PowerPoint: Guidelines for the management of differentiated thyroid cancer are discussed with special reference to the use of radioiodine imaging and therapy.

1. The role of nuclear medicine in
differentiated thyroid cancer
(DTC)
Preservation of iodide concentrating
capacity enables imaging and therapy.
Other radiological modalities like
ultrasound and PET also have roles.
Treatment is a multidisciplinary effort
(surgery, nuclear medicine,
endocrinology, etc.).

3. • Major source is ATA guidelines, 2009
• It’s good to have an overview of management.
• It’s necessary to simplify.
• Maybe have oversimplified.
• There are controversies.
• Some things are my opinion.

4. Topics
• Basics: radioiodines, thyroid hormones, feedback
• Managing nodules, and cancer: types, staging, risk
• Patient preparation, scanning, ablation, treating
metastases
• Manipulation of TSH levels: up or down
• Whether to image before ablation, stunning, post-
therapy scan
• Rationales for I-131 therapy
• Serum thyroglobulin; radioiodine negative, Tg positive
cases; PET
• Alternative treatments: surgery, RT, chemo
• Recombinant human TSH (Thyrogen)
• Iodine restriction: diet, contrast, meds, thyroid
hormone
• Risks of I-131 therapy
• Surveillance
• Dosimetry, lithium
• False positive scans

5. The radioactive iodine
choices
480-820
13.2
159
193
γ
10
I-123
160-175
8 d
365
3,120
β & γ
4
I-131
Price, $
Half-
life
γ
energy
kev
Rads
(thyr.,
15%)
Kind of
decay
Dose,
mCi
Tracer

6. Advantages
• I-131: Price, long half-life, you’re
likely to treat anyway
• I-123: More favorable energy for
imaging, less useless radiation
to patient, believed to avoid
stunning

7. 15
10
5
0
0
10
4
3.0
0.2
3.1
1.0
2.8
3.7
1.5
1.5
3.5
2.0
0.8
3.4
2.5
0.4
3.2
0.5
5.3
3.8
I-123
I-131
I-123
I-131
Decay of I-131 and I-123
Time (days)
mCi

8. • Imaging in thyroid cancer is typically 2 or 3 days
after 1-4 mCi of I-131 (high energy collimator).
• Alternative is 1 and sometimes 2 days after 3-10
mCi of I-123 (low or medium energy collimator).
• SPECT/CT may have a role.
• (Many examples in the talk are I-123.)
• Tc-99m pertechnetate is used for routine thyroid
scanning, not for thyroid cancer.
• I-124 is a possibly useful positron-emitter (PET).

9. O
HO
I
I
I
I
CH2
NH2
H
C COONa * xH2O
Levothyroxine: 63.5% iodine, absorption 40-80% , half-life 7 d.
O
HO
I
I
I
CH2
NH2
H
C COONa
Liothyronine: 56.6% iodine, absorption ~95%, half-life ~2.5 d.
“25 µg of liothyronine is equivalent to appoximately...0.1 mg of L-thyroxine.”
Source: Abbott Laboratories and King Pharmaceuticals Prescribing Information

10. Two thyroid hormones
• The thyroid makes levothyroxine (T4, storage and
transport form and
• Triiodothyronine (T3, metabolically active form).
• T4 is converted to T3 in skeletal muscle, liver, brain
and other tissues.
• T4 (Synthroid) is preferred for replacement.
• T3 (triiodothyronine, Cytomel) can be used in stage-
wise hormone withdrawal for scanning and I-
131therapy.

12. • Sodium-iodide symporter (NIS) is a membrane
glycoprotein that transports iodide into normal
thyroid cells and (less well) into cells of
differentiated thyroid cancer.
• Serum thyroglobulin (Tg) is a protein
synthesized in normal thyroid cells and in cells of
differentiated thyroid cancer. It is directly
involved in the synthesis and storage of thyroid
hormone in normally functioning thyroid tissue.
Its level in serum is a marker of thyroid cancer.

14. Actions of TSH on the thyroid (and to some degree
on DTC tissue) include stimulation of:
• I-uptake by means of the NIS, enables scan
and therapy.
• Synthesis of thyroid hormone
• Release of thyroid hormone
also
• Growth of differentiated thyroid cancer
• Increased sensitivity of thyroglobulin test,
as thyroid cancer marker

15. Normal serum values
• TSH 0.3-5.0 µIU/ml
• Desired is lower for suppressive therapy,
higher (>25 or 30) for scanning and therapy
• Serum thyroglobulin 3.0-40.0 ng/ml
• Desired is lower after thyroidectomy and
radioiodine treatment

16. This isn’t just “basic science!”
It’s relevant to nuclear medicine
diagnosis and therapy of DTC, as you
will see.

17. A patient with a thyroid nodule, if
and only if TSH is suppressed, may
undergo a thyroid scan, typically
with I-123.

19. Toxic nodule’s hormone production
suppresses TSH; hence, poor
visualization of the rest of the gland.
“Hot” (autonomous or toxic) nodule:
very small likelihood of cancer.
Uptake was elevated. Patient can be
(and was) treated with I-131 for
hyperthyroidism.

