CHARACTERISTICS OF NON-RENAL NORMOCALCIEMIC HYPERPARATHYROIDISM IN THE CHORNOBYL NPP ACCIDENT SURVIVORS. / ДОСЛІДЖЕННЯ ОСОБЛИВОСТЕЙ НЕРЕНАЛЬНОГО НОРМОКАЛЬЦІЄМІЧНОГО ГІПЕРПАРАТИРЕОЗУ У ОСІБ, ПОСТРАЖДАЛИХ ВНАСЛІДОК АВАРІЇ НА ЧАЕС.

OBJECTIVE: to assess the hormonal and metabolic disorders in the Chernobyl nuclear power plant (ChNPP) accident survivors (AS), having got secondary normocalcemic non-renal hyperparathyroidism (HPT) in the late period upon exposure to ionizing radiation (IR). MATERIALS AND METHODS: The routine clinical, anthropometric, instrumental (thyroid and parathyroid diagnosticultrasound), laboratory (biochemical, hormonal), statistical methods were applied. In both prospective (n = 48, control group n = 19) and retrospective studies the data of 2,234 subjects including 1,372 irradiated adults (862 non-irradiated persons in the control group) were evaluated. Clinical consequences of exposure to IR on the endocrine system were evaluated in ChNPP AS. RESULTS: High prevalence of vitamin D lack or deficiency was established retrospectively in 81.8 % of the ChNPP AS and in 89.5 % of the control group subjects. In general, there was neither effect of exposure to IR on the vitamin D status in study subjects, nor any difference between the study groups. According to diagnostic ultrasound patterns the parathyroid hyperplasia was diagnosed in 629 cases (28.2 %). Among the ChNPP AS it was found in 32.7 % of cases (n = 450) vs. 20.7 % (p > 0.005) in the control group (a 1.6-fold difference). HPT diagnosed as serum parathyroid hormone content > 65 ng/ml was diagnosed in 123 cases (21.1 %) i.e. in almost every fifth person. Increased serum level of parathyroid hormone was found in the 94 ChNPP AS and in 25 persons of the comparison group. In other words, the frequency of HPT was 23.7 % among the AS being significantly more than in the comparison group (13.2 %, p < 0.005). Frequency of normocalcemic non-renal HPT was slightly different by years of observation with a trend to the year-by-year increase. CONCLUSIONS: High prevalence of vitamin D lack or deficiency was established in the ChNPP AS, being however independent of exposure to IR. Frequency of parathyroid hyperplasia/adenoma was 1.6 times higher in the irradiated subjects than in persons of the control group. Annual increase in frequency of the non-renal normocalcemic HPT was also revealed reaching nowadays 23.7 % among the AS, which is significantly higher than in the comparison group.

PROBLEMATIC ASPECTS, COMPLICATIONS, MISCONCEPTIONS AND DEBATABLE ISSUES OF IODINE PROPHYLAXIS IN RADIATION EVENTS (REVIEW). / PROBLEMNI ASPEKTY, USKLADNENNIa, KhYBNI UIaVLENNIa TA DYSKUSIINI PYTANNIa IODNOÏ PROFILAKTYKY PRY RADIATsIINYKh PODIIaKh (OGLIaD).

