The Results of the Assessment of Iodine & Selenium Deficiency in the Soil Cover and Thyroid Disease Incidence in the Population of the Central Federal District of the Russian Federation

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INTRODUCTION
Human iodine balance, production and secretion of thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) are controlled by the thyroid gland [1].  Thyroid hormone production is influenced by the availability of iodine, a trace element that is unevenly distributed on Earth and is essential for the synthesis of thyroid hormones. Iodine deficiency causes decreased levels of T3 and T4. In addition, there is increasing evidence linking thyroid dysfunction with depression and anxiety disorders, obesity, metabolic syndrome, kidney disease and cardiovascular disease [2].
Iodine in the body is involved in various biochemical reactions. In particular, oxidative processes are enhanced under its influence, and iodide metals inactivate or inhibit the activity of many enzyme systems. Iodine deficiency is the most important pathogenetic factor that is responsible for the occurrence of endemic thyroid diseases [3; 4]. With prolonged insufficient intake of the trace element into the body, adaptation mechanisms are disrupted and iodine deficiency diseases occur [5].  

Numerous studies have confirmed the importance of selenium in maintaining homeostasis of various vital processes, including immune-endocrine function [6]. Selenium plays an important role in thyroid function [7-13], it is assumed that this connection is through a specific enzyme called 5'-deiodinase type 1, which is responsible for thyroid hormone conversion and contains selenium [14]. 
Since 1990, the number of thyroid cancer cases worldwide has increased by 169% [15]. The introduction of new screening technologies, such as ultrasound echography, computed tomography and magnetic resonance imaging, and the increasing availability of medical care worldwide have enabled health professionals to detect small lesions caused by a large number of asymptomatic non-lethal thyroid diseases [16].

After the Chernobyl accident in 1986, a unique ecological and geochemical situation was created in the Central Federal District (CFD). As a result of radioactive isotope fallout in the territories with different, including deficient levels of trace elements in the environment, which contributed to the spread of thyroid diseases among the population. Normal functioning of the thyroid gland requires maintenance of a certain level of iodine and selenium intake with daily diet. Thus, a unique situation of combined (natural and anthropogenic) impact on the affected population arose in these territories. This situation requires continuous monitoring of geochemical risk indicators and study of their spatial distribution.
Although the main source of iodine intake into soil and plants is the world ocean, the level of iodine content and migration depend largely on the terrain, agrophysical and agrochemical properties of soils, climate and hydrological regime. The least amount of iodine in our country is observed in podzolic and gray forest soils of light granulometric composition, and the highest - in solonchaks [18].

When estimating the gross iodine content in Russian soils, the following gradations are used: <5.0 mg/kg air-dry weight (a.d.m.) - insufficient content, 5.1-40.0 mg/kg a.d.m. - normal, >40.0 mg/kg a.d.m. - excessive [19; 20]. 
Low iodine values are observed for most of the agricultural soils of the Central Federal District: even in ordinary chernozems of the Voronezh region, the gross iodine content in the upper horizon ranges from 4.8 to 5.0 mg/kg w.s.m., and for the protected areas of the region - 4.1-6.5 mg/kg w.s.m. [21]. [21]. For sod-podzolic and podzolic soils of the European part of the Russian Federation, the average iodine content does not exceed 2.5 mg/kg w.s.m. [22]. [22].
Thus, the assessment of iodine status of the territory of the Central Federal District is relevant, since iodine deficiency in the body, caused by its deficiency in the lower links of the trophic chain, leads to the occurrence of endemic diseases.

Thyroid diseases can be caused not only by iodine deficiency, but also by iodine content close to normal against the background of imbalance of other essential elements, such as selenium, copper, cobalt. In particular, selenium deficiency has been identified in 1 billion people worldwide [23]. In Russia, 90% of the population consumes insufficient amounts of selenium with food [24]. In addition to thyroid disease, selenium deficiency in food chains has been found to contribute to about 40 different diseases.
Although the average selenium content in soils of the Russian Federation is 300 mg/kg, many areas of the country are selenium deficient. Soil content of gross forms of selenium varies within a very wide range from 50 μg/kg in sod-podzolic and gray forest soils of the Non-Chernozem region to 1100 μg/kg in soils of arid territories [25]. At the same time, contrasting contents of both selenium and iodine can be observed in soils of different types within one region and even a district. For example, it was shown that in the Bryansk region, gray forest loamy soil on loess-like loams in the upper 20 cm layer contains twice as much iodine and almost four times as much selenium as sod-podzolic sandy loam on bicarbonate sediments in the same layer [22]. 

