Radiation in

Chelyabinsk

Region.

Created by:

Kulish Dmitry

11^a

The influence of ionizing radiation on the incidence of autoimmune thyroiditis in the region of radioactive contamination

 

 

 

 

 

Autoimmune thyroiditis is widely distributed disease with relatively high incidence.

It is most frequent among big cities inhabitants (10 ) and the incidence is higher in industrial countries as opposite to developing countries. . 

Since Hashimoto had described the disease for the first time in 1912, it is considered to be an example of classical autoimmune disturbance. Nevertheless, little is known about etiology of the disease. Many authors indicate the influence of iodination of food and a quantity of dietary iodine ingested daily by average person as one of the leading etiological factors. At a present time the connection between amount of dietary iodine and incidence of autoimmune thyroiditis (AIT) is well documented    . Another factor most probably involved -is urbanization. It is well established that persons leaving in big industrial cities are most prone to develop AIT (12).

There are just few works in the world that describe an influence of ionizing radiation on the incidence of AIT             ( 4;8;13;). This is because fortunately, there are few places on the Earth where continuous radionuclide contamination is present.  One of them, the Chernobyl region is well known to most researchers (4;9;14;15). On the other hand, little is known about another- not less contaminated area– Chelyabinsk region.

Chelyabinsk region-one of the most contaminated spots on the Earth.

In the end of 40-ties the first industrial nuclear reactor had started its function in Chelyabinsk region. The main purpose of its work was to provide the Plutonium for Soviet nuclear weapons. One year later the plant for extracting of radioactive Plutonium from irradiated nuclear fuel had started its work. Liquid technologies that were applied there quickly became the source of a huge amount of radioactive by-products.

Unperfected technology of utilization of  radioactive by-products on the one hand and underestimation (and probably absence of knowledge in that period of time) of possible consequences of radioactive influence on population on the other, became a main reason of radioactive contamination of  the part of Chelyabinsk, Sverdlovsk (Ekaterinburg) and Kurgan regions ( see the map).

Retrospectively, we may certainly indicate three radionuclear disasters that had happened as a result of functioning of the above nuclear factory (now it is called “Majak “corporation). (Akleev and Goloshapov):

First catastrophe.  Seventy six million liters of radioactive by-products were thrown to river Techa from 1949 to 1953.  This river is a part of river system Techa- Iset- Tobol- Irtish-Ob.  There are 38 country settlements with the total of 28 thousands inhabitants are located along river shores.  People were using the water for preparing food, laundry, washing, watering gardens and so on. In summer 1951 the mean concentration of Beta-irradiation in the water of upper parts of the river was  …… mci, in the bottom – 1000 mci/kg and in the ground close to river shores 10 mci/kg. The strength of radiation in villages of upper river part rose up to 5 roentgen per hour. Total amount of irradiated people was 124 thousands. The dose they got was in the limits of 3.5 to 170 BER (Biological Equivalent of Roentgen).

 

Second catastrophe. Constructive defects of first containers and reservoirs for storing liquid highly active nuclear by-products resulted in damage of one of reservoir containing mixture of dividing products. In September 29, 1957, it resulted in spontaneous termochemical explosion of mixture of Na-Nitrate and Na- Acetate salts.  Than, 20 millions milicuri (mci) of radioactive by-products were thrown into the atmosphere. The explosion resulted in formation of huge radioactive cloud containing radioactive dust and drops of radioactive liquids. The main part of the cloud passed sedimentation close to the place of explosion but 2 million milicuri of radioactive by-products were taken up by wind on the height of 2 kilometers and started to move with the speed of 5-10 m/sec in north-east direction falling on the ground slowly. Such kind of sedimentation resulted in appearance of so called “ East-Ural Radioactive Trace” (EURT). 272 thousands people were in the zone of EURT.

They got from 6 to 52 BER.

 

East-Ural Radioactive Trace

The dates of the map correspond to initial contamination density on Sr-90, Ci/km2

  

 

 

The distribution of initial contaminated areas corresponding to contamination levels
Initial contamination Ci/km^2		Area, km^2
of Sr-90	of total activity
0.1-2	3.7-74	15000-20000
2-20	74-740	600
20-100	740-3700	280
100-1000	3700-37000	100
1000-4000	37000-150000	17

 

 

Third catastrophe took place in spring 1967 and was connected to transferring by wind of shore and bottom ground of Karachay lake where liquid radioactive by-products were thrown out and accumulated for years. Summary intensity of radiation was 600.000 mci.

The trace of contamination mainly overlapped the previous one from 1957.      41 thousand people were involved. For 4800 of them the external dose was estimated to be more than 1.3 BER.