20. I-123 THYROID April 30, 2010

21. The scan
1. Shows an
autonomous
nodule
2. Shows thyroid
cancer
3. Shows a solitary
hypofunctional
nodule
4. Rules out Graves’
disease.
5. None of the above.
0% 0% 0% 0% 0% 0% 0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%

22. • Uptake was elevated.
• There was a second nodule in the isthmus.
• Take home lesson: it helps to palpate the thyroid.
• Confirmed by ultrasound. Both nodules biopsied (FNA) and
negative for cancer.
• Pyramidal lobe may be seen in Graves’ disease.
• She too could be treated with I-131 for hyperthyroidism.

23. ATA Guidelines (simplified)
• Nodules are commonly found by palpation or
imaging (e.g. ultrasound, incidental FDG-positive
nodules).
• In general, only nodules >1 cm need evaluation,
barring risk factors (e.g. childhood radiation
exposure).
• Get TSH: low level indicates NM thyroid scan.
• Continued concern indicates US and FNA.
• (Some sonographic features mitigate for or against
cancer).
• One may biopsy suspicious or largest nodule in
multinodular goiter.
• Follow presumed benign nodules by US, for growth.

24. Total
Thyroidectomy
Indeterminate
Thyroid
Lobectomy
Completion
Thyroid-
ectomy
Negative for
Malignancy
FNA cytology
Management of Patients with Thyroid
Nodules
Positive for
Malignancy
Unnecessary
surgery
Suboptimal
surgery
~5% of thyroid FNAs
~70% of thyroid FNAs
~30% of thyroid FNAs

25. • Last slide courtesy of Dr. Yuri Nikiforov.
• FNA and other pathology specimens yield not only
histopathology but also mutations like BRAF, which
points toward papillary cancer, in fact, aggressive
papillary cancer.

26. Total thyroidectomy is the procedure of
choice for nodules with FNA findings
clearly suggestive of cancer and for
tumors that are very large, demonstrate
some suspicious findings, or occur with a
history of radiation exposure. In certain
cases, lymph node dissection may be
indicated.

27. Preoperative neck US is recommended.
US-guided FNA of sonographically
suspicious LN’s should be performed to
confirm malignancy if this would change
management.

28. Some major kinds of thyroid
cancer
• Differentiated (DTC)
---Papillary
---Follicular
• Medullary
• Anaplastic
• Only DTC is amenable to diagnosis and therapy with
radioactive iodine

29. • We are concerned with staging and risk.
• DTC usually has a good prognosis; with good
long term survival, but some present initially
as high risk cases and late recurrence may
happen.

30. Staging, simplified, as per American Joint
Committee on Cancer (AJCC) (not the only
scheme)
• T1-4 depending on size and degree of extrathyroidal
extension
• T3 = primary tumor >4 cm limited to the thyroid or
with minimal extrathyroidal extension
• N0-1 depending on involvement of regional lymph
nodes
• M0-1 depending on distant metastases
• Stage I-IV depending on above, but also age (greater
risk ≥ 45 y.o.)

31. Factors in decision making in remnant ablation (ATA, examples)
--------------expected benefit---------------
Factors Description ↓death risk ↓ recurrence May facilitate
staging &
F/U
Ablation
usually
recommen-
ded
T1 ≤1 cm N N Y N
T3 >4 cm
<45 y.o. N ? Y Y
≥45 y.o. Y Y Y Y
T4 Gross
extrathy-
roidal
extension
Y Y Y Y
M1 Distant
met(s)
Y Y Y Y

32. • Other risk factors: aggressive tumor
histology, e.g. tall cell, insular, columnar
cell carcinoma
• BRAF V600E mutation has been associated
with more aggressive behavior of papillary
carcinoma.
• The whole body radioiodine scan result
affects staging and risk.
• These factors have implications for I-131
therapy (whether and how much).

33. A Continuum of Risk
AJCC/TNM Cancer Staging
Low High
RISK
Low-Risk:
• No locoregional invasion
• No distant metastases
• No vascular invasion
• No aggressive histology
• Complete resection
• Negative post Tx scan
• No high-risk oncogenes
(BRAF, RET/PTC)
Intermediate
Risk:
Mixed
Features
High-Risk:
• Invasive or metastatic
disease
• Incomplete tumor
resection
• Marked
Thyroglobulinemia
without anatomic
correlate
I II III IV
Cooper DS Thyroid 2009;19:1167
Mortality
Recurrence

34. • The role of radioiodine in thyroid cancer is
diagnostic scanning to find remnants or
iodine-avid metastases (I-131 or I-123,
based on gamma emission) and to ablate
remnants and treat metastases (I-131,
based on 1 to 2 mm path-length beta rays
causing cell death).

35. Patient preparation for WBI scan
and/or I-131 therapy
• Low-I diet
• Older scheme: T4 → T3 (shorter half-
life) → no hormone (2 weeks) → TSH ≥
25 or 30 uIU/ml
• Currently we just withdraw T4 for 4
weeks.

