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Original Article
Thyroid Comparison of Thyroid Size-Specific Radioiodine Dose and New Modified Dose Calculation in the Treatment of Graves’ Disease
Keypoint
Patients with Graves' disease who do not meet the criteria of radioiodine ablation should have a chance of achieving euthyroidism.
A calculated-dose method delivering a specified radiation dose to the thyroid is optimal, but this method is more costly and inconvenient for some institutions.
The fixed-dose method can serve as an acceptable alternative, but there is a lack of consensus on the optimal radioiodine activity.
The new modified protocols for use in fixed-dose treatment in this study achieved a good therapeutic outcome in patients with thyroids smaller than 75.0 g.
Alisara Wongsuttilert1orcid, Ruchirek Thamcharoen2, Yoswanich Maiprasert3, Sathapakorn Siriwong3orcid
Endocrinology and Metabolism 2024;39(5):758-766.
DOI: https://doi.org/10.3803/EnM.2024.1950
Published online: October 14, 2024

1Department of Radiology and Nuclear Medicine, Faculty of Medicine, Burapha University, Chonburi, Thailand

2Department of Internal Medicine, Queen Sirikit Hospital, Chonburi, Thailand

3Department of Medicine, Queen Savang Vadhana Memorial Hospital, Thai Red Cross Society, Chonburi, Thailand

Corresponding author: Sathapakorn Siriwong. Department of Medicine, Queen Savang Vadhana Memorial Hospital, Thai Red Cross Society, 290 Chermchomphon Road, Si Racha District, Chonburi 20110, Thailand Tel: +66-3832-0200, Fax: +66-3831-1008, E-mail: sathapakorn@somdej-mec.or.th
• Received: January 24, 2024   • Revised: April 3, 2024   • Accepted: July 9, 2024

