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Response rate and factors affecting outcome of fixed dose of RAI131 therapy in
Graves` disease: A 10 year Egyptian experience
--Manuscript Draft-Manuscript Number:
NMC-11-1171R1
Full Title:
Response rate and factors affecting outcome of fixed dose of RAI131 therapy in
Graves` disease: A 10 year Egyptian experience
Article Type:
Review Article
Keywords:
Graves` disease; Radioactive iodine therapy; fixed dose; Tc-99 pertechnetate thyroid
uptake.
Corresponding Author:
Maha Abd Elkareem Husseni, M.D
Kasr A l Ainy hospital, cairo university
Cairo, EGYPT
Corresponding Author Secondary
Information:
Corresponding Author's Institution:
Kasr A l Ainy hospital, cairo university
Corresponding Author's Secondary
Institution:
First Author:
Maha Abd Elkareem Husseni, M.D
First Author Secondary Information:
Order of Authors:
Maha Abd Elkareem Husseni, M.D
Wajeeh Abdulrazak Derwish, M.sc
Hosna Mohammed Moustafa, Professor
Order of Authors Secondary Information:
Manuscript Region of Origin:
EGYPT
Abstract:
Purpose: Evaluate response and compare success rate of two different doses of I-131
therapy in treatment of Graves` disease and investigate the factors that may affect
outcome.
Patient and methods: Retrospective analysis was performed on 321 patients treated
with I-131 for Graves` disease. Group 1 (155 patients) received 8 mCi and Group 2
(166 patients) received 12 mCi. The therapy was considered successful if euthyroidism
or hypothyroidism was achieved within one year of therapy. The outcome was
compared with multiple parameters.
Results: Significant difference in the outcome between the two groups was found in
favor of the second group (P<0.001). Logistic regression analysis revealed that lower
dose, Tc-99 pertechnetate thyroid uptake > 20.9 %, moderate and marked goiter were
independent variables that significantly associated with less response rate (OR 2.601,
4.023 and 3.309 respectively) and prior surgical treatment with higher response rate
(OR 3.071). No correlation between outcome and age, presence of exopthalomos,
previous treatment with methimazole and its duration was found. Response rate to the
second dose was significantly increased compared to the first one by 27.8 %, there
was no correlation among the above mentioned factors and its outcome. The third
dose controlled 81.3 % of the remaining patients and the rest were achieved controlled
after the fourth dose.
Conclusions: I-131 is very effective therapy for Graves` disease with cure rate 100%
after 4 doses. Higher first dose activity is recommended in the presence of poor
prognostic factors. Second dose is not necessary increased in the non responders.
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Response rate and factors affecting outcome of fixed dose of RAI131
therapy in Graves` disease: A 10 year Egyptian experience
Maha Abd El-Kareem M.D, Wajeeh Abdulrazak Derwish M.sc and Hosna Mohamed
Moustafa M.D
Department of radiotherapy and nuclear medicine (NEMROCK), Nuclear medicine
unit, Cairo University.
Abstract
Purpose: Evaluate response and compare success rate of two different doses of I-131
therapy in treatment of Graves` disease and investigate the factors that may affect
outcome.
Patient and methods: Retrospective analysis was performed on 321 patients treated with
I-131 for Graves` disease. Group 1 (155 patients) received 8 mCi and Group 2 (166
patients) received 12 mCi. The therapy was considered successful if euthyroidism or
hypothyroidism was achieved within one year of therapy. The outcome was compared
with multiple parameters.
Results: Significant difference in the outcome between the two groups was found in favor
of the second group (P<0.001). Logistic regression analysis revealed that lower dose, Tc99 pertechnetate thyroid uptake > 20.9 %, moderate and marked goiter were independent
variables that significantly associated with less response rate (OR 2.601, 4.023 and 3.309
respectively), while prior surgical treatment with higher response rate (OR 3.071). No
correlation between outcome and age, presence of exopthalomos, previous treatment with
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methimazole and its duration was found. Response rate to the second dose was
significantly increased compared to the first one by 27.8 %, there was no correlation
among the above mentioned factors and its outcome. The third dose controlled 81.3 % of
the remaining patients and the rest were achieved controlled after the fourth dose.
Conclusions: I-131 is very effective therapy for Graves` disease with cure rate 100%
after 4 doses. Higher first dose activity is recommended in the presence of poor
prognostic factors. Second dose is not necessary increased in the non responders.
Keywords: Graves` disease; radioactive iodine therapy; fixed dose- Tc-99 pertechnetate
thyroid uptake.
Introduction: Graves` disease (GD) is the most common cause of hyperthyroidism
responsible for approximately 50-60% of the cases (1). The most common clinical
presentations related to the cardiovascular system. Other disease manifestations include
Graves’ ophthalmopathy and myxedema(2). Diagnostic modalities include suppressed
serum TSH and an elevated serum FT4, FT3 levels, thyroid scintigraphy either with Tc99m pertechnetate or radioactive iodine-131 (RAI-131) and ultrasonography (U.S) to
detect the presence of an associated nodules (3). Three therapeutic modalities are
commonly used today; anti-thyroid drugs (ATDs), RAI-131 and surgical treatment (3).
The aim of RAI -131 treatment is to cure the hyperthyroidism by rendering the patient
either euthyroid or hypothyroid through destruction of the over-functioning thyroid
tissues (4). The use of RAI-131 in treatment of GD is increasing, particularly as a first
line treatment (5) as it is easy to administer, relatively inexpensive, reliable , safe and
highly effective with a cure rate approaching 100% after one or more dose (6) . Different
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methods have been used for determining the administered activity, varied from fixed
doses to adjusted calculations based on gland size, iodine uptake and turnover (7). The
dose calculation method aims to optimize the therapeutic results through administration
of radioactive iodine in proportional to the size of the gland, increasing the probability of
cure and providing the lowest possible radiation dose to the rest of the body (8). There is
little evidence that using a calculated dose has any advantage over a fixed-dose regimen
in preventing hypothyroidism or improvement in cure rate (9), but it increases
significantly the cost of the therapy owing to increase the procedure complexity (10).
Taking in mind that the radioactive iodine therapy is relatively inexpensive, thus the
increase in its cost to determine the administered activity must be clearly justified (10).