Main characteristics of nuclear disasters are summarized in the table.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The main Characteristics of  radioactive contamination of Chelyabinsk region

 

 

Materials.  Retrospective analysis of endocrine morbidity was undertaken . This calculation included data obtained from annual medical reports of endocrinologists of different areas of Chelyabinsk region.  The data regarding contaminated regions was calculated separately.

Methods.  Diagnosis of Autoimmune thyroiditis had been established when at least one of diagnostic criteria were present (11) :

1 High ( diagnostic) titer of anti-thyroid antibodies.

The titer of antibodies was detected in hemaglutinating reaction with sheep erythrocytes to thyroid extract. According to our laboratory data – titer of 1:640 and higher is diagnostic.

2. Lymphoid infiltration of thyroid on fine-needle  biopsy.

Only statistical data of adult ( no children) morbidity had been taken into account.

Results .   The data obtained is summarized in the table ( see table2).

In order to demonstrate changes of incidence of AIT in whole region and in contaminated areas as a part, we also show here the incidence of endemic goiter. It is worthwhile to remark that whole Chelyabinsk region is considered as endemic iodine-deficient region. Nevertheless, the incidence of endemic goiter is not the same in different areas. Thus, in the south parts (dry land areas) of Chelyabinsk region there is  a minimal incidence of endemic goiter, while in north parts and mountains the incidence is maximal. The explanation is that there are different degrees of iodine deficiency in these areas (12).

Interestingly, the contaminated areas are characterized by relatively high Iodine deficiency.  Our previous works has demonstrated clear reverse correlation between a degree of iododeficiency on one hand and the incidence of AIT on the other hand   ( 10;12 ).

That means, that one should expect a minimal incidence of AIT in contaminated  areas.  

Our results show that in contaminated areas  the incidence of endemic goiter remained unchanged while in a whole region there was clear decrease of incidence.

The probably explanation of such kind of events is that iodine - prophylaxis takes place in Chelyabinsk region for many years. So, it is not surprising that the incidence of endemic goiter had been decreased in most of areas. Nevertheless, endemic goiter remained unchanged in contaminated areas ( 5.1 per 10.000 of population in 1971 versus 5.1 per 10.000  in 1989).The most realistic explanation to these phenomena is that fact that the number of endocrinologists in contaminated areas was rather small. Than, their ability to reveal different diseases including endemic goiter  and AIT was very low (see figure).

 

 

The same is true regarding other endocrine pathology like diabetes and

thyrotoxicosis.

Surprisingly, and despite of o bad specialists supply and relatively prominent  iodine deficiency,  the incidence of  AIT rose sharply.(see figure). The incidence of AIT is somewhat higher in areas of radionuclear contamination than in whole region, but the difference was not significant ( 12.3 versus 13.7 cases per 10000 population p > 0.05 ). However, when adjustment to specialist’s number and degree of  iodine deficiency had been performed– highly significant results were obtained ( p < 0.001).  The relation of AIT to whole number of  endocrine patients is even more prominent. Thus,  in average, a  part of AIT in contaminated areas was 19.2% ( as related to total number of endocrine patients in areas) opposite to 8.8% in a whole region ( p< 0.001 ). Interesting, that the insidence of AIT was higher in in contaminated areas even from the beginning of follow – up.

  Then, we may conclude, that  the insidence of AIT in contaminated areas significantly higher than in entire region.

      The difference would be  even more impressive if we would take into account that fact, that the above data referres mostly to agricultural population:  the only city that located in contaminated region is – Kasli.  It accounts 38000 of adult inhabitants that is only 1/5 part of total population living on contaminated areas. As we previously said, big town population is most predisposed  to the development of AIT. This is in contrast to agricultural population, where the insidence of AIT is   significantly lower( 12  ).

  For further confirmation of our hypothesis we have undertaken a comparision between  insidence of AIT in contaminated region and  in entire Chelyabinsk region, relying on statistics ,  availible from regional endocrine dispancer (institute).

 

      Our regional endocrinological dispancer is the single medical organisation in Chelyabinsk region where verification of diagnosis of AIT is made. Here is the data of  insidence of  AIT in contaminated  and “ clear” areas that was received in the dispancer ( see the figure).(p< 0.001)

 

 

 

Discussion

      According to demonstrated results, we have revieled  the determinative connection between ionizing radiation and AIT, because other etiologic factors, like urbanization, are not relevant in the region we are talking about.

 Literature review gives us an evidence that such dependence does realy exists.

        It was the common sense for a long time, that AIT may be induced only by radioiodine as a result of its ability to accumulate in thyroid and to damage the thyroid directly .Thus, Dedov I. et al(1992) (16) showed a clear connection between the dose of radioiodine and titre of antithyroid antibodies in the children of Chernobyl.