Copyright © 2024 Korean Endocrine Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Background
    Previous studies of fixed-dose radioiodine therapy (RIT) for Graves’ disease (GD) have utilized a variety of techniques and reported differing success rates. This study sought to compare the efficacy of RIT using two fixed-dose protocols and to estimate the optimal radioiodine (RAI) activity for the treatment of GD.
  • Methods
    This retrospective trial enrolled 658 patients with GD who received RIT between January 2014 and December 2021. Participants were divided into two groups: protocol 1, which utilized a thyroid size-specific RAI dose, and protocol 2, which employed a modified dose calculation approach. The primary outcome assessed was the presence of euthyroidism or hypothyroidism at the 6-month follow-up. The success rates of RIT were compared between the two protocols.
  • Results
    The RIT success rate was marginally lower for protocol 2 than for protocol 1 (63.6% vs. 67.2%); however, the risk of treatment failure did not differ considerably between the groups (relative risk, 1.1089; 95% confidence interval, 0.8937 to 1.3758; P=0.3477). The median RAI activity associated with protocol 2 was lower than that for protocol 1 (10.7 mCi vs. 15.0 mCi, P=0.0079), and the frequency of hypothyroidism was significantly lower in the protocol 2 group (39.0% vs. 48.9%, P=0.0117).
  • Conclusion
    The success rate of the modified dose calculation protocol was comparable to that of the thyroid size-specific RAI dose protocol. The former approach reduced RAI activity and the incidence of hypothyroidism following RIT without compromising the success rate.
Graves’ disease (GD) is an autoimmune disorder that targets thyroid cells and represents the most prevalent form of hyperthyroidism. The annual incidence of GD is estimated at 20 to 30 cases per 100,000 individuals, with rates of 3.0% in females and 0.5% in males [1,2]. The primary goal of GD treatment is to normalize thyroid hormone levels. If unresolved, hyperthyroidism increases the risk of mortality from cardiovascular disease, thyroid storm, and other serious conditions [2]. Most patients with GD are treated with radioiodine therapy (RIT) or undergo total thyroidectomy (TT). However, TT carries the risk of serious complications, including recurrent laryngeal nerve palsy, hypoparathyroidism, wound infection, and hemorrhage [3]. Sundaresh et al. [4] reported that RIT is the most common treatment modality due to its superior safety and efficacy. Donovan et al. [5] conducted a cost-utility analysis comparing RIT, antithyroid drugs (ATDs), and TT as first-line treatments for GD, concluding that RIT is the most cost-effective option. A recent survey on GD management among clinicians in Asia and the Pacific region revealed a preference for RIT (19%) over surgery (2%) [6]. RIT offers the convenience of outpatient administration through self-administered capsules, eliminating the need for hospitalization. Presently, two main strategies are employed for RIT dosing: fixed doses or calculated doses [1,2]. The calculated-dose method provides a personalized approach, delivering a precise radiation dose to the thyroid and potentially achieving a euthyroid state. However, this approach is relatively expensive, requiring additional tests, potential travel and overnight stays, and more time away from work. Consequently, calculated doses may not be practical for patients in remote locations or those with limited financial resources. For these individuals, the fixed-dose method offers an acceptable alternative.
To date, no consensus has been reached on the optimal radioiodine (RAI) activity for treating GD using the fixed-dose method. The 2016 American Thyroid Association guidelines recommend a single RAI dose of 10 to 15 millicuries (mCi) [2]. Research on the use of fixed-dose RIT for GD over the past decade has shown varying success rates, ranging from 49.0% to 94.8%, with higher success rates associated with larger RAI doses (Supplemental Table S1) [7-13]. However, techniques for determining dosage vary among studies. Some have based RAI doses on thyroid size [9,13], while many have administered the same dosage to all patients [7,8,10-12]. Other factors in addition to thyroid size have been reported to influence treatment outcomes. Mariani et al. [14] proposed RAI doses of 5, 10, or 15 mCi based on disease severity, thyroid size, and radioiodine uptake (RAIU) values. However, their report did not provide guidance on how to integrate these factors to select the appropriate dose [14]. Consequently, applying the fixed-dose method based on the current literature is challenging.
To determine the optimal RAI activity for fixed-dose treatment in real-world practice, we developed two protocols. Protocol 1, which was based on thyroid size, was implemented at our facility from 2014 to 2017. Protocol 2, utilized from 2018 to 2021, incorporated a dose calculation formula that considers clinical factors associated with treatment failure. We hypothesized that the latter protocol would yield a higher success rate and a lower frequency of hypothyroidism compared to protocol 1. Our objective was to compare the success rates of RIT using these protocols to estimate the optimal RAI activity for treating patients with GD.
Ethical considerations
The study was conducted in accordance with the tenets of the 2013 revision of the Declaration of Helsinki. Approval was obtained from the Institutional Review Board of Queen Savang Vadhana Memorial Hospital (No. 010/2565) and the Thai Clinical Trial Registry (TCTR20220527002). Due to the retrospective nature of the study, the need for informed consent was waived by the Institutional Review Board.
Study design
This retrospective quasi-experimental trial was conducted at Queen Savang Vadhana Memorial, Burapha University, and Queen Sirikit Hospitals.
Participants
We enrolled 824 Thai patients with GD, aged 18 years or older, who received RIT at the Radiology and Nuclear Medicine Unit of Burapha University Hospital between January 2014 and December 2021. Patients were diagnosed with GD based on the following criteria: suppressed thyroid-stimulating hormone (TSH) levels, elevated serum-free thyroxine (fT4) or triiodothyronine levels, and the presence of thyroid-associated ophthalmopathy and/or diffuse goiter [4]. All participants received fixed-dose RIT. From the initial cohort of 824 patients, we excluded 166 for various reasons: loss to follow-up or a follow-up period shorter than 6 months (57.8%); the need for high RAI activity to ablate the patient’s thyroid gland, as determined by the clinician (25.3%); a thyroid larger than 105 g (9.0%); or a history of RIT or thyroid surgery (7.8%). We excluded patients who required high doses of RAI to ablate the thyroid gland because these cases did not require the application of a formula to calculate RAI dosage. We also excluded patients with thyroids larger than 105 g because the formula would yield an RAI dose of 30 mCi or greater, which is not suitable for outpatient administration. Additionally, patients who had previously undergone RIT or thyroidectomy were excluded, as the determination of RAI activity would be influenced by prior treatments. The remaining patients were considered eligible for inclusion. Patients treated between 2014 and 2017 received RAI doses based on thyroid size (protocol 1), while those treated between 2018 and 2021 received RAI based on our modified dose calculation approach (protocol 2).
The sample size for this trial was calculated using the following equation.
n=2(p)(1p)(Zα/2+Zβ)2(p1p2)2
Here, n represents the required sample size, while p1−p2 denotes the difference in the success rates of RIT between two groups: one treated with 10 to 15 mCi RAI (p1=0.75) [7] and the other treated with protocol 2 (estimated p2=0.85). p* indicates the average of both groups (p*=0.80). Using an alpha value of 5% (Zα/2=1.96) and a power of test of 80% (Zβ=0.84), we calculated that each group required a sample size of 250 cases. To account for potential loss to follow-up, we increased the sample size by an additional 30%, resulting in a requirement of 325 cases per group. Consequently, the total sample size for this study was 650 cases.