There are some predictive factors associated with RAI-131 success rate. Previous works
have shown lower treatment success rates in young male patients, more severe cases of
hyperthyroidism (11)(12) , larger goiters (12) (13) and in cases with low or high
pretreatment thyroid uptake (12) (14). The influence of pretreatment with anti-thyroid
drugs on the efficacy of radioiodine therapy is controversial. Some authors believe that
the thyrostatic drugs methimazole (MMI) and propylthiouracil (PTU) have a radioresistance effect and can lead to half-life reduction and accelerate turnover (15) (16) (17),
but others have shown an effect confined to PTU only (18).
Patients and Methods: We retrospectively evaluated 321 hyperthyroid patients due to
GD referred to the nuclear medicine unit, Kasr Al ainy hospital (NEMROK), Cairo
University, during the period of January 2000 till January 2010 for RAI-131 therapy as
first or as a second treatment modality (following medical or surgical treatment). Our
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institutional medical ethics committee approved the protocol. The diagnosis of GD was
primarily based on clinical (hyperthyroid manifestations and diffusely enlarged thyroid
gland) and laboratory data, including high serum free T4 level (FT4; reference Values,
RV = 0.9 - 1.8 ng/dL) and low serum thyrotropin levels (TSH; RV = 0.41- 4.5 µ IU/mL).
The patients who had thyrotoxicosis due to toxic multi-nodular goiter (Plummer disease),
toxic autonomous adenoma, GD associated with (cold) nodule by (scan) or palpation
respectively and patients who not completed the follow up were excluded from the study.
Data were retrieved from the thyroid clinic database include: age at diagnosis, gender,
symptoms, dose and duration of anti-thyroid drugs , previous surgical treatment, clinical
data for the presence of palpable nodules & other neck swellings and the presence or
absence of eye signs, TSH level and thyroid scan using Tc-99m pertechnetate that was
done 20 min after intravenous injection of 5 mCi of the tracer to evaluate the associated
nonfunctioning (cold) nodule and quantitation of thyroid uptake using the methodology
previously described by Maisey et al(19) and simplified for routine use. The reference
values for Tc-99m pertechnetate uptake range from 0.3 to 4 % (20). Gland size were
determined by combining clinical examination (palpation) and thyroid scan and was
divided in to either normal size (impalpable), mild (palpably enlarged but not visible) and
moderate or markedly enlargement (palpable and visible goiter). In view of our socioeconomical circumstances; the simple fixed dose protocol has considerable cost saving
advantages, we have adopted this protocol for the treatment of GD in our institution. The
patients were divided according to the given RAI-131 dose in to 2 groups: Group 1:
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received 8 mCi (155 patients) (48.3%) and Group 2: received 12 mCi (166 patients)
(51.7%), they are the commonly preferred doses in the treatment of GD in our institute.
Anti-thyroid drugs, if given before therapy, were withdrawn a week before therapy and
for a minimum of 1 week after to avoid any drug influence on the therapeutic
effectiveness. Iodine-containing medications were also discontinued several weeks before
therapy; in addition, the patients were started on a low-iodine diet for 10 days before
therapy, fasted before and for 2 hours after the administration of the dose to achieve
higher absorption. Patients were advised to avoid physical contact and transfer of
secretions to others for several days after treatment. Regular clinical and laboratory
follow up to evaluate therapeutic efficacy was done and the patients were classified
according to the outcome in to: Euthyroidism: Absence of signs or symptoms of
hyperthyroidism or hypothyroidism with normal serum TSH value without levothyroxin
therapy. Resistant to therapy: persistence of thyrotoxic manifestation and suppressed
TSH value or by requirement of repeat administration of RAI-131 therapy within 6
months of the therapy and Hypothyroidism: presence of symptoms or signs of
hypothyroidism together with elevated TSH value on two occasions four weeks apart,
that require permanent treatment with levothyroxine. RAI-131 treatment was considered
to be successful if the patient was either euthyroid or hypothyroid.
Statistical methods: Data was analyzed using IBM SPSS advanced statistics version 20
(SPSS Inc., Chicago, IL). Numerical data were expressed as mean and standard deviation
or median and range as appropriate. Qualitative data were expressed as frequency and
percentage. Chi-square test (Fisher’s exact test) was used to examine the relation between
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qualitative variables. For quantitative data, comparison between two groups was done
using Mann-Whitney test (non-parametric t-test). The receiver operator characteristic
(ROC) curve was used to identify the best threshold for thyroid uptake to discriminate
success and failure of RAI-131 therapy. Multivariate analysis was done using forward
stepwise logistic regression method for the significant factors affecting response on
univariate analysis. Odds ratio (OR) with 95% confidence interval (CI) were used for risk
estimation. P-value < 0.05 was considered significant.
Results:.
Baseline, pre-therapy clinical characteristics and commonly presenting
symptoms for the patients are listed in Table 1 and 2. The recorded data documented
development of early complications within the 1st 3 months in 31 patients (9.6%),
included transient mild increased thyrotoxic manifestations in 21 patients and transient
hypothyroidism which occurred for 8 patients, 5 after a high dose and 3 after low dose.
Six of the 8 patients developed transient hypothyroidism after 1st dose, while the
remaining 2 patients developed it after 2nd dose. Also neck pain developed in 2 patients.
There was statistically significant difference in the incidence of early complications
between the patients who received 8 mCi and the second group who received 12 mCi, in
favor of the latter group (p = 0.024), whereas as there was no statistically significant
difference between age, gender, presence of exopthaloms, size of thyroid gland and
thyroid uptake and early complications either between the two groups as shown in the
table (3) or in each group separately (not included).
Exopthalmos was increased in 9 patients (9.6%) after RAI-131 therapy and remained
stationary in rest. Three new cases (1.3%) developed exophthalmos from the remaining
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227 patients and they were among the 170 patients who had permanent hypothyroidism
(1.7%). No relation was found between the presence of exopthalmos and development of
early complications as shown in tables 3.
The success rate to the first given dose was 59.8% with development of euthyroidism in
56 patients (17.4%) and hypothyroidism in 136 patients (42.4%). There was statistically
significant difference in the successes rate between the patients who received 8 mCi
(49%) and 12 mCi (69.9%) P <0.001. Of the 76 patients in whom therapy was successful
in group1, 25 (16.1%) developed euthyroidism and 51(32.9 %) developed
hypothyroidism and at a median period of 6 months (range: 3 –18 months) and among the
116 responding patients in the second group, euthyroidism was achieved in 37 patients
(22.3%) and hypothyroidism in 79 patients (47.6%) with a median cure time 4 months
(range: 2 –18 months).
