When performing whole body with 131I sodium
iodide scanning after thyroidectomy
a. Medium energy
d. When obtaining a blood pool image of the thyroid
with 99mTc pertechnetate to differentiate cystic
and solid masses
e. All except A.
Radioactive Iodine and 99mTc
pertechnetate cross the
placenta
a. True
b. False
Radioactive Iodine and 99mTc
pertechnetate cross the
placenta
a. True
b. False
An indication for a thyroid uptake is for
use in calculation of the amount of
radioiodine therapy for
hyperthyroidism
a) True
b) False
An indication for a thyroid uptake is for
use in calculation of the amount of
radioiodine therapy for
hyperthyroidism
a) True
b) False
2015 Thyroid Consensus
Guidelines
2015 American Thyroid Association
Management Guidelines for Adult
Patients with Thyroid Nodules and
Differentiated Thyroid Cancer: The
American Thyroid Association
Guidelines Task Force on Thyroid
Nodules and Differentiated Thyroid
Cancer
Does Screening people with familial
follicular differentiated thyroid cancer
(DTC) reduces morbidity/mortality?
Does Screening people with familial
follicular differentiated thyroid cancer
(DTC) reduces morbidity/mortality?
Screening people with familial follicular
differentiated thyroid cancer (DTC)
reduces morbidity/mortality
No study ever reported
Name any syndromes associated with increased
risk of DTC:
Syndromes associated with
Increased risk of DTC
Mutations in PTEN gene (phosphatase and tensin
homolog)
Hamartoma tumor syndrome (Cowdens disease)
Familial adenomatous polyposis (FAP)
Carney complex:
autosomal dominant conditions comprising myxomas of
the heart and skin, hyperpigmentation of the skin
(lentiginosis), and endocrine overactivity.
MEN2
Werner syndrome (adult progeria)
Progeria
Should One Obtain TSH After
Finding Thyroid Nodule?
Serum thyrotropin (TSH)
should be measured during
initial evaluation of thyroid
nodule (true)
If TSH is low then I-123 study
should be performed
If TSH is normal or elevated,
then radionuclide scan should
not be performed (true)
Name Clinical Signs of
thyroid malignancy
Signs of thyroid
malignancy
Vocal cord paralysis
Cervical lymphadenopathy
Fixation of nodule to surrounding
tissue
Should one routinely measure
serum thyroglobulin (Tg) in
evaluation of nodules?
Should one routinely measure
serum thyroglobulin (Tg) in
evaluation of nodules?
No since insensitive and non-specific
Should serum calcitonin be
routinely measured in patients
with thyroid nodules?
Should serum calcitonin be
routinely measured in patients
with thyroid nodules
Insufficient evidence
What should you do with incidentally
detected focal PET uptake? If nodule
more than 1 cm then do FNA
Should PET be performed when new
thyroid nodule is discovered?
How often is FDG uptake seen in FDG
studies:
Should FNA be performed with
diffuse thyroid uptake?
What should you do with incidentally
detected focal PET uptake? If nodule
more than 1 cm then do FNA
Should PET be performed when
new thyroid nodule is discovered?
No
How often is FDG uptake seen in
FDG studies: 1 to 2%, diffuse
uptake in 2%
Should FNA be performed with
diffuse thyroid uptake?
no
Is 18FDG-PET recommended for the evaluation
of thyroid nodules with indeterminate
cytology?
18FDG-PET is not routinely
recommended for the evaluation of
thyroid nodules with indeterminate
cytology
Nuclear Imaging Tests
Radioactive Iodine
Uptake Test (RAIU)
How is the study performed?
What radiopharmaceutical?
How much is given?
When is uptake measured?
What are the normal values?
Technique
RAIU can be determined using
either I-131 (7 uCi) or I-123
(200-300 uCi)
Normal 24 hour RAIU is between
8 to 35%
Normal 4 hour RAIU is generally
between 5 to 15%.
Is RAIU Valuable in Both
Hyper and Hypothyroidism?
Value of RAIU Test
The RAIU test provides a useful assessment of
thyroid function: in general, the higher the iodine
uptake, the more active the gland
Note, however, that in patients with
hypothyroidism such as Hashimoto's disease, the
% uptake may be low, normal or high depending on
the steps affected in thyroid hormone synthesis
The RAIU is therefore of no value in establishing
the diagnosis of hypothyroidism.
Indications for RAIU
To confirm hyperthyroidism
To calculate therapeutic dose of I-
131
To determine autonomous thyroid
tissue (i.e. toxic nodules, - combined
with thyroid scan)
To help sort out the cause of
thyrotoxicosis
Thyrotoxicosis
The most useful role of RAIU test is in
determining the etiology of thyrotoxicosis
Thyrotoxicosis simply refers to excess thyroid
hormone in the body and may be due to
overactivity of the thyroid gland
(hyperthyroidism), or other causes such as
inflammation of the gland (thyroiditis) or
ingestion of excess thyroid hormone
In "true hperthyroidism" - RAIU uptake will be
high
Thyrotoxic patients with thyroiditis or who abuse
thyroid hormones will have a low RAIU
Name Some Entities that
Increase RAI Uptake?
Entities that Result in
Increased RAIU
Hyperthyroidism
Grave's disease
TSH-secreting pituitary adenoma
Rebound following abrupt withdrawal
of antithyroid meds
Long term antithyroid therapy
Prolonged therapy may result in
decreased circulating levels of T4-
hence TSH levels will increase and
uptake will increase
Enzyme defects
Iodine starvation
Lithium Therapy
Early Hashimoto's Thyroiditis
Patients rarely present at this stage,
RAIU is typically normal [early] or
decreased [late] in these patients)
Rebound during recovery from
subacute thyroiditis
Name Some Entities that
Decrease RAI Uptake?
Entities that Result in
Decreased RAIU
Blocked Trapping:
Iodine load (most common). An iodine load can
"falsely" lower the RAIU through two
mechanisms
1) producing the Wolf-Chaikoff effect
transient decrease in iodide
organification and hormone synthesis in
normal or Graves patients following an
iodide load.
2) causing a dilutional effect, i.e., diluting the I-123
atoms with nonradioactive I-127 atoms
Exogenous thyroid hormone replacement
depressing TSH levels
Entities that Result in
Decreased RAIU
Ectopic thyroid: Struma Ovarii
Blocked Organification
Antithyroid medication (PTU): Note- Tc-99m uptake
should not be affected
Parenchymal Destruction
Acute, Subacute and Chronic Lymphocytic Thyroiditis
Hypothyroidism:
Primary or Secondary (insufficient pituitary TSH
secretion)
Surgical/Radioiodine Ablation of Thyroid
Medications That
Decrease Uptake
Antithyroid drugs
Propythiouracil and methimazole result in a
poor 24 hour scan because they block
iodide oxidation and organification (and to
a lesser extent thyroid hormone excretion)
Because the agents do not inhibit iodine
trapping, a pertechnetate scan, may be
technically adequate.
Thyroid hormone
Amiodarone
What is the Thyroid
Supression Test?
Thyroid Suppression Test
Technique
The thyroid suppression test is based on the
premise that normal thyroid activity is
suppressed by exogenously administered
thyroid hormone
The test is used to determine the autonomy of
a hot nodule or diffusely enlarged gland. A
baseline scan and uptake are performed
The patient is then placed on T3 (Cytomel 25
ug TID [50-75 ug daily] for 7 days) to suppress
TSH production
Iodine uptake should normally fall to 50% of
pre-suppression value in a non-autonomously
functioning nodule
Indications For Thyroid Supression Test
The availability of sensitive TSH assays
has virtually eliminated the need to do
thyroid suppression test. Some conditions
where this test may provide additional
information include:
Early Graves' disease with borderline
hyperthyroidism or in euthyroid Graves'
disease (patients presenting with
opthalmopathy but normal function tests)
Nodules which are indeterminate (warm or
nondelinated) where a distinction between hot
and cold is unclear
A repeat scan on cytommel (T3) or levothyroxine
therapy with suppression of TSH may reveal
whether the thyroid nodule is autonomous (hot on
non autonomous (cold)
Evaluation of Toxic Multinodular Goiter
(Plummer's Disease)
TSH Stimulation Test
The TSH stimulation test is used to
identify thyroid tissue which is being
suppressed by:
an autonomously functioning thyroid nodule
(high levels of circulating thyroid hormone may
suppress TSH release and thus, normal
glandular function)
functioning thyroid metastases
Exogenous bovine TSH is administered
once daily for 1 to 3 days
Suppressed normal thyroid tissue should
be visualized following TSH stimulation
Patients with thyroid atrophy or diseased
or damaged thyroid tissue will not have
significant change in the appearance of
their scans
Recombinant Human TSH
Thyrogen
The administration of recombinant human TSH
(rhTSH) is an effective agent for detecting
residual or metastatic thyroid tissue in patient
with thyroid carcinoma
The traditional procedure for performing a
follow-up whole body radioiodine scan requires the
withdrawal of thyroid medications to allow
endogenous TSH levels to increase above 40 mU/L
so as to stimulate residual thyroid tissue
The use of rhTSH has been found to be just as
safe and effective in stimulating I-131 uptake by
residual thyroid tissue without the disadvantages
of having to withdraw thyroid hormones and
causing hypothyroidism
Perchlorate Washout
Test
Used to identify congenital or acquired
organification defects
These defects commonly involves the enzyme iodide
peroxidase which turns iodide into iodine for T3 and T4
In normal subjects, radioiodine when taken up by
the thyroid is immediately organified and bound
to thyroglobulin
However, in patients with defects in peroxidase
activity (usually hypothyroid), trapped radioiodine
is rapidly discharged when sodium perchlorate (an
inhibitor of thyroid iodide trapping) is
administered.
How is the Study
Performed?
Thyroid uptake is determined between 2 and 4
hours after administration of the dose
Potassium perchlorate is then administered orally
and a repeat measurement of RAIU performed in
30 to 60 minutes
A decrease in RAIU greater than 10-15%
following perchlorate administration is indicative
of an organification defect
The test is rarely performed since the treatment
for primary hypothyroidism is thyroid hormone
replacement regardless of the cause or site of
defective thyroid hormone synthesis
Congenital Lesions of the
Thyroid Gland
Dyshormonogenesis/
Organification Defect
Dyshormonogenesis results from a
deficiency or absence of one or more of
the enzymes involved in thyroid hormone
synthesis or secretion
The most common enzyme abnormality is
absent or insufficient thyroid peroxidase
activity which results in failure of
oxidation (organification) of iodide to
iodine
Signs of Peroxidase
Deficiency
Frequently have an enlarged gland, an elevated
TSH (due to decreased levels of circulating
thyroid hormone), and a high uptake of I-123 (at
4 hours) and Tc-pertechnetate
T4 and Free Thyroxine Index are usually
decreased.
The perchlorate washout test will be positive in
these patients
Deficient peroxidase activity associated with a
familial goiter and deafness or hearing loss is
referred to as which syndrome?
Pendred's Syndrome
Deficient peroxidase activity, familial
goiter and deafness or hearing loss
Case; Neck Mass
Lingual Thyroid
The Tc-pertechnetate
exam demonstrated the
abnormality to be due
to a lingual thyroid
No normal thyroid
tissue can be seen in
the thyroid bed.
Lingual Thyroid
A lingual thyroid occurs due to an extreme
failure of thyroid migration
The gland may provide adequate amounts
of thyroid hormone, or may fail in early
childhood (fails in 15-30% of cases)
In over 70% of patients with a lingual
thyroid, no other thyroid tissue can be
found in the neck
Can resemble and there actually is an
association with thyroglossal duct cysts.
Ectopic Thyroid
Tissue/Thyroid Dysgenesis
Ectopic thyroid tissue can be lingual,
substernal, or pelvic/ovarian
teratoma (struma ovarii)
Pertechnetate is generally not useful
for imaging the substernal area due
to attenuation or superimposed blood
pool activity.
Substernal Thyroid
I-123 is the preferred imaging agent
due to mediastinal blood pool activity
with Tc-99m
Most intrathoracic goiters
demonstrate anatomic continuity with
cervical thyroid tissue
Hemiagenesis of the
Thyroid
Females are affected more than
males (3:1)
The remaining lobe is hypertrophied,
but normal in shape
Which lobe is usually affected and
how often?
Hemiagenesis
The left lobe of the gland is absent
in about 80% of the cases
Case
This patient was well until one month ago when
she developed fatigue, weight loss, decreased
appetite, fevers and neck pain with swallowing.
The patient has no eye symptoms
On physical examination, the patient has an
increased heart rate, warm skin, and fine hair
The thyroid is not enlarged
The patient's free serum T4 was 3.4 ng/dl
(normal range 0.8-1.8 ng/dl) and the serum TSH
was less than 0.01 uU/ml (normal range 0.4-5.5
uU/ml)
What is the most likely diagnosis or what are the
most likely diagnoses? What else might be
helpful in this case?
5.0 uCi I-131 sodium iodide p.o. and
5.0 mCi Tc-99m Pertechnetate i.v.
What are the Findings?
The 24-hour I-131 uptake is 0.2% (normal
range 10-30%)
After checking with the technologist and the
patient, it was confirmed that she received
the I-131 dose. Thyroid scintigraphy was
performed. There is no thyroid uptake.
Subacute Thyroiditis
Subacute thyroiditis is thought to be
caused by a virus
The clinical picture and thyroid
function tests can be mistaken for
Graves' disease
Subacute Thyroiditis
However, unlike Graves the I-131 uptake
usually is low
Later, during recovery, the symptoms will
subside and the thyroid hormone level may
be low. At that time the TSH level will be
elevated.
Subacute thyroiditis should not be
mistaken for Graves' disease in patient
referred for radioactive iodine therapy
Name Some Types of Thyroiditis.
Which is Most Common?
Thyroiditis
Acute (Suppurative) Thyroiditis
Subacute Thyroiditis (de Quervain's
Syndrome)
Chronic Lymphocytic Thyroiditis:
Hashimoto's (most common)
Silent (Painless/Thyrotoxic
Lymphocytic) Thyroiditis
Riedel's Thyroiditis: (Riedel's
Struma)
Acute (Suppurative)
Thyroiditis
Acute suppurative thyroiditis is a rare, and life
threatening infection (abscess) of the thyroid
gland
It is most commonly a bacterial infection caused
by Strep., Staph., or Pneumococcus
Patients present with fever, localized tenderness
warmth and erythema, and difficulty in swallowing
In 50-70% of cases, a preexisting thyroid disease
is present
Most patients are clinically euthyroid (more focal
thyroid involvement)
Acute (Suppurative)
Thyroiditis
The RAIU is usually decreased due to
destruction of the gland
The local infection/inflammation in
the neck can result in marked
swelling which can compromise the
airway, or cause vascular thrombosis
in some of the major vessels
Acute (Suppurative)
Thyroiditis
Treatment is multifaceted and consists of
surgical drainage, tracheostomy and
antibiotics
In the rare patient who is clinically
thyrotoxic, large doses of beta-blockers,
saturated iodine solution or steroids may
be beneficial
Subacute Thyroiditis (de
Quervain's Syndrome)
Characterized by lymphocytic, granulomatous, and
foreign body giant cell infiltration
Probably viral
Mononuclear cell infiltrate and disruption of the
normal follicular architecture
Hormone leaks out into the blood producing
thyrotoxicosis
Iodine uptake will be low
After hormone production resumes, the patient
generally recovers without further complications.
Clinical Findings
Most patients are between 20-50 years of
age
Females are affected more than men (5:1)
Symptoms of subacute thyroiditis include
the rapid onset of thyroid swelling and
tenderness, which may mimic acute
suppurative thyroiditis
Patients often have a preceding upper
respiratory tract infection 2-3 weeks
before and may also experience a
prodrome of fever, aches, and fatigue
Patients typically recover fully without
residual thyroid dysfunction
Imaging Subacute
Thyroiditis
Single or multiple hypofunctioning areas
are occasionally seen and the disease can
be focal and present as a cold area/nodule
On ultrasound, there are patchy areas of
hypoechogenicity which disappear as the
clinical symptoms subside.
Treatment
Treatment of subacute thyroiditis
includes salicylates and steroids if
necessary to control the
inflammation
Large doses of beta-blockers are
used to control symptoms of
thyrotoxicosis
What is Silent
Thyroiditis?
Silent (Painless/Thyrotoxic
Lymphocytic) Thyroiditis
Autoimmune disease
Characterized by elevated levels of thyroid
peroxidase antibodies and thyroglobulin
antibodies
It is a form of lymphocytic thyroiditis
with lymphocytic infiltration of the
thyroid follicles that results in follicular
cell damage and consequently, release of
excess amounts of T4 and T3.
Silent (Painless/Thyrotoxic
Lymphocytic) Thyroiditis
Patients typically have symptoms of
thyrotoxicosis, but without a tender or painful
thyroid associated with subacute thyroiditis
T3 and T4 are elevated, the TSH is decreased,
and the RAIU is decreased (unlike Graves)
The condition will generally resolve spontaneously
The thyrotoxicosis is usually mild to moderate and
lasts for 1 to 4 weeks followed by a euthyroid
period, and then transient hypothyroidism
Treatment with beta-blockers can palliate
thyrotoxicosis symptoms and thyroid hormone
therapy is sometimes needed during the recovery
phase
Postpartum Thyroiditis
It is generally considered to be a subtype of
silent thyroiditis that appears most commonly
between 4 to 6 months
The course and findings are similar to silent
thyroiditis- thyrotoxicosis lasts 2 to 6 weeks and
this is followed by a period of hypothyroidism
which also lasts 2 to 6 weeks
In contrast to the recovery of normal thyroid
function that is expected in most patients with
silent thyroiditis, between 23-33% of patients
with painless thyroiditis will become permanently
hypothyroid
What Percentage of Post-
partum Patients Develop
Thyroiditis?
Postpartum Thyroiditis seen in 5 %
of post-partum patients and it often
recurs in subsequent pregnancies
Chronic Lymphocytic
Thyroiditis: Hashimoto's
Hashimoto's thyroiditis is also known as chronic
autoimmune thyroitditis
It is an autoimmune disorder characterized by
goiter and lymphocytic infiltration
There is a familial predisposition
Antimicrosomal (anti-thyroid peroxidase [TPO]
antibodies) are the most commonly found- 90-
95% of patients and are markedly elevated during
the acute phase of the disorder
Clinical Findings
Hashimoto's is the most common inflammatory
thyroid disease (accounting for about 85% of
cases of thyroiditis)
It is the most frequent cause of goiterous
hypothyroidism in adults. Females are affected
more than males (9:1)
Generally, patients are between the ages of 30-
50 years
Patients with Hashimoto's thyroiditis develop
other autoimmune disorders with higher
frequency and are at increased risk for
developing B-cell lymphoma of the thyroid
Hashimotos Thyroiditis
Clinically patients present with gradual painless
thyroid enlargement (firm rubbery gland)
Most patients are euthyroid at the time of
presentation.
TSH is typically normal, but will become elevated
as patients become hypothyroid.
TSH secretion stimulates the gland to synthesize
more T3 and T4 so that levels stay normal
RAIU is typically normal until late in the disease
course
Eventually, as thyroid tissue is replaced by
fibrosis, serum hormone levels will fall and
patients become hypothyroid.
Hashitoxicosis
Hashimoto's thyroiditis can also manifest
as an acute mild to moderate
hyperthyroidism in 3-5% of cases
Hashitoxicosis refers to the presence of
chronic lymphocytic thyroiditis PLUS
hyperthyroidism.
Imaging
The scintigraphic appearance of Hashimoto's is variable. A
multinodular goiter appearance is common with multiple
(40%) or single (30%) cold defects
There can be diffuse, uniform increased tracer activity, to
a coarse patchy distribution of tracer, or focal/diffuse
absence of activity
A normal scan is seen in only 8% of patients
On ultrasound, the gland is generally enlarged with a loss of
the normal homogeneous echo texture of the thyroid. The
gland is typically hypoechoic, inhomogeneous, and discrete
nodules may be noted occasionally
Later, fibrosis results in increased echogenicity (coarsened
echotexture).
Treatment
Patients are treated with thyroxine (T4).
This helps to prevent further thyroid
enlargement and decreases the formation
of nodules by suppressing TSH
Thyroxine therapy does not decrease the
risk for subsequent thyroid lymphoma.
Riedel's Thyroiditis:
(Riedel's Struma)
Riedel's struma is a rare condition that
has also been referred to as invasive
fibrous thyroiditis
In this disorder, there is painless
replacement of the thyroid by dense
fibrous tissue and which may also involve
adjacent soft tissues of the neck and is
often mistaken for cancer
Between 30 to 40% of patients will
progress to hypothyroidism
Case
Case
History
29 year old female was referred for thyroid scan and uptake after
a small thyroid nodule was detected by her physician in the lower
right aspect of her gland. Patient was asymptomatic and without
any significant medical history.
Imaging Technique
Imaging was performed 24 hours following the oral ingestion of
322 uCi of I-123 sodium iodide
Images were obtained using a pinhole collimator in the anterior,
LAO, and RAO positions. A marker view was also obtained by
placing cobalt disc markers at the sternal notch and 10 cm above
the notch
An anterior view was repeated with a Co-57 pen point marker
placed around the palpable nodule. The patient was then imaged in
the anterior position. Following the imaging portion of the exam,
thyroid uptake was measured.
Imaging Findings
Thyroid scintigraphy (RAO, Ant, LAO; 10 cm marker, string marker
on nodule) showed decreased tracer uptake in the right lower pole
The other portions of the thyroid gland had a normal appearance.
The cobalt marker image demonstrated that the area of
decreased uptake corresponded to the palpable abnormality.
24 hr thyroid uptake of radioiodine was 13% (normal range 5-35%).
Results
Because the palpable abnormality had decreased uptake on thyroid
scintigraphy, the nodule was biopsied using fine needle aspiration,
and a diagnosis of papillary carcinoma was made. The patient then
underwent subtotal thyroidectomy and the diagnosis of carcinoma
was confirmed. Lymph node sampling revealed no evidence of
distant tumor. Future plans include a metastatic survey with I-131.
What is the Prevalence of Thyroid
Nodules in the US?
Thyroid Nodules
Thyroid nodules occur in 4-15% of the adult population and
can be found in up to 90% of women over the age of 60
years
Incidence of malignancy is low
The major challenge that faces a clinician is to determine
whether a thyroid nodule is benign or malignant
Although certain aspects of the history and physical
examination may suggest a malignant process, in most cases
these are nonspecific and are of no predictive value.
Additional tests that may be helpful in establishing a
diagnosis include:
thyroid function tests
thyroid scan
thyroid ultrasound
fine needle aspiration biopsy (FNAB).
Does the Prevalence Change With Age?
The prevalence of nodules also seems
to increase with age.
Some of estimated the prevalence of
thyroid nodules in the US as high as
50%
Ultrasound: What is itss
Role in Thyroid Nodules?
Hyperechoic solid nodules are usually benign
(96%), but sclerosing papillary neoplasms can also
have this appearance
Mixed lesions represent solid lesions which have
undergone variable degrees of cystic
degeneration and are benign in 85% of cases)
Cystic lesions that are completely smooth walled
and anechoic are almost always benign
Iso- or hypoechoic lesions may be benign or
malignant
Role of US in Thyroid
Nodules
Since thyroid ultrasound cannot determine if a
nodule is benign or malignant, it is not routinely
recommended in the initial evaluation of a thyroid
nodule
However, it may be useful to guide fine needle
aspiration biopsy (FNAB) of a thyroid nodule
Thyroid ultrasound can also document the size of
a thyroid nodule and provide an objective
parameter for assessing response to hormone
suppression
Fine Needle Aspiration
If appropriate expertise is available,
fine needle aspiration of a thyroid
nodule is the most cost effective
management
FNAB has decreased the need for
thyroid surgery by about 50% and
increased the yield of cancer in
excised thyroid nodules by about 40%
FNA
Although relatively simple to perform, FNAB of
thyroid nodules can result in unsatisfactory
cytologic analysis in 20-25% of cases
Cystic nodules are more likely to yield
unsatisfactory results
Because up to 10% of nodules with non-diagnostic
aspirates may be malignant, repeat biopsy should
be performed in those cases
Biopsy of ultrasound detected nodules which are
smaller than 1.0 cm and not palpable is probably
not indicated
Nodules on Nuclear Scan
Cold
Hot
Indeterminate (function, non-
delineated, warm)
What is a Cold Nodule?
Are Most Solitary Thyroid
Nodules Cold, Warm, or Hot?
Cold Nodules
A cold nodule demonstrates decreased tracer
uptake compared to the surrounding normal
thyroid tissue
A cold nodule reflects lack of organification (or
trapping if Tc-pertechnetate is the imaging
agent) and subsequent thyroxine synthesis
The great majority of solitary thyroid nodules are
cold (hypofunctioning), but only 10 to 25% of
these are malignant
Cold Nodule: Risk of Cancer in
Patients with Multi-Nodular Goiter
Although some authors have
reported a lower incidence of
cancer in cold nodules in patients
with multinodular goiter (1 to 6%
risk of malignancy if the patient
has a MNG), this is not confirmed
in other reports
Risk of Cancer in a Multi-
nodular Goiter
The American Thyroid Association and the
American Association of Clinical Endocrinologists
recommend FNAB on dominant nodules in patients
with MNGs
Multi-nodularity of a goiter should no longer be
considered an indicator of probable benign
disease
The likelihood of a cold nodule being malignant
was lower in iodine deficient patients (roughly
2.5-3%)
Benign Cold Nodules
Simple cysts
True epithelial lined cysts are rare
More often degenerating adenomas or
colloid nodules
Predominantly cystic lesions with a solid
component such as a mural nodule are
benign in 85% of cases
What is the Most Common
Histology Associated with a
Cold Nodule?
Benign Cold Nodules
Adenomatous hyperplasia (colloid
cyst/non-functioning follicular
adenoma)
Most common cause of cold nodule (60%)
Commonly see areas of hemorrhage or
cystic degeneration
Patients present with enlarging thyroid
(hemorrhage) nodule and pain
Lesions are hypoechoic and solid on US in
70% of cases or complex with hypoechoic
rim or halo (only 10-15% of carcinomas
have a halo)
Other Causes of Benign
Cold Nodules
Focal hemorrhage
Inflammatory
Focal thyroiditis
Abscess
Parathyroid adenoma
Malignant Cold Nodules
(20%)
Thyroid carcinoma
Parathyroid adenoma/carcinoma
Thyroid lymphoma
Metastatic disease
Name Some Factors That
Increase the Odds that a Cold
Nodule is Malignant
Increase Chances that
Cold Nodule is Malignant
History of XRT to head and neck as an
adolescent or child
The likelihood of malignancy in a solitary nodule
is about 30% if there is a history of XRT
Adenopathy (Regional)
Age
Less than 20 years old, about 2 fold increased
risk
Over 60 years, about 6 fold increased risk
Increase Chances that
Cold Nodule is Malignant
Male sex
The chance that a cold nodule is malignant is about 2
times greater in a male patient
Generally, carcinoma is found in about 20-25% of cold
nodules in men.
Evidence of local invasion
Recurrent laryngeal nerve involvement
Size of nodule greater than 4 cm
Nodule enlarges while on thyroxine suppression
Most benign nodules will shrink or remain unchanged.
Family history of thyroid cancer
Case
This is a 16-year old white female patient who over the last year
has been noted by her family to have increasingly difficult
behavior with poor impulse control, worsening relationships with
family members, and temper tantrums. Psychiatric evaluation
performed one month prior to this study suggested a bipolar
disorder. Two weeks prior to this study, lithium carbonate
treatment was instituted. Subsequently, the patient brought a
thyroid nodule to the attention of the psychiatrist
Thyroid function tests done at the time of this study
demonstrated total serum thyroxine of 9.8 (4.5-12.5 ug/dl), a T3
resin uptake of 34 (22-35%), and a serum TSH of less than 0.1
(0.4-5.5 uIU/mL)
Physical examination demonstrated a 4 x 2 cm oblong smooth
nodule in the left lobe of the thyroid gland.
Case
16-year old female patient with
increasingly difficult behavior
Diagnosis: Hyperfunctioning Thyroid
Adenoma