Prerequisite. Since the advent of nuclear energy, industry and weapons, a possibility of radiation events i.e. incidents and accidents had emerged. Given the presence of radioactive iodine as part of environmental contamination, the response of authorities and medical services consists, in particular, in carrying out the emergency iodine prophylaxis among specialists and general population. And along with the fact that emergency iodine prophylaxis is a generally accepted measure in radiation events accompanied by the release of radioactive iodine, some methods of its implementation were and remain in certain sources and instructions/recommendations contradictory and even false. Such inconsistency increases the potential risks of health effects of radioactive iodine and exacerbates the sense of fear and uncertainty among the population involved in the incident. OBJECTIVE: to consider and review the essence of emergency iodine prophylaxis during radiation events, physiological aspects of iodine metabolism in the body, properties of individual iodine prophylaxis agents that are recommended, and to justify the rationality of using some of them along with absurdity/inadmissibility of others; substantiate the creation of a unified preventive information strategy regarding the event in order to reduce anxiety and other negative psychological consequences among the affected population. MATERIALS AND METHODS: The review was performed by searching the abstract and scientometric databases and printed publications. RESULTS: In the event of serious radiation events at nuclear power plants and industry facilities, radioactive iodine is highly likely to enter the environment. With the threat of radioactive iodine incorporation or with its incorporation that has already begun, it is absolutely necessary to carry out the emergency iodine prophylaxis. Such prevention should be carried out with stable iodine preparations such as potassium iodide or potassium iodate in special pharmaceutical formulas. Dosing of drugs in age and population groups should be carried out by specialists in radiation medicine and radiation safety in accordance with internationally recognized guidelines. The use of iodinecontaining food additives, iodine solution for external use and Lugol's solution is categorically unacceptable due to complete ineffectiveness, impracticality of implementation, and sometimes due to the threat of serious harm to health. CONCLUSIONS: Clear preparedness plans for possible radiation accidents and incidents, as well as successfullyimplemented appropriate preventive measures, including emergency iodine prophylaxis, are crucial for the effective and successful response to such events. Emergency iodine prophylaxis during radiation events should be carried out exclusively under the guidance of specialists in radiation medicine and radiation safety using special pharmaceutical formulas of potassium iodide or potassium iodate in doses recognized by the international scientific community. Other means of emergency iodine prophylaxis, including «handicraft¼/home preparations, are absolutely unacceptable. Implementation of this protective measure should be accompanied by a coordinated information campaign in order to minimize purely radiation risks and to preserve the psychological well-being of the population.

CLINICAL-METABOLIC AND HORMONAL RELATIONSHIPS BETWEEN PARATHYROID DISEASE AND OTHER NON-CANCEROUS ENDOCRINE DISORDERS IN THE CHORNOBYL NPP ACCIDENT SURVIVORS. / KLINIKO-METABOLIChNI TA GORMONAL'NI VZAIeMOZV'IaZKY MIZh PATOLOGIIeIu PRYShchYTOPODIBNYKh ZALOZ TA INShYMY NEZLOIaKISNYMY ENDOKRYNNYMY ZAKhVORIuVANNIaMY U POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChAES.

OBJECTIVE: to investigate the clinical, hormonal-metabolic and structural features of parathyroid injuries in sur-vivors exposed to ionizing radiation after the Chornobyl NPP accident in adulthood and childhood, both with theirconnections to other non-cancerous endocrine disorders, and to establish the respective interhormonal and dys-metabolic relationships. MATERIALS AND METHODS: Clinical effects of ionizing radiation on the endocrine system in persons affected by theChornobyl NPP accident (n = 224) and their descendants (n = 146), compared with the general population sample(n = 70) were the study object. All patients underwent the ultrasound thyroid and parathyroid examination. Thegenerally recognized clinical, anthropometric (body weight, height, thigh volume, body mass index), instrumental(ultrasound examination of thyroid and parathyroid glands), laboratory (biochemical, hormonal), and statisticalmethods were applied. Parametric and nonparametric statistical methods were used in data processing. The value ofp < 0.05 was considered a statistically significant. RESULTS: No significant difference was found in the incidence of carbohydrate metabolic disorders in the ChornobylNPP (ChNPP) accident consequences clean-up workers (ACCUW), evacuees from the NPP 30-km exclusion zone, res-idents of radiologically contaminated areas and in the control group in whom the parathyroid hyperplasia wasdetected. There was a significant increase in the incidence of arterial hypertension among ACCUW who had parathy-roid hyperplasia (76.9%) vs. the control group (51.2%). In cases of parathyoid hyperplasia the vitamin D levels weresignificantly lower than without it. Vitamin D insufficiency/deficiency was found in 94% of the surveyed subjects.The average level of parathyroid hormone in blood serum was significantly higher in the ACCUW of «iodine¼ period withdiagnosed parathyroid hyperplasia than in the control group: (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml,p < 0.05. Results of multivariative analysis indicated a strong association of vitamin 25(OH)D insufficiency/defi-ciency with development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, osteo-penia/osteoporosis. parathyroid ultrasound scan was at that an effective diagnostic method for primary screeningfor parathyroid hyperplasia and regular monitoring of the treatment efficiency. When examining children bornto parents irradiated after the ChNPPA the parathyroid hyperplasia (58%) and low serum content of vitamin D(11.6 ± 3.5) nmol / l were most often found in children living on radiologically contaminated territories (RCT).A strong correlation was established between the HOMA insulin resistance index and serum content of vitamin D(r = 0.65), parathyroid hormone (r = 0.60), and free thyroxine (r = 0.68) in the group of children born to parents irra-diated after the ChNPPA, having got chronic autoimmune thyroiditis, which indicated a relationship between thy-roid function, impaired carbohydrate and fat metabolism and the state of parathyroids. CONCLUSIONS: No difference in the incidence of carbohydrate metabolic disorders was found in the ChNPP ACCUW,evacuees from the 30-km exclusion zone, and residents of radiologically contaminated territories in whom parathy-roid hyperplasia was detected vs. the control group. Patients with parathyroid hyperplasia were found to be defi-cient in vitamin D in 94% of cases, and level of latter was significantly lower than under the normal parathyroid size.There was a significant increase in the incidence of diagnosed arterial hypertension among ACCUW who had parathy-roid hyperplasia vs. the control group: (76.9 ± 3.5)% vs. (51.2 ± 3.7)%. According to multivariate analysis a strongassociation between the vitamin 25(OH)D insufficiency/deficiency and development of thyroid disease, carbohydratemetabolic disorders, cardiovascular disease, and osteopenia/osteoporosis was established. The average level of pa-rathyroid hormone in the blood serum of the ChNPP ACCUW of the «iodine¼ period with diagnosed parathyroid hyper-plasia was significantly higher (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml; p <0,05) in the control group.

