Iodine nutrition and the risk from radioactive iodine: a workshop report in the chernobyl long-term follow-up study.

The major fallout of radionuclides from the nuclear power station accident at Chernobyl on 26 April, 1986, occurred in regions of Ukraine and Belarus that are believed to be moderately deficient in dietary iodine. On 17 November, 2000, in conjunction with the Ukraine-Belarus-USA study of developing thyroid disease in a cohort of individuals exposed as children, a workshop was held to review what is known about iodine nutrition in the region, how this might influence the risk of thyroid tumor formation from radioiodine, and whether and how iodine nutrition should be monitored in this long-term project. This report is a summary of the workshop proceedings. Although no precise information about iodine intake in 1986 was found, the prevalence of mild goiter in the region's children suggested iodine deficiency and urinary iodine measurements begun in 1990 indicated that mild to moderate deficiency existed. Increased thyroid iodine uptake and increased thyroid size in 1986 resulting from iodine deficiency would have had counteracting influence on the thyroid radiation dose and knowledge of these parameters is required for dose reconstruction. More problematic is the possible role of iodine deficiency in the years following the accident. Theoretically, the resulting increase in thyroid cellular activity might increase the risk of tumorigenesis but experimental or clinical evidence supporting this hypothesis is meager or absent. Despite this limitation it was considered important to monitor iodine nutrition in the cohort subjects in relation to their place of residence and over time. Methods to accomplish this were discussed.     

Childhood thyroid cancers and radioactive iodine therapy: necessity of precautious radiation health risk management

One of the lessons from Chernobyl's legacy on health impact beyond 20 years is not only how to detect and treat the patients with radiation-associated thyroid cancers but how to follow up those who received radioactive iodine treatment repetitively after surgery in order to monitor any recurrence/worsening and also how to predict the risk of secondary primary cancers for their lifetime period. To evaluate the possibility of second primary tumors after radioactive iodine treatment, we reviewed the reports on risks from both external and internal radiation exposure, especially at high doses during childhood through an internet service of the National Library of Medicine and the National Institutes of Health, PubMed by the end of June, 2007, together with our own experience of Chernobyl childhood thyroid cancers. Children who were internally exposed after Chernobyl accident have a long-term risk of well differentiated thyroid cancers. Once they have disease, ironically radioactive iodine ablation is one of the useful therapies after surgical treatment. Elevated risks of solid cancers and leukemia have been found in radioiodine-treated patients, however, so far precious few reports from Chernobyl thyroid cancer patient were published. To reduce the adverse effects of radioactive iodine therapy on non-target tissues, recombinant human TSH has been applied and proved effective. Period of latency of second primary cancers may be very long. Therefore patients treated with high activities of radioactive iodine, especially children cases, should be carefully followed up during their whole lifespan.     

Risk of thyroid cancer after the Fukushima nuclear power plant accident

The appropriateness of the initial response and countermeasures taken following the Fukushima nuclear power plant accident after the Great East Japan Earthquake on March 11, 2011 should be further examined. Implementation of a prospective epidemiological study on human health risks from low-dose radiation exposure and comprehensive health protection from radiation should be emphasized on a basis of the lessons learnt from the Chernobyl nuclear power plant accident. In contrast, the doses to a vast majority of the population in Fukushima were not high enough to expect to see any increase in incidence of cancer and health effects in the future, however, public concerns about the long-term health effects of radioactive environmental contamination have increased in Japan. Since May 2011, the Fukushima Prefecture started the Fukushima Health Management Survey Project with the purpose of long-term health care administration and early medical diagnosis/treatment for prefectural residents. In this report, risk and countermeasures of thyroid cancer occurrence after nuclear accidents, especially due to early exposure of radioactive iodine, will be focused upon to understand the current situation of risk of thyroid cancer in Fukushima, and the difficult challenges surrounding accurate estimations of low-dose and low-dose rate radiation exposures will be discussed.     

Radioiodine-induced thyroid cancer: Studies in the aftermath of the accident at Chernobyl.