36. 33 y.o. woman with multifocal (largest 2.2 cm) papillary
carcinoma, follicular variant., uptake 1.5%. Tg 1.6
ng/ml. Rx 155 mCi.

37. Which is a correct interpretation?
1. Metastatic disease
in the neck
2. Metastatic disease
in the right upper
quadrant
3. Metastatic disease
in the pelvis
4. 2 and 3
5. Normal post-
surgical thyroid
remnant
0% 0% 0% 0% 0% 0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%

38. • T2N0M0, Stage I, low risk. ATA: “Selective
use of ablation.”
• Likely would have been treated with less I-
131 today.

39. • Thyroidectomy almost always leaves a remnant.
Too aggressive an approach to thyroid removal can
endanger the parathyroids and the recurrent
laryngeal nerve.
• Normal distribution on scan: Salivary, GI, urinary
tract.
• Liver may be seen on post-therapy scan because of
radioactive thyroid hormone metabolism.
• Tg may reflect normal remnants, also a marker of
metastases.

40. 16 months later, Thyrogen-stimulated scan was negative with Tg <0.5.

41. This can legitimately be called “ablation”,
i.e. destruction of remaining normal
thyroid tissue, and apparently was
successful.
Typical of many cases. Note preparation for
second study using rhTSH.

42. 43 y.o. man with papillary carcinoma,
multifocal, extension to skeletal muscle and
metastasis to multiple lymph nodes. TSH 58.
Tg 22.4. Uptake 15%. 24- and 48-hour I-123
scans.
43 y.o. man with papillary carcinoma, multifocal,
extension to skeletal muscle and metastasis to multiple
lymph nodes. TSH 58. Tg 22.4. Uptake 15%. 24- and
48-hour I-123 scans.

43. Which is correct?
1. He should not be
considered for more
surgery.
2. The patient is not a
candidate for
radioiodine therapy
3. The patient is in a
high risk category
4. The scan shows
multiple foci of
ectopic normal
thyroid tissue.
5. None of the above.
0% 0% 0% 0% 0% 0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%

44. By ATA criteria, his regional lymph
node metastases make him at least
intermediate risk and his macroscopic
tumor invasion promotes him to high
risk.
T4N1M0, Stage I (higher if he were 45
y.o.), high risk. I-131 Rx recommended
even if he didn’t have I-avid
metastases!

45. xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx

46. One year later, no detectable lesions, Tg <0.5.

47. • We had apparently successfully not only
eliminated his thyroid remnant, but also
treated his metastatic disease, as judged
both by the scan, and serum
thyroglobulin, so this was not simply an
ablation. Scan and Tg were negative and
remained so subsequently.

48. Criteria for choosing initial treatment dose
There are different schemes, but, in general, a dependence on risk
Amdur and Mazzaferri, Essentials of Thyroid Cancer
Management:
• Low risk
Stage T1N0M0 (small, no metastases evident) 50 mCi
• Standard risk
All situations that do not qualify as low or high risk 150 mCi
• High risk
Stage T4 or M1 (locally invasive and/or distant metastases) or
any situation where there is known to be residual disease
200 mCi

49. Choice of doses
American Thyroid Association
• No RAI ablation for unifocal or multifocal cancer <1
cm if no higher risk features
• Minimum (30-100 mCi) necessary for remnant
ablation, particularly for low-risk patients.
• 100-200 mCi may be appropriate if residual
microscopic disease is suspected or documented, or
with more aggressive tumor histology (e.g. tall cell,
insular, columnar cell carcinoma).
• My interpretation of the latter category (“suspected”)
is whether there is evidence of a decreased risk of
death and recurrence as shown in previous table.
• BRAF V600E mutation has been associated with
more aggressive behavior of papillary carcinoma

50. • Dose choice is, thus, commonly
“empirical.”
• However, high doses (e.g. 200 mCi) may
exceed the maximum tolerable dose as
predicted by dosimetry. Therefore (as per
Memorial Sloan-Kettering), doses should
seldom exceed 150 mCi in patients ≥ 70
y.o. unless guided by dosimetric studies.
• Likewise, renal failure or hemodialysis call
for an altered approach.

51. Manipulation of TSH to optimize scanning
and therapy
• DTC cells express the TSH receptor on the cell
membrane and react to TSH stimulation, including
radioiodine uptake and cell proliferation.
• DTC not as I-avid as normal thyroid (less active NIS)
(hence cold nodules)
• ↑TSH required to optimally visualize and treat both
normal remnants DTC
• Post-thyroidectomy (iatrogenic) hypothyroidism
produces high TSH
• Therefore, patient stops (or postpones taking)
thyroid hormone for 1st and later scans
• Usually require TSH > 25 to 30 µU/mL before
proceeding
• The rhTSH alternative avoids the unhealthy
condition of hypothyroidism

52. Manipulation of TSH to improve outcome
The flip side: suppression of TSH
• TSH can stimulate tumor growth
• Suppression decreases recurrence, improves
survival, at least in high risk cases.
• ATA recommends adjusting thyroid hormone to
achieve TSH of 0.1-0.5 µU/mL for low-risk and <0.1
µU/mL for high risk patients. (Remember 0.3 is lower
limit of normal.)
• Caution needed re risks like osteoporosis and
adverse cardiac events.