OBJECTIVE
To analyze regional peculiarities of thyroid diseases morbidity in the population of the Central Federal District depending on the microelement status of the territory. 
MATERIALS AND METHODS
The Central Federal District (CFD) occupies the central part of the East European Plain. The area of the district is 650,205 km², which is larger than any of the European states. The district includes 18 subjects: 17 regions (Belgorod, Bryansk, Vladimir, Voronezh, Ivanovo, Kaluga, Kostroma, Kursk, Lipetsk, Moscow, Orel, Ryazan, Smolensk, Tambov, Tver, Tula, Yaroslavl) and the federal city of Moscow [17]. The Central Federal District significantly surpasses other federal districts of the country in terms of population (26.9% of Russia's population), with a population density of 57.7 people/km2. Agriculture specializes in the cultivation of cereals, vegetables, oilseeds, dairy and meat cattle breeding and is characterized by a developed market infrastructure.

Since the federal city of Moscow, as the largest metropolitan area in Europe, practically does not consume food products made from locally grown fruit and vegetables and meat and dairy products, as well as due to significant differences in the standard of living of the population and availability of medical services, compared to the regions of the Central Federal District, it was excluded from the comparative analysis. The spatial heterogeneity of endemic diseases distribution in urbanized areas (including the Moscow agglomeration) requires additional assessment.
To analyze the population health of the CFD regions, we used depersonalized data on the number of patients with first diagnosed thyroid diseases for 2013-2017 according to the collections of statistical materials “Morbidity of the entire population of Russia” (Table 1), data for 2013-2014, 2013-2014, 2015, 2015, and 2014. [26], 2015 г. [27], 2016-2017. [28].

The data on the primary morbidity rate of thyroid malignant neoplasms for 1995-2023, including age-disaggregated data for 2003-2023, were obtained on the basis of the aggregated form of the population register of cancer patients in the Russian Federation [29] and the population morbidity rate of thyroid malignant neoplasms on the basis of the data of the federal statistical observation form No. 7 “Information on malignant neoplasms” (Table 2).
The method of constructing maps of ecological risk of diseases is based on the establishment of spatial heterogeneity of diseases and factors causing it by analyzing the favorability of geochemical conditions. Gross concentrations of trace elements (iodine and selenium) were used as indicators of such conditions as a potential maximum content available to plants. In the deficiency case under consideration, such an assessment represents the upper (i.e., the most favorable) limit [30].

To build a spatial model of the heterogeneity of geochemical factors associated with the morbidity of the population, we used an algorithm for the construction of maps of natural geochemical heterogeneity of territories on the basis of electronic soil maps with subsequent assessment and an algorithm for the construction of maps of environmental-geochemical risk, the first stage of which is the mapping of natural geochemical heterogeneity of territories on the basis of electronic soil maps.
The cartographic basis used for the construction of estimated maps of trace element distribution in the soil cover of the region was the Unified State Register of Soil Resources of Russia with a cartographic basis at a scale of 1:2,500,000 [31]; data [32, 33]; Se - [20] were used as initial data on the concentration of I in soils. Quantitative attributes of average concentrations were assigned to each qualitative classification pair of cartographic units “soil type - soil-forming rock” (Table 3).

To analyze the correctness of the estimates, we used data from field studies conducted in 2007-2023 in the Bryansk, Orel and Kaluga regions [34]. Soil samples were collected from the top 20 cm layer of soil with a hand drill on pre-selected pasture plots near rural settlements. Iodine and selenium were determined in the laboratory of environmental biogeochemistry of GEOHI RAS. Gross forms of iodine were determined by the accelerated kinetic rhodanide-nitrite method [35] on a photometer KFK-3-01-“ZOMZ” (ZOMZ, Russia) from fresh soil samples. The sensitivity of the method is 1-4 ng/mL, and the reproducibility is 2-7%. All results of iodine measurements were converted to air-dry suspensions for comparability. Total and hygroscopic moisture were determined by standard methods [36]. Selenium was determined by the spectrofluorimetric method in air-dry samples [37] on a spectrofluorimeter MPFS-2A (Hitachi, Japan). The sensitivity of the method was 1 ng/mL and the reproducibility was 7%.
After assigning the appropriate attributes, the average concentration of trace elements in the soil cover of a larger subdivision - the subject of the federation as the territory for which medical information is available - was estimated using formula (1) [38]. The analysis was performed in the geographic information system ArcGIS 10.8.1 (ESRI, USA)