NEUROENDOCRINE EFFECTS OF PRENATAL IRRADIATION FROM RADIOACTIVE IODINE (review). / NEY̆ROENDOKRYNNI EFEKTY PRENATAL'NOGO OPROMINENNIa RADIOAKTYVNYM Y̆ODOM (ogliad).

BACKGROUND: Neuroendocrine effects of the prenatal radiation exposure from radioactive iodine in an event of nuclear power reactor accidents are a key issue in the field of radiation medicine and radiation safety because of a dramatic radiosensitivity of the developing organism. OBJECTIVE: Review of contemporary epidemiological, clinical and experimental data on neuroendocrine effects of prenatal exposure to 131I. OBJECT AND METHODS: Search in the PubMed/MEDLINE and Google Scholar abstract databases, along with a manual search for the relevant data sources. RESULTS: Estimated absorbed doses of intrauterine thyroid irradiation from radioactive iodine were obtained based on ICRP Publication 88, both with estimates of effective radiation doses on embryo and fetus, and estimates of the brain equivalent doses upon exposure in utero. The latter ones are subject to updating. The evidence-based data has been presented regarding a radiation-associated reduction of head and chest circumference at birth, as well as a radiation-associated excess of goiter with large thyroid nodules, and possibly of thyroid cancer after a prenatal exposure to 131I radionuclides. Data on intrauterine brain damage are controversial, but most researchers share the view that there are cognitive and emotional-behavioral disorders due to prenatal and postnatal irradiation and psy- chosocial impacts. Incidence increase of non-cancerous endocrine disorders and degenerative vascular disease of retina was noted. An experimental model of intrauterine irradiation from 131I on Wistar rats was for the first time ever created, extrapolating the radioneuroembryological effects in rats to individuals prenatally exposed after the Chornobyl disaster. Late neuropsychiatric and endocrine effects may be resulted from the relatively short-term impact of ionizing radiation at a level previously been considered safe. The necessity of neuropsychiatric and endocrinological monitoring of individuals exposed prenatally to ionizing radiation after the Chornobyl catastrophe throughout their life is substantiated. Experimental animal studies are a key direction in the further research of radiation effects, especially associated with low radiation doses. Further experimental and clinical neuroradiobio- logical studies aimed at exploration of the effect of ionizing radiation on hippocampal neurogenesis are most rele- vant nowadays.