Radiopharmaceutical:
Tc-99m pertechnetate i.v. Findings:
Thyroid scintigraphy with Tc- 99m pertechnetate demonstrates
intense uptake of the radiopharmaceutical corresponding to the
palpable nodule in the left lobe of the thyroid. There is also
suppression of uptake in the remainder of the left lobe as well as the
entire right lobe
Discussion:
The scintigraphic findings in conjunction with the patient's history and
elevated thyroid function tests are most consistent with an autonomous
toxic nodule. Surgical resection was performed, which demonstrated
follicular adenoma.
Hot Nodule
A hot nodule has greater more activity than the
normal surrounding thyroid tissue
It can be autonomous (non-responsive to TSH
manipulation), semiautonomous (partially
responsive), or non-autonomous (responsive)
An autonomous nodule will continue to function
and show uptake of iodine even when TSH has
been suppressed by administering exogenous
thyroid hormone (refer to TSH suppression test)
A toxic nodule is an autonomous nodule that produces
enough thyroid hormone to cause thyrotoxicosis.
How Often Does a Hot Nodule
Turn Out to be Cancer?
How Often Does a Hot Nodule
Turn Out to be Cancer?
Less than 4%
What are the 4 Types of
Hot Thyroid Lesions
Benign hyperfunctioning follicular
adenomas
Adenomatous hyperplasia
Compensatory hypertrophy
Physiologic thyroid hyperplasia
Which of the four types
is most common?
Adenomatous hyperplasia
Benign hyperfunctioning follicular
adenomas
Compensatory hypertrophy
Physiologic thyroid hyperplasia
Which of the four types
of most common?
Adenomatous hyperplasia
Benign hyperfunctioning follicular
adenomas (accounts for almost all hot
nodules)
Compensatory hypertrophy
Physiologic thyroid hyperplasia
Benign hyperfunctioning
follicular adenomas
Account for almost all hot
nodules, 50% are autonomous-
i.e.: TSH independent
Patients can be euthyroid or
hyperthyroid (Plummer's disease)
as a result of the
hyperfunctioning nodule
Benign Hyperfunctioning
Follicular Adenomas
The remainder of the thyroid gland is
suppressed with a toxic nodule, but
can be imaged if TSH is given to
stimulate this tissue
As these nodules enlarge, they
frequently undergo central necrosis
and may be centrally photopenic.
Autonomous Nodule:
Another Example