While a great deal is known about the relationship between external radiation exposure and thyroid cancer, much less is known about the oncogenic effects of internal radiation exposure from isotopes of iodine. The accident at the Chernobyl nuclear power plant released massive quantities of radioiodine isotopes into the atmosphere. The large number of ensuing thyroid cancers in exposed children leaves little doubt that these malignancies have occurred as a result of the accident. However, carefully planned epidemiological studies are needed to confirm that these are due predominantly to I-131 exposure, to determine the dose-response relationship, to monitor for continuing effects and to evaluate other contributing factors. Preliminary evidence indicates that there is a distinct pattern of somatic genetic changes in the thyroid cancers from the Chernobyl area.     

Thyroid Cancer Following Exposure to Radioactive Iodine

The thyroid gland is one of the most sensitive organs for radiation-induced oncogenesis and the magnitude of the risk from external radiation is well understood. This is not the case for internal radiation derived from the radioiodines, a matter of practical importance because of medical use and potential accidental exposure. This article reviews current knowledge derived from the follow-up of patients receiving diagnostic or therapeutic 131I and populations exposed to radioactive fallout. The latter includes the nuclear power station accident at Chernobyl and the results of atomic bomb development and testing at Hanford, the Nevada Test Site and the Marshall Islands. The most cogent information comes from Chernobyl where an epidemic of childhood thyroid cancer has followed exposure to radioiodine that was mainly 131I. Although much has been learned from this experience about the nature of radioiodine induced thyroid cancer in young children, the reconstruction of thyroid radiation doses is too preliminary to provide accurate knowledge of the risk in comparison to that from external radiation. In the Marshall Islands, much of the exposure was from short-lived radioiodines as well as external radiation, obviating the possibility to determine the risk from 131I. Exposure to 131I in the continental United States from atomic bomb testing is expected to have caused some thyroid cancers, but only in the immediate vicinity of the Nevada Test Site has any evidence of radiation-induced thyroid neoplasms been adduced. This evidence is minimally significant statistically, and not significant for thyroid cancer per se. Medical use of radioiodine has not been observed to cause thyroid cancer but very few of the patients studied were young children, the group most sensitive to thyroid radiation. Despite these limitations, this information is sufficient to make some suggestions concerning protective measures in the case of nuclear accidents and the follow up of individuals who have been exposed.     

Thyrotoxic thyroiditis after radiotherapy for Hodgkin's disease

Exposure of the thyroid gland to ionizing radiation has been associated with a variety of abnormalities. Among these are tardive hypothyroidism and an increased risk of developing thyroid nodules and cancer. Although acute thyroiditis has been known to complicate radioactive iodine 131 therapy, it has rarely been associated with external beam irradiation. Thyrotoxic painless thyroiditis developed in two patients after mantle-field irradiation for Hodgkin's disease.     

ret/PTC activation is not associated with individual radiation dose estimates in a pilot study of neoplastic thyroid nodules arising in Russian children and adults exposed to Chernobyl fallout

BACKGROUND: Ionizing radiation is the strongest risk factor known for the development of thyroid neoplasia. While previous studies have demonstrated a high prevalence of ret/papillary thyroid cancer (PTC) activation in cohorts of patients developing thyroid nodules after childhood exposure to ionizing radiation, no study has directly compared ret/PTC activation with individual estimates of radiation dose to the thyroid. This study combines individual thyroid dosimetry data with molecular analysis of surgically removed thyroid nodules in order to determine if ret/PTC activation in thyroid nodules is associated with increasing estimated radiation dose from Chernobyl. METHODS: This pilot study included adults and children diagnosed with PTC (n = 76) and children diagnosed with follicular adenomas (n = 24) during May 1986 through December 1999, who were living in the Bryansk Oblast of the Russian Federation at the time of the Chernobyl accident, who had paraffin-embedded thyroid surgical samples available and for whom an individual dose to the thyroid could be estimated. The frequency of ret/PTC activation was determined using RT-PCR analysis. Individual radiation doses to the thyroid were estimated using a semiempirical model, and data were collected by detailed interview, primarily of the participant's mother. RESULTS: ret/PTC oncogene activation was detected in 23.8% (5/21) and 14.5% (8/55) of the childhood and adult PTC cases, respectively, and 8.3% (2/24) of the follicular adenoma cases. No statistically significant differences were noted in age at the time of exposure or diagnosis, gender, latency period, or estimated radiation dose between PTC patients with or without ret/PTC activation. Further, no significant dose-response relationship was detected among PTC patients with ret/PTC activation. CONCLUSIONS: Factors other than individual thyroid radiation doses may influence the development and subsequent detection of ret/PTC oncogene activation in radiation related PTC arising in the Bryansk Oblast of the Russian Federation in the aftermath of the Chernobyl accident.     