Procedure
In 2018, we developed an RIT data collection method following the introduction of the new fixed-dose protocol at our institution. The procedures for both fixed-dose protocols were meticulously planned and standardized. All female patients of childbearing age were required to undergo pregnancy testing within 24 hours before receiving RAI therapy and were counseled to use contraception for at least 6 months after treatment. Furthermore, radiation protection guidance was provided to patients and their families. Patients with inactive moderate ophthalmopathy were treated with RIT in conjunction with corticosteroid therapy [4]. Those taking ATDs were instructed to discontinue these medications for 3 days before and after RIT. Thyroid volume (TV) was assessed using two ultrasound devices: the Aplio 200 and the Aplio 300, both equipped with a 7 to 14 MHz linear transducer and manufactured by Toshiba (Tokyo, Japan). We measured each thyroid lobe in three dimensions and calculated the total TV using the standard ellipsoid volume formula, where TV=0.52×(width×depth×length) [15].
Between 2014 and 2017, we estimated the optimal RAI activity based on thyroid size (protocol 1) as follows: 10 mCi for thyroids ≤15.0 g (normal size), 15 mCi for thyroids between 15.1 and 45.0 g (enlarged to three times normal size), 20 mCi for thyroids between 45.1 and 75.0 g (enlarged to five times normal size), 25 mCi for thyroids between 75.1 and 105.0 g (enlarged to seven times normal size), and 30 mCi for thyroids ≥105.0 g. After 2017, we developed a new protocol (termed protocol 2) that utilized the following dose calculation formula:
RAI activity (µCi)=thyroid size (g)×200 µCi/g×(1/24-hour RAIU [%]) [4].
We estimated the mean 24-hour RAIU to be 70.0%, based on the analysis of data from 304 patients who received calculated-dose RIT between 2014 and 2017. To determine the appropriate RAI activity, we considered key clinical risk factors such as male sex and smoking [16,17], and the presence of first-degree family members with autoimmune thyroid diseases [17]. These factors were corroborated by the results of our pilot study, which included 136 patients with GD treated under a fixed-dose protocol from 2014 to 2016. The study identified male sex (relative risk [RR], 1.2; 95% confidence interval [CI], 0.8 to 2.0; P=0.371) and smoking (RR, 1.7; 95% CI, 0.9 to 3.1; P=0.984) as factors associated with RIT failure within 6 months. When calculating the dose, we increased the RAI activity by 10% for each clinical risk factor. Patients adhered to a low-iodine diet for 7 days before RIT. They then ingested a sodium iodide capsule on an empty stomach. To assess each patient’s thyroid functional status, we conducted thyroid function tests and measured thyroid size at 6 months and again at 12 to 13 months after RIT. The primary outcome was treatment success or failure. Treatment success was indicated by the presence of euthyroidism (normal TSH and fT4 levels) without ATDs or the development of hypothyroidism (high TSH and low fT4 levels) requiring levothyroxine therapy within 6 months following RIT. Treatment failure was indicated by continued hyperthyroidism (low TSH and high fT4 levels) and/or the continued necessity for ATDs post-RIT [4]. The secondary outcome was also treatment success or failure, defined by the same criteria but evaluated at 12 to 13 months after RIT. Patients who experienced hyperthyroidism after at least 6 months of remission were classified as having relapsed.
Data analysis
Baseline assessment and follow-up data were obtained from our hospital’s medical database. Clinical parameters were reported as mean±standard deviation (SD), median (interquartile range [IQR]), or median (range) for quantitative variables and as frequency (%) for qualitative variables. The Mann–Whitney U test was employed to compare continuous baseline variables between the two independent dosage method groups. The chi-square test was utilized to assess proportional differences in RIT success rates between the groups. Confounding factors, including sex (female/male), thyroid size category (≤45.0 g vs. >45.0 g, and ≤75.0 g vs. >75.0 g), smoking status (yes/no), and age, were evaluated using logistic regression to determine the ratio of success rates for protocols 1 and 2. RRs were also reported with 95% CIs. A P value of less than 0.05 was considered to indicate statistical significance.
The mean±SD patient age was 39.2±11.9 years, and most patients were female (64.8%). The median thyroid size was 26.8 g (IQR, 15.0 to 42.8). Table 1 presents the success rates of RIT for the two protocol groups. The group receiving protocol 2 displayed a slightly lower RIT success rate compared to those undergoing protocol 1 (63.6% vs. 67.2%), but the protocol 2 group also displayed significantly fewer cases of hypothyroidism (39.0% vs. 48.9%, P=0.0117). Based on the effect measures of protocol 2 and protocol 1, the risk of treatment failure did not differ significantly between groups (RR, 1.1089; 95% CI, 0.8937 to 1.3758; P=0.3477). Additionally, the median dose of RAI for protocol 2 was significantly lower than for protocol 1 (10.7 mCi vs. 15.0 mCi, P=0.0079). The prevalence of thyrotoxic periodic paralysis was higher in the protocol 2 group (13.6% vs. 7.8%, P=0.0217), as shown in Table 1. Moreover, no significant differences were noted in clinical factors or indications for RIT between the groups.
Table 2 presents the effects of age, sex, thyroid size, and smoking status on the success rates of the two protocols. A smaller thyroid gland (≤75.0 g) was associated with higher treatment success rates for both protocol 1 (RR, 2.230; 95% CI, 1.430 to 3.476; P=0.011) and protocol 2 (RR, 1.968; 95% CI, 1.407 to 2.753; P=0.003). Neither age nor smoking status significantly influenced the success rates. However, female sex was associated with a lower success rate for protocol 2 (RR, 0.815; 95% CI, 0.704 to 0.943; P=0.009).
After 12–13 months of RIT, 29.9% (197) of patients were lost to follow-up. Loss to follow-up was more common among recipients of protocol 2 compared to protocol 1 (33.6% vs. 24.6%), yielding a significantly lower RIT success rate for the protocol 2 group (64.1% vs. 74.2%). Additionally, the incidence of treatment failure was significantly greater for protocol 2 than for protocol 1 (34.0% vs. 23.8%, P<0.05). During the follow-up period, the RAI dose used in protocol 2 remained significantly lower than that for protocol 1 (10.9 mCi vs. 15.0 mCi, P=0.0263). Relapse rates after achieving at least 6 months of remission were exceedingly low in both groups, with no significant difference between them (1.9% vs. 2.0%, P=0.9695) (Table 3).
The European Association of Nuclear Medicine (EANM) recently published new guidelines on the use of RIT for benign thyroid disease. They proposed two strategies for determining the RIT dosage in the treatment of GD. The first strategy is functional dosing, in which the primary outcome is achieving euthyroidism. The second is ablative dosing, which targets the induction of hypothyroidism as rapidly as possible [18]. In our clinical practice, we have opted for ablative dosing for patients with GD who have extremely large thyroid glands (exceeding 105 g), who exhibit hyperthyroidism, or who have recently experienced a severe complication. We believe that patients who do not meet these criteria should have the opportunity to attain euthyroidism following the use of RIT for thyroid size reduction. Research indicates that most patients with GD (approximately 80%) treated with ablative dosing, who subsequently require lifelong management of hypothyroidism, are dissatisfied with this outcome [19]. Furthermore, over one-quarter of these patients encounter issues with thyroid hormone replacement therapy related to overtreatment or undertreatment (21% and 9%, respectively) [20].