$Creg=\sum _{i=1}^n{C}_i{A}_i\left(1\right)$

where Creg - average concentration of a trace element in the soil of the region, Ci - average concentration of a trace element characteristic for the type of soil formed on the given soil-forming rock, Ai - share of the polygon area in the area of the region, n - number of polygons of the soil map on the territory of the region, i - number of the polygon.
Assessment of radiation contamination of the study area due to the Chernobyl NPP accident was carried out according to the data on the distribution of the number of settlements by the level of 137Cs contamination (as of January 2024) based on the data [39]. It should be noted that it is possible to recalculate measurement data on soil contamination with 137Cs into data on 131I contamination of the territory [40].
Statistical processing of the results was carried out in Microsoft Excel (Microsoft, USA) and TIBCO STATISTICA 13.3 (TIBCO, USA). Estimates of soil iodine and selenium availability and the distribution of morbidity rates by regions had a distribution different from normal (Fig. 1), as well as a small sample (n=17), so Spearman's Rank Correlation Coefficient was used to interpret the relationships between geochemical and medical data.

RESULTS
Comparison of cartographic assessments of availability of different types of soils with the studied trace elements and data of chemical analysis of samples showed good convergence: for iodine in 16 soil-rock pairs (n=136) R=0.92 (p<0.01), for selenium in 6 soil-rock pairs (n=44) R=0.80 (p=0.05) (Fig. 2).
Cartographic representation of iodine and selenium status of the CFD soil cover, obtained on the basis of data on variation of average iodine and selenium content in soils of different types, is shown in Figure 3.
Analysis of the obtained distribution of iodine in soils (Figure 3) allowed us to identify three groups of regions with different levels of iodine supply [41]: 1) iodine deficiency (less than 4.0 mg/kg w.s.m.) is characteristic of the Moscow, Tver, Bryansk, Smolensk, Vladimir, Yaroslavl, Ivanovo, Kostroma and Kaluga regions; 2) iodine content from mild deficiency to norm (within 4.1 - 4.8 mg/kg w. c.m.) - for Voronezh, Tambov, Lipetsk, Belgorod and Kursk Regions; 3) contrasting regions in terms of iodine content, where there are comparable soils with iodine content from weak deficiency (3.0-4.0 mg/kg a.d.m.) to the norm: 3.0-4.0 mg/kg a.d.m. - for Voronezh, Tambov, Lipetsk, Belgorod and Kursk Regions. c.m.) to the norm: a) - Ryazan region, where podzols and gray forest soils in the north-west are combined with chernozems in the south and peat bogs in Meshchera lowland in the north-east); b) - Tula and Orel regions (combination of sod-podzol, gray forest soils and chernozems).

Assessment of selenium distribution in soils allowed us to single out regions with relatively low (0.30-0.40 mg/kg a.d.m.) content of the trace element in the Central Federal District. ) content of the trace element: Tambov, Ryazan, Lipetsk, Yaroslavl, Belgorod, Ivanovo, Kaluga, Tula, Bryansk and Vladimir regions, and relatively high (0.41-0.59 mg/kg a.d.m.) - Kostroma, Tver, Orel, Moscow, Voronezh, Kursk and Smolensk regions. At the same time, in all regions the selenium content in soils is within the biogeochemical norm (0.20-0.70 mg/kg) [42]. The results are summarized in Table 4.
Comparison of geochemical parameters with thyroid incidence rates in 2013-2017 showed a significant relationship (at p=0.06 level) (Table 5).
It should be noted that no significant relationships with Se concentration in soil, as well as with radiation contamination of the territory, were found.
Comparison of thyroid cancer morbidity with the concentration of microelements and radioactive pollution showed a significant direct relationship between morbidity and anthropogenic pollution for the whole period: from 1995 to the present (Table 6).

