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Peerapon Kiatkittikul, M.D.*, Yutapong Raruenrom, M.D.*, Daris Theerakulpisut, M.D.*, Charoonsak
Somboonporn, M.D., Ph.D.*,**
*Department of Radiology, Faculty of Medicine, Khon Kaen University, **Clinical Epidemiology Unit, Faculty of Medicine, Khon Kaen University
40000, ailand.
Success Rate of Radioactive Iodine Therapy in
Graves’ Disease Using Dose Corrected for Thyroid
Gland Size
ABSTRACT
Objective: Dose corrected for thyroid gland size is one of the methods used to determine I-131 activity for patients
with Graves’ disease. is study aimed to nd the success rate of this method and the predictors for successful I-131
treatment.
Methods: is retrospective descriptive study conducted was in patients with Graves’ disease who received the rst
dose of radioactive iodine (RAI) therapy. Patients received a xed RAI dose of either 10, 15, 20, 25, or 30 mCi for
corresponding thyroid gland size of ≤ 50, 51-100, 101-150, 151-200, and >200 grams, respectively. e treatment
outcome assessed was between 6 to 9 months aer the therapy based on serum free thyroxine and serum thyroid
stimulating hormone. Successful treatment was dened as euthyroid and hypothyroid.
Results: A total number of 179 patients (126 females; mean age: 40.8 years) were enrolled. ere was one patient
exclusion from the outcome analysis due to undetermined laboratory results. e success rate of RAI therapy was
50% (95% CI: 42.4-57.6). Patients with gland size ≤ 50 gm had the highest success rate of 59.6%. Multivariable
analysis showed no signicant association between sex, thyroid gland size, prior antithyroid drug use and successful
treatment.
Conclusion: First RAI therapy using dose corrected for thyroid gland size had a modest success rate of 50% in
patients with Grave’s disease. Sex, thyroid gland size, and prior antithyroid drug use were not signicantly associated
with the treatment outcomes.
Keywords: Radioactive iodine; Graves’ disease; hyperthyroidism; success rate (Siriraj Med J 2021; 73: 108-113)
Corresponding author: Yutapong Raruenrom
E-mail: yutara@kku.ac.th
Received 1 September 2020 Revised 12 December 2020 Accepted 12 December 2020
ORCID ID: http://orcid.org/0000-0002-2384-0649
http://dx.doi.org/10.33192/Smj.2021.15
INTRODUCTION
Graves’ disease is an organ-specic autoimmune
disease and the most common cause of hyperthyroidism. e
annual incidence is 20 to 30 cases per 100,000 individuals
with approximately 3% and 0.5% lifetime risk in women
and men, respectively.
1-3
Untreated or partially treated
Graves’ disease can lead to serious complications such
as atrial brillation, neuropsychiatric symptoms, thyroid
storm, or even death.
4,5
us, an appropriate treatment
is the key to success for controlling hyperthyroidism
symptoms and prevention of serious complications.
Radioactive iodine (RAI) therapy using the beta
particle-emitting isotope, I-131, is the denitive treatment
for Graves’ disease by destroying thyroid follicular cells.
3,6
Kiatkittikul et al.
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e goal of RAI therapy is to use sucient activity of
RAI to render the patient’s hypothyroid.
4
ere are two
main methods to determine the RAI activity in clinical
practice: estimation (the so called “xed dose”) and
calculation of radioiodine uptake measurement and
thyroid gland size.
7,8
e systematic reviews and meta-
analyses showed equally successful treatment outcomes
between the two methods.
9
However, the xed dose
regimen is simpler and more cost-eective.
10,11
Another
approach to nd an optimal I-131 activity in Graves’
disease is dose corrected for thyroid gland size method
by prescribing RAI activity according to the estimated
thyroid gland size.
12
e advantages of this method are
similar to the xed dose in terms of cost and procedure.
However, the treatment outcome of this method is not
been well studied. us, we primarily aimed to nd the
success rate of rst RAI therapy using dose corrected
for thyroid gland size method in patients with Graves’
disease. Moreover, we also evaluated predictive factors
associated with the successful treatment.
MATERIALS AND METHODS
Patient selection
is retrospective descriptive study was approved
by the Khon Kaen University Ethics Committee for
Human Research (Reference number: HE601393) and
the requirement for the informed consent was waived.