Iodine and cancer.

Thyroid carcinomas are the most frequent endocrine malignancies. Among thyroid carcinomas the most frequent types are the differentiated forms (follicular, papillary or mixed papillary-follicular), whereas anaplastic thyroid carcinoma and medullary thyroid carcinomas are rare. Animal experiments have demonstrated a clear increase in incidence of thyroid epithelial cell carcinomas after prolonged iodine deficiency leading to a situation of the thyroid gland by thyrotropin and possibly other growth factors. However, the overall incidence of differentiated thyroid carcinoma is generally not considered to be influenced by the iodine intake of a population, whereas the distribution of the types of thyroid carcinoma seems to be related to the intake of iodine, with fewer of the more aggressive follicular and anaplastic carcinomas and more papillary carcinomas in iodine rich areas. Populations starting iodine prophylaxis demonstrate an increase in the ratio of papillary to follicular carcinoma. Because a population with higher iodine intake usually has fewer benign nodules in the thyroid gland and the incidence of thyroid carcinomas is similar to an iodine-deficient region, the diagnostic work-up of nodules in the thyroid gland may become affected. The incidence of other cancers, such as breast cancer, may be influenced by the iodine intake, but too few studies are available at present. The present article summarizes available data from both epidemiological studies, animal experiments, and basic gene transfection studies. The overall incidence for a relationship between iodine and cancer is poor and future studies are warranted.     

Thyroid disorders in mild iodine deficiency.

Comparative epidemiologic studies in areas with low and high iodine intake and controlled studies of iodine supplementation have demonstrated that the major consequence of mild-to-moderate iodine deficiency for the health of the population is an extraordinarily high occurrence of hyperthyroidism in elderly subjects, especially women, with risk of cardiac arrhythmias, osteoporosis, and muscle wasting. The hyperthyroidism is caused by autonomous nodular growth and function of the thyroid gland and it is accompanied by a high frequency of goiter. Pregnant women and small children are not immediately endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable. Moreover, a shift toward less malignant types of thyroid cancer and a lower radiation dose to the thyroid in case of nuclear fallout support that mild-to-moderate iodine deficiency should be corrected. However, there is evidence that a high iodine intake may be associated with more autoimmune hypothyroidism, and that Graves' disease may manifest at a younger age and be more difficult to treat. Hence, the iodine intake should be brought to a level at which iodine deficiency disorders are avoided but not higher. Iodine supplementation programs should aim at relatively uniform iodine intake, avoiding deficient or excessive iodine intake in subpopulations. To adopt such a strategy, surveillance programs are needed.     

Nuclear detonation, thyroid cancer and potassium iodide prophylaxis

The recent nuclear disaster at Japan has raised global concerns about effects of radioactive leakage in the environment, associated hazards, and how they can be prevented. In this article, we have tried to explain about the guidelines laid down by World Health Organization for a potassium iodide prophylaxis following a nuclear disaster, and its mechanism of action in preventing thyroid cancer. Data was collected mainly from the studies carried out during the Chernobyl disaster of Russia in 1986 and the hazardous effects especially on the thyroid gland were studied. It was seen that radioactive iodine leakage from the nuclear plants mainly affected the thyroid gland, and especially children were at a higher risk at developing the cancers. Potassium Iodide prophylaxis can be administered in order to prevent an increase in the incidence of thyroid cancers in the population of an area affected by a nuclear disaster. However, one has to be cautious while giving it, as using it without indication has its own risks.     

Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey

Around 3-4 billion people in the world are covered by iodine supplementation programs to prevent developmental brain damage and other iodine deficiency (ID) disorders. Mild ID is associated with more hyperthyroidism and less hypothyroidism in the population than a high iodine intake. Knowledge of the iodine intake levels where the shifts in incidences occur is important for planning of iodine supplementation programs. A computer-based register linked to thyroid diagnostic laboratories was used to continuously identify all new cases of overt hyper- and hypothyroidism in two population cohorts with moderate and mild ID, respectively (Aalborg, n = 310,124; urinary iodine, 45 micro g/liter; and Copenhagen, n = 225,707; urinary iodine, 61 micro g/liter). The investigation was initiated before iodization of salt in Denmark and was part of the monitoring program. In 1997-1998, the incidence rate of overt hyperthyroidism was high in the area with the lowest iodine intake (92.9/100,000 per year) compared with the area with only mild ID (65.4/100,000 per year). Standardized rate ratio was 1.49, and 95% confidence interval was 1.22-1.81. The opposite relationship was present for overt hypothyroidism (moderate ID, 26.5/100,000 per year; mild ID, 40.1/100,000 per year; standardized rate ratio, 0.73; 95% confidence interval, 0.55-0.97). The different incidence rates were confirmed during each of the two following years. The results of this prospective investigation of the incidence of overt hyper- and hypothyroidism suggest that iodine supplementation of a population may increase the incidence of overt hypothyroidism, even if the population is moderately iodine-deficient. In such a population, the increase in risk of hypothyroidism should be weighed against the risk of ID disorders such as hyperthyroidism due to multinodular toxic goiter. The optimal level of iodine intake to prevent thyroid disease may be a relatively narrow range around the recommended daily iodine intake of 150 micro g.     

Morphologic characteristics of chernobyl-related childhood papillary thyroid carcinomas are independent of radiation exposure but vary with iodine intake

BACKGROUND: The Chernobyl accident caused an unprecedented increase in papillary thyroid carcinoma (PTC) incidence with a surprisingly short latency and unusual morphology. We have investigated whether unexpected features of the PTC incidence after Chernobyl were radiation specific or influenced by iodine deficiency. METHODS: PTCs from children from Belarus, Ukraine, and the Russian Federation exposed to fallout from Chernobyl were compared with PTCs from children not exposed to radiation from the same countries, from England and Wales (E&W) and from Japan. The degree and type of differentiation, fibrosis, and invasion were quantified. RESULTS: There were no significant differences between PTCs from radiation-exposed children from Belarus, Ukraine, and the Russian Federation and PTCs from children from the same countries who were not exposed to radiation. Childhood PTCs from Japan were much more highly differentiated (p < 0.001), showed more papillary differentiation (p < 0.001) and were less invasive (p < 0.01) than "Chernobyl" tumors, while tumors from E&W generally showed intermediate levels of degree and type of differentiation and invasion. There was a marked difference between the sex ratios of children with PTCs who were radiation exposed and those who were not exposed (F:M exposed vs. unexposed 1.5:1 vs. 4.2:1; chi(2) = 7.90, p < or = 0.01005). CONCLUSIONS: The aggressiveness and morphological features of Chernobyl childhood PTCs are not associated with radiation exposure. The differences found between tumors from the Chernobyl area, E&W, and Japan could be influenced by many factors. We speculate that dietary iodine levels may have wide implications in radiation-induced thyroid carcinogenesis, and that iodine deficiency could increase incidence, reduce latency, and influence tumor morphology and aggressiveness.     

Childhood thyroid cancer in Belarus, Russia, and Ukraine after Chernobyl and at present

Thyroid cancer in children is usually rare, but in the individuals exposed to radiation risk of disease increases considerably. After the Chernobyl accident in 1986, an over 10-fold maximal elevation in the incidence of thyroid cancer was registered about a decade later, cumulatively resulting in more than a thousand of newly diagnosed cases in children who lived in the territories of Belarus, Russia, and Ukraine affected by radioactive fallouts. Experience from the epidemic substantially promoted knowledge in clinical pediatric oncology, pathology and basic sciences. This article overviews epidemiology, clinical features, results of treatment and follow-up of childhood patients with radiation-induced Chernobyl thyroid cancer in comparison to sporadic cases diagnosed at present. In addition, we discuss general issues of pathology and molecular findings in childhood thyroid carcinomas.     