To date, the fixed-dose method remains the simplest and most convenient approach for accurately estimating RAI activity. However, this method may lead to an increased incidence of hypothyroidism after RIT due to excessively high RAI activity; alternatively, persistent or recurrent hyperthyroidism can arise due to insufficient RAI activity. Over the past decade, numerous fixed-dose methods have been developed to determine the optimal RAI activity. However, these studies have produced a wide range of results and success rates, varying from 49.0% to 94.8% (Supplemental Table S1) [7-13]. In the present study, we developed and evaluated two fixed-dose methods for functional dosing, aiming to achieve either euthyroidism or short-term hypothyroidism in patients with GD. The technique in protocol 2 facilitated more precise and individualized calculations of RAI activity than the one in protocol 1, as it was adapted from a dose calculation formula based on individual thyroid size. Although the success rate of RIT using protocol 2 was marginally lower than that of protocol 1 (63.6% vs. 67.2%) (Table 1), no significant difference was observed in the risk of treatment failure between groups (RR, 1.1089; 95% CI, 0.8937 to 1.3758; P=0.3477). Furthermore, we were able to reduce the RAI dose (10.7 mCi in protocol 2 vs. 15.0 mCi in protocol 1; P=0.0079) while maintaining a similar treatment success rate to that of protocol 1 (Table 2). Thus, less radiation was administered. Moreover, the incidence of hypothyroidism during short-term follow-up was significantly lower in the protocol 2 group, with a difference of 9.9% relative to those receiving protocol 1 (39.0% vs. 48.9%, P=0.0117).
At the 12- to 13-month follow-up, the incidence of hypothyroidism had increased in both protocol groups (44.8% in the protocol 2 group vs. 58.4% in the protocol 1 group; P=0.0037), yet it remained significantly lower in the protocol 2 group. Additionally, the rise in incidence was less pronounced for protocol 2 compared to protocol 1 (5.8% vs. 9.5%) (Table 1). Notably, the incidence of disease relapse after at least 6 months of GD remission was exceedingly low for both groups (1.9% vs. 2.0%, P=0.9695) (Table 3). We compared this finding with results from a study by Kiatkittikul et al. [13], which also employed a fixed-dose protocol based on thyroid size. Relative to that study, our protocol 2 yielded a higher rate of hypothyroidism (39.0% vs. 33.1%) due to the effects of higher RAI activity across all thyroid sizes. Consequently, the success rate in our second protocol was greater than that reported by Kiatkittikul et al. [13] (63.6% vs. 50.0%).
Although protocol 2 reduced the incidence of post-RIT hypothyroidism, the success rate of 63.6% fell short of our anticipated target. Our findings indicate that a larger thyroid gland has a detrimental impact on the success of RIT. Specifically, thyroid sizes greater than 45.0 and 75.0 g were associated with lower success rates of 50.5% and 31.6%, respectively (Table 2). These findings align with previous research, which has shown that larger thyroid glands—ranging from 25.6 to 60.0 g—represent a key factor in RIT failure when fixed-dose protocols are employed [7,9,10,13]. The EANM guidelines acknowledge that higher RAI activity may be necessary for patients with GD who have a thyroid larger than 26.0 g [18]. This recommendation is supported by a clinical trial conducted by Vija Racaru et al. [21], which achieved an excellent RIT success rate of 91.0% and supported the use of the calculated-dose method in patients with GD whose thyroid exceeds 26.0 g.
Interestingly, and unlike the results observed for protocol 1, female patients exhibited a lower success rate for protocol 2 relative to male participants (RR, 0.815; 95% CI, 0.704 to 0.943; P=0.009) (Table 2). The prior identification of male sex as a risk factor prompted a 10% increase in the RAI dose for male patients, which improved the success rate of RIT (72.4% for protocol 2 and 60.0% for protocol 1). However, the success rate for female patients was lower in protocol 2 compared to protocol 1, at 59.0% versus 70.8%. One key factor influencing the success or failure of RIT was the rapid turnover rate of the thyroid gland. Rapid turnover rate is characterized by an early-tolate uptake ratio of ≥1, or a 4-hour RAIU that exceeds the 24- hour RAIU [22]. Factors associated with rapid turnover include a thyroid larger than 56 g (odds ratio [OR], 3.7; 95% CI, 3.032 to 4.559), age under 38 years (OR, 2.3; 95% CI, 1.906 to 2.856), and female sex (OR, 2.2; 95% CI, 1.757 to 2.791) [23]. Our institution employs both methods to determine RAI activity, considering clinician requirements and patient convenience. Thus, we collected RAIU values for patients with GD who received the calculated RIT dose during phase I (n=304, 2014–2017) and phase II (n=124, 2018–2021). We observed more patients exhibiting a rapid thyroid turnover rate in phase II compared with patients in phase I (11.3% vs. 5.6%) (Supplemental Table S2). Notably, the rapid thyroid turnover rate was exclusively observed in female patients (n=14), with a median age of 29.5 years (IQR, 26.5 to 38.8). Regarding RAI kinetics within the thyroid gland, patients with GD and a rapid turnover of RAI are expected to have a significantly shorter effective half-life for RAI clearance. This leads to lower absorption of the radiation dose delivered to the thyroid gland, necessitating an increase in RAI activity by approximately 1.5 to 2.0 times [24].
Based on the above results, we recommend using protocol 2 for patients with GD who have a thyroid 45.0 g or smaller. For thyroids exceeding 45.0 g but no larger than 75.0 g, we prefer the calculated-dose method, especially for female patients under 30 years of age. Alternatively, protocol 2 is recommended for patients who prefer a fixed dose approach and are willing to undergo a second RIT should the disease not be cured. For those with a thyroid larger than 75.0 g, we advise treatment with an ablative dose.
GD is a multifactorial disorder influenced by both genetic and environmental factors. While genetics are thought to account for 70% to 80% of GD cases, modifiable environmental factors, such as smoking, also contribute to the outcomes of RIT [17]. Plazinska et al. [25] found that current smokers with GD had a significantly lower RIT success rate than their non-smoking counterparts. Furthermore, a recent study indicated an elevated risk of GD in patients who smoke and have a first-degree relative with the disease (hazard ratio, 4.68), noting a statistically significant interaction between these factors (relative excess risk due to interaction, 0.94; 95% CI, 0.74 to 1.19). Consequently, it is advisable for patients with GD and their first-degree relatives to quit smoking [26]. Our institution is in the eastern economic corridors of Thailand, a region characterized by its industrial and coastal nature. Consequently, patients in this area tend to consume diets high in iodine and experience a relatively high incidence of stress-related conditions. Several studies have revealed correlations between these factors and the risk of GD [17]. However, no research to date has been focused on the impacts of stress and high iodine intake on the outcomes of RIT. Future studies are warranted to explore how these patient-specific variables affect the success of RIT.
Our study had several limitations. First, TSH receptor antibody titer is known to correlate with RIT failure [12]; however, we were unable to analyze this variable due to the prohibitive cost of testing all patients with GD. Second, 197 of our participants (29.9%) were lost to follow-up at 12 to 13 months, with an unequal rate of loss between the two groups (24.6% for protocol 1 vs. 33.6% for protocol 2). This discrepancy may have introduced attrition bias, potentially affecting the precision of the long-term success rates reported in this study. Third, TV measurements were conducted by three radiologists experienced in ultrasound, who concurred on the ultrasound technique used. However, we did not assess interobserver variation, as the data were collected retrospectively and one of the radiologists transferred to another hospital in 2020. Finally, our study was a quasi-experimental retrospective trial, which may have been influenced by confounding factors due to the absence of randomization.
In conclusion, the success rate of the modified dose calculation protocol was not inferior to the thyroid size-specific RAI dose protocol. This protocol yields a favorable success rate, especially in patients with GD who have a thyroid no larger than 45.0 g.

