Radioactive Iodine Therapy for Pediatric Graves’ Hyperthyroidism

Abstract

Background

The aim of this study was to determine the remission rate and factors influencing radioactive iodine (RAI) therapy in pediatric patients with Graves’ hyperthyroidism (GH) who received treatment for the first time.

Material/Methods

This retrospective study analyzed a total of 44 pediatric patients with GH who received their first RAI therapy in the nuclear treatment ward of Linyi People’s Hospital from December 2018 to December 2023. Follow-up was conducted for 6 months after treatment, and based on treatment outcomes, the patients were divided into the remission group and the failure group. SPSS 22.0 statistical software was used to compare and analyze the predictive factors between the 2 groups.

Results

The total remission rate of GH at 6 months after RAI therapy was 52.3% (23/44). There were significant differences between the remission group and the failure group in terms of duration of GH, thyroid weight, and RAI dose. Logistic regression analysis indicated that duration of GH and thyroid weight were the factors influencing remission of RAI therapy. Patients with a duration of GH more than 27 months and a thyroid weight greater than 50.17g were less likely to be cured.

Conclusions

The disease duration and thyroid weight influenced the RAI therapy outcome in pediatric patients with GH. Higher doses of RAI should be administered to patients with a disease duration exceeding 27 months or thyroid weight surpassing 50.17 g.

Introduction

The epidemiology of pediatric hyperthyroidism remains unclear. Most relevant research has concentrated on Europe, North America, and Asia. The prevalence rates vary significantly among different countries and regions, ranging from 0.9 to 14.1 per 100 000 people annually. Among these, over 90% are cases of Graves’ hyperthyroidism (GH) [1–9]. Although the epidemiology of GH remains unclear, it exhibits the following characteristics. First, the incidence of pediatric GH is much lower than that in adults. Among all age groups, pediatric patients account for about 1–5% of the total incidence [1,7]. Second, the incidence of pediatric GH increases with age, and the incidence in adolescents is significantly higher than that in prepubertal children [2,6]. Third, within various age groups, girls exhibit a significantly higher incidence of GH compared to boys [1–5]. Fourth, there appears to be an upward trend in the incidence of pediatric GH [4,5].

The 3 primary treatment methods for pediatric patients with GH include antithyroid drugs (ATD), radioactive iodine (RAI) therapy, and surgery. In clinical practice, most physicians generally prefer ATD treatment. However, studies have shown that only about 30% of pediatric patients can achieve long-term remission after 2 years of standardized ATD treatment. Even after 8 or 10 years of ATD treatment, the remission rate is only 45% or 49%, and the remaining patients are forced to choose other methods [8,10–12]. Due to its safety, cost-effectiveness, and convenience, RAI therapy becomes the second choice for many patients. However, there is currently no unified treatment dosage for RAI therapy in pediatric patients with GH. The “2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis” recommends that the dosage of RAI for pediatric patients with GH should be >0.15 mCi/gram of thyroid tissue, and for patients with larger thyroid glands (50–80 g), the dosage of RAI should be 0.2–0.3 mCi/gram of thyroid tissue [13]. The “131I Guidelines for the Treatment of Graves Hyperthyroidism (2021 edition)” recommends that pediatric patients with GH should receive a sufficient dose of RAI to achieve hypothyroidism as the goal, but the guidelines do not provide a specific range of RAI dosage [14]. The “2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease” recommends a dosage of RAI >0.4 mCi/gram of thyroid tissue for children with GH [15]. It should be noted that the studies referenced in the guidelines all had relatively small patient numbers, and none of them achieved a 100% success rate. Consequently, the existing studies are insufficient to conclusively determine the optimal dose of RAI [16–20].

Considering the significant differences in treatment dosage ranges among different guidelines, our research group conducted a retrospective study on 44 pediatric patients who received their first RAI therapy in the nuclear treatment ward of Linyi People’s Hospital from December 2018 to December 2023. We analyzed the treatment outcomes and attempted to find a reasonable range for RAI dosage, as well as identify clinical factors that affected treatment outcomes, with the aim of improving treatment strategies for GH in a broader context.