Pinhole images from an I-123 scan


demonstrate an autonomously functioning
nodule within the lower pole of the right lobe
of the thyroid gland
The remainder of the thyroid is suppressed
by this hyperfunctioning nodule
The patients radioactive iodine uptake was
27%.
Compensatory
Hypertrophy
Compensatory hypertrophy can cause
a palpable nodule which concentrates
pertechnetate better than the
surrounding tissue
Such hypertrophy is seen when there
is widespread damage to the gland
(Hashimoto's).
Physiologic Thyroid
Hyperplasia
Patients who have congenital lobar
agenesis (more commonly the left
lobe [80%]),or are post surgical
lobectomy, may appear to have a hot
nodule which is suppressing the
remainder of the gland.
Indeterminate Nodule
An interminant , 'warm' or 'non-
delineated' nodule has activity equal to the
adjacent thyroid gland
One reason the lesion may not be
identified is due to shine through of
normal thyroid tissue activity
A thyroid suppression test may be
performed to determine if the nodule is
autonomous or cold
Discordant Nodule
A discordant nodule is hot on Tc-99m images, but
cold on the I-123 exam
Discordant nodules can be explained by either:
Preservation of Tc-pertechnetate trapping, but failure
of organification
Rapid release of organified iodine from the nodule
(iodine has washed out of gland by time of scanning at
24 hours)
Discordant Nodule
Solitary discordant thyroid nodules are
generally considered to be rare (2 to 8%)
and cases of discrepancy between the Tc-
99m and I-123 studies appear most often
in multinodular goiters
Discrepancies are also far more likely to
be caused by benign thyroid disorders
rather than malignancy
Discordant Nodule
A conservative approach to this problem
would be to re-scan any patient with a hot
nodule on the Tc-99m pertechnetate exam
with I-123
Fine Needle Biopsy
A major dilemma in the evaluation of small
thyroid nodules is the determination of
which nodules should undergo fine needle
biopsy
Some nodules may not be evident on
scintigraphy due to their small size or
superimposition of normal thyroid tracer
activity
Management Thyroid Nodules
Ultrasound Consensus Statement Oct 2004