53. A young woman scanned 5 years after initial treatment.

54. Same patient scanned after therapeutic dose.

55. Post-therapy scan
• Routinely done at about 4-7 d.
• Takes advantage of 30-200 mCi of I-131
(typically) vs 1-4 in diagnostic scan.
• Hence, more sensitive, showing new sites
that alter prognosis in a variable percentage
of patients, as per reports.
• Possible role for SPECT/CT

56. Considerations at the time of ablation: Whether to
image at all before first I-131 treatment. Arguments
for omission of imaging:
• Diagnostic doses of I-131 may lead to “stunning”, i.e.
reduced uptake of subsequent therapeutic
radioiodine due to sublethal radiation delivered by
the diagnostic dose.
• There is conflicting evidence and uncertainty as to
the threshold dose for this effect.
• You’ll get a post-therapy scan anyway, which, in any
case can upgrade staging
• Ultrasound can be done to determine if there is too
much and patient should be referred for more
surgery.

57. Response to those arguments:
• To avoid stunning, use a low diagnostic
dose of I-131 (e.g. 1 mCi) or use I-123
(no beta emission) instead.
• It’s better to have fuller staging
information from the pretherapy scan
before the treatment.

58. • There can be surprises on an initial scan.
• An 83-year-old woman presented after thyroid
surgery and hormone withdrawal. She had
papillary carcinoma, tall cell variant, BRAF
mutation, gross extrathyroidal extension and
regional metastatic disease T4bN1bM0, stage
IVB (high risk).
• Her TSH failed to go up, in fact was
suppressed..

59. I-131 WHOLE BODY July 01, 2010

60. • Uptake was 99%.
• Ultimately it was appreciated that she
had been hyperthyroid and had had only
a partial thyroidectomy.
• She was referred back for antithyroid
medication preparatory to I-131
treatment, initially, of hyperthyroidism (to
avert thyroid storm).

61. If the TSH does not go up after hormone
withdrawal, which of the following would not
be an explanation?
1. Failure of the patient
to stop thyroid
hormone
2. Overactive pituitary
gland
3. Too much residual
thyroid tissue post-
surgery
4. Cancer lesions
making excess
thyroid hormone
0% 0% 0% 0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%

62. 54 y.o. man, S/P total laryngectomy (squamous cell ca), total thyroidectomy
and lymph node dissection. Papillary ca multifocal (largest 2.1 cm), focal
angiolymphatic invasion, positive LN’s. Tg <0.5. 24-hour urinary iodine:
specimen lost.

63. What should we do?
1. Just treat with
thyroid hormone
with no I-131
therapy
2. Refer the patient
back for more
surgery
3. A PET scan
4. Treat with I-131,
100 mCi
5. Treat with I-131,
150 mCi
0% 0% 0% 0% 0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%

64. • He is T2N1, >45 y.o., consistent with intermediate
(“standard”) risk, might have been treated with
100-150 mCi without a diagnostic scan.
• Because he did not appear to need ablation, he
was not treated and has done well in follow-up.
• Some might have treated him even in the presence
of this negative scan, although there is not clear
evidence that treatment would decrease the risk of
death or recurrence with his presentation. ATA:
“conflicting data, selective use.”

65. • In general, what is the benefit of ablation and
treating metastatic disease with I-131?
• The examples show that one can get rid of a
remnant and eliminate thyroid cancer metastases
with I-131 (shown with Tg as well as scan). There
is much empirical experience with this.
• Little or nothing has been shown with randomized
prospective studies.
• Retrospective data support the use of I-131, e.g.
Mazzeferri re ablation.

66. Ref. 2. Mazzaferri (1997).
1004 patients with DTC followed for median
14.7 years or more. Tumor recurrence was
about 3-fold lower (p<0.001) and fewer patients
developed distant metastases (p<0.002) after
ablation than thyroid hormone alone or no
therapy. There were fewer cancer deaths after
ablation ((p<0.001); this difference occurred
only in patients ≥ 40 y.o. These effects are not
apparent in patients with isolated tumors
< 1.5 cm that are not metastatic to regional
lymph nodes or invading the thyroid capsule.

67. Years After Initial Therapy
Cumulative
Deaths
(%)
0 5 10 15 20 25 30 35
16
14
12
10
8
6
4
2
0
No medical therapy
Thyroid hormone only
P<0.001
P<0.05
131 l Remnant ablation
Cancer death rate after thyroid remnant ablation, thyroid hormone therapy alone,
or no postoperative medical therapy.

68. • Note, study did not distinguish among
patients who did or did not have positive
scans for metastatic disease.
• Also, the advantage was not shown for low-
risk disease.

