Table 1.
Characteristics and outcomes of included studies reporting on the efficacy and side effects of RAI treatment in pediatric GD
| Study | Treatment goal | Iodine-131 activity | Outcome of RAI treatment | Short-term side effects | Long-term side effects |
|---|---|---|---|---|---|
| Azizi and Amouzegar, 2018 [36] | Hypothyroidism | Calculation based: 5.5 MBq/g thyroid tissue | 85.3% were euthyroid or hypothyroid after 1st RAI course; 14.7% needed a 2nd RAI course Three years after RAI therapy: 33.8% euthyroid 66.2% hypothyroid | None | None |
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| Ballai et al., 2015 [15] | Biochemical state of hypothyroidism or euthyroidism, and normal RAIU values 3 months after RAI | Fixed activity: 185 MBq | Remission rate after 1st course: With prior ATD: 70% (28% hypothyroid and 42% euthyroid) Without prior ATD: 82.5% (45% hypothyroid and 37.5% euthyroid) |
None | − |
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| Clark et al., 1995 [23] | Biochemical or clinical state of euthyroidism or hypothyroidism | Calculation based: 185–677.1 MBq Average 284.9±107.3 MBq = 5.96 MBq/g thyroid tissue |
Remission rate after 1st course: 83% Requiring a 2nd course for persistent hyperthyroidism: 17% | Vomiting (n = 3) Severe vomiting (n = 1) Mild radiation thyroiditis (n = 1) |
Solitary thyroid nodules (n = 2; 4 and 7 months after RAI) |
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| Cohen et al., 2015 [30] | No elevated T4 or T3, no suppressed TSH, and no use of ATD for at least 1 year after RAI | Calculation based: After thyroid ultrasound to determine gland size and RAIU study Mean activity for ablation: 9.72±7.95 MBq/g of thyroid tissue |
Remission rate after 1st course: 87.9% | None | No long-term side effects after 2.4-year follow-up (1 month-7.8 years) |
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| Crile and Schumacher, 1965 [17] | Euthyroidism after a single course of iodine-131 | Calculation based: Aiming at 1.85–3.7 MBq/g after estimating thyroid weight by palpation and RAIU at 24-h 74–1,443 MBq, with an average of 3.52 MBq/g of thyroid tissue |
Hyperthyroidism was controlled and did not reoccur in all 30 fully treated patients: After 1 course: 18 patients After 2 courses: 8 patients After 3 courses: 4 patients Clinical hypothyroidism (n = 6) |
Myxedema (n = 6) | No long-term side effects after an average follow-up of 6.5 years |
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| Enes Romero et al., 2014 [29] | Remission of GD | Calculation based: Mean RAI activity 403.3±40.33 MBq Range of RAI activity 314.5–481 MBq |
78.6% remission after 1st RAI course 100% final remission: 2 patients needed 2nd, and 1 patient needed 3rd RAI course 90% became permanent hypothyroid |
None | None |
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| Freitas et al., 1979 [21] | A state of euthyroidism or hypothyroidism | Calculation based: 3.7–5.55 MBq/g of thyroid tissue corrected for 24-h RAIU Mean activity of 521.7±458.8 MBq (111–3,019.2) |
One course: 37 patients (72.5%) Two courses: 12 patients Three courses: 1 patient Four courses: 1 patient Hyperthyroidism was controlled in 49 patients within 12 months 24 patients were hypothyroid within 12 months Recurrent hyperthyroidism in 2 patients after 2 and 11 years |
− | No long-term side effects after a mean follow-up period of 14.6±7.9 years (5–27) |
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| Getsuwan et al., 2016 [31] | Hypothyroidism or euthyroidism | Calculation based: Using the estimated thyroid weight Median first activity 444 MBq |
Hypothyroidism after 1st course: 71.7% Hyperthyroidism after 2nd course: 4.4.% |
None | No long-term side effects after 42.5 months of follow-up |
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| Hayek et al., 1970 [19] | Euthyroidism | Calculation based: Before 1962: 5.92 MBq/g of estimated thyroid weight After 1962: maximal 2.96 MBq/g of estimated thyroid weight Single activity: 74–740 MBq Maximal cumulative activity was 1,184 MBq with an average of 244.2 MBq and a median activity of 177.6 MBq Treatment before 1948: iodine-130 (n = 2) |
Remission after single course: n = 25 (83.3%) Requirement of 2nd course: n = 5 Euthyroidism at last follow-up: n = 22 Permanent hypothyroidism at last follow-up: n = 8 Recurrent hyperthyroidism with benign nodular hyperplasia after 17 years: n = 1 |
− | No long-term side effects; multinodular benign goiter in one patient 17 years after RAI |
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| Kaplowitz et al., 2020 [33] | Normal or low T4 values | Calculation based: aiming at delivering 7.4 MBq/g of thyroid tissue | 73% hypothyroid 4% euthyroid Six patients received a 2nd RAI course at a mean of 15 months after the first RAI Smaller thyroid size (36.5 vs. 47.4 g; p = 0.037) and higher RAI activity (8.95 vs. 7.84 MBq/g; p = 0.013) associated with higher likelihood of hypothyroidism |
− | − |
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| Kogut et al., 1965 [18] | Euthyroidism | 0.026–0.16 MBq in one or multiple courses* | Follow-up in 16 patients: Good response to 1 course (n = 12; 75%) Euthyroid (n = 10) Hypothyroidism (n = 5) Requiring a 2nd course (n = 4) |
− | Papillary thyroid carcinoma (no metastases) in 1 patient 20 months after 2nd RAI course; no cases of leukemia |