Analysis of age groups showed a differentiated picture for adults (over 18 years old) and children (under 18 years old). Thus, for the adult population a significant contribution of the level of radiation contamination of the territory to the morbidity was noted (Table 7).
For children, the presence of a significant relationship between thyroid cancer morbidity and radiation contamination of the territory is also characteristic; however, the presence (on the verge of significance) of an inverse relationship between morbidity and the level of natural iodine deficiency, especially in 2003-2013, is also shown (Table 8).
DISCUSSION
Comparison of cartographic estimates showed good convergence with the actual material sampled in Bryansk, Orel and Kaluga oblasts. The lower content of trace elements in the studied soil types (chernozems, gray forest, sod-podzolic, alluvial soils) detected as a result of the study in comparison with their cartographic estimates can be associated with a high degree of agricultural exploitation of the studied soils, mainly cattle grazing. Iodine losses by the upper horizons due to changes in such soil parameters as organic matter content, granulometric composition, and soil solution reaction, including as a result of agricultural impact, have been shown earlier [18; 20].

Field and laboratory studies in combination with cartographic analysis of the soil map have shown that iodine distribution in soils of agricultural lands of the Central Federal District generally obeys the law of geographical zonality. The iodine content in the soil cover of the East European Plain in the upper soil horizons increases from the northwest to the southeast, which does not contradict the previously obtained data. As our study has shown, the reasons for the uneven distribution of selenium in these soils certainly deserve further study, but are of little importance from the point of view of thyroid cancer development.
The revealed iodine deficiency in the CFD subjects confirms earlier status assessments: the population of the CFD in the Non-Black Earth Zone is less supplied with iodine and selenium, which are contained in the basic foodstuffs produced from fruit and vegetables and meat and dairy products grown on local agricultural lands, than the population of steppe chernozem areas [41].

The data obtained in this work on the levels of selenium content in soils of the Central Federal District allow us to refer the territory to the biogeochemical norm for this indicator, which is confirmed by studies on the assessment of selenium availability in plants and soils in Russia [43]. However, since Se transfer to plants (and further, through the food chain, to the human body) depends not only on the availability of the mobile form of the element in soils, but also on the biological characteristics of plants [20], the presented estimates of the selenium status of the regions can be improved by replacing gross Se concentrations by the content of mobile forms (assimilated by plants) in soil.
The results of the study of spatial heterogeneity of element content in the territories affected by the Chernobyl NPP accident are consistent with the data we obtained earlier (2007-2023) for some regions of the CFD. Thus, for the Bryansk region it was found that thyroid cancer incidence in rural settlements is negatively correlated with the level of iodine consumption and positively - with the spatial assessment of radioactive contamination [38]. The vulnerability of the pediatric population (8-12 years old) to natural iodine deficiency has been identified for the same region [44]. Further studies should pay more attention to this age group, since it is children who are characterized by the response of thyroid morbidity to a combination of natural and anthropogenic risk factors [45]. 

The low values of correlation coefficients obtained for a number of dependencies should be attributed to the multifactorial nature [46] of the risk of occurrence of the diseases under study. In addition, the study analyzed the general morbidity by region, while the association with the natural deficiency of trace elements in the surrounding soils should be higher for rural areas than for urban areas, since there are differences in the structure of food consumption in households and sources of their inputs [47].
The described relationships have also been found in other regions of the world. In China [48], an association between soil and soil-forming rock conditions and thyroid cancer has been shown, indicating that a soil type-based approach can be used to assess thyroid cancer risk. A similar relationship between average concentrations of trace elements has been found in European countries: in Belarus, the lowest iodine levels in the population were found in the Mogilev region [49] on iodine-poor soils.

It should be noted that it is the combination of multiple factors that leads to a significant difference in the morbidity of urban and rural populations, including higher provision and accessibility of medical and diagnostic services, a greater share of imported products (grown not on the soil of the region) in the diet due to urbanization of the region and more comfortable living conditions. The spatial distribution of the studied diseases in densely populated urbanized areas (such as the Moscow agglomeration, the largest in Europe) requires further evaluation. 
CONCLUSION
Our proposed model for the distribution of trace element concentrations in the soil cover of the region has clearly demonstrated the spatial heterogeneity of iodine and selenium distribution in the soil cover of the CFD at the regional and municipal levels. 