Vykhovanets E. et al (9) revealed the biological background of above disturbances. They describe the changes in humoral and celullar immunity that were found to be proportional to the dose of I 131 the children got.

Contrastly to those data -  in our region there was no radioiodine. Neveretheless, we showed  the elevation of incidence of AIT in contaminated areas  as well.         
 

Than, the question to be answered – is how does the radiation cause autoimmune thyroiditis and whether or not its incidence depends on radioactive agent.

         All of the previous works try to explain this phenomenon by direct thyroid damage with radioactive agents. Thus, in the work of Pacini et al. ( 15), titres of antithyroid autoantibodies in children and adolescent of two villages of Belarus with different irradiation exposure were compared.   Authors have found that a high prevalence of antithyroid antibodies (19.5%) was  in children living in a heavily contaminated area of Belarus. Age-matched controls from a non-contaminated area had a much lower prevalence of thyroid antibodies ( 3.8%), comparable with that, reported in non-irradiated population of the same age group in Italy. Authors suggest, that the release of thyroid antigen from damaged thyroid cells after radiation  injury of thyroid is a likely mechanism , triggering an autoimmune reaction. This postulate seems to be very simplistic and doubtful . Interestingly, most investigators now leave the theory of “Out – of- barrier thyroid tissue”, which was much attractive twenty-thirty years before. Indeed, we did not found in a literature indications on higher incidence of  thyroid autoimmunity after thyroid resection. Hence, thyroid autoimmunity depends more likely not on a thyroid destruction per se, but , probably, on a kind of agent , causing thyroid damage. Thus, radioiodine may cause thyroid autoimmunity. According to data, presented by Huisman et al and Nygaard et al,  (17;18) - 4 to 5 percents of patients given radioiodine for volume reduction of nontoxic multinodular goiter will develop autoimmune phenomenon-so called "Graves'-like hyperthyroidism", with elevated thyrotropin receptor antibodies, appearing 3-10 months after treatment. We also know today about " Autoimmune phenomenon of Chernobyl region", where authors found up to 50% incidence of coexisting " Hashimoto" in patients, operated because of thyroid carcinoma (4;15).

But radioiodine seems to be not specific agent causing autoimmunity.  Even "simple"  X-ray irradiation may cause an autoimmune thyroid disease in experiment. Hancock S. Et al (7) found, that there is up to 20.4 times increase of risk of Grave's disease in patients with Hodgkin's disease treated by external irradiation.

Among a variety of different radioactive agents there are those, that directly destruct the thyroid  (Iodine) and those, accumulating in the other organs. 

It is very interesting, that high incidence of thyroid antibodies was found by Pacini et al particularly in the areas of high Cesium fallout     ( 15 ). Authors report progressive increase in the incidence of autoimmune thyroid disease from the Chernobyl accident up to 10 years thereafter. Obviously, it would be misleading to explain this phenomenon by prolonged influence of  radioiodine alone, because the radioiodine has a very short half-life. On the other hand, Cesium lives for many years. The problem is, that it does not accumulate in the thyroid, but mainly in bones! In a village with low Cesium fallout authors did not found significant elevation of thyroid autoantibodies.  S. Nagataki (8) has found 6-times elevation of hypothyroidism as a result of AIT 40 years after atomic bomb explosion in Hiroshima. The main destructing agent there was an external irradiation. Of particular interest, that thyroid destruction takes place at irradiation dose of more than 150 Gy, whereas the dose of Nagataki's patients was between 0.01- 0.49 Gy.

   Dedov I. et al ( 13), found significant correlation between thyroid enlargement, presence of antithyroid antibodies and 131 I dose got by children in another contaminated area - Kaluga  region..

    All of those data, mentioned above, rises a suspicion that local thyroid destruction is not necessary for AIT development and than, most acceptable theory- is that an immune disturbances, caused by irradiation, are critical, because

AIT- is not an organ- specific disturbance, but disease of a whole immune system.

 

      Another work, based on investigation of atomic bomb survivors (6) revealed serious immune disturbances in that group of population. Thus, an alteration in balance/interaction between the T- and B-cell subsets, a decrease in the T-cell population and an increase in the B-cell population has been found.

Galitzkaja et al., 1993, has also found the disturbances in humeral immunity of children from Chernobyl region, exposed to high doses of Cesium and Strontium. (1).

Grinevich U.et al, 1993 ( 2 ) indicate , that thymus is especially sensitive to external irradiation.

Comissarenko et al., 1993 ( 19 ) revealed an impressive decrease of humoral and cell immunity in population of Kiev 5 years after Chernobyl catastrophe.