Material and Methods

Study Design and Participants

As shown in Figure 1, from December 2018 to December 2023, a total of 68 pediatric patients received RAI treatment in the nuclear medicine treatment ward of Linyi People’s Hospital. Among these, 15 patients underwent repeated treatments and were subsequently excluded from this study. Of the remaining 53 patients, 9 were unable to adhere to follow-up for at least 6 months, leading to incomplete data, and were also excluded. Consequently, a final total of 44 pediatric patients with complete follow-up data were included in this research. The diagnostic criteria for GH were as follows: (1) symptoms and signs of hypermetabolism; (2) elevated levels of FT3 and FT4, and decreased TSH levels; (3) diffuse enlargement of the thyroid gland (confirmed by palpation and ultrasound); (4) elevated levels of TRAb. The inclusion criteria were as follows: (1) meeting the diagnostic criteria for GH; (2) pediatric patients aged 6–18 years old); (3) long-term ineffective ATD treatment (≥2 years) or ATD allergy; (4) unable to continue ATD treatment due to leukopenia (<3.0×10⁹/L) or severe liver dysfunction (alanine aminotransferase >3 times the upper limit of the normal reference range). The exclusion criteria were as follows: (1) patients with moderate-to-severe active Graves’ ophthalmopathy; (2) patients who received repeated RAI therapy; and (3) patients who did not complete the 6-month follow-up after RAI therapy. The study was approved by the Ethics Committee of Linyi People’s Hospital Affiliated to Shandong University (Approval number: 30067). Because this was a retrospective clinical study, the Ethics Committee of our hospital waived the need to obtain written informed content from all patients. All methods were performed in compliance with the Declaration of Helsinki’s tenets.

Figure 1.

The flowchart patient enrolment in the study. (WPS Office, Version12.9.0.19241, Beijing Kingsoft Office Software, Inc.).

Preparations Before Radioactive Iodine Therapy

1) Discontinuation of propylthiouracil (PTU) for 2 weeks or methimazole (MMI) for more than 3 days. 2) Low-iodine diet for at least 2 weeks. 3) Prior to receiving RAI therapy, all patients completed laboratory testing, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid-stimulating hormone receptor antibody (TRAb), and thyroperoxidase antibody (TPOAb). They also underwent thyroid palpation, thyroid color Doppler ultrasound, radioactive iodine uptake (RAIU), and thyroid scintigraphy. 4) Parents or legal guardians of the patients voluntarily signed an informed consent form to perform for RAI therapy.

Thyroid Volume and Weight Estimation

The thyroid weight was determined by 2 experienced ultrasound physicians through thyroid color Doppler ultrasound measurement and calculation. The formula for calculating the volume of a single lobe of the thyroid gland was π/6×width of lobe (cm)×height of lobe (cm)×length of lobe (cm). The total volume of the thyroid gland was the sum of the left and right lobe volumes, and the thyroid weight (in grams) was calculated assuming a density of 1.0 gram per milliliter thyroid tissue.

Administration of Radioactive Iodine Therapy

After assessment by experienced radiologists and pediatric endocrinologists, the dose of RAI was calculated based on thyroid weight and RAIU, as previously described [21]. When the thyroid weight was less than 20 grams, the patient received RAI therapy at a dosage of 0.1 mCi/gram of thyroid tissue; when the thyroid weight was 20–50 grams, the patient received RAI therapy at a dosage of 0.15 mCi/gram of thyroid tissue; but when the patient’s thyroid weight exceeded 50 grams, the dosage range increased to 0.2–0.3 mCi/gram thyroid tissue. The final dose of each patient was adjusted based on the thyroid weight and 24-h RAIU. It was calculated according to the following formula:

$$\text{Oral\hspace{0.17em}RAI\hspace{0.17em}dose\hspace{0.17em}}(\text{mCi})=\frac{\text{thyroid\hspace{0.17em}weight\hspace{0.17em}}(\text{gram})\hspace{0.17em}0.1-0.3\hspace{0.17em}(\text{mCi}/\text{gram})}{24\hspace{0.17em}\text{h\hspace{0.17em}RAIU\hspace{0.17em}}(\%)}$$