Supplemental Table S1.

Previous Studies of Fixed-Dose Radioiodine Therapy for Graves’ Disease [6-12]
enm-2024-1950-Supplemental-Table-S1.pdf

Supplemental Table S2.

Thyroid Characteristics and RAIU of Patients with Graves’ Disease between 2014 and 2017 (n=304)
enm-2024-1950-Supplemental-Table-S2.pdf

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

AUTHOR CONTRIBUTIONS

Conception or design: A.W., Y.M., S.S. Acquisition, analysis, or interpretation of data: A.W., R.T., Y.M., S.S. Drafting the work or revising: A.W., Y.M., S.S. Final approval of the manuscript: A.W., R.T., Y.M., S.S.

Acknowledgements
This research project received funding from Queen Savang Vadhana Memorial Hospital.
The authors would like to thank the staff of our institute, Burapha University Hospital, and those at Queen Sirikit Hospital for their support.
enm-2024-1950f1.jpg
Table 1.
Clinical Characteristics and Treatment Outcomes in Patients with Graves’ Disease 6 Months after Treatment with Two Different Radioiodine Dosage Protocols (n=658)
Variable Protocol 1 (n=268) Protocol 2 (n=390) P value
Age, yr 39.7±12.0 38.8±11.9 0.3425
Female sex 178 (66.4) 256 (65.6) 0.8363
First-degree family history of AITD 68 (25.4) 110 (28.2) 0.4217
Smoker 46 (17.2) 82 (21.0) 0.2189
Number of cigarettes per daya 1.5±4.1 2.3±6.1 0.0612
0.0 (0.0–20.0) 0.0 (0.0–60.0)
Indication for RAI treatment
 Medical failure 114 (42.5) 138 (35.4) 0.0637
 Relapse or recurrent 72 (26.9) 92 (23.6) 0.3398
 Cardiovascular complications 24 (9.0) 47 (12.1) 0.2085
 Thyrotoxic periodic paralysis 21 (7.8) 53 (13.6) 0.0217c
 Progressive disease 16 (6.0) 30 (7.7) 0.3947
 Adverse drug reaction of ATDs 12 (4.5) 10 (2.6) 0.1797
 Thyroid storm 9 (3.4) 20 (5.1) 0.2771
Medication before RIT
 Methimazole (5 mg) 230 (85.8) 358 (91.8) 0.0146c
  Dose, tablets/dayb 2.8 (2.0–3.0) 2.0 (1.5–3.0) 0.1025
 Propylthiouracil (50 mg) 34 (12.7) 24 (6.2) 0.0037c
  Dose, tablets/dayb 6.0 (6.0–9.0) 7.5 (3.0–12.0) 0.0222c
 Lithium (300 mg) 5 (1.9) 4 (1.0) 0.3620
  Dose, tablets/dayb 1.0 (1.0–3.0) 2.0 (1.8–2.0) 1.0000
 No medication 1 (0.12) 3 (0.46) 0.4494
Thyroid size using US, gb 26.7 (14.7–43.1) 27.0 (18.5–42.4) 0.1053
Presence of thyroid nodule using US 27 (10.1) 43 (11.0) 0.6975
RAI activities, mCib 15.0 (10.0–15.0) 10.7 (7.6–17.3) 0.0079c
Treatment outcome at 6 months
 Euthyroid 49 (18.3) 96 (24.6) 0.0542
 Hypothyroid 131 (48.9) 152 (39.0) 0.0117c
 Hyperthyroid 88 (32.8) 142 (36.4) 0.3448

Values are expressed as mean±standard deviation or number (%) unless otherwise indicated.

AITD, autoimmune thyroid disease; RAI, radioiodine; ATD, antithyroid drug; RIT, radioiodine therapy; US, ultrasound.

a Median (range);

b Median (interquartile range);

c P<0.05.

Table 2.
Relative Risks of Various Factors Associated with Success Rate for Protocols 1 and 2
Variable Protocol 1
Protocol 2
Success rate RR (95% CI) P value Success rate RR (95% CI) P value
Categorical data
 Sex
  Male 54/90 (60.0) 1 97/134 (72.4) 1
  Female 126/178 (70.8) 1.180 (0.972–1.431) 0.076 151/256 (59.0) 0.815 (0.704–0.943) 0.009a
 Thyroid size, g
  ≤45.0 155/219 (70.8) 1.387 (1.041–1.849) 0.008a 197/289 (68.2) 1.350 (1.096–1.663) 0.001a
  >45.0 25/49 (51.0) 1 51/101 (50.5) 1
 Thyroid size, g
  ≤75.0 177/258 (68.6) 2.230 (1.430–3.476) 0.011a 242/371 (65.2) 1.968 (1.407–2.753) 0.003a
  >75.0 3/10 (30.0) 1 6/19 (31.6) 1
 Smoking
  Yes 28/46 (60.9) 0.806 (0.535–1.213) 0.318 57/82 (69.5) 1.246 (0.872–1.780) 0.210
  No 152/222 (68.5) 1 191/308 (62.0)
Continuous data
 Age 1.012 (0.991–1.035) 0.265 1.010 (0.992–1.028) 0.286

Values are expressed as number/total number (%).