From January 2012 to April 2017, patients enrolled for
research had conrmed Graves’ disease and had received
rst RAI therapy at Srinagarind Hospital. Patients were
stratied into ve groups according to thyroid gland
size. ose with a history of thyroid surgery, received
repeated doses of RAI therapy prior to rst treatment
outcome evaluation, or had undetermined laboratory
results during the follow-up period because of recent
thyroid hormone or antithyroid medication use were
excluded.
Patient preparation and treatment
Patients treated at our center followed strict patient
preparation as per our center’s standard protocol.
Antithyroid Drug (ATD) either methimazole (MMI)
or propylthiouracil (PTU), was discontinued three to
seven days prior to RAI therapy. Patients had an advice
to take low-iodine diet for one week before the therapy.
Pregnancy tests done potentially on all pregnant females
on the day of treatment. e thyroid gland size estimation
of each patient performed by one of four expert nuclear
medicine physicians. e recorded thyroid gland size was
used to determine RAI activity according to our center’
standard protocol. Patients received a xed RAI dose of
either 10, 15, 20, 25, or 30 mCi orally for corresponding
thyroid gland size of ≤ 50, 51-100, 101-150, 151-200, and
>200 grams as assessed by palpation. Beta-blockers and/
or restarting ATD allowed for controlling symptoms
aer RAI therapy. en, clinical outcomes evaluated
between 6 to 9 months aer rst I-131 administration.
yroid function tests including serum free thyroxine
(FT4) and serum thyroid stimulating hormone (TSH),
clinical symptoms, and thyroid gland size assessed at
the follow-up time point.
Outcome measurement
Successful RAI therapy was dened as patients
with euthyroid (normal FT4 and TSH), subclinical
hypothyroidism (normal FT4 and high TSH), or overt
hypothyroidism (low FT4 and high TSH) 6 to 9 months
aer the treatment. e patients who had subclinical
hyperthyroidism (normal FT4 and low TSH) or overt
hyperthyroidism (high FT4 and low TSH) had classied
as treatment failure. e normal reference range of
serum FT4 is 0.78-2.11 ng/dL and serum TSH is 0.2-4.2
µIU/mL.
Statistical analysis
e success rate of RAI therapy presented as the
number and percentage of patients with euthyroid,
subclinical hypothyroid and overt hypothyroid divided
by the numbers of all patients. e categorical data (sex,
group of gland size, type of ATD use) presented the
number and percentage. e continuous data (age, follow-
up time, serum FT4, serum TSH) presented as mean ±
standard deviation (SD) or median (with interquartile
range). Univariable analysis and multivariable analysis
by multiple logistic regression used to test association
between sex, prior ATD use, thyroid gland size and
successful treatment. All the statistics two-sided and
p values of less than 0.05 considered statistically signicant.
Accompanying 95% condence intervals (95% CI) were
reported where appropriate. Statistical analysis carried out
was using STATA 10.1 (StataCorp LP, College Station,
TX, USA).
RESULTS
A total number of 179 patients enrolled with a
mean age of 40.8±13.6 years. Most of the patients were
female (n = 126, 70.4%). When patients were grouped by
thyroid gland size, 52 (29.1%), 52 (29.1%), 39 (21.8%),
22 (12.2%), and 14 (7.8%) had gland size of ≤ 50, 51-
100, 101-150, 151-200, and ≥ 200 grams, respectively.
Regarding the ATD, most of the patients used MMI prior
to RAI therapy (n = 131, 73.2%). Only ve patients (2.8%)
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Kiatkittikul et al.
did not receive ATD before I-131 administration. e
median follow-up time aer treatment was 6.6 (6.1-7.5)
months. e patient’s demographic and clinical data are
as shown in Table 1.
Aer the 6- to 9-month follow-up, there was one
patient with indeterminate laboratory results (low serum
FT4 and TSH). us, the success rate of treatment in 178
patients analyzed. Eighty-nine patients (50%) achieved
successful treatment, among which 30 (16.9%) were
euthyroid, 30 (16.9%) were subclinical hypothyroid, and
29 (16.2%) were overtly hypothyroid. e remaining 89
patients (50%) had treatment failure, among which 51
(28.7%) were subclinical hyperthyroid and 38 (21.3%)
were overtly hyperthyroid. The details of treatment
outcomes are as shown in Table 2.
Regarding the treatment outcomes based on the
thyroid gland size, patients with gland size equal or less
than 50 grams had the highest success rate of 59.6% (95%
CI: 45.1-73.0), while patients with larger gland size tended
to have lower success rate. Patients with gland size of
151-200 grams had the lowest success rate, 22.7% (95%
CI: 7.8-45.4). e success rate in each group of thyroid
gland size is as shown in Table 3.