On the day of RAI therapy, all patients fasted and abstained from drinking for at least 2 hours. Then, the prescribed therapy was administrated orally in the form of sodium iodide 131I solution. After RAI therapy, all patients fasted for another 2 hours to avoid the effects of food on iodine absorption.

Outcome of Radioactive Iodine Therapy

All patients received routine follow-up clinical assessment every 1–3 months in the Nuclear Medicine Department of Linyi People’s Hospital after receiving RAI therapy. During each follow-up visit, thyroid function was assessed, and patients were classified into either the remission group or the failure group based on the outcome by the 6^th month. The criteria for the remission group were as follows: (1) euthyroid (FT3 3.5–6.5 pmol/L, FT4 11.5–22.7 pmol/L, TSH 0.55–4.78 μU/mL, and no symptoms of hyperthyroidism or hypothyroidism); (2) hypothyroidism (FT3 <3.5 pmol/L, FT4 <11.5 pmol/L, TSH >4.78 μU/mL, with or without symptoms of hypothyroidism) within 6 months’ follow-up. When hypothyroidism occurred during the follow-up period, levothyroxine replacement therapy was promptly administered. The criteria for the failure group were as follows: persistent hyperthyroidism (FT3 >6.5 pmol/L, FT4 >22.7 pmol/L, TSH <0.55 μU/mL, with or without symptoms of hyperthyroidism) after 6 months’ follow-up. Depending on the patient’s preference, they underwent repeated RAI therapy or received alternative treatment methods.

Statistical Analysis

Statistical analysis was performed using SPSS 22.0 software. For categorical data analysis, the chi-square test was used. For continuous data analysis, normality distribution was first assessed. Normally distributed data were analyzed using the independent-sample t test, while non-normally distributed data were analyzed using the Mann-Whitney U test. After screening for variables with statistically significant differences using univariate analysis, logistic regression analysis was conducted to identify factors influencing the success of RAI therapy for GH. Receiver operating characteristic (ROC) curve analysis was used to assess the impact of duration of GH and thyroid weight on treatment outcomes. A significance level of P<0.05 was considered statistically significant for all analyses.

Results

The Baseline Clinical Characteristics of Pediatric Patients with GH

Among the pediatric patients, there were 34 females and 10 males, aged 11–18 years, with a median age of 15 years. The average duration of the disease was 12 months. Six patients had a family history of hyperthyroidism. The main symptoms and signs of these patients included goiter, palpitation, tremors, irritability, and hyperphagia. Twenty-five patients experienced comorbidity, included leukopenia, abnormal liver function, and hypokalemic periodic paralysis, but none of them experienced atrial fibrillation. Thirty-seven patients had previously received ATD, while 7 patients did not receive ATD therapy due to drug allergies or leukopenia. However, before RAI therapy, 40 patients were still in a state of overt hyperthyroidism, and 4 patients were in a subclinical hyperthyroidism state (Table 1).

Table 1.

The baseline clinical characteristics of pediatric patients with GH.