69. Rationale for initial therapy, adapted from
Ref. 5, NCCN Guidelines (2006)
1. There is evidence that outcomes are
better.
2. Attack metastases that are visible on
the initial scan.
3. Ablate normal tissue destined to become
malignant,
4. Attack residual malignancy
a. microscopic in remnant
b. remote from remnant, e.g. tiny foci
c. outside remnant and obscured by
uptake in remnant

70. Rationale for initial therapy, cont.
5. Demonstration of unsuspected malignancy on
post-therapy scan (10-26%), which alters disease
stage and affects patient management.
6. Simplified patient follow-up, because elimination
of “thyroid bed” uptake eliminates mis-
interpretation of it as disease.
7. Remnant ablation eliminates normal tissue as a
source of Tg production, which facilitates
identification of patients who are free of disease
and promotes early identification of those with
residual cancer.
8. Elimination of normal tissue may reduce anti-Tg
antibody production.

71. Topics
• Basics: radioiodines, thyroid hormones, feedback
• Managing nodules, and cancer: types, staging, risk
• Patient preparation, scanning, ablation, treating
metastases
• Manipulation of TSH levels: up or down
• Whether to image before ablation, stunning, post-
therapy scan
• Rationales for I-131 therapy
• Serum thyroglobulin; I-131 negative, Tg positive cases;
PET
• Alternative treatments: surgery, RT, chemo
• Recombinant human TSH (Thyrogen)
• Iodine restriction: diet, contrast, meds, thyroid
hormone
• Risks of I-131 therapy
• Surveillance
• Dosimetry, lithium
• False positive scans

72. 44 y.o. M s/p thyrx, multifocal diffuse
sclerosing variant of pap. adenoca with active
vascular and lymphatic permeation, intraglandular
metastasis, and +LN’s. Tg 160. Rx 202 mCi.
Post –Rx 6 d.

73. One year later. Serum Tg = 70 ng/mlear later from film.

74. Which is the correct inference?
1. The patient is cured of
thyroid cancer
2. The patient may have
thyroid cancer lesions
whose symporter (NIS) is
inactive
3. The patient may have
thyroid cancer lesions too
small to detect with
radioiodine scan
4. The patient may benefit
from a PET scan
5. 2, 3, and 4 are all correct
answers.
0%0%0%0%0%0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
The
patient…
The
patient…
The
patient…
The
patient…
2,
3,
and
4…
(6)

76. • Lesions removed surgically with apparent
benefit.
• Remember that radioiodine is not always
taken up by lesions of differentiated thyroid
carcinoma; that ability (based on the
symporter) may be absent or lost--but the
differentiated feature of thyroglobulin
production may be preserved.

77. Serum thyroglobulin
• A 660,000 molecular weight protein involved
in synthesis and storage of thyroid hormone
in normal thyroid.
• It may be secreted in detectable levels by
thyroid remnants or by foci of DTC.
• Following surgery and I-131, its serum level
should sink to subnormal levels, preferably
<2 ng/ml vs 3-40 ng/ml in a normal people.

78. • So Tg serves as a marker of DTC.
• The Tg test is more sensitive if “stimulated”
with TSH.
• Antithyroglobulin antibodies, if present,
interfere with the measurement.

79. • What should be done with radioiodine
negative, thyroglobulin positive cases?
• Rule out technical fault (e.g. TSH too low,
iodine contamination).
• Imaging, e.g. PET scanning, neck
ultrasound.
• Basically, look for lesions that can be
treated by other means such as surgery or
RT.

80. • Otherwise, may do “empirical” I-131
treatment.
• Controversial, but justified by
---Tg decline and
---positive post-therapy scans (which can
pinpoint lesions)
• FDG-positive lesions are usually quite
refractory to I-131 therapy.

81. In WBI-negative Tg-positive cases, I-131
treatment is contraindicated (according
to Amdur and Mazzaferri) when there is
• no uptake on prior post-Rx WBS after adequate
preparation
• rapidly rising Tg after I-131 therapy with minimal I-
131 uptake on post-therapy WBS
• FDG PET with intense uptake of large tumor
deposits
• macroscopic disease previously not responsive to
I-131 therapy

82. • What then, if lesions are not amenable to
surgery or RT?
• Chemotherapy options are limited, tyrosine
kinase inhibitor, BRAF inhibitors, clinical
trials.

83. The rhTSH alternative
• A hypothyroid patient is ill, loses work time, may
experience tumor growth secondary to prolonged TSH
stimulation.
• IM recombinant human TSH (thyrotropin alfa, Thyrogen)
results in a short-lived, usually higher TSH elevation
while patient continues thyroid hormone.
• Originally for diagnostic purposes ( scanning and Tg),
then validated for ablation.
• Has been used when treating metastases, e.g. when the
patient is too ill or endogenous TSH fails to rise.

84. rhTSH, continued
• There is some reluctance to use it in high risk cases,
based on existing literature.
• Frequently used for surveillance scans.
• May be advantageous to give before PET scan.
• rhTSH is expensive but in a broad sense may be
economically justified by patients’ well-being,
reduced sick leave, ability to drive safely, etc.

85. Routine for surveillance
• Day 1: rhTSH, 0.9, IM
• Day 2: rhTSH, 0.9, IM
• Day 3: Diagnostic dose of I-131, 4 mCi, or I-123, 4-10 mCi
• Optionally, draw serum TSH.
• Day 4: Scanning day for I-123
• Day 5: Scanning day for I-131 (or I-123)
Best day to draw thyroglobulin. TSH may be drawn, but is past
peak. Optional in any case.