Thyroid nodules common:


4-8% of population on palpation
10-41% by US
50% by autopsy
Incidence malignancy in patients
selected for FNA is 9-13% (regardless
of # total nodules seen)
In 1/3 of cases with multiple nodules,
cancer is not in dominant nodule
Cancer rate in palpable nodules not
different from non palpable ones
Management Thyroid Nodules
Ultrasound Consensus Statement Oct 2004

75-80% cancers papillary, 10-20% follicular, 3-5%


medullary, 1-2% anaplastic
No US feature has a high predictive value for
cancer
Feature with highest sensitivity is (70%) is solid
composition but low positive predictive value
Feature of highest positive predictive value is
microcalcifications (only seen in 25-60% of tumors)
Results of color doppler are mixed
15-20% of FNAs are non-diagnostic
When Should FNA of a
Thyroid Nodule be Performed?
Management Thyroid Nodules
Ultrasound Consensus Statement Oct 2004
Recommendations
FNA for nodule 1.0 cm or more with
microcalcifications or for solid or coarsely
calcified 1.5 cm nodule
FNA if > 2.0 cm if solid and cystic or
cystic with mural nodule, or if has grown
Biopsy node or thyroid nodule in the
presence of abnormal lymph nodes
No FNA if almost entirely cystic
What is the Sensitivity
and Specificity of FNA?
For fine needle aspirates considered sufficient
for diagnosis the sensitivity and specificity are
93% and 96%, respectively
No needle tract implants occurred in an early
series of 1,400 needle biopsies and it is a rarity in
other series
False negative biopsy results can occur in 1 to 6%
of cases and a patient with a benign FNA has a 4-
6% chance of ultimately proving to have a cancer
How Often Does a False
Positive Thyroid FNA Occur?
False positive biopsy results can
occur in 7.4% to 25% of positive
biopsies
This is mostly a problem for lesions
described as suggestive of follicular
neoplasm
43 year old female with exophtalmus, agitated, elevated
free T4, undetectable TSH
Thyroid gland on physical exam 35-40 grams.
43 year old female with exophtalmus, agitated, elevated free
T4, undetectable TSH was presented to evaluate thyroud
pathalogy and differentiate thyroiditis vs. Grave disease.
Thyroid gland on physical exam 35-40 grams.

Findings:
Uniformly increased activity in the both lobes of the enlarged
thyroid gland. There is no evidence of nodular increased activity to
suggest a toxic nodular goiter, nor decreased uptake to suggest
thyroiditis. Findings consistent with hyperthyroidism due to Grave
disease
Discussion:
On Tc-99m petechnetate scan,the thyroid has increased activity,
and salivary glands are difficukt to identify. 24-hour iodine uptake
usually in the range of 40-70%
Followup:
On 2/28/02 24-hour radioactive iodine uptake was 66%. She was
treated with 7.1 mci of I-131.
Another Example of
Graves
Diffuse Toxic Goiter (Graves
Disease): Pathophysiology
Autoimmune disorder characterized by the
presence of a TSH receptor antibody
Antibody was previously referred to as Long-
Acting Thyroid Stimulator (LATS) but is
currently more appropriately called as Thyroid
Stimulating Immunoglobulin (TSI) or Thyroid-
Stimulating Antibody (TSAb)
TSI is found in 90 to 95% of cases of Graves
disease.
Clinical Findings
The age of onset is most commonly
between 30-40 years
Females are much more commonly affected
than men (7:1)
Patients present with a goiter,
exophthalmos, tachycardia, weight loss,
heat intolerance, hyperactive reflexes,
warm skin, lid lag, and/or a tremor
Clinical Findings
Other findings include lid retraction, periorbital
edema, optic neuritis, and enlargement of the
extraoccular muscles
Another extrathyroidal manifestation is an
infiltrative dermopathy (pretibial myxedema)
There is no increased risk of thyroid cancer in
these patients
Clinical Findings
T3 and T4 levels are elevated and TSH is
decreased in patients with Graves disease
T3 levels are typically three times normal,
while T4 values are usually double
Early in the disease, only T3 toxicosis may be
seen, with the FT4I falling within normal limits
There is a flat TSH response to TRH
stimulation in patients with Graves disease.
Neonates Born To
Mothers with Graves
At an increased risk for hyperthyroidism
secondary to transplacental passage of
thyroid stimulating antibodies
Onset of symptoms is within hours to days
and death can result in 15% of cases. With
proper therapy the condition will resolve
spontaneously over a period of about 3
months as the thyroid stimulating antibody
disappears.
Imaging Graves
If iodide turnover is rapid, early RAIU values will be
markedly elevated, but may be normal by 24 hours.
The pyramidal lobe, a variant projection of thyroid tissue
arising from the isthmus or the medial aspect of one of the
lobes and ascending superomedially, is more frequently
visualized by scintigraphy in the presence of Graves'
disease (up to 40% of patients)
Ultrasound evaluation of the thyroid in Graves' disease
demonstrates markedly increased vascular flow and velocity
suggests thyroid hyperfunction
Treatment for Graves
Disease: Surgery
Surgery is not the preferred method
of treatment because of the
potential complications of general
anesthesia and the possibility of
recurrent laryngeal nerve damage.
Treatment for Graves
Disease: Drugs
Antithyroid drugs such as the thionamides
Propylthiouracil and Tapazole (Methimazole)
Act by blocking the intrathyroidal organification
(iodination) of the tyrosine residues on the thyroglobulin
molecule by interacting with the enzyme thyroid
peroxidase- thereby inhibiting thyroid hormone
formation
Therapeutic actions of these agents begin as early as 4 to
12 hours after administration.
PTU has the added extrathyroidal effect of exerting a
non-competitive inhibition on the peripheral conversion
of T4 to T3.
Antithyroidal drugs
Can control symptoms of hyperthyroidism
in 90% of patients
Permanent remission may be achieved in 10
to 30% of patients
Unfortunately, relapse rates are frequent
(about 50%) even in patients who are
treated for over 2 years
Common side effects include fever, rash,
pruritis (3-5%), and neutropenia
Case
Graves disease and
papillary carcinoma

Cold nodules (blue arrows) can be seen in the lower


pole of the right lobe and the upper pole of the left
lobe
Although these could represent TSH dependent
nodules, the lesions in this case were related to
multifocal papillary thyroid carcinoma
Although patients with Graves disease are not at an
increased risk for thyroid cancer, the lesion may be
more aggressive in this patient population
Solitary Toxic Nodule
Infrequent cause of hyperthyroidism in the US
(but it can account for up to 9% of cases of
thyrotoxicosis in Europe)
The risk of developing thyrotoxicosis in an
autonomous nodule is higher for older patients
and in patients living in areas of relatively low
iodine intake
Antithyroid drugs are not a treatment option due
to the high frequency of recurrence on cessations
of the treatment
I-131 is the prefered therapy
Some also refer to a solitary toxic nodule as
Plummer's disease
Toxic Nodular Goiter:
Plummers Disease
The disorder is more commonly seen in patients
40-50 years old
Females are affected more than men (3:1)
Patients generally present with:
Mildly elevated thyroid hormone levels
Decreased TSH
Slightly elevated or normal RAIU
Plummer's disease, however, is more frequently
associated with T3 toxicosis (i.e.: T3 is elevated
in preference to T4) than is Graves' disease.
Plummers Disease:
Nuclear Imaging
Usually a patchy appearance to the thyroid due to
the presence of multiple cold, warm, and hot
nodules
One to several autonomous nodules which
suppress the activity in the remainder of the
gland are usually identified
Suppression, however, does not connote toxicity per se.
Autonomously functioning nodules less than 2.5 cm in
diameter are rarely toxic and have little likelihood of
becoming so unless they enlarge
Nodules larger than 3 cm are much more likely to
become toxic (20% by 6 years)
Uptake measurements are usually normal or low at 24
hours in a toxic multinodular goiter and generally
elevated with a toxic adenoma.
Plummer's Disease: Rx
Treatment is based upon the patients clinical
status
In euthyroid patients (i.e.: hyperfunctioning
nodule maintains a normal level of thyroxine) only
about 5% of these individuals will progress to
become thyrotoxic
The vast majority of patients [80%] with
multinodular goiter are euthyroid and have a
normal RAIU
Treatment in these patients is observation.
Plummer's Disease: Rx
An empirical dose of 25-29 mCi of I-131
can be used to treat hyperthyroid patients
with multiple nodules
If the patient has a solitary
hyperfunctioning nodule, the great
majority of the administered dose will be
concentrated there, thus protecting the
remainder of the thyroid gland and post-
therapy hypothyroidism is rarely seen in
this setting
Factitious
Hyperthyroidism
Factitious hyperthyroidism occurs when a patient
ingests thyroid hormone in sufficient quantities to
induce a thyrotoxic state
A helpful diagnostic tool for confirming facticious
hyperthyroidism is the thyroglobulin level
Thyroglobulin levels are low or undetectable in
facticious hyperthyroidism, while other forms of
hyperthyroidism will demonstrate normal or elevated
thyroglobulin levels
These patients will have decreased RAIU and poor
uptake of tracer on thyroid exams.
There is elevation of T3 and T4 which suppress TSH
If T3 alone is ingested, serum T4 is usually depressed
as a result of inhibition of thyroid secretion
secondary to T3 suppression of TSH
Iodine induced hyperthyroidism:
Jod-Basedow Phenomenon
Iodine induced hyperthyroidism refers to
excessive T4 synthesis and release in an
iodine deficient patient upon resumption of
dietary iodine intake or administration of IV
contrast
The disorder occurs insidiously when there is
excessive exposure to iodine- such as with
iodine containing medications (SSKI drops or
amiodarone)
Under normal conditions, there is a
protective mechanism which prevents
increased iodine ingestion from leading to
excess thryoid hormone production
This is known as the Wolff-Chaikoff effect
Iodine induced hyperthyroidism:
Jod-Basedow Phenomenon
Antithyroid drugs in high doses are the
treatment of choice, with or without the
addition of potassium perchlorate, which
blocks further iodine uptake by the gland
Thyroid hormone levels are elevated, the
TSH level is suppressed, and the RAIU is
low (due to excess iodine in the gland)
TSH induced
Thyrotoxicosis
TSH hyperthyroidism occurs secondary to
a TSH secreting pituitary adenoma- this is
an exceedingly rare neoplasm accounting
for less than 1% of all pituitary tumors
TSH stimulation leads to increased levels
of thyroid hormone and increased RAIU
Unlike other causes of hyperthyroidism,
the TSH level will be elevated
Radiotherapy: Non-
Neoplastic Diseases
Radiotherapy of thyroid disease uses
the high energy beta particle
emissions of I-131 to treat
hyperthyroidism due to Graves or
Plummers disease
Radioiodine has also been used in
treating patients with large
compressive goiters who are
nonsurgical candidates
A decrease in thyroid volume by about
40% may occur following I-131 therapy
Factors Affecting I-131
Therapy
Iodine uptake by the gland
Bulk of tissue to be destroyed
Length of time radioactive iodine is
retained in the gland
Distribution within the tissue
Drugs that need to be
discontinued prior to therapy