RR, relative risk; CI, confidence interval.

a P<0.05.

Table 3.
Clinical Characteristics and Outcomes of Two Treatment Protocols in Patients with Graves’ Disease 12 to 13 Months after RIT (n=461)
Variable Protocol 1 (n=202) Protocol 2 (n=259) P value
Age, yr 40.3±12.3 38.9±11.8 0.2154
Female sex 135 (66.8) 164 (63.3) 0.4333
First-degree family history of AITD 49 (24.3) 66 (23.1) 0.7629
Smoker 33 (16.3) 59 (22.8) 0.0859
Number of cigarettes per daya 1.6±4.2 2.4±5.7 0.0952
0.0 (0.0–20.0) 0.0 (0.0–40.0)
Indication for RAI treatment
 Medical failure 88 (43.6) 100 (38.6) 0.2828
 Relapse or recurrent 50 (24.8) 51 (19.7) 0.1924
 Cardiovascular complications 18 (8.9) 31 (12.0) 0.2905
 Thyrotoxic periodic paralysis 18 (8.9) 37 (14.3) 0.0773
 Progressive disease 15 (7.4) 21 (8.1) 0.7864
 Adverse drug reaction of ATDs 8 (4.0) 4 (1.5) 0.1060
 Thyroid storm 5 (2.5) 15 (5.8) 0.0829
Medication before RIT
 Methimazole (5 mg) 174 (86.1) 236 (91.1) 0.0907
  Dose, tablets/dayb 2.5 (2.0–3.0) 2.0 (1.5–3.0) 0.5174
 Propylthiouracil (50 mg) 26 (12.9) 18 (6.9) 0.0318c
  Dose, tablets/dayb 6.0 (4.5–9.0) 7.5 (3.3–12.0) 0.0071c
 Lithium (300 mg) 4 (2.0) 2 (0.8) 0.2562
  Dose, tablets/dayb 2.0 (1.0–3.0) 2.0 (2.0–2.0) 1.0000
 No medication 0 1 (0.39) NA
Thyroid size using US, gb 27.0 (14.8–43.7) 27.8 (18.8–43.4) 0.3156
Presence of thyroid nodule using US 21 (10.4) 29 (11.2) 0.7838
RAI activity, mCib 15.0 (10.0–15.0) 10.9 (7.6–17.6) 0.0263c
Treatment outcome at 12–13 months
 Euthyroid 32 (15.8) 50 (19.3) 0.3346
 Relapse after RIT 4 (2.0) 5 (1.9) 0.9695
 Hypothyroid 118 (58.4) 116 (44.8) 0.0037
 Hyperthyroid 48 (23.8) 88 (34.0) 0.0170

Values are expressed as mean±standard deviation or number (%) unless otherwise indicated.

RIT, radioiodine therapy; AITD, autoimmune thyroid disease; RAI, radioiodine; ATD, antithyroid drug; NA, not available; US, ultrasound.

a Median (range);

b Median (interquartile range);

c P<0.05.