Variables	Range
Sex (Female/Male)	34/10
Mean age at diagnosis (years)	15 (13.25, 16.75)
Mean age at RAI (years)	17 (16, 18)
Duration of GH (months)	12 (5, 36)
Family history of GH (yes/no)	6/38
Symptom and sign (yes/no)	44/0
Goiter	39/5
Palpitation	28/16
Tremors	13/31
Irritability	19/25
Hyperphagia	12/32
Comorbidity (yes/no)	25/19
Leukopenia	9
Abnormal liver function	8
Hypokalemic periodic paralysis	4
Atrial fibrillation	0
Two or more	4
ATD therapy history (yes/no)	37/7
Methimazole	36
Propylthiouracil	0
Both	1
None	7
Thyroid function before RAI (abnormal/normal)	44/0
Overt hyperthyroidism	40
Subclinical hyperthyroidism	4

Comparison of Clinical Variables Between the Remission Group and the Failure Group

The duration of follow-up was 6 to 67 months after RAI therapy. The overall remission rate of GH at 6 months after RAI therapy was 52.3% (23/44 individuals). In the remission group, only 1 patient was euthyroidism and 22 patients were hypothyroidism. The duration of GH, thyroid weight, and RAI dose had significant differences between the remission group and the failure group (P<0.05). However, there were no statistically significant differences in sex, age, family history of GH, FT3, FT4, TSH, TPOAb, TRAb, 2-hour RAIU, 6-hour RAIU, 24-hour RAIU, 2/24-hour RAIU, 6/24-hour RAIU, iodine dosage per gram of thyroid tissue, and actual iodine uptake per gram of thyroid tissue (Table 2).

Table 2.

Comparison of clinical variables between the remission group and the failure group.

	Remission group	Failure group	P
Sex (Female/Male)	18/5	16/5	0.870
Mean age at RAI (years)	16 (15, 18)	17 (16.5, 18)	0.134
Duration of GH (months)	12 (3, 24)	30 (6, 48)	0.009
Family history of GH (yes/no)	1/19	5/16	0.103
Thyroid weight (gram)	27.02 (21.3, 39.49)	50.41 (32.28, 56.96)	0.004
FT3	21.34 (15.33, 30.80)	27.37 (16.47, 30.80)	0.358
FT4	38.68 (31.08, 60.23)	51.42 (28.17, 88.69)	0.285
TSH	0.008 (0.005, 0.008)	0.008 (0.007, 0.009)	0.329
TPOAb	1300 (320.4, 1300)	1300 (1300, 1300)	0.073
TRAb	13.49 (8.33, 40)	22.82 (9.11, 39.15)	0.768
2 h RAIU	51.7 (36.5, 62.3)	40 (29, 52.75)	0.133
6 h RAIU	73.4 (60.4, 80.8)	69.5 (51.7, 74.8)	0.102
24 h RAIU	74.3 (66.1, 80.7)	67.2 (56.85, 76.85)	0.148
2 h/24 h RAIU	66.48 (56.72, 81.29)	65.46 (50.97, 76.04)	0.581
6 h/24 h RAIU	98.32 (92.93, 108.25)	92.49 (85.64, 104.95)	0.192
RAI dose (mCi)	8 (6, 10)	11 (9,15)	0.002
RAI dose (mCi/gram thyroid)	0.30 (0.23, 0.37)	0.27 (0.19, 0.39)	0.549
Actual RAI dose (%mCi/gram thyroid)	0.21 (0.15, 0.26)	0.18 (0.12,0.27)	0.378

Predictor of Remission After Radioactive Iodine Therapy

The results of logistic regression analysis showed that duration of GH disease and thyroid weight were the most important factors influencing the success of RAI therapy (Table 3). ROC curve analysis indicated that the areas under the curves for predicting the efficacy of RAI therapy using duration of GH and thyroid weight were 0.7229 (Figure 2A) and 0.7277 (Figure 2B), respectively. The duration of GH corresponding to the maximum Youden index was 27 months and the thyroid weight corresponding to the maximum Youden index was 50.17 g. Further analysis showed that the remission rate was significantly higher in the group with shorter duration (66.7% vs 21.4%) and smaller thyroid weight (68.8% vs 8.3%) (Table 4).

Table 3.

Logistic regression analysis to investigate predictor of remission after RAI therapy.