Multiple logistic regression demonstrated that
females tended to have successful treatment than males
but there was no statistical signicance (adjusted OR =
1.28, 95% CI: 0.62-2.64, p value = 0.51). Regarding the
thyroid gland size, patients with gland size 151-200 grams
seemed to have lower successful treatment than those
with gland size ≤ 50 gm but there was also no statistical
signicance (adjusted OR = 0.35, 95% CI: 0.08-1.59,
p value = 0.17). Furthermore, use of MMI or PTU prior
to the RAI therapy showed no signicant association
with the successful treatment as shown in Table 4. In
addition, we also evaluated the impact of dierent ATD
use prior to the therapy on successful treatment and
found that there was no statistically signicant dierence
between either MMI or PTU and the treatment outcomes
(adjusted OR = 1.83, 95% CI: 0.86-3.92, p value = 0.12).
TABLE 1. Patient’s demographic and clinical data.
Variables Total 179
n (%)
Sex
Male 53 (29.6)
Female 126 (70.4)
Age (year)
Mean 40.8
SD 13.6
Estimated thyroid gland size (gram)
≤ 50 52 (29.1)
51-100 52 (29.1)
101-150 39 (21.8)
151-200 22 (12.2)
> 200 14 (7.8)
Antithyroid drug
Methimazole (MMI) 131 (73.2)
Propylthiouracil (PTU) 42 (23.5)
Both MMI and PTU 1 (0.5)
None 5 (2.8)
Follow-up time (month)
Median 6.6
Interquartile range 6.1-7.5
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TABLE 2. Outcomes of RAI therapy at the 6 to 9-month follow-up.
Outcome Total 178
a
n (%)
Success 89 (50)
Euthyroid 30 (16.9)
Subclinical hypothyroid 30 (16.9)
Overt hypothyroid 29 (16.2)
Failure 89 (50)
Subclinical hyperthyroid 51 (28.7)
Overt hyperthyroid 38 (21.3)
a
ere was one patient with thyroid gland size > 200 grams whose thyroid function test cannot be determined. us, the treatment outcomes
were analyzed in 178 patients.
TABLE 3. Outcomes of RAI therapy at the 6 to 9-month follow-up based on thyroid gland size.
Thyroid gland size Median size (IQR) Success Failure Percent success rate
(gram) (95% CI)
≤ 50 35 (30-40) 31 21 59.6 (45.1-73.0)
51-100 70 (60-80) 28 24 53.9 (39.5-67.8)
101-150 120 (120-145) 19 20 48.7 (32.4-65.2)
151-200 200 (200) 5 17 22.7 (7.8-45.4)
> 200 250 (250-287.5) 6 7 46.2 (19.2-74.9)
Overall 80 (50-130) 89 89 50.0 (42.4-57.6)
Abbreviation: IQR, interquartile range
DISCUSSION
We studied the success rate of RAI therapy by
dose corrected for thyroid gland size method in 178
patients with Graves’ disease who received rst-dose I-131
administration. e treatment outcomes evaluated at 6
to 9 months aer the therapy. We decided to determine
the treatment outcomes at this time point because there
was variation in the follow-up period in each patient
and hypothyroid could achieve up to 12 months aer
the therapy.
13
Eighty-nine patients achieved successful
treatment accounts for only 50% success rate (95% CI:
42.4-57.6). is gure was lower than reported in the
previous studies using the estimation method to determine
I-131 activity with the success rate between 60-85%.
10,11,14-18
Several factors aected our therapeutic outcome. e rst
important factor that aected the outcome was thyroid
gland size, well known to be an independent predictor
of the response to I-131 therapy.
13
e median thyroid
gland size of our patients was higher than those in other
studies (80 grams vs 35-70 grams)
10,11,14,17
and 71.35% of
our patients had thyroid gland size larger than 50 grams.
us, this could lower the overall success rate. However,
the patients with thyroid gland size ≤ 50 grams could
achieve higher success rate approximately at 60%. Second,
we used the palpation method for thyroid gland size
estimation which could underestimate the size of larger
goiter (greater than 40 mL).
19
e study by Canto et al.
used thyroid ultrasound for gland size estimation and
found that the overall success rate was 80% even though
there were one-third of patients with gland size between
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Kiatkittikul et al.
TABLE 4. Univariable and multivariable analyses of successful treatment.