Urinary iodine levels and thyroid diseases in children; comparison between Nagasaki and Chernobyl.

We evaluated the incidence of childhood thyroid diseases and urinary iodine levels in Nagasaki, Japan and in Gomel, Belarus, which was greatly radio-contaminated by the Chernobyl accident, in order to obtain the comparative data of thyroid diseases between iodine-rich (Japan) and -deficient (Belarus) areas. In Nagasaki, the median level of urinary iodine, measured by ammonium persulfate digestion in microplate method, was 362.9 microg/L. In order to evaluate the geographical differences in Japan, other samples were collected in Hamamatsu and in South Kayabe, Hokkaido, where the median levels were 208.4 microg/L and 1015.5 microg/L, respectively. Furthermore, thyroid screening by ultrasound (US) in Nagasaki revealed only four cases that showed goiter (1.6%) and two cases (0.8%) that had cystic degeneration and single thyroid cyst. There was no evidence of thyroid nodule detected by US examination. In contrast, the median of urinary iodine level was 41.3 microg/L in Gomel. The incidences of goiter (13.6%) and echogenic abnormality (1.74%) in Gomel were much higher than in Nagasaki, suggesting the critical involvement of iodine deficiency in increased childhood thyroid abnormality around Chernobyl. Radioactive iodine released just after the Chernobyl accident may have influenced predominantly children residing in iodine-deficient areas. Our results suggest that management of thyroid screening for schoolchildren at ordinary times may be beneficial for monitoring the adverse effects of radioactive iodine from the standpoint of future prospective study.     

Autoimmune thyroid disease associated with environmental thyroidal irradiation.

Reports of increased rates of thyroid disease in populations exposed to radiation as a result of the Chernobyl accident have increased awareness and concern about the risk of autoimmune-related thyroid disease possibly associated with environmental radiation exposure. While the association between thyroidal irradiation and an increased risk of thyroid neoplasia is well established, much less attention has been devoted to the potential effects of environmental irradiation on the function of the thyroid. However, since the Chernobyl accident new studies have been published that appear to link radiation exposure to an increased risk of autoimmune thyroiditis. In order to assess the plausibility of this association, we reviewed published studies that evaluate the possible association between environmental thyroidal radiation and the presence of antithyroid antibodies as well as autoimmune thyroid disease (hypothyroidism and hyperthyroidism). These data have not been summarized elsewhere. Although some epidemiologic evidence of an association exists, long-term, well-designed studies are needed to accurately evaluate the complex association between low-dose environmental radiation exposure and clinically significant non-neoplastic thyroid disease. The results of these studies will be important in determining the appropriate clinical follow-up of persons exposed to environmental thyroidal irradiation.     

Environmental iodine intake affects the type of nonmalignant thyroid disease.

The relationship between the iodine intake level of a population and the occurrence of thyroid diseases is U-shaped with an increase in risk from both low and high iodine intakes. Developmental brain disorders and endemic goiter caused by severe iodine deficiency may seriously deteriorate overall health status and economic performance of a population. Severe iodine deficiency with a median 24-hour urinary iodine excretion of the population below 25 microg needs immediate attention and correction. Less severe iodine deficiency with median urinary iodine excretion below 120 microg per 24 hours is associated with multinodular autonomous growth and function of the thyroid gland leading to goiter and hyperthyroidism in middle aged and elderly subjects. The lower the iodine intake, the earlier and more prominent are the abnormalities. At the other end of the spectrum, severely excessive iodine intake starting at median urinary iodine excretion levels around 800 microg per 24 hours is associated with a higher prevalence of thyroid hypofunction and goiter in children. A number of studies indicate that moderate and mild iodine excess (median urinary iodine >220 microg per 24 hours) are associated with a more frequent occurrence of hypothyroidism, especially in elderly subjects. The exact mechanism leading to this has not been clarified, and more studies are needed to define the limits of excessive iodine intake precisely. Due to the frequent occurrence of thyroid disorders, proper monitoring and control of the population iodine intake level is a cost-effective alternative to diagnosing, therapy and control of the many individual cases of thyroid diseases that might have been prevented.     

