The increased risk of thyroid cancer after thyroid irradiation in childhood has been recognized for nearly 50 years . Thus, a major concern of 131I therapy relates to the risk of thyroid cancer. Detractors of 131I therapy point to the increased rates of thyroid cancer and thyroid nodules observed in young children exposed to radiation from nuclear fallout at Hiroshima or after the Chernobyl nuclear reactor explosion.
The thyroid gland is unique in its developmental sensitivity to malignancy following radiation exposure. Individuals older than 20 years of age do not have an increased risk of thyroid cancer when exposed to low-level thyroid irradiation [71-73]. Yet, when individuals are less than 20 years of age at the time of low-level thyroid irradiation, the thyroid cancer risks increases the younger one is [71-73].
In addition to age, the radiation dose plays a major role in cancer risk [70-73]. The risk of thyroid cancer and thyroid nodules is highest with exposure to low or moderate levels of external radiation (0.1-25 Gy), and not with the considerably higher doses used internally to treat Graves' disease (>150 Gy) [70-74].
It is important to note that iodine deficiency and exposure to nuclides other than 131I may have contributed to the increased risk of thyroid cancer in the young following the Chernobyl reactor explosion [70-72]. In comparison, rates of thyroid cancer were not increased in the more than 3,000 children exposed to 131I from the Hanford reactor site in an iodine replete region . An increase in thyroid cancer has not been observed in about 6,000 children who received 131I for diagnostic procedures [72, 76].
The Cooperative Thyrotoxicosis Therapy Follow-up Study showed that long-term thyroid problems occur in children treated with lower, rather than higher doses of 131I. Thyroid adenomas developed in 30% of 30 children treated in one center with low doses of 131I estimated to result in thyroid exposure of 25 Gy [33, 50]. Yet, when children are treated with higher doses of 131I (100-200 Gy), the incidence of thyroid neoplasms was not increased .
Outcomes after 131I treatment of more than 1,200 children and adolescents treated with higher doses of radioiodine for Graves' disease have been reported . The duration of follow-up in these studies ranged from <5 to 15 years, with some subjects followed for more than 20 years. These studies have not revealed an increased risk of thyroid malignancy. The longest follow-up studies of children recently treated with 131I come from Read et al. . When more than 100 patients were surveyed nearly four decades after receiving radioactive iodine at ages ranging from 3 to 19 years, no adverse events or deaths could be attributed to 131I therapy . None of the patients developed thyroid cancer or leukemia. One individual developed breast cancer, and one individual developed colon cancer, numbers in keeping with the incidence of these malignancies in the population at large.
We are aware of four reported cases of thyroid malignancy in children previously treated with 131I (5 years of age at treatment with 50 |xCi/g; 9 years of age at treatment with 5.4 |xCi; 11 years of age at treatment with 1.25 |xCi; 16 years of age at treatment with 3.2 |xCi) . These individuals were treated with low doses of 131I. We are not aware of reports of thyroid cancer in patients treated with >100Gy of radioactive iodine for childhood Graves' disease that can be attributed to radioactive iodine therapy. Thus, low doses of 131I in children should be avoided. Ablation of the thyroid gland will decrease the risks of tumors and recurrence of hyperthyroidism. The child will need long-term thyroid hormone replacement, but such will be the situation if total thyroidectomy is performed.
Although radioactive iodine is being used in progressively younger ages, we do not know if there is an age below which high-dose 131I therapy should be avoided. Risks of thyroid cancer after external irradiation are highest in children less than 5 years of age and progressively decline with advancing age [70, 72, 78, 79]. If there is residual thyroid tissue in young children after radioactive iodine treatment, there is a theoretical risk of thyroid cancer. It may therefore be prudent to avoid radioactive iodine therapy in children less than 5 years. However, children as young as 1 year have been treated with radioactive iodine with excellent outcomes [6, 23].
Radiation exposure of the gonads during 131I therapy approximates 2.5 cGy, which is comparable to the gonadal exposure from a barium enema or an intravenous pyelogram . The literature contains data on 500 offspring born to approximately 370 subjects treated with 131I for hyperthyroidism during childhood and adolescence . The incidence of congenital anomalies reported among the offspring of patients treated with radioiodine does not differ from the incidence in the general population. In addition, there was no increased prevalence of congenital anomalies in the offspring of 77 patients treated for thyroid cancer in childhood with 80-700 |xCi of 131I . There is also no evidence of an increased rate of birth defects in survivors of the Hiroshima and Nagasaki atomic bomb blasts who were exposed to higher levels of external irradiation of the gonads than are associated with radioactive iodine therapy [25, 82].
In addition to thyroid cancer, potential influences of 131I therapy on other cancers need to be considered. Follow-up from the large cohort of the Cooperative Thyrotoxicosis Therapy Follow-up Study did not find increased risks of leukemia in the 131I-treated group, as compared with the drug and surgery treated groups . No increase in overall cancer mortality was seen in the 131I-treated patients either . In other studies, excess thyroid cancer mortality following 131I therapy for Graves' disease was observed during early, but not later, years of follow-up . This observation is believed to reflect mythological issues related to increased cancer surveillance and detection, rather than 131I effects .
Total-body radiation doses after 131I vary with age, and the same absolute dose of 131I will result in more radiation exposure to a young child than to an adolescent or adult [10, 59, 80, 86]. At 0, 1, 5, 10, 15 years of age, and in adulthood, respective total body radiation doses are 11.1, 4.6, 2.4, 1.45, 0.90, and 0.85rem per |xCi of 131I . Based on the Biological Effects of Ionizing Radiation Committee V (BEIR V) analysis of external radiation exposure, the theoretical risk of cancer death following acute radiation exposure is 0.16% per rem for children and 0.08% per rem for adults [87-89], although there is uncertainty associated with these projections [87-89]. Thus, if the same 10-^Ci dose is given to a 10-year-old child and an adult, total-body doses will be 14.5 and 8.5 rem, respectively, and the theoretical risks of cancer mortality will be 2.2 and 0.68%. These values can be compared with the natural life-time risk for cancer death of 20% [87, 89].
We do not have good dosimetry information regarding 131I use in children with Graves' disease to assess actual total body exposure and the long-term theoretical risks associated with this exposure, especially in young children. At present, data are not available to assess actual lifetime cancer risks in children treated with 131I or medication for Graves' disease.
Radiation exposure of the gonads during 131I therapy approximates 2.5 cGy, which is comparable to the gonadal exposure from a barium enema or an intravenous pyelogram . The literature contains data on 500 offspring born to approximately 370 subjects treated with 131I for hyperthyroidism during childhood and adolescence . The incidence of congenital anomalies reported among the offspring of patients treated with radioiodine does not differ from the incidence in the general population. In addition, there was no increased prevalence of congenital anomalies in the offspring of 77 patients treated in childhood with 80-700 |xCi of 131I . Furthermore, there was no evidence of an increased rate of birth defects in survivors of the Hiroshima and Nagasaki atomic bomb blasts who were exposed to higher levels of external irradiation of the gonads than are associated with radioactive iodine therapy .
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