There was no statistically significant association between age, presence of
ophthalmopathy and previous medical treatment & its duration and outcome, whereas
there was statistically significant difference regarding gender, size of thyroid gland,
Tc99m pertechnetate thyroid uptake and previous surgical treatment as demonstrated in
table 4. We did not find any relationship between the previous use of methimazole & its
duration and the outcome of patients either in the whole study population or G1 and G2
separately (tables 4 and 5 A&B).
Thyroid uptake was analyzed using ROC curve to discriminate the group of patients who
achieved success with treatment from the group that remained hyperthyroid and we found
a thyroid uptake threshold of 20.9 % with a sensitivity of 76.1 % and specificity of 65.4
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% for treatment success (Fig. 1). We were unable to find an adequate cutoff value for
base line TSH level.
Multiple logistic regression analysis demonstrated that age, gender and previous medical
treatment were not significantly associated with the outcome, whereas Tc99m
pertechnetate thyroid uptake > 20.9% (OR= 4.023) , moderate and markedly enlarged
thyroid gland (OR= 3.309) and the low given dose (OR= 2.601) were identified as
significant prognostic risk factors for treatment failure and previous thyroidectomy for
treatment success (OR= 3.071) (odds ratio; 95% confidence interval = 2.218 -7.297,
1.707 - 6.414, 1.403 - 4.822 and 1.109 - 8.502 respectively).
Response to the second dose: A second dose was given to the 129 non responded
patients after a mean time of 6.77 months (minimum 3 months and maximum 12
months). Of these 63 patients received 8 mCi and 66 received 12 mCi. The overall
response rate to the second therapy dose significantly increased compared to the first one
by 27.8 % with development of euthyroidism in 56 patients (17.4%) and hypothyroidism
in 136 patients (42.4%). There was no statistically significant difference in the response
rate between the patients who received 8 mCi and who received 12 mCi (P value =
0.921), also there was no statistically significant difference in the response rate in relation
to size of thyroid gland, Tc99m pertechnetate thyroid uptake, previous surgical treatment,
age and gender (p values 0.265, 0.665, 0.242, 0.209 and 0.923 respectively) as shown in
table 6.
Fifty two patients from the 79 non responded in the first group received second dose of 8
mCi while the remaining 27 patients received 12 mCi.
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There was no statistically
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significant difference in the response rate between the patients received 8 mCi (86%) and
12 mCi (92.6 %) with P value = 0.422. No statistically significant difference in the
response rate in relation to size of thyroid gland, Tc-99m pertechnetate thyroid uptake
and previous surgical treatment was found (p values = 0.436, 0.225 and 0.361
respectively). Eleven from the 50 non responded patients in the second group were
received second dose 8 mCi while the other 39 patients received 12 mCi. There was no
statistically significant difference in the response rate between the patients received 8
mCi (90.9 %) and 12 mCi (384.6 %) with P value = 0.595 and no statistically significant
difference in the response rate in relation to size of thyroid gland, Tc99m pertechnetate
thyroid uptake and previous surgical treatment (p values = 0.418, 0.117 and 0.471
respectively). Thirteen patients from the remaining 16 non responders to the second dose
responded to the 3rd RAI-131 dose with development of euthyroidism in 7 patients (43.8
%) and hypothyroidism in the remaining 6 patients (37.5%). The 4th dose controlled the
remaining 3 patients with development of hypothyroidism in 2 patients and euthyroidism
in the third.
The median dose for controlling GD was 12 mCi (minimum 8 mCi which controlled
23.7% of the patients and maximum 47 mCi), the doses of 12 mCi, 16 mCi, 20 mCi, 24
mCi, 28 mCi, 32 mCi, 36 mCi, 43 mCi and 47 mCi increase the overall control rate to
59.8 %, 74.1%, 85%, 96%, 96.9%, 97.8%, 99.4%, 99.7% and 100% respectively as
shown in table 7. The mean dose number for controlling the hyperthyroidism was 1.46 ±
0.62 (range 1- 4). The first dose controlled 59.8% of the patients, this percent increased to
95% after the second dose, 99.1% following the third one and 100% after the fourth dose
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as shown in table 8.
Discussion: About 80% of experts from Europe preferred to start treatment with ATDs in
patients over 21 years and 70% of those in the United States RAI is the initial treatment
modality of choice (21). In Egypt the ATDs represent, for most endocrinologists, the
initial choice of treatment. This trend was reflected in the present study, where only
22.4% of the patients underwent RAI as initial treatment modality, while 77.6% patients
were previously treated with ATDs.
The influence of ATDs on the outcome of RAI treatment has received attention. Some
studies have suggested that ATD treatment before or after RAI may provide a
radioprotective effect for the thyroid with significantly shortened the biological half-life
of RAI result in reduction of the absorbed dose and increased failure rate of single-dose
RAI treatment (16-17) (22). Thionamide withdrawal was among the predictive factors for
treatment success in a 10-mCi fixed-dose approach (23). More over Alexander et al.
treated 261 Graves’ patients with a mean dose of 14.6 mCi of RAI demonstrated high
risk of treatment failure in patients pretreated with anti-thyroid medications for greater
than 4 months(12). Other studies stated that this effect confined to the use of
propylthiouracil only (18). In contrast Braga et al. (24) and Andrade et al. (25)
demonstrated that methimazole pretreatment has no effect on the final treatment result,
including the time required for cure
or the 1-year success rate of
RAI therapy.
Thientunyakit T et al. (26) showed that duration of anti-thyroid drug given prior to
radioiodine therapy seemed not related to the treatment outcome. Moura-Neto also found
that no statistically significant association between thyroid function outcome to a fixed,
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15 mCi approach for treatment of Graves’ hyperthyroidism and drug used (methi-mazole
or propylthiouracil; maintenance or withdrawal of thionamides prior to therapy (27). Our
results were in agreement with the later ones, where we don’t find statistical significant
difference between pre-iodine medical treatment or its duration and the outcome to RAI131 therapy.
Surgery is no longer recommended as first-line therapy for GD and use in selective
cases where RAI is not preferred and ATDs fail to control the disease(3). Lal et al.
concluded that total thyroidectomy (TT) is much better than Subtotal thyroidectomy
(STT) (28). In the present study, STT was performed in only 49 patients (15.3%) with
recurrent of disease in all of them at a median period of 66 months, confirming the
literature data of using it as an alternative option in selected patients.