86. Routine for ablation
• Day 1: rhTSH, 0.9, IM.
• Day 2: rhTSH, 0.9, IM; can give diagnostic I-123, 4-5 mCi 4
hours later.
• Day 3: Scan followed by treatment dose of I-131;
• Optionally, draw serum TSH.
• Day 4: Nothing.
• Day 5: Again, this would be the best day to draw thyroglogulin,
but probably pointless after therapeutic I-131, because of false
elevation.
• Post-therapy scan 4-7 days after dose.

87. 53 y.o. man, well differentiated papillary ca,
encapsulated follicular variant, ~5 cm. Relatively
low thyroid bed activity; abnormal focus upper
midline ant. thorax. Tg = 0.8. Rx 202 mCi. Pre-
and post-Rx scans.

88. This was 10.3 weeks after CT with contrast.
Urinary iodine was 346µg/24 h (<400 considered
important, under 50 desirable). 8 months later,
scan negative, Tg <0.5, urinary iodine 86 µg/24 h.

90. • Chemical and biochemical processes do not distinguish
isotopes of iodine.
• Dilution with cold iodine will predictably reduce uptake.
• This has implications for scan sensitivity and treatment
outcome.
• Therefore:
– Low iodine diet
– Avoid iodine-containing medications like amiodarone
– Avoid iodinated radiographic contrast

91. Background
Quantitative aspects of iodide intake and excretion
iodide is excreted 97% in urine, so
• Intake output.
• A teaspoon of Morton’s iodized salt contains = 270 µg of
iodine.
• A typical multivitamin contains 150 µg of iodine.

92. Low iodine diet (highlights)
Avoid:
• Iodized salt
• Seafood
• Dairy products
• Cured meats
• Vitamins containing iodine
• Etc., Etc.

93. 24-h urinary excretion (µg/d)
• DTC pt’s off hormone:
– controls: 158.8 ± 9.0
– low iodine diet: 26.6 ± 11.6
– P<0.001.
(Pluijmen MJHM et al, Clinical Endocrinology 58:428-235, 2003)
• Better uptakes and more successful ablations have been
reported with low iodine diets.
• Case: A hyperthyroid patient’s 24-hour uptake went
from 27% to 38% on a low iodine diet.

94. Will reducing 24-urinary excretion 5-fold cause a 5-
fold increase in uptake? In radiation dose?
Not so simple. There are other factors, e.g.
Sodium-iodide symporter (NIS) may be down-regulated by
iodide.
(Burman KD, “Low Iodine Diets,” in Wartofsky L and Van Nostrand D, Thyroid
Cancer: A Comprehensive Guide to Clinical Management, 2006)

95. Amdur RJ, Mazzaferri EL (Eds.), Essentials of
Thyroid Cancer Management, 2005, p.212:
“A single iodinated contrast exposure is likely to
compromise radioiodine uptake for 3-12
months…Measure a 24-hour urine iodine level on day 7
of a low-iodine diet in any patient with a history of
iodinated contrast exposure in the past 6 months. Do
not begin the preparatory program for radioiodine
administration unless the 24-hour urinary free iodine
level is ≤ 100 micrograms…”

97. Which is not true?
1. Lesions could be better
localized with
SPECT/CT
2. He may benefit from a
second treatment
3. He does not need a
PET scan
4. He had a partial
response to the I-131
treatment
5. His tumor has
dedifferentiated
0% 0% 0% 0% 0% 0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%

98. A 75-year-old man s/p thyroidectomy for a
multifocal papillary carcinoma, follicular variant,
largest lesion 9 cm, with vascular invasion.
Following hormone withdrawal and low-iodine diet,
his initial I-123 scan showed widespread
metastases. Tg = 1504 ng/ml (TSH = 11 µIU/ml).
He was treated with I-131, 202 mCi. A year later,
Tg = 148 ng/ml (TSH 151 µIU/ml).
But: Complications happened in the interim.

99. Initial scan and therapy ~ 8/20/08.
• 3/25/09. CT with contrast,
• 6/9/09. 24-h. urine iodine 254 µg
• 8/20/09. 24-h. urine iodine 251 µg.
• Patient was on levothyroxine, 250 µg/d. TSH was 0.05
IU/ml
• Health issues including renal insufficiency precluded
hormone withdrawal.

100. The patient’s daily dose of levothyroxine
250 ug will add to his 24-hour urinary iodine
about
1. 0 ug
2. 20-40 ug
3. 100-160 ug
4. 200-250 ug
5. None of the
above
0% 0% 0% 0% 0% 0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%

101. O
HO
I
I
I
I
CH2
NH2
H
C COONa * xH2O
Levothyroxine: 63.5% iodine, absorption 40-80% , half-life 7 d.
O
HO
I
I
I
CH2
NH2
H
C COONa
Liothyronine: 56.6% iodine, absorption ~95%, half-life ~2.5 d.
“25 µg of liothyronine is equivalent to appoximately...0.1 mg of L-thyroxine.”
Source: Abbott Laboratories and King Pharmaceuticals Prescribing Information

102. Hormone
regimen
Est. hormone
contribution
Predicted 24 .
urinary I
Actual 24 h
urinary I
T4, 250 µg 159 µg (251 µg) 251 µg
T3, 50 µg 28 µg 120 µg <110 µg
Change in 24-hour urinary iodine (from baseline + hormone) due
to hormone switch

103. • Continuing liothyronine, using rhTSH, we did
dosimetry and therapy, only 130 mCi calculated
to be tolerable (ascribed to renal insufficiency).
• Perhaps this is the best we could have done for
this patient.