[HYPERPARATHYROIDISM AND PARATHYROID LESIONS IN THE ChNPP ACCIDENT SURVIVORS]. / GIPERPARATYREOZ TA URAZhENNIa PRYShchYTOPODIBNYKh ZALOZ U OSIB, OPROMINENYKh VNASLIDOK AVARIÏ NA ChAES.

OBJECTIVE: Study of the status of parathyroid glands in individuals exposed to ionizing radiation as a result of the ChNPP accident and comparison with the general population of Ukraine. MATERIALS AND METHODS: Subjects exposed as a result of the ChNPP accident (n = 1,348) and people from the general population of Ukraine (n=655) were examined. Diagnostic ultrasound scan of thyroid and parathyroid glands (PTG) was conducted in all study subjects. The technique of parathyroid ultrasound screening was developed, which led to an increase in the efficiency of their imaging. Additionally, the 25-hydroxyvitamin D (25(OH)D), parathyroid hor- mone, ionized calcium and some other parameters were selectively assayed in serum. RESULTS: High incidence of parathyroid hyperplasia was detected 27-32 years after the irradiation in persons ex- posed as a result of the ChNPP accident, especially in evacuees from the 30-km exclusion zone (71.4%; χ2Yates' = 24.1; р = 0) and residents of radilogically contaminated territories (41.7%; χ2Yates' = 6.45; p < 0.01) having no primary hyperparathyroidism. High prevalence of vitamin D insufficiency and deficiency was revealed in all study subgroups, namely in 83.1 % of the general population of Ukraine along with a bit better vitamin D status in the ChNPP acci- dent survivors i.e. the vitamin insufficiency and deficiency was found in 78.7 % of them. Incidence of hyperparathy- roidism, predominantly of the secondary (normocalcemic) one, was 33.8 % among persons exposed as a result of the ChNPP accident (p > 0.3) being somewhat higher than in the general population of Ukraine (26.1%), despite above- mentioned better supply of vitamin D. CONCLUSIONS: There is a widespread insufficiency or deficiency of vitamin D (over 78.7%) in the population of Ukraine in general providing an unfavorable background for the higher prevalence of health disorders associated with calcium and phosphorus metabolism. The latter features parathyroid hyperplasia and musculosceletal, immune, cardiovascular, and endocrine system comorbidities. Such disorders should exacerbate with a secondary increase in parathyroid hormone secretion (26.1 %). Higher incidence of normocalcemic hyperparathyroidism (33.8% versus 26.1%) against a background of better vitamin D status among irradiated individuals indicates the existence of other factors, where the past combined effects of Chornobyl radioactive fallout and external parathyroid exposure are most likely to be involved. This could explain the greater number of cases of parathyroid hyperplasia and hyper- parathyroidism among the exposed subjects. However the additional precise studies are required here with clarifi- cation of the personal data in population groups of the ChNPP accident survivors. Participants of the ChNPP acci- dent clean-up work in the «iodine period¼ of 1986 are of especial concern here. Besides that, the study population should be expanded with inclusion of subjects exposed in prenatal period.

VITAMIN D CONTENT IN POPULATION OF RADIOLOGICALLY CONTAMINATED AREAS IN CHERNIVTSI OBLAST (pilot project). / VMIST VITAMINU D U NASELENNIa RADIOAKTYVNO ZABRUDNENYKh TERYTORII ChERNIVETs'KOÏ OBLASTI (pilotnyi proekt).