The size of thyroid gland is an important factor influencing the outcome of therapy; In
our study, mildly enlarged glands had more controlled rate than moderate or markedly
enlarged thyroid gland with higher incidence of hypothyroidism ( P = 0.042). This result
is in agreement with the other multiple studies which have demonstrated that patients
with larger-volume thyroid glands to fail to respond to a single dose of radioiodine (2327-29-30-31-32).
The impact of thyroid uptake on the RAI outcome has been investigated using either 131I
or Tc99m pertechnetate. Alexander et al (12) found that patients who have higher 24hour thyroid RAI uptake values were at higher risk than others for treatment failure.
Kung et al. (32) also identified 4-hour RAI uptake among the variables that could predict
early treatment outcome for Graves’ disease. These results were in agreement with other
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works demonstrating higher failure rates in patients with higher iodide thyroid uptake
values which could reflect faster iodide turnover in thyroid cells thus making the
residence time of therapeutic I-131 in the gland shorter (33). The authors suggested that a
higher radioactivity of RAI be given to these patients.
Using Tc99-m sodium
pertechnetate Zantut-Wittmann et al. (23) have reported that in a 10 mCi fixed dose
approach the pre-RIT Tc99-m sodium pertechnetate uptake under 12% among the
predictive factors for treatment success. In contrast, Moura-Neto et al. stated that no
statistically significant association between thyroid function outcome to a fixed 15 mCi
approach for treatment of GD and Tc-99m sodium pertechnetate thyroid uptake prior to
therapy(27). Tc-99 m pertechnetate uptake is routinely used in our department as a
surrogate measure of thyroid uptake because it has been proved to possess a good
correlation with iodide 125 uptake (34). Moreover, it is much less expensive, reliable and
convenient method allows uptake within 20 minutes after intravenous injection of the
radionuclide and the therapeutic dose of RAI can be administered immediately after. We
found that Tc-99m pertechnetate thyroid uptake more than 20.9% was among the poor
prognostic factors for the response, thus higher dose is recommended.
The different RAI doses have different impact on the thyroid gland function, less than
half of the patients (49%) in group 1 who received low dose of RAI achieved cure. On
the other hand 69.4 % from the second group, who received higher dose of RAI, had
achieved cure. This means that higher dose of RAI increase response rate by ~ 20.4 %.
Franklyn et al.(35) and Sankar et al.(36) studied the therapeutic outcome of low fixed
dose of RAI, the former concluded that persistent hyperthyroidism after 6 months was
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present in 55.9% of the patients using small fixed dose of 5 mCi of RAI and the latter
recommended increase dose of RAI to achieve response. This agree with Nordyke and
Gilbert (29) who analyzed a series of 605 patients treated with RAI to find out the
optimal dose to achieve cure and they concluded that cure was directly related to the dose
of RAI administered and the optimal dose for curing hyperthyroidism is approximated by
starting with 10 mCi and increasing it for unusually large glands or for special patient
circumstances.
In the present study, 88% of patients achieved cure after administration of second dose
of RAI with no statistically significant difference was found between the success rate and
the given dose, only few patients require 3rd or 4th doses. This is in concordant with
Sanyal et al. (37) and Franklyn et al. (35) studies that demonstrated high cure rate to
the second dose of RAI ( 82.4% and 74.5% respectively) with only few require other
doses.
Although it is very rare, McDermott et al.(38) reported thyroid storm in a small number
of patients between 1 and 14 days after treatment with RAI. In the present study thyroid
storm did not encountered in any patient. Also, Levy et al.(39) in a series of 7000 patients
treated with RAI in one centre, none developed this complication. Ponto et al. (40)
concluded that RAI therapy for GD is associated with definite increased risk of GO in
around 20% of patients (either developing new cases or worsening of preexisting one).
However In the present work there was worsening of exophtalmus in 9.6 % of the
patients and three new cases were developed (1.3%) among the rest who did not have
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prior exopthalmos, they were among the 177 patients who developed permanent
hypothyroidism.
Conclusion: Radioiodine is clearly successful in curing hyperthyroidism in GD patients
by 100 % after 4 doses; therefore it should be used as a first standard line in treatment.
Treatment results using fixed RAI dose are comparable to those studies of patients treated
with RAI using the prescribed absorbed dose method. The standard-dose prescription
strategy is therefore an efficient, cost-effective and is also convenient to the patient. It
may be possible to improve cure rates using a single fixed-dose regimen without
increasing the dose in all patients. This might be achieved by the identification of
subjects with poor prognostic factors who are unlikely to respond to standard doses and
by administering larger doses only to these individuals. A higher fixed (12 mCi) is more
effective than lower dose (8 mCi) for treatment of GD leading to better control of the
disease following the first dose. Higher response rate are expected in patients who
underwent previous surgery, on contrary patients with larger goiters and high thyroid
uptake > 20.9% had 3.3 and 4 times less chance of remission. This different impact of
different doses on the response rate is applied to the first dose, but not to the second dose
where the response rate to the second dose is nearly similar in both low and high dose
groups.
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[21]. Wartofsky, L, Glinoer, D, Solomon, B, Nagataki, S, Lagasse, R, Nagayama, Y ,et al.
Differences and similarities in the diagnosis and treatment of Graves' disease in Europe, Japan,
and the United States. Thyroid 1991; 1:129-135.
[22]. Hancock, LD, Tuttle, RM, LeMar, H, Bauman, J and Patience, T. The effect of
propylthiouracil on subsequent radioactive iodine therapy in Graves' disease. Clinical
endocrinology 1997; 47:425-430.
[23]. Zantut-Wittmann, DE, Ramos, CD, Santos, AO, Lima, MM, Panzan, AD, Facuri, FV, et al.
High pre-therapy [99mTc]pertechnetate thyroid uptake, thyroid size and thyrostatic drugs:
predictive factors of failure in [131I]iodide therapy in Graves' disease. Nuclear medicine
communications 2005; 26:957-963.
17
18
[24]. Braga, M, Walpert, N, Burch, HB, Solomon, BL and Cooper, DS. The effect of
methimazole on cure rates after radioiodine treatment for Graves' hyperthyroidism: a
randomized clinical trial. Thyroid 2002; 12:135-139.
[25]. Andrade, VA, Gross, JL and Maia, AL. The effect of methimazole pretreatment on the
efficacy of radioactive iodine therapy in Graves' hyperthyroidism: one-year follow-up of a
prospective, randomized study. The Journal of clinical endocrinology and metabolism 2001;
86:3488-3493.
[26]. Thientunyakit, T, Thongmak, S and Premprapha, T. Comparative evaluation of two
different dosage calculation protocols of iodine-131 in the treatment of hyperthyroidism. Journal
of the Medical Association of Thailand 2010; 93:969-977.