  The association of irradiation and thyroid cancer is well known (4;5).

Unfortunately, there is no published data regarding thyroid cancer in Chelyabinsk region. One of the reasons, is that statistically, thyroid cancer was not calculated separately until 1989(!). Before 1989 it has been accumulated in the     statistical group named "Other cancers". From 1989 to 1998 here is significant decrease of thyroid cancer in Chelyabinsk region , that is probably  connected to enhanced migration of population in that period.

   Autoimmune thyroiditis, like other autoimmune disturbances, seems to be the non- specific result of radiation influence on immune system and it should be considered as a "typical consequence" of delayed effects of chronic radiation exposure.  

 

 

Reference

 

 

1. Galitzkaja N., Blinov A., The Health care of Belarus. 1993,v.6, p. 7-9. Russian

2. Grinevich U.,Ganul V., Benduch G., et al, Vrachebnoe Delo, 1993, v.4, p.28-31. Russian

3. Dedov V., Dedov I., Stepanenko F., Radiative endocrinology , 1993. Russian

4.  Pacini F., Vorontzova T., ,Demidchik E., et al, Post-Chernobyl Thyroid carcinoma in Belarus children and adolescents: comparison with naturally occurring thyroid carcinoma in Italy and France. J. Clin. Endocrinol. Metab. - 1997- Nov. : 82( II) pp. 3563-3569.

5. Ron E. Ionizing radiation and cancer risk: evidence from epidemiology. Radit Res 1998 Nov; 150(5 suppl): S30-41

6.  Akiama M., Late effects of radiation on the human immune system: an overview ofimmune response among the atomic bomb survivors. Int J Radiat Biol 68: 497-508 (1995).

7. Hanock S., Cox R., McDougall I. Thyroid disease after treatment of  Hodgkin's disease. N Engl J Med           325:599-605.

8. Nagataki S., Shibata Y., Inoue S., et al., Thyroid disease among atomic bomb survivors in Nagasaki . JAMA 1994 Aug 3; 272 (5): 364-70.

9. Vykhovanets E., Chernyshov P., Slukvin I., et al. 131 I Dose- depended thyroid autoimmune disorders in children living around Chernobyl. Clin Immunol Immunopathol 84: 251-259 (1997).

10. Kalinin A., Levit I., [ Current aspects of autoimmune thyroiditis problem]. Ter Arkh 1985; 57(9): 137-42

11.  Levit I., [Use of aspiration biopsy of the thyroid and the determination of thyroid autoantibodies circulating in the blood in the diagnosis of autoimmune thyroiditis]. Sov  Med 1982; (1) 82-5

12. Levit I., [Clinico-morphological comparisons of autoimmune processes in the thyroid gland in the endemic goiter region.]Probl Endocrinol (Mosk) 1979 Sep-Oct; 25(5) : 29-34

13. Dedov II., Tsyb AF., Marveenko EG., et al.[ Paramters of thyroid status in children and adolescents living in one of the Kaluga regions contaminated with radionuclides]. Probl Endocrinol (Mosk) 1993 Sep-Oct; 39(5) : 10-3.

14. Pacini F., Vorontsova T., Molinaro E., et al Thyroid consequences of Chernobyl nuclear accident . Acta Pediatr Suppl 1999 Dec; 88 (433) : 23-7

15. Pacini F., Vorontsova T., Molinaro E., et al., Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to Chernobyl radioactive fallout. Lancet 1998 Sep 5;352(9130) : 763-6.

16. Dedov I., Tsyb A., Matvienko V.,et al. The evaluation of thyroid status in children from radionuclide contaminated regions of Russia (consequenses of Chernobyl catastrophe). Prob Endocrinol (Mosk) 1992, v4, p.21.

17. Huysmans, DA, Hermus RM, Edelbroek AL, et al. Autoimmune hyperthyroidism occuring late after radioiodine treatment for volume reduction of large multinodular goiter. Thyroid 1997; 7:535.

18. Nygaard B., Knudsen JH., Hegedus L., et al. Thyrotropin receptor antibodies and Grave's disease, a side - effect

of 131 I treatment in patients with non-toxic goiter.  J Clin Endocrinol Metab 1997 ; 82:2926.

19. Komissarenko V., Zvernova A., Fedorovskaja E., et al. Vrachebnoe Delo . 1993 v4 pp.23-25.

20. Josef Levit  M.D., Ph.D.,   Boris Levit M.D. Ph.D., et al Chelyabinsk regional endocrine dispancer, Chelyabinsk, Russia,  Hillel Yaffe  medical center, institute of endocrinology, Hadera.