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Medical Consequences of Chernobyl with Focus on the Endocrine System – Part 2


Zdravotní dopady černobylské katastrofy se zaměřením na endokrinní systém: část 2

Atomové katastrofy se udály v posledních 70 letech několikrát. Výbuch nukleárního zařízení v roce 1986 v severní částí střední Ukrajiny byl mimořádnou zkušeností proto, že radiační zátěž dopadla na všechny věkové kategorie populace. Následné studie pak přinesly velké množství informací o účinku záření na lidský organismus. Vzhledem k tomu, že se globální bezpečnost postupně zhoršuje, získávají znalosti o biologickém dopadu ionizujícího záření i preventivní opatření k omezeni jeho zhoubných účinků novy rozměr a týkají se nás všech. Tento přehled se zaměřuje na dlouhodobé důsledky černobylské katastrofy, zvláště pak na dopad na endokrinní systém u dětí a dospělých. Přehled zahrnuje souhrn preventivních opatření pro případ atomové katastrofy.

Klíčová slova:
černobylská atomová katastrofa – ionizující záření – endokrinní systém – štítná žláza – rakovina – mamma – těhotenství – děti


Authors: Thomas P. Foley 1;  Zdeňka Límanová 2;  Eliška Potluková 3
Authors place of work: Division of Endocrinology & Metabolism, School of Medicine, Graduate School of Public Health, University of Pittsburgh, Children’s Hospital of Pittsburgh, USA 1;  Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic 2;  Division of Medicine, University Hospital Basel, Switzerland 3
Published in the journal: Čas. Lék. čes. 2015; 154: 287-291
Category: Přehledový článek

Summary

In the last 70 years, atomic disasters have occurred several times. The nuclear power plant accident at Chernobyl in 1986 in North-Central Ukraine was a unique experience in population exposures to radiation by all ages, and ongoing studies have brought a large amount of information effects of radiation on human organism. Concerning the deteriorating global security situation and the strong rhetoric of some of the world leaders, the knowledge on the biological effects of ionizing radiation and the preventive measures designed to decrease the detrimental effects of radiation gains a new dimension, and involves all of us. This review focuses on the long-term effects of Chernobyl catastrophe especially on the endocrine system in children and in adults, and includes a summary of preventive measures in case of an atomic disaster.

Keywords:
Chernobyl atomic disaster – ionizing radiation – endocrine system – thyroid – cancer – breast – pregnancy – children

DIABETES MELLITUS ASSOCIATED WITH RADIATION EXPOSURE

Residential survivors of the atomic bomb detonation at Hiroshima were found to have an increased incidence of Type 1 diabetes mellitus [Type 1 DM] (70). The average increase/incidence ratio of Type 1 DM in Gomel Region in the period 1987–1999 when compared to the period 1976–1986 was 8.9% (p < 0.001). The crude rate of incidence increased significantly after 1986 compared to an essentially a flat rate before 1987 (15). Subsequent studies have confirmed the incidence of Type 1 DM in children and adolescents after Chernobyl when compared to children and adolescents from 1980 to 1986 (72). Subsequent comments disagree with the conclusions of the study in Gomel, Belarus, as the study in northern Poland did not show an increase in Type I DM after Chernobyl (73). However, the latter opinion was countered by a summary of studies in humans, including atomic bomb survivors (71), and experimental animals (74). The authors recommend regular investigations for early markers of diabetes after exposure to radiation, especially in children (74).

However, in the offspring of women or men exposed to variable radiation doses from atomic bomb detonations, there is no evidence that exposure was associated with any increased risk for multifactorial diseases (75). One modification of this conclusion is the fact that the mean age of the study population is 48.6 years such that the incidence of multifactorial diseases may not be fully expressed until sometime in the future, necessitating continued evaluations of the study populations (75). There are several reports of associations between radiation exposure and breast cancer (13–14, 17, 19, 62, 67) and thyroid cancer (8–11).