[27]. Moura-Neto, A, Mosci, C, Santos, AO, Amorim, BJ, de Lima, MC, Etchebehere, EC, et al.
Predictive factors of failure in a fixed 15 mCi 131I-iodide therapy for Graves' disease. Clinical
nuclear medicine 2012; 37:550-554.
[28]. Lal, G, Ituarte, P, Kebebew, E, Siperstein, A, Duh, QY and Clark, OH. Should total
thyroidectomy become the preferred procedure for surgical management of Graves' disease?.
Thyroid 2005; 15:569-574.
[29]. Nordyke, RA and Gilbert FI, Jr. Optimal iodine-131 dose for eliminating hyperthyroidism
in Graves' disease. Journal of nuclear medicine 1991; 32:411-416.
[30]. Watson, AB, Brownlie, BE, Frampton, CM, Turner, JG and Rogers, TG. Outcome
following standardized 185 MBq dose 131I therapy for Graves' disease. Clinical endocrinology
1988; 28:487-496.
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[31]. Allahabadia,A, Daykin, J, Sheppard, MC, Gough, SC and Franklyn, JA. Radioiodine
treatment of hyperthyroidism-prognostic factors for outcome. The Journal of clinical
endocrinology and metabolism 2001; 86:3611-3617.
[32]. Kung, AW, Choi, P, Lam, KS, Pun, KK, Wang, C and Yeung, RT. Discriminant factors
affecting early outcome of radioiodine treatment for Graves' disease. Clinical radiology 1990;
42:52-54.
[33]. Murakami, Y, Takamatsu, J, Sakane, S, Kuma, K and Ohsawa N. Changes in thyroid
volume in response to radioactive iodine for Graves' hyperthyroidism correlated with activity of
thyroid-stimulating antibody and treatment outcome. The Journal of clinical endocrinology and
metabolism 1996; 81:3257-3260.
[34]. Dige-Petersen, H, Kroon, S, Vadstrup, S, Andersen, ML, and Roy-Poulsen, NOA. A
comparison of 99Tc and 123I scintigraphy in nodular thyroid disorders. European journal of
nuclear medicine 1978; 3:1-4.
[35]. Franklyn, JA, Daykin, J, Holder, R and Sheppard, MC. Radioiodine therapy compared in
patients with toxic nodular or Graves' hyperthyroidism. QJM 1995; 88:175-180.
[36]. Sankar, R, Sekhri, T, Sripathy, G, Walia, RP and Jain, SK. Radioactive iodine therapy in
Graves' hyperthyroidism: a prospective study from a tertiary referral centre in north India. The
Journal of the Association of Physicians of India 2005; 53:603-606.
[37]. Sanyal, D, Mukhhopadhyay, P, Pandit, K, Chatterjee, J, Raychaudhuri,M, Mukherjee, S , et
al. Early treatment with low fixed dose (5 mCi) radioiodine therapy is effective in Indian subjects
with Graves' disease. Journal of the Indian Medical Association 2008; 106:360-361, 372.
[38]. McDermott, MT, Kidd, GS, Dodson LE, Jr and Hofeldt, FD. Radioiodine-induced thyroid
storm. Case report and literature review. The American Journal of Medicine 1983; 75:353-359.
19
20
[39]. Levy, WJ, Schumacher, OP and Gupta, M. Treatment of childhood Graves' disease. A
review with emphasis on radioiodine treatment. Cleveland Clinic journal of medicine 1988;
55:373-382.
[40]. Ponto, KA, Zang, S and Kahaly, GJ. The tale of radioiodine and Graves' orbitopathy.
Thyroid 2010; 20:785-793.
Figure Legend
Figure 1: ROC curve for Tc 99m pertechnetate thyroid scan uptake according to response
to 1st dose.
20
Response to Reviewers
The reason for choose a higher dose of 12 mCi because the protocol in our institution is to give a
maximum dose of 12 mCi in Graves` disease patients.
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1
Response rate and factors affecting outcome of fixed dose of RAI131
therapy in Graves` disease: A 10 year Egyptian experience
Maha Abd El-Kareem M.D, Wajeeh Abdulrazak Derwish M.sc and Hosna Mohamed
Moustafa M.D
Department of radiotherapy and nuclear medicine (NEMROCK), Nuclear medicine
unit, Cairo University.
Abstract
Purpose: Evaluate response and compare success rate of two different doses of I-131
therapy in treatment of Graves` disease and investigate the factors that may affect
outcome.
Patient and methods: Retrospective analysis was performed on 321 patients treated with
I-131 for Graves` disease. Group 1 (155 patients) received 8 mCi and Group 2 (166
patients) received 12 mCi. The therapy was considered successful if euthyroidism or
hypothyroidism was achieved within one year of therapy. The outcome was compared
with multiple parameters.
Results: Significant difference in the outcome between the two groups was found in favor
of the second group (P<0.001). Logistic regression analysis revealed that lower dose, Tc99 pertechnetate thyroid uptake > 20.9 %, moderate and marked goiter were independent
variables that significantly associated with less response rate (OR 2.601, 4.023 and 3.309
respectively), while prior surgical treatment with higher response rate (OR 3.071). No
correlation between outcome and age, presence of exopthalomos, previous treatment with
1
2
methimazole and its duration was found. Response rate to the second dose was
significantly increased compared to the first one by 27.8 %, there was no correlation
among the above mentioned factors and its outcome. The third dose controlled 81.3 % of
the remaining patients and the rest were achieved controlled after the fourth dose.
Conclusions: I-131 is very effective therapy for Graves` disease with cure rate 100%
after 4 doses. Higher first dose activity is recommended in the presence of poor
prognostic factors. Second dose is not necessary increased in the non responders.
Keywords: Graves` disease; radioactive iodine therapy; fixed dose- Tc-99 pertechnetate
thyroid uptake.
Introduction: Graves` disease (GD) is the most common cause of hyperthyroidism
responsible for approximately 50-60% of the cases (1). The most common clinical
presentations related to the cardiovascular system. Other disease manifestations include
Graves’ ophthalmopathy and myxedema(2). Diagnostic modalities include suppressed
serum TSH and an elevated serum FT4, FT3 levels, thyroid scintigraphy either with Tc99m pertechnetate or radioactive iodine-131 (RAI-131) and ultrasonography (U.S) to
detect the presence of an associated nodules (3). Three therapeutic modalities are
commonly used today; anti-thyroid drugs (ATDs), RAI-131 and surgical treatment (3).