Variables	β	S.E.	Wald χ2	P	OR	95% CI
Duration of GH	0.042	0.021	3.925	0.048	1.043	1.000–1.088
Thyroid weight	0.056	0.025	4.898	0.027	1.058	1.006–1.111

Figure 2.

(A) The ROC curve analysis of duration of GH on RAI therapy. (B) The ROC curve analysis of thyroid weight and RAI therapy. (GraphPad Prism, Version 8.0.2.263, GraphPad Software, Inc.).

Table 4.

The effect of duration of GH and thyroid weight on radioactive iodine therapy.

		Remission group	Failure group	P
Duration of GH	<27 m	20	10	0.006
	>27 m	3	11
Thyroid weight	<50.17 g	22	10	0.001
	>50.17 g	1	11

The Adverse Effects of Radioactive Iodine Therapy

We did not detect any exacerbation or new development of dizziness, dyspnea, fever, insomnia, muscle cramps, and Graves’ ophthalmopathy. However, we observed several other adverse events in both groups (Table 5). A total of 4 patients had neck tenderness following RAI therapy, primarily those with relatively large thyroids. Their symptoms were alleviated after prednisone treatment. Two patients experienced nausea and vomiting, which resolved without further treatment. Five patients experienced palpitation symptoms, possibly related to a transient elevation of thyroid hormone levels; their heart rates were effectively controlled after increasing the propranolol dosage. One patient reported fatigue and weakness, which improved after rest. Another patient had cutaneous pruritus, possibly related to hyperthyroidism itself, and the symptom was relieved after loratadine treatment. All adverse events were mild and resolved during hospitalization. There were no differences in any events for 1 patient in the remission group vs failure group (30.4% vs 28.6%, P=0.892).

Table 5.

The adverse events after RAI in remission and failure groups.

	Remission group	Failure group
Any adverse events for one patient	7	6
Neck tenderness	2	2
Nausea and vomiting	1	1
Palpitation	3	2
Fatigue	0	1
Cutaneous pruritus	1	0

Discussion

Antithyroid drugs are the preferred therapy for pediatric patients with GH. However, the success rate of pediatric patients is significantly lower than in adults. Even after long-term treatment, the efficacy in some patients is still not ideal. Therefore, many patients need to choose other treatments when ATD treatment fails [8,22,23]. Due to the potential risks of surgery, such as damage to the parathyroid gland and recurrent laryngeal nerve [24–26], patients often choose RAI therapy when long-term ATD therapy was ineffective. However, there is no consensus on the dose of RAI in the treatment of pediatric patients with GH, and there are significant differences in the understanding of different physicians in clinical practice. This retrospective study analyzed 44 pediatric patients with GH who received RAI therapy in Linyi People’s Hospital from December 2018 to December 2023, aiming to find a reasonable therapeutic dose range and identifying the clinical factors affecting the treatment outcome.