Although the debate about the association between exposure to ionizing radiation from the Chernobyl accident and the subsequent development of diabetes mellitus in children and adults remains inconclusive, there is sufficient evidence that justifies continued monitoring of those individuals exposed during fetal life, infancy, childhood and adolescence for markers of subclinical and overt diabetes mellitus.

RELATIONSHIPS BETWEEN BREAST CANCER AND AUTOIMMUNE THYROID DISEASES

The association between thyroid disease and breast cancer has been known for more than six decades (46, 75–79) with contradictory results for positive and negative correlations. There are a variety of thyroid disorders, especially autoimmune thyroiditis among iodine-sufficient populations (78). Despite advances in the molecular studies of both diseases, there remains no common pathogenesis to link the associations (46, 75–79). Studies have shown more linkage between breast cancer and thyroid disorders in women of younger ages. Those women who are affected with either benign or malignant thyroid diseases are reported to have a greater risk of breast cancer. The effect of thyroid autoantibodies on the course of disease and overall survival remains controversial (79). The PTEN Hamartoma Tumor Syndrome (PHTS) is an interesting combination of syndromes that include benign and malignant tumors of the thyroid, breast and endometrium (80). The lifetime risk of breast cancer is 85%, and usually develops between ages 38 and 46 years. There seems to be no association of breast or thyroid cancer with pre-natal or post-natal exposure to ionizing radiation. The diagnosis is based on the presence of the pathogenic variants of the PTEN gene (80).

PREVENTIVE MEASURES IN CASE OF AN ATOMIC DISASTER

Prevention of radiation-induced endocrine diseases is directed primarily toward evacuation from the contaminated environment and using inorganic iodine as potassium iodide* (KI) treatment to block radioiodine exposure to tissues from the radioisotopes of iodine that cause external and internal radiation exposure (1–5, 58–59, 63, 65), and to a lesser extent, external radiation from 137Cs and 60Co-cobalt. The greater radioiodine dose to the thyroid of a child and the biological factors that influence the increased sensitivity of the thyroid to radiation increase the risks of thyroid diseases in children (5, 61). The fetus in utero, neonates, and young infants under age 1 year who are breast fed are among the most sensitive of any population exposed to radiation and, therefore, have the greatest risk for thyroid carcinoma (5, 59–60).

Similar observations are reported as relevant to the hyperplastic state of the female breast at the time of exposure to radioiodine. The highest risk for breast cancer would be expected to occur in utero, during transient neonatal breast hyperplasia in male and female neonates, and in females during puberty, pregnancy and lactation (5, 13–14, 62–63).

With these observations in mind, the highest priority of management for those living within 100 km of the radiation source is an immediate evacuation of pregnant women and children. The safe distance would be at least 100 km, and vehicles with women and children should have an external identification such as a banner on an antenna or sticker on the front of the vehicle. Predetermined priority evacuation routes should have been established so that no priority vehicle is delayed.

At the same time when the news of evacuation is broadcast, individuals of all ages should take their initial dose of stable iodine as recommended by radiation health authorities (Table 2). The use of oral stable iodine to block radioiodine uptake by sensitive tissues was reported from the iodine prophylaxis program in Poland within hours after the Chernobyl accident (64) and remains the most important early mode of preventive medicine, especially in children whose benefit has been confirmed (64). The administration of potassium iodide is recommended if the estimated dose to the thyroid is 100 mGy or higher. Iodine in the form of KI or SSKI* (Saturated Solution of KI and Lugol’s Iodine*) should be administered early (within 36 hours of radioiodine release) to reduce the radiation dose to the thyroid and breast. The potassium Iodide (KI) dose varies with age and exposure (Table 2). KI causes a ~ 40% reduction in rem dose to the thyroid and with early prophylaxis there is  a ~ 60–70% reduction in the rem dose primarily because inhaled 131I is blocked (1, 65). In some countries, e.g. Switzerland, potassium iodide has been regularly distributed among the general population with detailed instruction how to use it in case of an atomic disaster.