The aim of RAI -131 treatment is to cure the hyperthyroidism by rendering the patient
either euthyroid or hypothyroid through destruction of the over-functioning thyroid
tissues (4). The use of RAI-131 in treatment of GD is increasing, particularly as a first
line treatment (5) as it is easy to administer, relatively inexpensive, reliable , safe and
highly effective with a cure rate approaching 100% after one or more dose (6) . Different
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3
methods have been used for determining the administered activity, varied from fixed
doses to adjusted calculations based on gland size, iodine uptake and turnover (7). The
dose calculation method aims to optimize the therapeutic results through administration
of radioactive iodine in proportional to the size of the gland, increasing the probability of
cure and providing the lowest possible radiation dose to the rest of the body (8). There is
little evidence that using a calculated dose has any advantage over a fixed-dose regimen
in preventing hypothyroidism or improvement in cure rate (9), but it increases
significantly the cost of the therapy owing to increase the procedure complexity (10).
Taking in mind that the radioactive iodine therapy is relatively inexpensive, thus the
increase in its cost to determine the administered activity must be clearly justified (10).
There are some predictive factors associated with RAI-131 success rate. Previous works
have shown lower treatment success rates in young male patients, more severe cases of
hyperthyroidism (11)(12) , larger goiters (12) (13) and in cases with low or high
pretreatment thyroid uptake (12) (14). The influence of pretreatment with anti-thyroid
drugs on the efficacy of radioiodine therapy is controversial. Some authors believe that
the thyrostatic drugs methimazole (MMI) and propylthiouracil (PTU) have a radioresistance effect and can lead to half-life reduction and accelerate turnover (15) (16) (17),
but others have shown an effect confined to PTU only (18).
Patients and Methods: We retrospectively evaluated 321 hyperthyroid patients due to
GD referred to the nuclear medicine unit, Kasr Al ainy hospital (NEMROK), Cairo
University, during the period of January 2000 till January 2010 for RAI-131 therapy as
first or as a second treatment modality (following medical or surgical treatment). Our
3
4
institutional medical ethics committee approved the protocol. The diagnosis of GD was
primarily based on clinical (hyperthyroid manifestations and diffusely enlarged thyroid
gland) and laboratory data, including high serum free T4 level (FT4; reference Values,
RV = 0.9 - 1.8 ng/dL) and low serum thyrotropin levels (TSH; RV = 0.41- 4.5 µ IU/mL).
The patients who had thyrotoxicosis due to toxic multi-nodular goiter (Plummer disease),
toxic autonomous adenoma, GD associated with (cold) nodule by (scan) or palpation
respectively and patients who not completed the follow up were excluded from the study.
Data were retrieved from the thyroid clinic database include: age at diagnosis, gender,
symptoms, dose and duration of anti-thyroid drugs , previous surgical treatment, clinical
data for the presence of palpable nodules & other neck swellings and the presence or
absence of eye signs, TSH level and thyroid scan using Tc-99m pertechnetate that was
done 20 min after intravenous injection of 5 mCi of the tracer to evaluate the associated
nonfunctioning (cold) nodule and quantitation of thyroid uptake using the methodology
previously described by Maisey et al(19) and simplified for routine use. The reference
values for Tc-99m pertechnetate uptake range from 0.3 to 4 % (20). Gland size were
determined by combining clinical examination (palpation) and thyroid scan and was
divided in to either normal size (impalpable), mild (palpably enlarged but not visible) and
moderate or markedly enlargement (palpable and visible goiter). In view of our socioeconomical circumstances; the simple fixed dose protocol has considerable cost saving
advantages, we have adopted this protocol for the treatment of GD in our institution. The
patients were divided according to the given RAI-131 dose in to 2 groups: Group 1:
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5
received 8 mCi (155 patients) (48.3%) and Group 2: received 12 mCi (166 patients)
(51.7%), they are the commonly preferred doses in the treatment of GD in our institute.
Anti-thyroid drugs, if given before therapy, were withdrawn a week before therapy and
for a minimum of 1 week after to avoid any drug influence on the therapeutic
effectiveness. Iodine-containing medications were also discontinued several weeks before
therapy; in addition, the patients were started on a low-iodine diet for 10 days before
therapy, fasted before and for 2 hours after the administration of the dose to achieve
higher absorption. Patients were advised to avoid physical contact and transfer of
secretions to others for several days after treatment. Regular clinical and laboratory
follow up to evaluate therapeutic efficacy was done and the patients were classified
according to the outcome in to: Euthyroidism: Absence of signs or symptoms of
hyperthyroidism or hypothyroidism with normal serum TSH value without levothyroxin
therapy. Resistant to therapy: persistence of thyrotoxic manifestation and suppressed
TSH value or by requirement of repeat administration of RAI-131 therapy within 6
months of the therapy and Hypothyroidism: presence of symptoms or signs of
hypothyroidism together with elevated TSH value on two occasions four weeks apart,
that require permanent treatment with levothyroxine. RAI-131 treatment was considered
to be successful if the patient was either euthyroid or hypothyroid.
Statistical methods: Data was analyzed using IBM SPSS advanced statistics version 20
(SPSS Inc., Chicago, IL). Numerical data were expressed as mean and standard deviation
or median and range as appropriate. Qualitative data were expressed as frequency and
percentage. Chi-square test (Fisher’s exact test) was used to examine the relation between
5
6
qualitative variables. For quantitative data, comparison between two groups was done
using Mann-Whitney test (non-parametric t-test). The receiver operator characteristic
(ROC) curve was used to identify the best threshold for thyroid uptake to discriminate
success and failure of RAI-131 therapy. Multivariate analysis was done using forward
stepwise logistic regression method for the significant factors affecting response on
univariate analysis. Odds ratio (OR) with 95% confidence interval (CI) were used for risk
estimation. P-value < 0.05 was considered significant.
Results:.
Baseline, pre-therapy clinical characteristics and commonly presenting
symptoms for the patients are listed in Table 1 and 2. The recorded data documented
development of early complications within the 1st 3 months in 31 patients (9.6%),
included transient mild increased thyrotoxic manifestations in 21 patients and transient
hypothyroidism which occurred for 8 patients, 5 after a high dose and 3 after low dose.
Six of the 8 patients developed transient hypothyroidism after 1st dose, while the
remaining 2 patients developed it after 2nd dose. Also neck pain developed in 2 patients.