  • 1. Kahaly GJ, Bartalena L, Hegedus L, Leenhardt L, Poppe K, Pearce SH. 2018 European Thyroid Association guideline for the management of Graves’ hyperthyroidism. Eur Thyroid J 2018;7:167–86.ArticlePubMedPMCPDF
  • 2. Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016;26:1343–421.ArticlePubMed
  • 3. Christou N, Mathonnet M. Complications after total thyroidectomy. J Visc Surg 2013;150:249–56.ArticlePubMed
  • 4. Sundaresh V, Brito JP, Thapa P, Bahn RS, Stan MN. Comparative effectiveness of treatment choices for Graves’ hyperthyroidism: a historical cohort study. Thyroid 2017;27:497–505.ArticlePubMedPMC
  • 5. Donovan PJ, McLeod DS, Little R, Gordon L. Cost-utility analysis comparing radioactive iodine, anti-thyroid drugs and total thyroidectomy for primary treatment of Graves’ disease. Eur J Endocrinol 2016;175:595–603.ArticlePubMed
  • 6. Parameswaran R, de Jong MC, Kit JL, Sek K, Nam TQ, Thang TV, et al. 2021 Asia-Pacific Graves’ disease consortium survey of clinical practice patterns in the management of Graves’ disease. Endocrine 2023;79:135–42.ArticlePubMedPDF
  • 7. Santos RB, Romaldini JH, Ward LS. A randomized controlled trial to evaluate the effectiveness of 2 regimens of fixed iodine (¹³¹I) doses for Graves disease treatment. Clin Nucl Med 2012;37:241–4.PubMed
  • 8. El-Kareem MA, Derwish WA, Moustafa HM. Response rate and factors affecting the outcome of a fixed dose of RAI131 therapy in Graves’ disease: a 10-year Egyptian experience. Nucl Med Commun 2014;35:900–7.PubMed
  • 9. Sfiligoj D, Gaberscek S, Mekjavic PJ, Pirnat E, Zaletel K. Factors influencing the success of radioiodine therapy in patients with Graves’ disease. Nucl Med Commun 2015;36:560–5.ArticlePubMed
  • 10. Sapienza MT, Coura-Filho GB, Willegaignon J, Watanabe T, Duarte PS, Buchpiguel CA. Clinical and dosimetric variables related to outcome after treatment of Graves’ disease with 550 and 1110 MBq of 131I: results of a prospective randomized trial. Clin Nucl Med 2015;40:715–9.PubMed
  • 11. Zaman MU, Fatima N, Zaman U, Sajjad Z, Zaman A, Tahseen R. Predictive value of pyramidal lobe, percentage thyroid uptake and age for ablation outcome after 15 mCi fixed dose of radioiodine-131 in Graves’ disease. Indian J Nucl Med 2015;30:309–13.ArticlePubMedPMC
  • 12. Fanning E, Inder WJ, Mackenzie E. Radioiodine treatment for graves’ disease: a 10-year Australian cohort study. BMC Endocr Disord 2018;18:94.ArticlePubMedPMCPDF
  • 13. Kiatkittikul P, Raruenrom Y, Theerakulpisut D, Somboonporn C. Success rate of radioactive iodine therapy in Graves’ disease using dose corrected for thyroid gland size. Siriraj Med J 2021;73:108–13.
  • 14. Mariani G, Tonacchera M, Grosso M, Orsolini F, Vitti P, Strauss HW. The role of nuclear medicine in the clinical management of benign thyroid disorders, part 1: hyperthyroidism. J Nucl Med 2021;62:304–12.ArticlePubMed
  • 15. Dighe M, Barr R, Bojunga J, Cantisani V, Chammas MC, Cosgrove D, et al. Thyroid ultrasound: state of the art. Part 1: thyroid ultrasound reporting and diffuse thyroid diseases. Med Ultrason 2017;19:79–93.ArticlePubMedPDF
  • 16. Wiersinga WM. Smoking and thyroid. Clin Endocrinol (Oxf) 2013;79:145–51.ArticlePubMed
  • 17. Wiersinga WM. Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease. Endocrinol Metab (Seoul) 2016;31:213–22.ArticlePubMedPMCPDF
  • 18. Campenni A, Avram AM, Verburg FA, Iakovou I, Hanscheid H, de Keizer B, et al. The EANM guideline on radioiodine therapy of benign thyroid disease. Eur J Nucl Med Mol Imaging 2023;50:3324–48.ArticlePubMedPMCPDF
  • 19. Mitchell AL, Hegedus L, Zarkovic M, Hickey JL, Perros P. Patient satisfaction and quality of life in hypothyroidism: an online survey by the British Thyroid Foundation. Clin Endocrinol (Oxf) 2021;94:513–20.ArticlePubMedPDF
  • 20. Tran A, Hyer S. The challenge of thyroid hormone replacement in primary care. J Pharm Clin Res 2018;5:555669.Article
  • 21. Vija Racaru L, Fontan C, Bauriaud-Mallet M, Brillouet S, Caselles O, Zerdoud S, et al. Clinical outcomes 1 year after empiric 131I therapy for hyperthyroid disorders: real life experience and predictive factors of functional response. Nucl Med Commun 2017;38:756–63.PubMed
  • 22. Aktay R, Rezai K, Seabold JE, Bar RS, Kirchner PT. Four- to twenty-four-hour uptake ratio: an index of rapid iodine-131 turnover in hyperthyroidism. J Nucl Med 1996;37:1815–9.PubMed
  • 23. Zhang R, Tan J, Wang R, Zhang G, Jia Q, Meng Z, et al. Analysis of risk factors of rapid thyroidal radioiodine-131 turnover in Graves’ disease patients. Sci Rep 2017;7:8301.ArticlePubMedPMCPDF
  • 24. Arora S, Bal C. Is there any need for adjusting 131I activity for the treatment of high turnover Graves’ disease compared to normal turnover patients?: results from a retrospective cohort study validated by propensity score analysis. Nucl Med Mol Imaging 2021;55:15–26.ArticlePubMedPMCPDF
  • 25. Plazinska MT, Sawicka-Gutaj N, Czarnywojtek A, Wolinski K, Kobylecka M, Karlinska M, et al. Radioiodine therapy and Graves’ disease: myths and reality. PLoS One 2020;15:e0226495.ArticlePubMedPMC
  • 26. Kim HJ, Hong G, Hwang J, Kazmi SZ, Kim KH, Kang T, et al. Familial risk of Graves disease among first-degree relatives and interaction with smoking: a population-based study. J Clin Endocrinol Metab 2023;108:e502–11.ArticlePubMedPDF