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| Moll and Patel, 1997 [24] | Euthyroidism | Calculation based: 3.7–7.4 MBq/g thyroid tissue; or 37–55.5 MBq per activity Administered in 1 or 2 courses (3–6 months apart) | Remission rate after 1 st RAI course: Patients with prior ATD: 53% euthyroid or hypothyroid Primary RAI therapy: 87.5% euthyroid, 12.5% hypothyroid |
None | None |
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| Nakatake et al., 2011 [28] | Hypothyroidism and decrease in thyroid volume | Calculation based: RAI activity based on thyroid weight corrected for estimated 24-h RAIU Mean activity: 6.81±3.11 MBq/g |
One year after RAI therapy: 59.2% hypothyroid 16.3% euthyroid Percentage of hypothyroidism based on administered activity: 4.44 MBq/g: 48% 7.4 MBq/g: 55% 11.1 MBq/g: 85% Higher RAI activity in hypothyroid versus nonhypothyroid patients: 7.49 versus 5.78 MBq/g (p = 0.048) Decrease in thyroid volume 1 year after RAI: 34.5 to 8.3 mL; p < 0.001 |
− | − |
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| Nebesio et al., 2002 [14] | State of hypothyroidism | Fixed activity of 555 MBq; delivered activity ranged 510.6–577.2 MBq | 97.5% hypothyroid after 1st course One patient (2.5%) required a 2nd course** |
− | − |
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| Pavia et al, 2002 [35] | Euthyroidism or hypothyroidism | Activity related to the size of the goiter ranging from 222 to 1,924 MBq In single course when activity <370 MBq In 2 courses when activity >370 MBq (interval 2 months) |
Hypothyroidism in 54.5% Five patients needed a 2nd course of RAI based on the treatment protocol |
Local inflammation (n = 1) | None |
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| Pinto et al., 2007 [27] | Reaching hypothyroidism 6–12 months after RAI |
Calculation based: 3.7 MBq/g thyroid tissue adjusted for 6-h RAIU Mean activity in successful cases with a single course of RAI: 377.8 MBq±151.7 |
Remission rate after 1st course: 73% | − | − |
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| Read et al., 2004 [26] | State of euthyroidism, based on clinical findings and PBI for 3–5 months after RAI | Calculation based: RAI activity based on thyroid weight and 24-h RAIU Mean activity ranged from approximately 129.5 to 240.5 MBq |
64% was euthyroid or hypothyroid (32%) after 1st course of RAI 6 patients had a recurrence of hyperthyroidism at least 8 years after RAI |
None | One patient developed hyperparathyroidism 14 years after RAI; no cases of thyroid cancer, leukemia; no deleterious effects on the progeny of males/females (36-years follow-up) |
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| Rivkees and Cornelius, 2003 [25] | State of hypothyroidism 12 months after RAI | Calculation based: RAI activity based on thyroid weight (determined by palpation and ultrasound) and 24-h RAIU Group 1: 2.96–4.44 MBq/g thyroid tissue (n = 7) Group 2: 7.4–9.25 MBq/g thyroid tissue (n = 8) Group 3: 11.1–14.99 MBq/g thyroid tissue (n = 16) |
Group 1: 42.8% hypothyroid, 28.6% euthyroid Group 2: 62.5% hypothyroid, 0% euthyroid Group 3: 93.75% hypothyroid; 6.25% euthyroid |
Palpitations 5 days after RAI (n = 1) | − |
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| Safa et al, 1975 [20] | Euthyroidism or hypothyroidism | Calculation based: RAI activity based on thyroid weight and RAIU Aiming at 3.7–7.4 MBq/g thyroid tissue Mean activity of 360.75±240.5 MBq, range 107.3–1,147 MBq |
Hyperthyroidism was controlled within 1–14 months (n = 85) One course: 66 patients (75.8%) Two courses: 13 patients Three courses: 6 patients Four courses: 2 patients At last follow-up visit (n = 76): Euthyroidism (n = 30) Hypothyroidism (n = 35) Subnormal response to TSH stimulation (n = 11) Recurrence of thyrotoxicosis in 1 patient after 11 years |
− | No long-term side effects reported after a follow-up of 5–24 years |
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| Sheline et al., 1961 [34] | Activity varied from 74 to 233.1 MBq | All patients who developed nodules were euthyroid | − | Multiple follicular adenomas in 6 female patients, of whom 5 patients also developed Hashimoto thyroiditis | |
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| Starr et al., 1964 [16] | Euthyroidism | <37 MBq (n = 8) 37–111 MBq (n = 25) 111–266.4 MBq (n = 25) 296–555 MBq (n = 4) 1,080.4 MBq in (n = 1) |
58% became euthyroid or hypothyroid after 1st RAI course | None | None |
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| Wu et al., 2016 [32] | No additional RAI courses, thyroidectomy or ATD required for at least 6 months after RAI | Calculation based: RAI activity based on thyroid weight (determined by palpation or ultrasound) and 24-h RAIU Aiming at 3.7–7.4 MBq/g thyroid tissue Mean first activity of 414.4±118.4 MBq |
Remission rate after 1st RAI course: 73.1% | None | − |
The studies in this table are listed in an alphabetical order based on the name of the first author. GD, Graves' disease; ATD, antithyroid drugs; g, gram; MBq, megabecquerel; n, number of patients; PBI, protein bound iodine; RAI, radioactive iodine; RAIU, radioactive iodine uptake; T3, tri-iodothyronine; T4, tetraiodothyronine; TSH, thyroid-stimulating hormone; -, not evaluated in this study. “The used activity was based on the original study-reported activity of 0.7–4.3 “microcurie.” Based on the numbers used and the therapeutic effect described, it is however likely that the unit used is erroneous and that instead “millicurie” would have been appropriate. “One additional patient never became hypothyroid after RAI and was therefore excluded from further analysis by the authors (read from Figure 1 of the article).