There was statistically significant difference in the incidence of early complications
between the patients who received 8 mCi and the second group who received 12 mCi, in
favor of the latter group (p = 0.024), whereas as there was no statistically significant
difference between age, gender, presence of exopthaloms, size of thyroid gland and
thyroid uptake and early complications either between the two groups as shown in the
table (3) or in each group separately (not included).
Exopthalmos was increased in 9 patients (9.6%) after RAI-131 therapy and remained
stationary in rest. Three new cases (1.3%) developed exophthalmos from the remaining
6
7
227 patients and they were among the 170 patients who had permanent hypothyroidism
(1.7%). No relation was found between the presence of exopthalmos and development of
early complications as shown in tables 3.
The success rate to the first given dose was 59.8% with development of euthyroidism in
56 patients (17.4%) and hypothyroidism in 136 patients (42.4%). There was statistically
significant difference in the successes rate between the patients who received 8 mCi
(49%) and 12 mCi (69.9%) P <0.001. Of the 76 patients in whom therapy was successful
in group1, 25 (16.1%) developed euthyroidism and 51(32.9 %) developed
hypothyroidism and at a median period of 6 months (range: 3 –18 months) and among the
116 responding patients in the second group, euthyroidism was achieved in 37 patients
(22.3%) and hypothyroidism in 79 patients (47.6%) with a median cure time 4 months
(range: 2 –18 months).
There was no statistically significant association between age, presence of
ophthalmopathy and previous medical treatment & its duration and outcome, whereas
there was statistically significant difference regarding gender, size of thyroid gland,
Tc99m pertechnetate thyroid uptake and previous surgical treatment as demonstrated in
table 4. We did not find any relationship between the previous use of methimazole & its
duration and the outcome of patients either in the whole study population or G1 and G2
separately (tables 4 and 5 A&B).
Thyroid uptake was analyzed using ROC curve to discriminate the group of patients who
achieved success with treatment from the group that remained hyperthyroid and we found
a thyroid uptake threshold of 20.9 % with a sensitivity of 76.1 % and specificity of 65.4
7
8
% for treatment success (Fig. 1). We were unable to find an adequate cutoff value for
base line TSH level.
Multiple logistic regression analysis demonstrated that age, gender and previous medical
treatment were not significantly associated with the outcome, whereas Tc99m
pertechnetate thyroid uptake > 20.9% (OR= 4.023) , moderate and markedly enlarged
thyroid gland (OR= 3.309) and the low given dose (OR= 2.601) were identified as
significant prognostic risk factors for treatment failure and previous thyroidectomy for
treatment success (OR= 3.071) (odds ratio; 95% confidence interval = 2.218 -7.297,
1.707 - 6.414, 1.403 - 4.822 and 1.109 - 8.502 respectively).
Response to the second dose: A second dose was given to the 129 non responded
patients after a mean time of 6.77 months (minimum 3 months and maximum 12
months). Of these 63 patients received 8 mCi and 66 received 12 mCi. The overall
response rate to the second therapy dose significantly increased compared to the first one
by 27.8 % with development of euthyroidism in 56 patients (17.4%) and hypothyroidism
in 136 patients (42.4%). There was no statistically significant difference in the response
rate between the patients who received 8 mCi and who received 12 mCi (P value =
0.921), also there was no statistically significant difference in the response rate in relation
to size of thyroid gland, Tc99m pertechnetate thyroid uptake, previous surgical treatment,
age and gender (p values 0.265, 0.665, 0.242, 0.209 and 0.923 respectively) as shown in
table 6.
Fifty two patients from the 79 non responded in the first group received second dose of 8
mCi while the remaining 27 patients received 12 mCi.
8
There was no statistically
9
significant difference in the response rate between the patients received 8 mCi (86%) and
12 mCi (92.6 %) with P value = 0.422. No statistically significant difference in the
response rate in relation to size of thyroid gland, Tc-99m pertechnetate thyroid uptake
and previous surgical treatment was found (p values = 0.436, 0.225 and 0.361
respectively). Eleven from the 50 non responded patients in the second group were
received second dose 8 mCi while the other 39 patients received 12 mCi. There was no
statistically significant difference in the response rate between the patients received 8
mCi (90.9 %) and 12 mCi (384.6 %) with P value = 0.595 and no statistically significant
difference in the response rate in relation to size of thyroid gland, Tc99m pertechnetate
thyroid uptake and previous surgical treatment (p values = 0.418, 0.117 and 0.471
respectively). Thirteen patients from the remaining 16 non responders to the second dose
responded to the 3rd RAI-131 dose with development of euthyroidism in 7 patients (43.8
%) and hypothyroidism in the remaining 6 patients (37.5%). The 4th dose controlled the
remaining 3 patients with development of hypothyroidism in 2 patients and euthyroidism
in the third.
The median dose for controlling GD was 12 mCi (minimum 8 mCi which controlled
23.7% of the patients and maximum 47 mCi), the doses of 12 mCi, 16 mCi, 20 mCi, 24
mCi, 28 mCi, 32 mCi, 36 mCi, 43 mCi and 47 mCi increase the overall control rate to
59.8 %, 74.1%, 85%, 96%, 96.9%, 97.8%, 99.4%, 99.7% and 100% respectively as
shown in table 7. The mean dose number for controlling the hyperthyroidism was 1.46 ±
0.62 (range 1- 4). The first dose controlled 59.8% of the patients, this percent increased to
95% after the second dose, 99.1% following the third one and 100% after the fourth dose
9
10
as shown in table 8.
Discussion: About 80% of experts from Europe preferred to start treatment with ATDs in
patients over 21 years and 70% of those in the United States RAI is the initial treatment
modality of choice (21). In Egypt the ATDs represent, for most endocrinologists, the
initial choice of treatment. This trend was reflected in the present study, where only
22.4% of the patients underwent RAI as initial treatment modality, while 77.6% patients
were previously treated with ATDs.
The influence of ATDs on the outcome of RAI treatment has received attention. Some
studies have suggested that ATD treatment before or after RAI may provide a
radioprotective effect for the thyroid with significantly shortened the biological half-life
of RAI result in reduction of the absorbed dose and increased failure rate of single-dose
RAI treatment (16-17) (22). Thionamide withdrawal was among the predictive factors for
treatment success in a 10-mCi fixed-dose approach (23). More over Alexander et al.
treated 261 Graves’ patients with a mean dose of 14.6 mCi of RAI demonstrated high
risk of treatment failure in patients pretreated with anti-thyroid medications for greater
than 4 months(12). Other studies stated that this effect confined to the use of
propylthiouracil only (18). In contrast Braga et al. (24) and Andrade et al. (25)
demonstrated that methimazole pretreatment has no effect on the final treatment result,
including
the time required for cure
or the 1-year success rate of
RAI therapy.