There is an incidence of 0.2% for medically significant side effects, but no serious side effects were observed although KI toxicity has been reported as very rare cases of iodinism (64, 66). For exposure to the radioiodines, evacuation and KI are the top priority, and the dose and duration of therapy should be based on the advice of physicians (Table 2). If persistent exposure to radioiodines occurs and more than a single dose of KI is advised, infants and young children should be monitored with TSH levels to assure that iodine-induced hypothyroidism does not develop. L-thyroxine therapy should be initiated when TSH levels are elevated so that hypothyroidism does not persist and iodine therapy can be discontinued.

Tab. 1. Guidelines for Administration of Potassium Iodide*
Guidelines for Administration of Potassium Iodide*
* Lugol’s Iodine (5% solution) contains 126.5 mg iodine in one ml. ** adolescents weighing more than 70 kg should receive the adult dose (130 mg) Source: www.fda.gov/downloads/Drugs/.../Guidances/ucm080549.pdf

Exposure from other radionuclides is not affected by KI, and for proper clinical management, the assessment of the magnitude of radiation exposure is very important (Table 3).

Tab. 2. Guidelines for Administration of Potassium Iodide*
Guidelines for Administration of Potassium Iodide*
* A radiation safety officer or other authority should be consulted in all aspects of management. Adapted from Jarrett DG. Medical Management of Radiological Casualties. Bethesda, MD: Armed Forces Radiobiology Research Institute; 1999. Source: Ref. # 1.

General measures for reduction of radioactivity exposure in case of a nuclear disaster are crucial and international guidelines have been developed accordingly (4, 17). These actions include controlling access to the site, recommending people to stay indoors or evacuating them, removing contaminated clothing, providing respiratory protection, administering potassium iodide, restricting certain foods, and decontaminating property. People should stay indoors for up to two days if a dose of 1 rem is likely to be reached, with evacuation for up to one week if the likely dose is 5 rem or higher (4).

Temporary relocation is recommended at a likely dose of 3 rem in the first month or 1 rem in a subsequent month. Permanent resettlement is recommended if the lifetime dose is expected to be 100 rem (4).

CONCLUSIONS

In summary, the thyroid gland is one of the most vulnerable organs during a nuclear disaster. The youngest are the most susceptible and have the highest risk for thyroid carcinogenesis, transient thyroiditis and primary hypothyroidism. Radioactive iodine and cesium are volatile and thus readily inhaled and absorbed from nutrition. The exposition of the thyroid is potentiated through iodine deficiency, leading to an increased accumulation of radioactive iodine in the thyroid gland.

The Chernobyl catastrophe has ongoing effects not only on the thyroid, but probably also on other organs (breast, pancreas-islet cells). These long-term effects are subtle when regarding an individual, but become epidemiologically important when whole populations are analyzed. Further studies are needed to evaluate the late effects of the Chernobyl catastrophe especially on the thyroid and breast tissues.

The incidence of breast cancer among women exposed to the higher doses of radiation could be greater than currently considered. Genetic susceptibility data, frequent monitoring of women at increased risk and fiscal support educational programs are essential for the coming decades in order to detect breast cancer at the very earliest stage. Recommendation to regular investigations for early markers of diabetes mellitus after exposure to radiation, especially in children, should be taken to an account as well.

Concerning the number of atomic power plants worldwide and the deteriorating security situation with continuing risk of terrorist attacks it is important for everybody to be aware of the preventive measures in case of another atomic disaster.

ADRESA PRO KORESPONDENCI:

Eliška Potluková, MD, Ph.D.

Division of Medicine

University Hospital Basel

Petersgraben 4, 4056 Basel, Switzerland

e-mail: eliska.potlukova@usb.ch


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