Medication Withdrawal Period

Antithyroid medication 3 days for antithyroid


(propylthiouracil, medication 7 days for
methimazole, carbimazole) multivitamins
and multivitamins
Thyroid hormone 2 weeks for cytomel
4 to 6 weeks for synthyroid
Kelp, Lugol's solution, SSKI 2 to 3 weeks
solution
IV contrast Over 1 month

Amiodarone 3 to 6 months
Contraindications to I-131 Therapy

Pregnancy
The fetal thyroid extracts/concentrates iodine after
the 12th week and the radiation will destroy the thyroid
gland and result in severe hypothyroidism.
Breast feeding: Both iodine and pertechnetate
are excreted in breast milk
Severe thyrotoxicity: Patients should be
pretreated (with beta-blockers) to avoid thyroid
storm which can occur from sudden release of
hormones following radiation destruction of the
thyroid follicles
How Do You Treat Patients
with Hyperthyroidism with I-
131 at Your Institution?
I-131 Therapy for
Hyperthyroidism Technique
I-131 is the treatment of choice for
patients over the age of 30, or those with
medical complications of their thyroid
disease
The dose of I-131 is approximately 80-200
uCi per gram of thyroid
By dividing this number by the measured
uptake of the gland, an actual dose can be
determined
Unfortunately, estimates of the thyroid
weight can be off by as much as 20 to 50%
Many centers treat patients with a standard
dose of between 8 to 12 mCi and perform no
calculations.
I-131 Therapy for
Hyperthyroidism Technique
It is well recognized that solitary nodules and
multinodular goiters are more radioresistant than
Grave's disease, and that large glands are less
sensitive than small ones
Antithyroid drugs should be discontinued for at
least 48 hours prior to the therapy and
preferably for 5 to 7 days as they may affect the
uptake of radioactive iodine
If necessary, these agents can be resumed 7 to
10 days following treatment
Dose Determination
Formula
Dose= (Thyroid mass[gms] x 80-200
uCi/gm)/ Percent uptake
Tapazole or PTU with I-131
Concern over the rapid release of glandular
hormone stores after I-131 treatment
provides the rationale for adjunctive therapy
with antithyroid drugs before or after
therapy in order to deplete thyroid hormone
Some authors feel that the adjunctive use of
antithyroid medications leads to a more rapid
remission of hyperthyroidism than with I-131
alone and the combination may also reduce
the risk of post-treatment thyroid storm and
hypothyroidism
Results of I-131
Treatment
No significant change in thyroid function
can be expected for 3 to 6 weeks
The maximum effects of the therapy
should occur between 3 and 4 months, but
final results may not be known for 6 to 9
months
The cure rate is proportional to the dose
deposited and runs from 50% (50 uCi/gm
deposited) to 80% (190 uCi/gm deposited)
Outcomes of Therapy
There are 3 potential outcomes of
therapy- patients may become
euthyroid, remain hyperthyroid, or
more commonly become hypothyroid
Between 5 to 15% of patients will
remain hyperthyroid despite
treatment and the therapy may be
repeated in these individuals-
approximately 10% of patients will
require a second treatment.
Therapy
Some centers favor using a lower dose of I-131 in an
attempt to render the patient euthyroid without the need
for thyroid hormone replacement
However, this is associated with a higher treatment failure
rate with patients often requiring a second or third
treatment with I-131
Since hypothyroidism is almost an inevitable consequence of
I-131 treatment for Graves' disease, larger doses of I-131
have been used with the purpose of ablating the thyroid and
deliberately causing hypothyroidism
Depending on the dose used for therapy, the incidence of
hypothyroidism following treatment ranges from 50-80%
during the first year and 1-3% per year thereafter
Side Effects
In the first week after treatment, some patients
may experience a transient sore throat or mild
dysphagia
Another potential, but rare complication of I-131
therapy for hyperthyroidism is temporary
thyrotoxicosis (or thyroid storm) due to the
sudden release of thyroid hormone from the gland
as it is destroyed
Side Effects
The period of greatest risk for thyroid
storm is usually between 3 - 15 days after
treatment
This can be a potentially fatal
complication. Patients who are at highest-
risk include the elderly, those with severe
thyrotoxicosis, large glands and markedly
elevated levels of T3 or those with other
underlying disease such as coronary artery
disease
Side Effects
Providing a "cool down period" by pretreatment with
antithyroid medications (PTU or Tapazole, beta blockers for
6-12 weeks) to deplete thyroid stores especially in high risk
patients may help prevent excessive thyroid hormone
release post-therapy
However, the benefits of this approach has been questioned
by Burch et al.
Initiating oral iodides (i.e. SSKI) 2-3 days after I-131
treatment inhibits hormone release from the thyroid gland
and may protect against thyroid storm.
Impact of I-131 Therapy on
ophthalmopathy And How To
Prevent This?
However, RAI therapy may exacerbate
clinically evident ophthalmopathy and the use
of adjuctive systemic corticosteroids
following treatment may be indicated
Additionally, post-therapy hypothyroidism
may aggravate the ophthalmopathy and
should be prevented through the early
institution of levothyroxine replacement
therapy
Ophthalmopathy may develop for the first
time, after therapy
Risk of Thyroid Cancer After
I-131 for Hyperthyroidism?
Actually reduced or not significantly different from the
general population (This may be related to destruction of
the thyroid gland)
The risk of leukemia or other malignancy is no greater than
in the general population
Additionally, there has been no demonstrable harmful
effect upon the health of progeny, fertility, or reproductive
history
No significant genetic effect has been demonstrated as
well.
Nonetheless, women should be advised to refrain from
becoming pregnant for at least 6 to 12 months following
therapy
I-131 Therapy for the
Autonomous Functioning Nodule

Clinical hyperthyroidism is uncommon in nodules


smaller than 2.5 cm and if the patient is not toxic,
radioiodine therapy is not indicated
Toxic autonomously functioning adenomas are
relatively radioresistant and effective treatment
generally requires doses in excess of 20 mCi
Because the remainder of the thyroid is
suppressed, the incidence of hypothyroidism
following therapy is low
If the nodule is not ablated on the first
dose, there is an increase dose
requirement for retreatment due to lower
uptake by the nodule. In general, a good
way to calculate the dose necessary to
ablate a solitary toxic nodule is:
Dose I-131= 10 mCi/Uptake
I-131 Therapy for Autonomously
Functioning Multinodular Goiter
(Plummer's Disease)
The gland is frequently very large, fairly
radioresistant (due to the non-
homogeneous distribution of I-131 within
the gland), and iodine uptakes between 25
to 30% are not uncommon
Large doses are typically required (29.9
mCi)
I-131 Therapy for Non-
toxic Nodular Goiter
I-131 therapy is effective for the
reduction of thyroid volume in patients
with non-toxic multinodular goiter
Goiter size can decreased by about
40% after 1 year and 50-60% after 3
to 5 years
The dose is approximately 100 uCi of
I-131 per gram of thyroid tissue,
corrected for RAIU at 24 hours
Pre-treatment with rhTSH allows the
therapeutic dose to be reduced by
about 50% without compromising
treatment results
Case
Diagnosis: Metastatic papillary thyroid carcinoma to the lungs and neck

Full history:
18-year old woman with papillary carcinoma of the thyroid status post
total thyroidectomy with removal of lymph nodes in the neck and
supraclavicular regions. MRI demonstrated multiple pulmonary
nodules.
Radiopharmaceutical:
200 mCi I-131 sodium iodide p.o.
Findings:
Anterior and posterior whole body I- 131 images demonstrate multiple
areas of increased uptake in the neck, as well as diffuse pulmonary
uptake.
Discussion:
Well differentiated papillary, follicular, and mixed carcinomas are
represented in about 75% of all primary thyroid malignancies
The overall 5-year survival rate of well differentiated carcinoma is
over 95% in properly treated patients. Papillary carcinomas tend to
metastasize via the interstitium to local nodal groups while follicular
carcinomas tend to metastasize hematogenously
Diagnosis: Metastatic Thyroid Carcinoma
6 YO child had a total thyroidectomy 6 weeks prior to whole body
radioiodine imaging for papillary carcinoma of the thyroid
The patient has no prior exposure to head and neck radiation
This examination was performed after a 30 mCi therapy dose