OBJECTIVE: To study the status of vitamin D in population of Chernivtsi region living on the radioactively contami-nated territories. MATERIALS AND METHODS: In a cross-sectional study under a pilot project the 180 people aged 19 to 78 years old per-manently residing in 3 regions of Chernivtsi oblast, namely in the village of Kyseliv in Kitsman district, which isattributed to the IIIrd zone of radiololgical contamination due to the Chornobyl catastrophe, as well as in the cityof Chernivtsi and the city of Vyzhnytsia were surveyed in summer. Assay of the 25(OH)D in blood serum was per-formed using the immune chemiluminescence method «ECLIA¼ on the Elecsys 2010 (Roche Diagnostics, Germany)analyzer using Cobas test systems. RESULTS: The average level of 25(OH)D in serum was (16.2 ± 0.8) ng/mL, the incidence of vitamin D deficiency was46.9%, and the incidence of vitamin D lack was 53.8%. Severe vitamin D deficiency has been detected in 6 cases inthe village of Kyseliv. At the same time, its share among the surveyed in this region was the highest (11.5%) beingsignificantly different from the proportion of severe deficits in Chernivtsi and Vyzhnytsia. A reliable correlationbetween the body mass index (BMI) and the blood serum level of 25(OH)D was found among persons with BMI of25-29.9 kg/m2. At the same time, the average value of 25(OH)D level among obese subjects (BMI greater than30 kg / m2) was practically the same as in subjects with normal body mass. CONCLUSIONS: Content of vitamin D was significantly lower among the population of radiologically contaminatedarea vs. the inhabitants of Chernivtsi and Vyzhnytsia. Status of vitamin D among the population of Chernivtsi regionremains far from optimal and requires urgent action for correction and prevention.

Pilot study of parathyroid glands in adult and pediatric subjects exposed to ionizing radiation after the ChNPP accident, methodology of parathyroid diagnostic ultrasound. / PILOTNE DOSLIDZhENNIa STANU PRYShchYTOPODIBNYKh ZALOZ OSIB, OPROMINENYKh VNASLIDOK AVARIÏ NA ChAES DOROSLOGO TA DYTIaChOGO VIKU, METODOLOGIIa ÏKh UL'TRAZVUKOVOGO DOSLIDZhENNIa.

OBJECTIVE: Estimation of the parathyroid hyperplasia prevalence after the ChNPP accident in adults exposed to ion izing radiation and their descendants using the diagnostic ultrasound and its methodology elaboration. MATERIALS AND METHODS: The pilot prospective study of the prevalence of parathyroid hyperplasia among the Chornobyl Nuclear Power Plant (ChNPP) accident adult survivors (n=686) and their descendants (54 children) was performed using diagnostic ultrasound examination of thyroid and parathyroids. Among the study subjects there were 339 ChNPP accident clean up workers (ACUW), 32 persons were evacuated from the 30 km exclusion zone and 224 ones were included to the control group. Diagnostic ultrasound of thyroid and parathyroids was performed according to the standard method. Additionally, in children with parathyroid hyperplasia an additional assay of 25 hydroxyvitamin D levels in serum was performed. In calculating the statistical significance, its level p < 0.05 was considered statistically significant. RESULTS: Parathyroids are a few small but critically important endocrine glands that synthesize parathyroid hormone, regulating mainly phosphoric calcium metabolism. Insufficient (hypoparathyroidism) or excessive (hyperparathy roidism) function of parathyroids is harmful to the patients affecting the state of nervous and cardiovascular sys tem. Parathyroidss can accumulate isotopes of cesium, strontium and radioactive iodine. The available data testify to an increased incidence of clinically significant hyperplasia of parthyroids (more than 9 mm in adults and more than 5 mm in children) among persons exposed toionizng radiation as a result of the accident at the ChNPP (28.64%) and their descendants (23.8-70.6%). First of all are concerned those adults who live in contaminated areas in comparison with the control group (24.15% in not irradiated). Evacuees from the 30 km exclusion zone being the category of people who were exposed to the absorbed iodine isotopes in the first days of the Chernobyl accident are the another risk group. These data demonstrate sensitivity of parathyroidss to the impact of incorpo rated isotopes (iodine, cesium and strontium), which in the long term exposure create conditions for structural and functional changes in regulation of phosphorous calcium metabolism being the basis for a significant prevalence of osteopenia and osteoporosis in irradiated individuals and their descendants. A number of further studies are required to clarify the findings and to disclose the hormonal mechanisms of radiation effects on parathyroids. CONCLUSIONS: Parathyroid glands are radiosensitive and susceptible to effects of strontium, cesium and iodine iso topes, which cause parathyroid irradiation and subsequent structural and functional changes, being a prerequisite for development of osteopenia and osteoporosis in the ChNPP accident survivors and their descendants. High inci dence of parathyroid hypertrophy is found in the inhabitants of the radiation contaminated territories (long term irradiation by cesium isotopes), as well as in evacuated from the 30 km exclusion zone (irradiation by iodine iso topes in the early days of the accident).