Firstly, considering euthyroidism or hypothyroidism as indicators of treatment success, our study revealed that 52.3% of patients (23 out of 44) achieved remission within 6 months following RAI therapy, 22 patients became hypothyroid, and 1 patient remained euthyroid. We retrieved the recent relevant literature on RAI therapy for pediatric hyperthyroidism and found that our study’s remission rate falls within a reasonable range (50–95%), but it is lower than in some studies [12,20,27–31]. Currently, there are 2 different treatment approaches for RAI therapy in pediatric patients with hyperthyroidism: one is the fixed-dose administration regimen, and the other is the calculated-dose administration regimen. There have been fewer studies employing fixed-dose administration regimens than those using calculated-dose administration regimens. Nebesio et al administered a fixed dose of 14.7 mCi to 40 hyperthyroid patients, and 39 achieved hypothyroid status after a single treatment. However, no significant factors were identified that could predict when a patient receiving fixed-dose RAI would become hypothyroid [27]. In another study that utilized the fixed-dose regime, Mizokami et al (2007) reported that after implementing the fixed-dose RAI regimen with 13.0 mCi in, approximately 90% (68 out of 78) of the patients developed overt hypothyroidism following a single dose of RAI [28]. Numerous studies have used calculated-dose administration regimens, with significant variations in dosing ranges across different research institutions. Among high-dose studies, Rivkees reported a 95% treatment remission rate among patients who received 300–400 μCi of RAI per gram of thyroid tissue [20]. In medium-dose studies, Kaplowitz led a study involving 78 patients treated with a therapeutic dose of 232 μCi RAI per gram of thyroid tissue; 73% became hypothyroid, and 4% remained euthyroid [29]. Azizi and Amouzegar tracked 304 patients, 136 of whom were administered RAI at a dose of 200 μCi/g, resulting in a 66.2% hypothyroidism rate [12]. Namwongprom’s study included 27 pediatric patients treated with 150 μCi RAI per gram of thyroid tissue, with 45% remaining hyperthyroid after treatment, 41% becoming hypothyroid, and 15% euthyroid, which aligns with our findings [30]. In low-dose studies, Pinto found that among 22 patients treated with 100 μCi RAI per gram of thyroid tissue, 27% remained hyperthyroid and required additional treatment [31]. Mizokami et al reported that before 2006, their clinic used a RAI dose calculated to be 80 μCi/gram of thyroid tissue, but nearly half (18/39) of the patients needed repeated RAI treatments due to persistent hyperthyroidism [28]. Overall, the remission rate of a single treatment with RAI for pediatric patients with GH is 50–95%, the proportion of patients with euthyroidism after treatment is 0–15%, with higher remission rates expected when administering higher doses of RAI.

Secondly, our study found that thyroid weight and duration of GH were important factors affecting the efficacy of RAI therapy. The ROC curve analysis indicated that a thyroid weight of 50.17 grams served as the threshold for remission or failure of RAI therapy. Patients with a thyroid weight greater than 50.17 grams experienced a significantly lower remission rate compared to those with a smaller thyroid weight (8.3% vs 68.8%), aligning with the findings of Kaplowitz [29]. Previous studies reported that larger glands require higher doses of RAI to induce hypothyroidism. When thyroid volume exceeds 80 grams, the remission rate after RAI therapy is lower [18,20]. Therefore, surgery is the preferred option when thyroid volume is large. Among our treated patients, 27% had thyroid weights exceeding 50.17 g. However, due to fear of surgical complications, these patients were unwilling to undergo surgical treatment. Although we used the RAI dosage range increased to 0.2–0.3 mCi/gram thyroid tissue in these patients, the remission rate was still only 8.3%, which may explain the relatively low remission rate observed in our total patient cohort. Both Kaplowitz and Namwongprom [29,32] recommended a dose of RAI >0.25 mCi/gram of thyroid tissue to reduce the failure rate. Watanabe also confirmed that patients with larger thyroid volumes benefited from high-dose RAI therapy [33]. The “2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease” recommends a treatment dose of >0.4 mCi/gram of thyroid tissue for children with GH, which may have better treatment outcomes for patients with a thyroid weight >50 g [15]. Based on our study’s findings, we believe that a dosage of 0.15 mCi RAI per gram of thyroid tissue is appropriate for patients with thyroid weights below 50 grams. However, for patients with thyroid weights exceeding 50 grams, the dosage range of 0.2–0.3 mCi RAI per gram of thyroid tissue is insufficient. To achieve satisfactory therapeutic outcomes, a dosage exceeding 0.3 mCi RAI per gram of thyroid tissue should be administered. However, our study found that the remission rate of patients with GH lasting more than 27 months was significantly lower than that of patients with shorter disease duration (21.4% vs 66.7%). This is consistent with previous studies. Zhao et al found that patients with shorter disease duration had higher rates of hypothyroidism at 3 and 6 months after RAI treatment [34]. Shrinivas et al discovered that hyperthyroidism patients with shorter disease duration exhibited higher remission rates after low-dose RAI therapy [35]. Among the patients included in our study, up to 32% had a duration of GH exceeding 27 months, which may be another important reason for the relatively low remission rate. Patients with a prolonged disease duration often have larger and firmer thyroid glands and have typically undergone long-term ATD therapy, which explains their lower remission rate. For these patients, guidelines suggest that the dosage may be appropriately increased to improve the remission rate. However, there is currently no clear standard for dosage increase, and further research is still needed to determine the optimal therapeutic dose in the future.