Diagnosis: Metastatic Thyroid Carcinoma


Radiopharmaceutical:
30 mCi I-131 (sodium iodide) p.o. (administered by the Division of Radiation
Oncology) Findings:
Initial whole body images demonstrate diffuse uptake throughout the lungs
as well as uptake within the neck.
Thyroid Carcinoma
Thyroid carcinomas almost invariably
appear as cold areas on routine thyroid
scanning
Most thyroid carcinomas appear
hypoechoic (65%) or isoechoic (25%) on
ultrasound
Hyperechoic thyroid lesions tend to be
benign (95%)
Risk Factors for Thyroid
Mass Being Cancer
Male sex
Two fold increased risk; however, females have an
overall higher incidence of thyroid cancer as they
have 8 times as many thyroid nodules as men
Age
Under 20 or over 60 years
Some authors recommend that in males over the age
of 60 years, the pretest probability of a thyroid
nodule being cancer is so high that surgery should
be considered even if the fine needle biopsy results
are negative
History of Radiation Therapy to the Head
and Neck
Risk Factors in Kids
There is clear evidence that
pediatric patients exposed to low
dose radiation of the thyroid are
at increased risk for developing
thyroid carcinoma, as well as
benign thyroid nodules
Risk Factors in Kids
The peak risk is seen 5-30 years post
radiation
Besides thyroid malignancies, other
thyroid abnormalities are seen in
20% of patients exposed to radiation
including adenomatous
hyperplasia/follicular adenoma (70%)
Pediatric Thyroid Cancer
Less than 10% of papillary and follicular thyroid
cancers occur in pediatric patients (age less than
20y) with about 2/3's of those affected being
female
The therapeutic approach to thyroid cancer in
children is identical to that in adults- it includes
surgery, radioactive iodine ablation, and TSH
suppression with exogenous thyroxine
Overall 15-20 year survival for pediatric thyroid
cancer patients is 90-95%
Most Common Type of
Thyroid Carcinoma
Papillary Thyroid
Carcinoma (Roughly
2/3rds of thyroid
cancers)
The term papillary carcinoma of the
thyroid describes both pure papillary
tumors and those lesions that
contain both papillary and follicular
elements ("mixed" tumors)
Papillary carcinoma is the most
common thyroid cancer accounting
for 50-89% of cases
Small papillary cancers have been
found in 6-13% of American patients
in autopsy series
Females are affected more
commonly than males
Papillary Thyroid
Carcinoma
The majority of tumors are unilateral (70-80%), but can be
multifocal in up to 25% of patients
Extrathyroidal extension is found in about 15% of patients
Coexistent benign nodules are found in 33% of patients
Chronic lymphocytic thyroiditis is found in about 20% of
patients and Graves' disease in about 4%
In general, papillary cancers tend to be slow growing and
there is about 93-97% long term survival (25 years) in
patients who have complete surgical resection of the tumor
and no evidence of metastatic disease
This is significantly better than survival in patients with
follicular thyroid cancer
Local Recurrence
Associated with an increase in mortality
It occurs in about 5-15% of patients and is
associated with an approximately 40%
mortality
The incidence of local recurrence is higher in
children, in patients over age 60 years, and in
patients initially noted to have
extrathyroidal invasion or very large tumors
(over 4 cm)
Radioiodine therapy has been shown to
decrease local recurrence by about 50%,
but unfortunately, therapy has not been
shown to statistically decrease mortality
in patients with thyroid cancer
Distant Metastatic Disease
in Papillary Carcinoma
Regional nodal mets are found in 30 to 50% of
patients at the time of diagnosis
The presence of initial local nodal mets does NOT
influence survival, but does increase the risk for
recurrence
Distant Metastatic Disease
in Papillary Carcinoma
Distant (hematogenous) mets uncommon in
differentiated thyroid cancer (either papillary or
follicular)
Distant mets are seen in only about 3-7% of
patients with papillary carcinoma at the time of
diagnosis
Approximately 4-5% of patients will go on to
develop distant mets at some time, generally
within the first 10 years after surgery
What is the most and next most common site for
thyroid metastatic disease?
The most common site for distant
mets is the lungs, followed by bone
and the mediastinum
Distant Metastatic Disease to the
Lungs in Papillary Carcinoma
Between 50-60% of metastatic pulmonary
lesions will concentrate radioiodine
Patients with iodine concentrating
pulmonary metastases have a 5-year
survival rate of 60% compared to 30% for
tumors which do not concentrate
radioiodine
In patients with a negative CXR, but
positive I-131 scans, there was a 10 year
survival rate of 96% and a complete
disease remission rate of 80% following I-
131 therapy
In patients with both a positive CXR and a
positive I-131 scan, the 10 year survival rate was
significantly lower (40%) and complete remission
was rarely achieved (4%). Patients with a positive
CXR, but a negative I-131 scan had the worst
prognosis with a 10 year survival rate of only 10%
and no complete remissions
It should be pointed out that the micronodular
pattern (miliary) of lung mets was invariably
related to good I-131 uptake and a better
prognosis, while macronodular (over 0.5 cm) mets
frequently showed poor uptake and had an
associated worse prognosis
Case
Diffuse Lung Mets

The patient was an 8 year old female with thyroid cancer. The I-131 exam
demonstrated diffuse pulmonary tracer accumulation consistent with metastatic
disease. The CXR demonstrated multiple small pulmonary nodules
Bone Mets
Bone metastases are uncommon in patients with
differentiated thyroid cancer and are usually seen after
the appearance of lung mets
In one study, bone metastases at presentation were found
in only 3.5% of patients
The most common site for bone mets is the spine
Thyroid mets to bone are best detected by whole body I-
131 scans
Only 60% of bone lesions detected on the iodine scan are
identified on bone scan
Follicular Thyroid Cancer (10-
20% of thyroid cancers)

Follicular cacinoma accounts for 10-32% of differentiated


thyroid cancers
Follicular carcinoma tends to occur in a slightly older age
group (50 years) than papillary cancer and have an overall
worse survival rate
The lesion is multifocal in 10 to 25% of cases and
angioinvasion is found in about 50% of cases
Hematogenous distant metastases are seen in 10-15% of
patients at the time of diagnosis
Subsequently, distant metastases will be occur in up to 25%
of patients
Follicular Thyroid Cancer
The most common location for metastases is the lungs
(70%), followed closely by the bones (65%), and also the
brain (20%)
The overall mortality from follicular thyroid cancer is about
20%, however, patients with no evidence of disseminated
disease at presentation have a 10 year survival of about
90%
Follicular neoplasms will usually concentrate technetium
pertechnetate, but may not concentrate I-131- producing a
"discordant nodule
Treatment with radioiodine following thyroidectomy has
been shown to decrease the risk of local recurrence and
improve patient survival
Hurthle cell carcinoma
Hurthle cell carcinoma is a follicular variant and it accounts
for less than 10% of thyroid carcinomas
The tumor is composed of large oxyphilic (Hurthle) cells
which contain abundant mitochondria
Most do NOT accumulate radioiodine (non-functional), but
are capable of synthesizing thyroglobulin
The tumors tend to invade locally (40%) and recur. The risk
for distant metastases is about 33%, compared to 22% for
follicular cancer and 10% for papillary cancer
These patients have an overall worse prognosis with a 5
year survival of 81% (Papillary 94%, Follicular 87%)
FDG PET imaging is very good for imaging Hurthle cell
neoplasms as intense tracer uptake is generally seen
Anaplastic/Poorly
Differentiated: (5%)
Anaplastic carcinoma is usually seen
in older patients (60-70y)
The lesions typically do not
concentrate iodine and the prognosis
is poor.
Medullary Thyroid
Carcinoma
Medullary carcinoma arises from the
parafollicular C-cells and accounts for only 1 to
5% of all thyroid malignancies
These tumors may actively secrete calcitonin
Medullary carcinoma is associated with MEN
syndrome IIa (MTC, hyperparathyroidism,
pheochromocytoma) and MEN IIb (MTC, mucosal
neuromas, pheochromocytoma) and is frequently
multifocal in these patients
Mets occur early to regional lymph nodes (50-
80%), liver, lung, and bone.
Medullary Thyroid
Carcinoma
The treatment of choice for medullary thyroid
carcinoma is surgical total thyroidectomy
I-131 therapy does not significantly affect
prognosis in patients with disease outside the
thyroid bed, but may be helpful in decreasing
recurrence in patients with residual foci in the
thyroid bed.
On scintigraphy medullary carcinoma appears as a
cold nodule on routine thyroid scanning
Primary Thyroid
Lymphoma
Thyroid lymphoma accounts for less than 5% of thyroid
malignancies and is usually of B-cell origin
It is seen more commonly in women than in men
It usually presents as a rapidly enlarging goiter
An increased risk for thyroid lymphoma is seen in
patients with chronic lymphocytic thyroiditis
Treatment is XRT and there is about 50% survival at 10
years
Thyroid lymphoma does not concentrate radioiodine
I-131 for Thyroid Cancer
I-131 has a physical half-life of 8.05
day
It decays by high energy gamma
photon (364 keV) and particulate
emissions (beta particles)
However, thyroid tumors usually
continue to express TSH receptors
and will increase iodine uptake under
TSH stimulation
In order to ablate the thyroid bed in post
surgical patients, between 30,000 to
100,000 rads is needed to be delivered to
the remaining thyroid tissue
Two important determinants of the
success of thyroid ablation are the mass
of remaining thyroid tissue in the neck,
and the initial dose rate to this tissue
Rx for Metastatic
Disease
Although it is generally recommended
to limit treatment to yearly intervals,
if necessary, therapy for metastases
may be repeated as necessary every
3 to 6 months for up to 5 to 10
treatments.
Indications for Thyroid
Cancer I-131 Therapy
Near-total thyroidectomy spares the
posterior capsule on the side contralateral to
the carcinoma in an attempt to preserve
parathyroid tissue
Ablation therapy with I-131 is performed for
the following indications:
Thryoid remnant ablation: To destroy the small
amount of thyroid tissue remaining in the neck
after surgery
For the treatment of functional metastases
For the treatment of recurrent thyroid cancer
For the treatment of patients with elevated
thyroglobulin levels, but a negative I-131 scan
Absolute Contraindications
to I-131 Therapy
Pregnancy
Breast feeding
Both iodine and pertechnetate are excreted in
breast milk
Elevated iodine levels
Patients with elevated urine iodine levels (over
200 ug/L) either from I.V. contrast or from
dietary intake should have therapy postponed
until levels return to normal
Diagnostic Scanning
following Thyroidectomy
In patients being considered for
ablation therapy, a pre-treatment
diagnostic I-131 scan can be
performed 5 to 6 weeks following
surgery to assess for the presence
of metastatic lesions
Case
Thyroid Stunning

Post thyroidectomy diagnostic I-131 scan revealed


neck bed activity (oral-pharyngeal activity can also be
seen)
Following treatment with 100 mCi of I-131 the post-
therapy scan demonstrated no evidence of tracer
uptake in the neck indicative of thyroid stunning.
Thyroid Stunning
I-131 given for a diagnostic scan can exert a negative
effect on the uptake or trapping of the therapeutic dose by
residual thyroid bed tissue and functioning metastases due
it's beta particle emission- this is referred to as "Thyroid
Stunning
Seen in up to 19% of patients
The "stunned" thyroid tissue then loses its iodine trapping
function partially or completely
On imaging studies, stunning appears as an area of uptake on
the diagnostic scan which shows less activity on the
patient's post-ablation scan
Most people feel that only 2 to 3 mCi of I-131 (and certainly
no more than 5 mCi) should be used for the pre-ablation
diagnostic scan
Unfortunately, lower diagnostic doses can miss more
metastatic lesions which would be detected with larger
doses (up to 10 mCi)
To decrease the effect of stunning, it may be beneficial to
lengthen the period of time between the diagnostic scan
and I-131 therapy to approximately one week
Some have suggested that stunning is generally not
observed until several days following the diagnostic scan
and that the therapeutic dose should be given immediately
following the diagnostic study
Although stunning is presumed to lessen the therapeutic
effect of I-131 ablation therapy and be associated with a
lower success rate for remnant ablation it does not appear
to have been reported to be associated with a decreased
patient survival
I-123 For Diagnostic
Scanning
I-123 has not been reported to cause
thyroid stunning as it has no beta
emission
I-123 scan findings are concordant
with post-I-131 therapy scans in 93%
of cases
Additionally, I-123 imaging may be less
sensitive than I-131 scanning for the
detection of metastases
I-123 Diagnostic Scan then Post I-
131 Therapy Scan: Findings?
I-123 Diagnostic Scan