Initial healthcare to pediatric population under the radiation events. / MEDYChNA DOPOMOGA DYTIaChOMU NASELENNIu PRY RADIATsIY̆NYKh PODIIaKh NA PERShYKh ETAPAKh.

The objective of this paper is to analyze the data from scientific literature and available recommendations for health professionals on healthcare providing to pediatric population in the events associated with risk of radiation exposure. Over the past sixty years there were several large scale radiological events with a large number of chil dren affected, namely the atomic bombing of Hiroshima and Nagasaki, accident at the Chornobyl nuclear power plant, contact to 137Cs radiation source unutilized at the hospital shutdown in Brazil etc. Further research has crys tallized injuries and health disorders in the survived children in all cases being much more significant vs. other pop ulations. Analysis of circumstances and features of a number of emergency situations or incidents in the nuclear industry for several decades has shown a high probability of radioactive materials release into the environment. The danger of terrorism with the use of ionizing radiation sources resulting in a considered inevitable hazard to the chil dren is estimated as serious in recent years and deserves an especial mention here.

Non cancer thyroid and other endocrine disease in children and adults exposed to ionizing radiation after the ChNPP accident. / NEZLOIaKISNA TYREOIDNA TA INShA ENDOKRYNNA PATOLOGIIa U DOROSLYKh I DITEY, OPROMINENYKh VNASLIDOK AVARII NA ChAES.

STUDY OBJECTIVE: To summarize the verified clinical and epidemiological data on the natural history of non cancer endocrine disease in remote period after the ChNPP accident in survivors of adult and children age. MATERIALS AND METHODS: Retrospective estimation was carried out of data on 24,588 adult persons and 20,087 chil dren survived after the ChNNP accident and being healthy or having any diseases. Data were retrieved from database of the Clinical Epidemiological Registry (CER), NRCRM for the 23 years (1992-2014) of survey. Average total external radiation dose in adults was 0.187 Gy, range of thyroid dose in children was 0.1-1.55 Gy. These data were verifies in a separate clinical study. Anthropometric, laboratory biochemical and hormonal assay values, thyroid ultrasound imaging patterns and radiation dose values were retrieved for the study. RESULTS: Retrospective data review for the 1992-2014 period indicated that incidence of thyroid disease in all per sons survived after the ChNPP accident run at 40.29% with 35.37% among the clean up workers, 27.24% among evac uees, and 28.6% among population of contaminated territories that all is significantly (p < 0.0001) higher vs. the entire population of Ukraine (3.9%). Following non cancer endocrine diseases were most prevalent in the ChNPP acci dent survivors: nodular goiter (14.35%), chronic autoimmune thyroiditis (~8%), pre obesity and obesity (41.9% and 36.8% respectively), prediabetes and diabetes mellitus (15.5% and 21.4% respectively). Nodular goiter (21.8%), chronic autoimmune thyroiditis (12.95%), pre obesity and obesity (41.71% and 33.61% respectively), and predia betes and diabetes mellitus (8.6% and 12.15% respectively) were most often diagnosed in the ChNPP accident clean up workers. Children evacuated from the 30 kilometer exclusion zone were a critical population group. They were diagnosed diffuse non toxic goiter in 43.68%, chronic autoimmune thyroiditis in 1.74%, primary hypothyroidism in 0.96%, and nodular goiter in 2.57%. Peak prevalence of chronic autoimmune thyroiditis occurred in 2001-2003 i.e. in a period of their intensive pubertal maturation. In children (first generation) of exposed parents the thyroid dis ease was revealed in 42.64%, that exceeded the incidence in control group, chronic autoimmune thyroiditis was found rarer i.e. in 0.45%, diffuse non toxic goiter in 9.5-13.8%, nodular goiter in 1.7%. CONCLUSIONS: Non cancer endocrine disease in children and adults exposed to ionizing radiation is frequent and reg istered in 3 53% of persons. It occurs in most of survivors 10-15 years upon the impact of radiation factor as a result of man made accident and continues to grow slowly in 30 years.