Third, there is likely an association between patient selection and remission rates. All patients involved in this study were required to maintain a long-term low-iodine diet, as they belonged to an iodine-deficient population. Under prolonged iodine-deficient conditions, the thyroid gland develops autonomous function, this autonomous function may coexist with GH within the same gland. Since eliminating functional autonomy requires a relatively high radiation dose of 300–400 Gy, its presence may reduce the radiosensitivity of thyroid [36,37]. In addition, studies have confirmed that administering ATD prior to RAI treatment can lower the RAI treatment’s remission rate [38,39]. Among our patients, 84% (37 out of 44) had previously undergone long-term ATD treatment, which is likely associated with the relatively low remission rate.

Fourth, the remission group had higher iodine uptake rates at 2, 6, and 24 hours compared to the failure group. Additionally, the actual iodine uptake per gram of thyroid tissue standardized by the iodine uptake rate was also higher in the remission group. This suggests that the iodine uptake capacity of thyroid tissue may be an important factor affecting the remission rate of RAI therapy. However, due to the small sample size of this study, the statistical difference between the 2 groups on these indicators was not significant. In addition, several studies [40–42] have suggested a correlation between the levels of FT4 before therapy and the remission rates of RAI therapy. The study also found that the failed group had higher levels of FT3 and FT4, although the difference was not statistically significant. Tay et al [43] also suggested that higher levels of TRAb before therapy might reduce the remission rate of RAI therapy, but this correlation was not statistically significant in our study. Further studies with larger sample sizes are needed to confirm these findings.

As a retrospective study, this study has some limitations. Firstly, potential parameters associated with RAI treatment failure, such as the dose of ATD and complete thyroid test results at diagnosis, including FT3, FT4, TSH, and TRAb, were not available in most of the cases. Therefore, we could not determine whether the selected patients had more severe hyperthyroidism or were less responsive to drug therapy. Second, the follow-up time of the patients in this study ranged from 6 to 67 months. The relatively short follow-up period of 6 months for some failure patients may not be sufficient to obtain long-term treatment effect and recurrence rates, but this 6 months’ follow-up period is feasible in clinical practice, because if the patients were not cured during the 6-month follow-up period, the patients would receive further treatment. Third, this was a single-center, non-randomized, retrospective study with a limited sample size, which reduces statistical power, potentially exaggerating or underestimating relevant effects, and thereby compromising the reliability and generalizability of the conclusions. Despite these limitations, our data still provide interesting information on predictors of RAI treatment success and failure in pediatric patients. In contrast to other studies, we used ultrasound to determine the volume of the thyroid gland, which has a higher accuracy than palpation. In addition, the therapeutic doses we used for each patient were calculated based on thyroid volume and RAIU, which may be more accurate than using a universal fixed dose.

Conclusions

The results of this study suggest that disease duration and thyroid weight are important factors affecting the outcome of RAI therapy in pediatric patients with GH. Higher doses of RAI should be administered to patients with a disease duration exceeding 27 months or thyroid weight surpassing 50.17 g.

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

RAI

radioactive iodine

GH

Graves’ hyperthyroidism

ATD

antithyroid drug

PTU

propylthiouracil

MMI

methimazole

FT3

free triiodothyronine

FT4

free thyroxine

TSH

thyroid-stimulating hormone

RAIU

radioactive iodine uptake

TRAb

thyroid-stimulating hormone receptor antibody

TPOAb

thyroperoxidase antibody