The diagnostic scan on the left was performed using


I-123. Extensive pathologic nodal uptake is seen
within the lower neck and mediastinum
A separate focus of increased tracer accumulation is
seen over the right upper abdomen (not seen on post-
therapy scans- possibly due to superimposed liver
activity)
The post-I-131 therapy scan (right) demonstrates
uptake in the nodal metastases and diffuse hepatic
tracer activity due to metabolism of radiothyroxine.
Findings?
False Negative I-
123 Diagnostic
Scan

The patient shown below had undergone


thyroidectomy for papillary thyroid cancer and was
presenting for evaluation prior to radio-iodine ablation
therapy
The diagnostic scan on the left was performed using
I-123. The exam revealed no evidence of neck bed
activity and no metastases (the uptake in the chest
was related to esophageal activity and cleared with
water)
Following treatment with 125 mCi of I-131 a 10 day
post-therapy scan demonstrated a large amount of
tracer activity in the thyroid bed and neck
I-131 Treatment Protocols
for Thyroid Carcinoma
The activity of radioiodine used for ablation of
thyroid remnants and treatment of metastatic
disease is not standardized and several treatment
options exist
In general, there is less need for radioactive
iodine ablation in low-risk patients (small lesion
under 1.5 cm) that have had a true total
thyroidectomy and a greater need when:
Large remnants are present
Patients who are at high risk for recurrence based on
lesion size (over 1.5 cm), multicentricity, histology, age,
or extrathyroidal extension
I-131 Treatment Protocols
for Thyroid Carcinoma
Before receiving the therapeutic dose, the
patient should be NPO for 2 to 4 hours,
and should also remain NPO for 2-4 hours
after dosing (to decrease the possibility
of nausea and vomiting.
The administered dose must be within 10%
of the ordered dose
3 Approaches to I-131
Thyroid Therapy for Cancer

Aggressive/Restrained (Beierwaltes)
Dosimetry
Low Dose: ALARA
Aggressive/Restrained
(Beierwaltes)
Fixed amounts of radioiodine are given based upon
the presence and location of metastases
This is a popular way for treatment as it is generally
effective and simple to apply.
Residual thyroid bed activity only: 100 mCi
Regional Metastases (Cervical Nodes): 150-175
mCi
Lung Metastases: 175-200 mCi
Skeletal Metastases: 200 mCi
Dosimetry
Dosimetry is utilized to determine what activity the
therapeutic dose should be based upon the individual
patients radioiodine pharmacokinetics
High/Maximum dose: Dosimetry guided I-131 therapy allows
the administration of the highest possible dose of I-131 in
order to achieve maximum therapeutic benefit
This treatment is based on the assumption that metastases
may lose their ability to concentrate iodine over time due to
repeated sub-therapeutic doses which permits surviving
cells to regrow (resulting in de-differentiation with loss of
iodine concentrating ability)
Therefore, the largest and safest dose possible should be
administered at the first therapy
Dosimetry
The administered dose is then individually tailored to keep
the blood dose (bone marrow) just below 200 rads (although
other centers use a blood dose of 300 rads
Patients with diffuse lung metastatses may be difficult to
treat due to the potential for radiation-related pulmonary
toxicity
Generally, patients receive about 300 mCi of radioiodine,
but doses up to 1 Ci have been administered
The most common side effect of high dose therapy is
transient bone marrow depression (thrombocytopenia and
leukopenia) with a nadir seen between 3 to 5 weeks post-
therapy
Altered Iodine Clearance
Conditions such as renal failure, ascites, or pleural effusions
can all result in prolonged retention of I-131
The therapeutic dose is then determined in order to
maximize its effectiveness and improve patient safety
Because a dose of 1-2 mCi of I-131 is usually adequate for
dosimetry it can be performed in conjunction with the pre-
therapy diagnostic examination.
Using dosimetry the expected radiation dose to the whole
body, blood, and sites of functioning thyroid tissue (thyroid
bed, mets) is calculated
Low Dose: ALARA
I-131 30 mCi (1110 MBq) is given repetitively as necessary in
order to ablate the thyroid bed
Patients do not require hospitalization and up to 27% of
patients will have successful ablation after only one dose
Reduction in cost and patient inconvenience are factors
which make this form of treatment attractive
This type of treatment may best be considered for the very
low risk patient
Age under 45 years
Primary lesion less than 1.5 cm
No evidence of vascular, lymphatic, or capsular invasion
Well-differentiated tumor.
Guidelines for Maximum
Dose Administration
Previously, following therapy,
patients had to be hospitalized until
the retained radioactivity was less
than 30mCi or the metered exposure
rate from the patient was less than
5 mR/hr at one meter
Patients can now be treated on an
outpatient basis providing that
certain exposure limits are
maintained for individuals that may
have contact with the patients
Ways to Increase Radiation Dose
Delivered to a Metastatic Lesion
TSH Manipulation
Low Iodine Diet
Lithium carbonate
TSH Manipulation
TSH should be greater than 30 uU/ml prior to
I-131 ablation therapy
Elevated TSH levels will stimulate iodine uptake
in functioning mets
TSH stimulation with human TSH should be
considered for patients with TSH values less
than 30
If the TSH level is less than 30, functioning
thyroid mets may not be identified on
diagnostic scans, and may not accumulate
sufficient I-131 during therapy
TSH Manipulation
In order to ensure adequate
elevation in TSH levels, T4 should
be discontinued for at least 4 to 6
weeks prior to the scan/therapy (the
half-life of T4 in the blood is about
1 week)
T3 (Cytomel) should be discontinued
for at least 10 to 14 days (the
half-life of T3 in the blood is about
18-24 hours)
Low Iodine Diet
Daily dietary iodine intake is maintained
below 50 ug/day for 7-10 days prior to
therapy
Patients avoid seafood, salt, iodine
containing medications, iodinated contrast
medium, and dairy products
These measures will decrease the
extracellular iodine pool and increase
uptake of radioiodine by about 2.5 times.
Lithium Carbonate
Lithium suppresses the release of thyroid
hormone from thyroid tissue and has been
found to prolong the biologic T1/2 of I-131
especially in tumors with biologic half-lives
of less than 6 days, with little effect on
whole body exposure
When given for 1 week prior to therapy, it
may serve to increase the radiation dose
delivered to functioning thyroid tissue
Follow-Up Post Therapy
Imaging
Follow-up whole body imaging is performed 7 to 10
days after high dose treatment with I-131
Scans performed before this time may miss
metastatic lesions
Post therapy scans can detect new lesions in up
to 15-50% of patients
Post-therapy I-131 SPECT imaging with CT fusion
can improve localization of metastatic lesions and
aid in identification of physiologic sites of tracer
uptake
Benefits of I-131
Therapy
Decreases local recurrence
Improves survival in patients following local
recurrence
Prolongs survival in patients with lung or bone
metastases
Eliminates the thyroid gland as source of
thyroglobulin
Thyroglobulin appears to be the most sensitive test for
determining the presence of persistent or recurrent
well differentiated thyroid cancer
Name some Acute
Complications of I-131 Thyroid
Ablation Therapy
Acute Complications of I-131
Thyroid Ablation Therapy
Sialoadenitis
The use of hard sour candies can reduce the incidence and
severity of sialoadenitis
Following therapy, about of third of patients have subjective
complaints of xerostomia during the first year
Radiation parotiditis
Loss of taste (Acute/Chronic)
Between 27% to 50% of patients will suffer from a transient
loss of taste or smell
Nausea and vomiting in < 1%
Minimal bone marrow suppression
Radiation pneumonitis and pulmonary fibrosis
In patients with lung mets
Acute Complications of I-131
Thyroid Ablation Therapy
Radiation gastritis/cystitis
Thyroid storm 2 to 10 days post treatment
Transient amenorrhea
Decreased testicular function/fertility
Cerebral edema/spinal cord compression in patients with spinal
mets
Radiation sickness (dose >200 mCi)
Headache, nausea, vomiting
Chronic or recurrent conjuctivitis, keratoconjunctivitis,
decreased lacrimal function
About one-quarter of patients treated will have subjective complaints
of xerophthalmia [1,26], and about 18% will have objective evidence of
decreased lacrimal function after one year
Chronic Complications of I-131
Thyroid Ablation Therapy
There is NO increased risk of
thyroid tumors and no evidence of
reduced fertility or genetic
abnormalities in patients offspring
Secondary Tumors:
Leukemia
The risk for acute myelogenous leukemia is only
minimally increased above the general population
with a peak incidence 2 to 10 years (mean 42
months) post therapy (0.5% increased risk)
Patients at risk are generally above the age of 50
and have received a dose of approximately 900
mCi
The risk is greatest when this large dose has been
given over a short period of time (6 to 12 weeks)
These patients have usually received a blood dose
greater than 200 rads
Secondary Tumors
B- Bladder carcinoma
There may be a slight increased incidence (6x) of bladder
carcinoma if total dose was given over a short interval and
exceeds 1000 mCi. The latency period is between 15 to 20
years.
C- Breast carcinoma
There may be a slight increase in breast carcinoma (3x) if the
total dose was given over a short interval and exceeds 1000
mCi. This may be related to a genetic disposition for both
breast and thyroid carcinoma, and not I-131 therapy.
D- Salivary carcinoma
There may be a very slightly increased risk for salivary tumors
Post-Therapy Hormonal
Treatment
Thyroid hormone (T4) suppression therapy
is effective in the management of
differentiated thyroid carcinoma and
doses sufficient to suppress TSH
decrease the risk of recurrence
This is because well differentiate thyroid
cancer responds to TSH stimulation, and
grows more slowly in the absence of TSH
Follow-up Post-Ablation Screening
for Recurrent Thyroid Cancer
The overall risk of recurrence of thyroid cancer is about
20%
Surveillance for recurrence is a lifelong process
Following surgery and thyroid ablation with I-131, thyroid
cancer patients are monitored for recurrence using serum
thyroglobulin (Tg) levels, neck ultrasound (commonly
performed as the first imaging test in patients with
elevated Tg levels), and in some cases with whole body I-131
scanning at increasing intervals.
Radioiodine imaging can be performed following
levothyroxine withdrawl or recombinant human TSH (rhTSH
stimulation)
Recombinant human thyroid stimulating hormone use in
post-ablation imaging and therapy
Recombinant human thyroid stimulating hormone
treatment (rhTSH [Thyrogen]) has also been used
prior to imaging post ablation patients for follow-
up screening
For this exam, patients do not need to discontinue
thyroid hormone suppression therapy and
therefore do not experience hypothyroid
symptoms
The potential of tumor growth during long-term
TSH stimulation is also avoided through the use
of rhTSH
Monitoring thyroglobulin
Thyroglobulin levels provide a means for detecting the
presence of recurrent disease and for monitoring response
to therapy
In a thyroid cancer patient who has had a total
thyroidectomy and has been successfully ablated with I-131
the Tg level should be undetectable
A rise in the Tg level is almost always an indicator of
recurrent/metastatic disease
Compared with whole body I-131 scanning, thyroglobulin
levels are a more sensitive test for detecting the presence
of recurrent/metastatic disease
Thyroglobulin levels (in conjunction with
the I-131 scan results) also provide
prognostic information
Patients with elevated thyroglobulin levels
and a positive scan have the lowest overall
mortality (44%), while those with
metastases and a negative thyroglobulin
level and negative scan have a mortality of
71%
Further evaluation of patients with
elevated thyroglobulin levels and negative
I-131 scans should be performed with FDG
PET imaging and with targeted sonographic
evaluation of the neck
Any enlarged lymph nodes identified
sonographically can be biopsied
False positive sites of I-
131 uptake
False-positive scans have been reported in association with
Contamination by physiologic secretions: Saliva or suptum on
the patients skin or handkerchief and esophageal activity
Inflammatory and post-traumatic conditions: Foci of infection,
severe burns, and post-traumatic superficial scabs
Gastrointestinal activity
Meckle's diverticulum or duplication cysts with gastric mucosa
Non-thyroid malignancies and pathologic transudates
Pericardial effusion
Breast uptake associated with lactation
Case
Recurrent Thyroid
Carcinoma