Variable Univariable analysis Multivariable analysis
Crude OR (95% CI) p value Adjusted OR (95% CI) p value
Sex
Male 1 1
Female 1.31 (0.69-2.49) 0.41 1.28 (0.62-2.64) 0.51
Thyroid gland size (gram)
≤ 50 1 1
51-100 1.36 (0.40-4.61) 0.62 1.15 (0.31-4.21) 0.84
101-150 1.11 (0.31-3.90) 0.87 0.97 (0.27-3.56) 0.97
151-200 0.34 (0.08-1.50) 0.16 0.35 (0.08-1.59) 0.17
> 200 1.72 (0.51-5.85) 0.38 1.63 (0.44-6.08) 0.47
Antithyroid medication
None 1 1
MMI 1.78 (0.29-10.98) 0.54 2.90 (0.43-19.38) 0.27
PTU 0.87 (0.13-5.78) 0.88 1.58 (0.22-11.37) 0.65
Abbreviations: Crude OR, crude odds ratio; Adjusted OR, adjusted odds ratio, MMI; methimazole, PTU; propylthiouracil
40-80 grams.
10
ird, we did not perform radioiodine
uptake test (RAIU) that might identify patients with rapid
I-131 turnover Graves’ disease that maybe found in up to
15% of all Graves’ disease patients and needed a higher
I-131 activity or other therapeutic intervention such as
lithium carbonate.
20
Fourth, although with a one-week
low-iodine diet intake advised to the patients before RAI
therapy, the actual amount of iodine intake is dicult to
quantify. e study by Meller et al. found that there was
2-fold increased iodine excretion prior to the therapy
corresponded to a decrease of the radioiodine uptake by
25%.
21
However, the prospective study by Santarosa et
al. showed no dierence in the rate of hypothyroidism 6
months aer RAI therapy between patients with Graves’
disease patients who consumed low-iodine diet and patients
who took regular diet (86.7% vs 82.6%, p value = 0.74).
22
Lastly, since most of the patients had been referrals from
other hospitals, some patients who had a higher chance
to be cured with a single dose of I-131, such as patients
with small gland size or mild hyperthyroidism, had
been referred back to their primary hospitals for further
follow-up. us, the assessment count of successful
treatment numbers was dicult to achieve in our study
results of this group of patients and this could lead to
underestimation of treatment success.
Regarding the predictors for the therapeutic outcome,
sex showed no signicant association with successful
treatment which was in line with most studies. ere
was no exact reason to explain the dierence in the
biological response to radioiodine between male and
female.
13
For thyroid gland size, it was also no signicant
association with the treatment outcomes. is maybe
explains the method to determine I-131 activity. We
used dose correction for thyroid gland size; the larger
gland size received the higher prescribed radioiodine
activity. In addition, prior MMI or PTU use before
RAI therapy, although known to have radioprotective
eect
13
, showed no signicant association with successful
treatment in our study. e result was consistent with
a randomized clinical trial by Bonnema et al. which
demonstrated no dierence between failure rate of RAI
therapy among Graves’s disease patients who were and
were not pretreated with PTU (40.0% vs 30.8%, p value
= 0.81).
23
e prospective randomized study by Pirnat
et al. also showed equally eective outcomes in Graves’
disease patients who did not receive MMI and patients
who had discontinued MMI seven days before RAI
therapy (99.6% vs 99.0%).
24
ere were some limitations of our study. First, due
to being a retrospective study, other potential predictive
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factors such as pretreatment serum FT4 and TSH, duration
of disease, duration of ATD use, and thyroid autoantibodies
were dicult to evaluate. Second, the thyroid gland size
was assessed by dierent nuclear medicine physicians
could cause variation in estimating gland size. us, this
could aect the prescribed I-131 activity in each patient.
ird, the follow-up duration was varied among the
patients ranging from 6 to 9 months which can aect
the treatment outcomes.
An issue that needs clarication is the strategy
to improve success rate of RAI therapy by using dose
corrected for thyroid gland size method. Higher prescribed
I-131 activity for each stratum of thyroid gland size needs
consideration and further prospective study is required.
CONCLUSION
First RAI therapy using dose corrected for
thyroid gland size had a modest success rate of 50% in
patients with Grave’s disease. Sex, thyroid gland size,
and prior antithyroid drug use showed no signicant
association with the successful treatment.
ACKNOWLEDGEMENTS
We would like to thank Dr.Kaewjai epsuthammarat
for statistical advice via Clinical Epidemiology Unit,
KKU. We also would like to acknowledge Mr.Gurdeep
Singh for editing the manuscript via Publication Clinic
KKU, ailand.
Conict of interest: ere is no potential conict of
interest relevant to this article.
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