105. • The advent of human recombinant TSH, enabling
procedures while patient has the benefits of continuing
thyroid hormone, raises the question of dealing with the
iodine supplied by the hormone.
• Method of Amdur and Mazzaferri, p. 236:

106. Barbaro D et al, J Clin endocrinol Metab 88:4110-4115, 2003.
DTC patients:
Groups 1 and 2 given I-131 30 mCi; 3 = control group:
rhTSH continuing T4
Group % ablated Urinary iodine
(µg/L)
P vs. control group
1: rhTSH, 4 d off T4 81.2% (n.s.) 47.2 ± 4.0 0.019
2: T4 withdrawal 75.0% 38.6 ± 4.0 <0.001
3: Control on T4 N/A 76.4 ± 9.3 ---

107. Ladenson PW et al, N Engl J Med, 337:888-96, 1997.
127 DTC patients underwent I-131 imaging (I-131, 2-4
mCi), first with rhTSH, continuing thyroid hormone,
subsequently after withdrawal.
97 patients took levothyroxine, 6 triiodothyronine, 49 both.
In 62 patients with at least one positive scan,
Scans equivalent 41 (66%)
rhTSH scan superior 3 (5%)
Withdrawal scan superior 18 (29%) (P = 0.001)

109. Hänscheid H et al, J Nucl Med, 47:648-654, 2006
and
Pacini F et al, J Clin Endocrinol Metab 91:926-932, 2006
•Randomized, controlled study of 63 patients after
thyroidectomy: withdrawal of levothyroxine or
rhTHS, studied following 100 mCi ablative dose
(no diagnostic study).
•Remnant ablation 100% in both groups.

110. rhTSH Hormone
withdrawal
P
48 h remnant
uptake (%)
0.51 ± 0.70 0.91 ± 1.05 0.10
Effective T-1/2 (h) 67 ± 48.8 48.0 ± 52.6 0.01
Blood dose
(mGy/MBq)*
0.109 ± 0.028 0.167 ± 0.061 <0.0001
*similar for several methods reported

111. • “…A phase of a persistently high TSH level [as with
hormone withdrawal]…could promote release of
organified radioiodine from thyroid remnant tissue, thus
reducing the half-time.”
• “…The higher renal clearance in euthyroidism
causes a faster excretion…and significantly reduced
radiation dose to the blood… Higher activities of
radioiodine might be administered safely after stimulation
by rhTSH.”

112. Likely comparative points
• Withdrawal and rhTSH are comparable for remnant ablation (and
possibly for treatment of metastases)
• Withdrawal gives better uptake (which could make scans more
sensitive).
• rhTSH with sustained thyroid hormone gives longer effective half-
time in remnant, compensating with respect to therapy. Conversely,
prolonged elevated TSH may promote turnover/washout of
radioiodine.
• rhTSH also improves marrow dosimetry, presumably by faster
clearance of free radioiodine, by sustaining renal function, allowing
more radioiodine for the treatment of metastases.

113. Likely comparative points (continued)
• If renal iodide clearance is worse with withdrawal, that
blunts the benefit of lower iodine intake and urinary
excretion. (Net effect isn’t clear.)
• Substitution of liothyronine with rhTSH may improve the
situation, by maintaining the benefits of longer remnant
half-life and preserved renal function while also reducing
competing nonradioactive iodine, causing better uptake
and higher radiation dose per administered mCi.
Most of the relevant work has been with remnants.
Question of effects on metastases.

114. Contraindications and precautions
in I-131 therapy
• Pregnancy
• 6-8 weeks (or more) after
cessation of lactation
• Radiation precautions after
treatment

115. Risks (remedies) in I-131 therapy,
general
• Nausea (e.g. prochlorperazine)
• Salivary gland-related risks (NIS!)
---Sialadenitis, typically parotid swelling and pain (sour candy-?,
anti-inflammatory drugs)
---Xerostomia, dental caries
---Decreased sense of taste, usually transient
• Bone marrow depression, generally minimal and transient for doses
under the 200 rad marrow limit (good hydration and, as needed,
laxatives to help clear I-131). Special risk factors relating to renal
function and age.

116. Risks (remedies) in I-131 therapy,
general (cont.)
• Radiation thyroiditis and pain (large remnants)
• Nasolacrimal duct obstruction
• Pulmonary fibrosis in cases with high pulmonary uptake
• Hemorrhage and edema e.g. with intracranial and spinal
cord metastases

117. Risks, reproductive
• Temporary oligospermia and elevated FSH levels in men
• Possible male infertility with multiple treatments
• Temporary amenorrhea or oligomenorrhea; transient ovarian
failure
• Higher rate of miscarriage for 1 year (avoid pregnancy for 6
mo.-1 y.)
• Rare genetic and chromosomal abnormalities in children
generally after high doses.
• Long-term rates of infertility, miscarriage and fetal
malformation do not appear to be elevated.