Thientunyakit T et al. (26) showed that duration of anti-thyroid drug given prior to
radioiodine therapy seemed not related to the treatment outcome. Moura-Neto also found
that no statistically significant association between thyroid function outcome to a fixed,
10
11
15 mCi approach for treatment of Graves’ hyperthyroidism and drug used (methi-mazole
or propylthiouracil; maintenance or withdrawal of thionamides prior to therapy (27). Our
results were in agreement with the later ones, where we don’t find statistical significant
difference between pre-iodine medical treatment or its duration and the outcome to RAI131 therapy.
Surgery is no longer recommended as first-line therapy for GD and use in selective
cases where RAI is not preferred and ATDs fail to control the disease(3). Lal et al.
concluded that total thyroidectomy (TT) is much better than Subtotal thyroidectomy
(STT) (28). In the present study, STT was performed in only 49 patients (15.3%) with
recurrent of disease in all of them at a median period of 66 months, confirming the
literature data of using it as an alternative option in selected patients.
The size of thyroid gland is an important factor influencing the outcome of therapy; In
our study, mildly enlarged glands had more controlled rate than moderate or markedly
enlarged thyroid gland with higher incidence of hypothyroidism ( P = 0.042). This result
is in agreement with the other multiple studies which have demonstrated that patients
with larger-volume thyroid glands to fail to respond to a single dose of radioiodine (2327-29-30-31-32).
The impact of thyroid uptake on the RAI outcome has been investigated using either 131I
or Tc99m pertechnetate. Alexander et al (12) found that patients who have higher 24hour thyroid RAI uptake values were at higher risk than others for treatment failure.
Kung et al. (32) also identified 4-hour RAI uptake among the variables that could predict
early treatment outcome for Graves’ disease. These results were in agreement with other
11
12
works demonstrating higher failure rates in patients with higher iodide thyroid uptake
values which could reflect faster iodide turnover in thyroid cells thus making the
residence time of therapeutic I-131 in the gland shorter (33). The authors suggested that a
higher radioactivity of RAI be given to these patients.
Using Tc99-m sodium
pertechnetate Zantut-Wittmann et al. (23) have reported that in a 10 mCi fixed dose
approach the pre-RIT Tc99-m sodium pertechnetate uptake under 12% among the
predictive factors for treatment success. In contrast, Moura-Neto et al. stated that no
statistically significant association between thyroid function outcome to a fixed 15 mCi
approach for treatment of GD and Tc-99m sodium pertechnetate thyroid uptake prior to
therapy(27). Tc-99 m pertechnetate uptake is routinely used in our department as a
surrogate measure of thyroid uptake because it has been proved to possess a good
correlation with iodide 125 uptake (34). Moreover, it is much less expensive, reliable and
convenient method allows uptake within 20 minutes after intravenous injection of the
radionuclide and the therapeutic dose of RAI can be administered immediately after. We
found that Tc-99m pertechnetate thyroid uptake more than 20.9% was among the poor
prognostic factors for the response, thus higher dose is recommended.
The different RAI doses have different impact on the thyroid gland function, less than
half of the patients (49%) in group 1 who received low dose of RAI achieved cure. On
the other hand 69.4 % from the second group, who received higher dose of RAI, had
achieved cure. This means that higher dose of RAI increase response rate by ~ 20.4 %.
Franklyn et al.(35) and Sankar et al.(36) studied the therapeutic outcome of low fixed
dose of RAI, the former concluded that persistent hyperthyroidism after 6 months was
12
13
present in 55.9% of the patients using small fixed dose of 5 mCi of RAI and the latter
recommended increase dose of RAI to achieve response. This agree with Nordyke and
Gilbert (29) who analyzed a series of 605 patients treated with RAI to find out the
optimal dose to achieve cure and they concluded that cure was directly related to the dose
of RAI administered and the optimal dose for curing hyperthyroidism is approximated by
starting with 10 mCi and increasing it for unusually large glands or for special patient
circumstances.
In the present study, 88% of patients achieved cure after administration of second dose
of RAI with no statistically significant difference was found between the success rate and
the given dose, only few patients require 3rd or 4th doses. This is in concordant with
Sanyal et al. (37) and Franklyn et al. (35) studies that demonstrated high cure rate to
the second dose of RAI ( 82.4% and 74.5% respectively) with only few require other
doses.
Although it is very rare, McDermott et al.(38) reported thyroid storm in a small number
of patients between 1 and 14 days after treatment with RAI. In the present study thyroid
storm did not encountered in any patient. Also, Levy et al.(39) in a series of 7000 patients
treated with RAI in one centre, none developed this complication. Ponto et al. (40)
concluded that RAI therapy for GD is associated with definite increased risk of GO in
around 20% of patients (either developing new cases or worsening of preexisting one).
However In the present work there was worsening of exophtalmus in 9.6 % of the
patients and three new cases were developed (1.3%) among the rest who did not have
13
14
prior exopthalmos, they were among the 177 patients who developed permanent
hypothyroidism.
Conclusion: Radioiodine is clearly successful in curing hyperthyroidism in GD patients
by 100 % after 4 doses; therefore it should be used as a first standard line in treatment.
Treatment results using fixed RAI dose are comparable to those studies of patients treated
with RAI using the prescribed absorbed dose method. The standard-dose prescription
strategy is therefore an efficient, cost-effective and is also convenient to the patient. It
may be possible to improve cure rates using a single fixed-dose regimen without
increasing the dose in all patients. This might be achieved by the identification of
subjects with poor prognostic factors who are unlikely to respond to standard doses and
by administering larger doses only to these individuals. A higher fixed (12 mCi) is more
effective than lower dose (8 mCi) for treatment of GD leading to better control of the
disease following the first dose. Higher response rate are expected in patients who
underwent previous surgery, on contrary patients with larger goiters and high thyroid
uptake > 20.9% had 3.3 and 4 times less chance of remission. This different impact of
different doses on the response rate is applied to the first dose, but not to the second dose
where the response rate to the second dose is nearly similar in both low and high dose
groups.
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Figure Legend
Figure 1: ROC curve for Tc 99m pertechnetate thyroid scan uptake according to response
to 1st dose.
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