The patient shown below had a history of thyroid


cancer and presented with an elevated thyroglobulin
level
The patient received 125 mCi of I-131 tracer uptake
in the region of the thyroid bed and faint liver
activity (left image above) is seen. FDG PET imaging
demonstrated widespread pulmonary metastases and
pathologic adenopathy in the lower left neck
FDG PET for Thyroid
Cancer
I-131 scanning has been the mainstay for
the evaluation of recurrent thyroid
carcinoma
50-60% of papillary and 64-67% of
follicular cancer recurrences are iodine
avid
Patients with elevated human thyroglobulin
levels (greater than 10 ug/L), but negative
I-131 scans pose a diagnostic and
therapeutic dilemma
FDG PET Imaging
FDG PET imaging can aid in the detection of metastatic disease in
post-thyroidectomy/I-131 ablation patients with negative
diagnostic I-131 imaging
Unlike conventional imaging, FDG PET imaging can detect
metastatic disease to normal sized lymph nodes
I-131 scintigraphy and FDG PET imaging are actually
complementary diagnostic methods for the evaluation of recurrent
or metastatic thyroid cancer
In general, well differentiated thyroid carcinoma will be I-131
positive and FDG PET negative, while less differentiated cancers
will show the reverse (i.e.: FDG PET positive and I-131 negative)
Another benefit of FDG PET imaging is the identification of
unsuspected secondary malignancies
FDG PET in Thyroid
Cancer in General
FDG PET is probably not indicated for the
diagnosis of thyroid cancer
Not all malignant thyroid lesions will
accumulate FDG and some benign lesions
will show increased metabolic activity
Therefore, FDG PET should not be
considered a substitute for I-123 or I-131
whole-body scintigraphy
Case
Recurrent Hurthle cell
carcinoma

The patient had a history of Hurthle cell carcinoma of the thyroid


Pulmonary metastases are significantly more evident on the
coincidence FDG PET examination (above middle black arrows) when
compared to the I131 scan (above left blue arrows). A CT scan
confirmed the presence of pulmonary metastases (above right).
Note that a subtle bone metastasis to the high left parietal bone
can be seen on I131 images
The FDG PET exam did not include this region.
Hurthle cell carcinoma
Hurthle cell cancer of the thyroid is a follicular
variant composed mostly of oxyphilic follicular
cells and the tumor generally has a low avidity for
iodine
Hurthle cell is more aggressive than follicular
thyroid cancer and has an overall worse prognosis
FDG accumulation is generally very intense in
patients with Hurthle cell cancer and can reveal
disease not detected by other imaging methods in
about 50% of cases
FDG in Medullary Thyroid
Carcinoma
Medullary thyroid cancer usually
demonstrates very positive FDG
uptake and PET imaging is useful for
the staging and follow-up of patients
Sensitivity is 76-78% and specificity
is 79%
Amiodarone Associated
Thyroid Disease
Amiodarone is an antiarrhythmic cardiac
drug rich in iodine (75 mg of iodine per
200 mg tablet)
The agent can be associated with iodine-
induced thyroid dysfunction
Hypothyroidism can be seen in 20% of
patients and is associated with the
presence of anti-thyroid peroxidase
antibodies
Hypothyroidism 3
Types
Primary
Secondary
Tertiary
Primary Hypothyroidism
Primary hypothyroidism is due to an endogenous thyroid disorder
The most common cause of hypothyroidism in adults is Hashimoto's
thyroiditis
Asymptomatic hypothyroid patients typically have low normal T4
values and normal T3 values, but markedly elevated TSH levels
Once patients become symptomatic, both T3 and T4 levels are
decreased
Thyroid nuclear imaging studies are of no value in establishing the
diagnosis of primary hypothyroidism
In the past, TRH stimulation test was often performed to diagnose
primary hypothyroidism as these patients exhibit an exaggerated
TSH response
However, this test does not add any useful information since an
elevated TSH level in patients with low serum T4 values is diagnostic
for primary hypothyroidism.
Secondary
Hypothyroidism
Secondary hypothyroidism is the result of decreased TSH
production due to pituitary disease
The diagnosis should be suspected in patients who are
hypothyroid that present with low serum T4 or T3
concentrations but with a serum TSH level that is low or
inappropriately normal
Treatment should be directed at the pituitary gland which
may involve surgical removal of a pituitary tumor or
replacing deficient pituitary hormones (in particular, steroid
replacement prior to thyroid hormone replacement to avoid
precipitating an adrenal crisis).
Tertiary Hypothyroidism
Tertiary hypothyroidism is the result of
decreased TRH production secondary to a
hypothalamic disorder
Central hypothyroidism should also be
suspected in hypothyroid patients with
inappropriately low or normal TSH levels
Management is similar to patients with
secondary hypothyroidism and be directed
at identifying the hypothalamic lesion.
Radiation Detectors Post Nuclear
Diagnostic Study or Therapy
Maximum length of time that diagnostic and therapeutic
radiopharmaceuticals could set off radiation detectors such
as those used for homeland security
# FDG PET scan -- less than 24 hours
# Bone and thyroid scans -- 3 days
# Cardiac exams with thallium -- up to 30 days
# Iodine therapy -- up to 95 days
Society of Nuclear Medicine (SNM) and the U.S. Nuclear
Regulatory Commission recommend that hospitals develop an
official letter or card indicating what type of nuclear medicine
procedure a patient received, the date of service and whom to call
at the hospital for verification.
Thyroid Imaging
2015 Thyroid Consensus
Guidelines
Does Screening people with familial
follicular differentiated thyroid cancer
(DTC) reduces morbidity/mortality?
Does Screening people with familial
follicular differentiated thyroid cancer
(DTC) reduces morbidity/mortality?
Screening people with familial follicular
differentiated thyroid cancer (DTC)
reduces morbidity/mortality
No study ever reported
Name any syndromes associated with increased
risk of DTC:
Syndromes associated with
Increased risk of DTC
Mutations in PTEN gene (phosphatase and tensin
homolog)
Hamartoma tumor syndrome (Cowdens disease)
Familial adenomatous polyposis (FAP)
Carney complex:
autosomal dominant conditions comprising myxomas of
the heart and skin, hyperpigmentation of the skin
(lentiginosis), and endocrine overactivity.
MEN2
Werner syndrome (adult progeria)
Progeria
Should One Obtain TSH After
Finding Thyroid Nodule?
Serum thyrotropin (TSH)
should be measured during
initial evaluation of thyroid
nodule (true)
If TSH is low then I-123 study
should be performed
If TSH is normal or elevated,
then radionuclide scan should
not be performed (true)
Name Clinical Signs of
thyroid malignancy
Signs of thyroid
malignancy
Vocal cord paralysis
Cervical lymphadenopathy
Fixation of nodule to surrounding
tissue
Should one routinely measure
serum thyroglobulin (Tg) in
evaluation of nodules?
Should one routinely measure
serum thyroglobulin (Tg) in
evaluation of nodules?
No since insensitive and non-specific
Should serum calcitonin be
routinely measured in patients
with thyroid nodules?
Should serum calcitonin be
routinely measured in patients
with thyroid nodules
Insufficient evidence
What should you do with incidentally
detected focal PET uptake? If nodule
more than 1 cm then do FNA
Should PET be performed when new
thyroid nodule is discovered?
How often is FDG uptake seen in FDG
studies:
Should FNA be performed with
diffuse thyroid uptake?
What should you do with incidentally
detected focal PET uptake? If nodule
more than 1 cm then do FNA
Should PET be performed when
new thyroid nodule is discovered?
No
How often is FDG uptake seen in
FDG studies: 1 to 2%, diffuse
uptake in 2%
Should FNA be performed with
diffuse thyroid uptake?
no
Is 18FDG-PET recommended for the evaluation
of thyroid nodules with indeterminate
cytology?
18FDG-PET is not routinely
recommended for the evaluation of
thyroid nodules with indeterminate
cytology
What do you do with negative FNA
but high suspicion US pattern?
Repeat US and US guided FNA within 12
months
If scan shows normal or equal to
thyroid then no need for
aspiration/biopsy
Higher serum TSH is associated with
increased risk of malignancy in nodule
What is the recommended
system for reporting
thyroid cytopathology
Bethesda System
Nondiagnostic or unsatisfactory 20%
and carries 1 to 4% chance of
malignancy
Benign
Atypia or follicular lesion of uncertain
significance
Follicular neoplasm or suspicious for one
Suspicious for malignancy
Malignant
If nodule benign on cytology then
further immediate diagnostic
studies or treatment not required
Strong high quality
If cytology result is diagnostic for primary
thyroid malignancy, surgery is generally
recommended (despite lots of studies to
contrary) except for:
Low risk tumors such as papillary microcarcinomas
without clinically evident mets or local invasion
High surgical risk
Short remaining life span
Concurrent medical or surgical issues that need to be
addressed first
Molecular profiling is very promising to
determine who should get surgery
Recommendation for surgery for
cytologically indeterminate thyroid
nodules?
lobectomy
How Should One
Approach Patient with
Multiple Thyroid Nodules
Patients with multiple thyroid nodules
at least 1 cm should be evaluated in
the same fashion as with a solitary
and each evaluated independently
Patients with multiple thyroid nodules
at least 1 cm should be evaluated in
the same fashion as with a solitary
and each evaluated independently