119. Second cancers
• The effective dose of a radiological
or nuclear medicine procedure is
an estimate of the equivalent whole
body dose in terms of harmful
effects and has been used
specifically to estimate the risk of
cancer, but is a crude method and
controversial.

120. Whole body dose
• Bier Report: 1/100 cancers per 100 mSv (10 rem).
Effective dose
Helical CT abdomen/pelvis: 14 mSv (1.4 rem)
100 mCi I-131 with no thyroid uptake: 226 mSv
(22.6 rem)
100 mCi I-131 = 16 CT’s = 226 mSv = 2.26
cancers/100, likely overestimate
0.56/100 in 10 years reported after 100 mCi, but
reports vary.
It is hard to quantify, but appropriate for the
consent.

121. • Most patients do well after I-131 therapy
• Some practitioners view I-131 therapy as somewhat risk-free and have
a low threshold for therapy, even in instances where the likelihood of
benefit is low.
• I have a higher threshold than some.
• Out of concern for cancer,
---I wish to comply with the guideline for no ablation in very low risk
patients
---When ablating low risk patients, I like to keep the dose low (e.g. 50
mCi)
• I am concerned about bone marrow toxicity when giving high doses.
• In high risk patients, especially those with demonstrable iodine-avid
metastases, when I like to give a high dose, I am not concerned about
second cancers.
• In general, I am concerned about the salivary-related complications.

122. Followup after ablation
• We have often done WBI scan after 6-12 months to assess success of
ablation and whether there is iodide-avid metastatic disease, with
retreatment as necessary, but, in low risk cases, this is likely not
necessary (as per ATA).
• Subsequent WBI scans may depend on features of the case.
Unstimulated or stimulated Tg and neck ultrasound may suffice in low
risk cases.
• Surgery is favored for cervical LN’s or soft tissue tumor in neck when
distant metastases are not present.
• Elevated or rising Tg may indicate WBI scan and/or I-131 therapy.
• Remember Tg is more sensitive if stimulated by TSH, just as
radioiodine scans are more sensitive and treatments more effective.

123. Follow Up Algorithm
Risk of
Recurrence
Basal Tg
(unstimulated)
Stimulated Tg
(rhTSH or
THW)
Neck
Ultrasound
Other Imaging
Low Annually for 1-2
years then
periodically
Possibly year 1 Annually for 1-2
years then
periodically
None
Moderate Annually Possibly
unnecessary
after 1st annual
negative follow
up
Annually Possible use of
surveillance
WBS
Chest CT?
High Every 6-12
months and
possibly more
often
Annually Annually and as
needed
Strong
consideration
of possible
benefit of WBS
PET/CT in
appropriate
circumstances
TSH:
Low Normal
TSH:
0.1-0.3
TSH:
Below 0.1

124. “Medical sociology”
• This isn’t like referrals for bone scans.
• You should cultivate expertise.
• The referring clinician may or may not have
expertise.
• Diplomacy, collegiality and mutual respect are to
be desired.

125. Dosimetry: Maximum tolerated
radiation absorbed dose
• This is generally considered to be 200
rads (2 grays) to blood (as surrogate for
bone marrow and entails serial
measurements of whole body and blood
radioactivity following test dose of I-131.
• I.e. if result is 0.5 rad per mCi, you can
give 400 mCi. (400 x 0.5 = 200.)
•Maximum tolerated radiation absorbed dose.

126. Dosimetry: absorbed tumor dose
• Derived from serial uptake measurements of
tumor plus its mass (e.g. SPECT/CT?).
• 8,000 rads (80 Gy) reported to be necessary for
effective treatment.
• If, in previous case, lesion dose is 10 rads per
mCi, the highest tolerable dose of 400 rads
would deliver 400 x 10 = 4,000 rads, implying
that there would be insufficient benefit from the
highest safe administered dose.

128. • A patient with an aggressive tumor, prior
thyroidectomy and prior standard I-131
doses.
• He was given lithium carbonate to prolong
the half-life in lesions.

130. • Estimated he could tolerate 300 mCi,
which would deliver 11,000 rads to lesion.
• Treatment was well tolerated with partial
response.

131. Use of lithium
• Lithium has been shown to prolong I-
131 retention by thyroid remnants and
metastases. Tumor dose may increase
2-fold or more. It is therefore
sometimes used as an adjunct to
therapy. ATA: “…The data are
insufficient to recommend lithium…”

133. What is the interpretation?
1. Multiple
metastases to
viscera
2. Multiple
metastases to
skin
3. Artifact/false
positive
0% 0% 0% 0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%

135. Some causes of false positives
• Breast uptake
• Salivary gland uptake
• Thymus
• Exudates
• Dilated hepatic ducts
• Nonthyroid benign tumors