The impact of 25 years of iodine prophylaxis on the adult thyroid weight in Finland

The effect of iodine prophylaxis on endemic goiter was studied in an adult Finnish population by comparing autopsy records from 1959 and 1984. In the 1950's the iodine intake calculated both from urinary excretion of stable iodine and from food analysis data was 50-70 micrograms per day the intake being lower in the main endemic area in the eastern part of the country. The use of iodized salt raised these figures only by 15 micrograms per day. At the beginning of the 1980's the iodine intake calculated in the same way was around 300 micrograms per day all over the country. Initially 696 records from 1959 and 525 from 1984 were analyzed. Excluded were cases with primary or secondary malignant thyroid tumors, autopsies with incompletely recorded thyroid weight, and autopsies from patients submitted to pituitary or thyroid surgery or radiation therapy. Finally, 318 cases from 1959 and 478 from 1984 were accepted. A significant decrease in thyroid weight from a mean of 44 to a mean of 34 g was observed. The difference between the two populations was most marked in the age groups below 45 yr. In these age groups the mean thyroid weight was about 20-27 g which can be regarded as normal. In the age groups over 75 years there were no significant differences. These data indicate that the iodine prophylaxis gradually eradicates the endemic goiter in Finland but that it requires still some 25-35 yr before it has disappeared also in the oldest age groups.     

碘与甲状腺疾病

微量元素碘摄入过低或过高均可诱发各种甲状腺疾病。碘摄入量过低与结节性甲状腺肿以及甲状腺恶性肿瘤的患病率有一定的联系,而碘摄入量过高与多种甲状腺疾病（包括结节性甲状腺肿、甲状腺功能亢进症、甲状腺功能减退、自身免疫性甲状腺疾病、甲状腺肿瘤等）的相关性已经得到不同文献的证实。为防治缺碘性甲状腺疾病推行补碘策略后,某些地区在碘摄入量增加的情况下却发现一些甲状腺疾病的患病率也有所增加。现对近年来流行病学、临床研究、分子生物学等领域的相关研究进展进行归纳与总结,并探讨碘摄入量对甲状腺疾病的影响及其相应作用机制。     

碘与甲状腺疾病

微量元素碘摄入过低或过高均可诱发各种甲状腺疾病.碘摄入量过低与结节性甲状腺肿以及甲状腺恶性肿瘤的患病率有一定的联系,而碘摄入量过高与多种甲状腺疾病(包括结节性甲状腺肿、甲状腺功能亢进症、甲状腺功能减退、自身免疫性甲状腺疾病、甲状腺肿瘤等)的相关性已经得到不同文献的证实.为防治缺碘性甲状腺疾病推行补碘策略后,某些地区在碘摄入量增加的情况下却发现一些甲状腺疾病的患病率也有所增加.现对近年来流行病学、临床研究、分子生物学等领域的相关研究进展进行归纳与总结,并探讨碘摄入量对甲状腺疾病的影响及其相应作用机制.     

Thiocyanate in food and iodine in milk: from domestic animal feeding to improved understanding of cretinism.

Transport of iodine in the mammary gland into breast milk plays a central role in various fields of prevention of thyroid diseases. First, a sufficient content of iodine in the mother's milk is necessary for normal brain development in the breastfed child. This is attained by expression during lactation in the mammary gland of the sodium iodide symporter (NIS), also responsible for iodine transport in the thyroid. Milk iodine content varies with the iodine intake of the mother, and urinary iodine excretion in groups of mothers seems to be a valuable indicator of the iodine status of their breastfed children. Second, iodine in dairy products provides a considerable part of iodine intake in many populations. Thiocyanate from rapeseed feeding of cows decreases milk iodine content, probably by competitive inhibition of NIS in the mammary gland. Alterations in feeding of dairy cows may alter the iodine content of consumer milk, and this may influence the risk of thyroid diseases in the population. Thiocyanate inhibition of iodine transport into milk may also be operative in humans with a high thiocyanate intake. This could further impair iodine status in breastfed children in low-iodine intake areas of the world. It can be speculated that a low-iodine content of mother's milk because of inhibition of NIS in the mammary gland may be one factor of importance for development of myxedematous cretinism.