Figure & Data

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    Comparison of Thyroid Size-Specific Radioiodine Dose and New Modified Dose Calculation in the Treatment of Graves’ Disease
    Image
    Graphical abstract
    Comparison of Thyroid Size-Specific Radioiodine Dose and New Modified Dose Calculation in the Treatment of Graves’ Disease
    Variable Protocol 1 (n=268) Protocol 2 (n=390) P value
    Age, yr 39.7±12.0 38.8±11.9 0.3425
    Female sex 178 (66.4) 256 (65.6) 0.8363
    First-degree family history of AITD 68 (25.4) 110 (28.2) 0.4217
    Smoker 46 (17.2) 82 (21.0) 0.2189
    Number of cigarettes per daya 1.5±4.1 2.3±6.1 0.0612
    0.0 (0.0–20.0) 0.0 (0.0–60.0)
    Indication for RAI treatment
     Medical failure 114 (42.5) 138 (35.4) 0.0637
     Relapse or recurrent 72 (26.9) 92 (23.6) 0.3398
     Cardiovascular complications 24 (9.0) 47 (12.1) 0.2085
     Thyrotoxic periodic paralysis 21 (7.8) 53 (13.6) 0.0217c
     Progressive disease 16 (6.0) 30 (7.7) 0.3947
     Adverse drug reaction of ATDs 12 (4.5) 10 (2.6) 0.1797
     Thyroid storm 9 (3.4) 20 (5.1) 0.2771
    Medication before RIT
     Methimazole (5 mg) 230 (85.8) 358 (91.8) 0.0146c
      Dose, tablets/dayb 2.8 (2.0–3.0) 2.0 (1.5–3.0) 0.1025
     Propylthiouracil (50 mg) 34 (12.7) 24 (6.2) 0.0037c
      Dose, tablets/dayb 6.0 (6.0–9.0) 7.5 (3.0–12.0) 0.0222c
     Lithium (300 mg) 5 (1.9) 4 (1.0) 0.3620
      Dose, tablets/dayb 1.0 (1.0–3.0) 2.0 (1.8–2.0) 1.0000
     No medication 1 (0.12) 3 (0.46) 0.4494
    Thyroid size using US, gb 26.7 (14.7–43.1) 27.0 (18.5–42.4) 0.1053
    Presence of thyroid nodule using US 27 (10.1) 43 (11.0) 0.6975
    RAI activities, mCib 15.0 (10.0–15.0) 10.7 (7.6–17.3) 0.0079c
    Treatment outcome at 6 months
     Euthyroid 49 (18.3) 96 (24.6) 0.0542
     Hypothyroid 131 (48.9) 152 (39.0) 0.0117c
     Hyperthyroid 88 (32.8) 142 (36.4) 0.3448
    Variable Protocol 1
    Protocol 2
    Success rate RR (95% CI) P value Success rate RR (95% CI) P value
    Categorical data
     Sex
      Male 54/90 (60.0) 1 97/134 (72.4) 1
      Female 126/178 (70.8) 1.180 (0.972–1.431) 0.076 151/256 (59.0) 0.815 (0.704–0.943) 0.009a
     Thyroid size, g
      ≤45.0 155/219 (70.8) 1.387 (1.041–1.849) 0.008a 197/289 (68.2) 1.350 (1.096–1.663) 0.001a
      >45.0 25/49 (51.0) 1 51/101 (50.5) 1
     Thyroid size, g
      ≤75.0 177/258 (68.6) 2.230 (1.430–3.476) 0.011a 242/371 (65.2) 1.968 (1.407–2.753) 0.003a
      >75.0 3/10 (30.0) 1 6/19 (31.6) 1
     Smoking
      Yes 28/46 (60.9) 0.806 (0.535–1.213) 0.318 57/82 (69.5) 1.246 (0.872–1.780) 0.210
      No 152/222 (68.5) 1 191/308 (62.0)
    Continuous data
     Age 1.012 (0.991–1.035) 0.265 1.010 (0.992–1.028) 0.286
    Variable Protocol 1 (n=202) Protocol 2 (n=259) P value
    Age, yr 40.3±12.3 38.9±11.8 0.2154
    Female sex 135 (66.8) 164 (63.3) 0.4333
    First-degree family history of AITD 49 (24.3) 66 (23.1) 0.7629
    Smoker 33 (16.3) 59 (22.8) 0.0859
    Number of cigarettes per daya 1.6±4.2 2.4±5.7 0.0952
    0.0 (0.0–20.0) 0.0 (0.0–40.0)
    Indication for RAI treatment
     Medical failure 88 (43.6) 100 (38.6) 0.2828
     Relapse or recurrent 50 (24.8) 51 (19.7) 0.1924
     Cardiovascular complications 18 (8.9) 31 (12.0) 0.2905
     Thyrotoxic periodic paralysis 18 (8.9) 37 (14.3) 0.0773
     Progressive disease 15 (7.4) 21 (8.1) 0.7864
     Adverse drug reaction of ATDs 8 (4.0) 4 (1.5) 0.1060
     Thyroid storm 5 (2.5) 15 (5.8) 0.0829
    Medication before RIT
     Methimazole (5 mg) 174 (86.1) 236 (91.1) 0.0907
      Dose, tablets/dayb 2.5 (2.0–3.0) 2.0 (1.5–3.0) 0.5174
     Propylthiouracil (50 mg) 26 (12.9) 18 (6.9) 0.0318c
      Dose, tablets/dayb 6.0 (4.5–9.0) 7.5 (3.3–12.0) 0.0071c
     Lithium (300 mg) 4 (2.0) 2 (0.8) 0.2562
      Dose, tablets/dayb 2.0 (1.0–3.0) 2.0 (2.0–2.0) 1.0000
     No medication 0 1 (0.39) NA
    Thyroid size using US, gb 27.0 (14.8–43.7) 27.8 (18.8–43.4) 0.3156
    Presence of thyroid nodule using US 21 (10.4) 29 (11.2) 0.7838
    RAI activity, mCib 15.0 (10.0–15.0) 10.9 (7.6–17.6) 0.0263c
    Treatment outcome at 12–13 months
     Euthyroid 32 (15.8) 50 (19.3) 0.3346
     Relapse after RIT 4 (2.0) 5 (1.9) 0.9695
     Hypothyroid 118 (58.4) 116 (44.8) 0.0037
     Hyperthyroid 48 (23.8) 88 (34.0) 0.0170
    Table 1. Clinical Characteristics and Treatment Outcomes in Patients with Graves’ Disease 6 Months after Treatment with Two Different Radioiodine Dosage Protocols (n=658)

    Values are expressed as mean±standard deviation or number (%) unless otherwise indicated.

    AITD, autoimmune thyroid disease; RAI, radioiodine; ATD, antithyroid drug; RIT, radioiodine therapy; US, ultrasound.

    Median (range);

    Median (interquartile range);

    P<0.05.

    Table 2. Relative Risks of Various Factors Associated with Success Rate for Protocols 1 and 2

    Values are expressed as number/total number (%).

    RR, relative risk; CI, confidence interval.

    P<0.05.

    Table 3. Clinical Characteristics and Outcomes of Two Treatment Protocols in Patients with Graves’ Disease 12 to 13 Months after RIT (n=461)

    Values are expressed as mean±standard deviation or number (%) unless otherwise indicated.

    RIT, radioiodine therapy; AITD, autoimmune thyroid disease; RAI, radioiodine; ATD, antithyroid drug; NA, not available; US, ultrasound.

    Median (range);

    Median (interquartile range);

    P<0.05.


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