The obtained model estimates are comparable with the results of field studies, which indicates the possibility of using the developed mapping model for multilevel risk assessment.
Significant inverse correlation between iodine content in soil and thyroid gland morbidity in the CFD regions was confirmed. 
The level of selenium in the soil of all studied regions is within the normal range, so no significant relationship between the Se content in the soil and morbidity of the population was found. 

A significant direct correlation between the level of anthropogenic soil contamination with 137Cs radioisotopes and the incidence of thyroid cancer in the population of the Central Federal District has been shown.
Thus, iodine, along with radiation contamination of the territory, are risk factors for thyroid disease, including cancer. 
 It is necessary to be aware of the negative consequences of microelement deficiency if you are in the risk group for thyroid cancer incidence in the CFA. Our results showed that the spatial heterogeneity of geochemical factors and thyroid gland morbidity deserves more detailed study.
The results of the study can be used to develop a system of informing residents about natural and anthropogenic risks associated with thyroid diseases, in the development of risk assessment methods for all territorial entities, as well as for the development of programs for the prevention of thyroid diseases, including malignant neoplasms, at the population and regional levels and for the formation of individual programs for the prevention of thyroid pathologies.

About the authors

Yulia Zhuravleva

Federal State Budgetary Institution “Central Research Institute of Healthcare Organization and Informatization” of the Ministry of Healthcare of the Russian Federation

Email: zhuravlevays@mednet.ru
ORCID iD: 0000-0002-2278-9415
SPIN-code: 8322-3369

senior researcher of the department of public health and demography 

Russian Federation, 127254, Russia, Moscow, Dobrolyubova str., 11

Vladimir I. Starodubov

Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation

Email: starodubov@mednet.ru
ORCID iD: 0000-0002-3625-4278
SPIN-code: 7223-9834

science, professor, academician

Russian Federation, 127254, Moscow, Dobrolubov str., 11

Vladimir Sergeevich Baranchukov

Federal State Budgetary Institution of Science of the Order of Lenin and the Order of the October Revolution Institute of Geochemistry and Analytical Chemistry named after. V.I. Vernadsky Russian Academy of Sciences.

Author for correspondence.
Email: baranchukov@geokhi.ru
ORCID iD: 0000-0003-1519-9983
SPIN-code: 2266-2251

researcher

Russian Federation, 119991, Russia, Moscow, st. Kosygina, 19

Elena Alekseevna Varavikova

Federal State Budgetary Institution “Central Research Institute of Healthcare Organization and Informatization” of the Ministry of Healthcare of the Russian Federation

Email: dr.e.varavikova@mail.ru
ORCID iD: 0000-0003-3408-3417
SPIN-code: 3026-3615

Candidate of Medical Sciences, Leading Researcher, Department of Public Health and Demography

Russian Federation, 127254, Russia, Moscow, Dobrolyubova str., 11

Viktor Yurievich Berezkin

Federal State Budgetary Institution of Science of the Order of Lenin and the Order of the October Revolution Institute of Geochemistry and Analytical Chemistry named after. V.I. Vernadsky Russian Academy of Sciences.

Email: victor76@list.ru
ORCID iD: 0000-0002-1025-638X
SPIN-code: 7074-9478

Candidate of Geological and Mineral Sciences, Senior Researcher

Russian Federation, 119991, Russia, Moscow, st. Kosygina, 19

Liudmila Igorevna Kolmykova,

Federal State Budgetary Institution of Science of the Order of Lenin and the Order of the October Revolution Institute of Geochemistry and Analytical Chemistry named after. V.I. Vernadsky Russian Academy of Sciences.

Email: kmila9999@gmail.com
ORCID iD: 0000-0003-4070-9869
SPIN-code: 2111-3310

Candidate of Geological and Mineral Sciences, Scientific Secretary, Researcher

Russian Federation, 119991, Russia, Moscow, st. Kosygina, 19

Valentina Nikolaevna Danilova

Federal State Budgetary Institution of Science of the Order of Lenin and the Order of October Revolution V.I. Vernadsky Institute of Geochemistry and Analytical Chemistry of the Russian Academy of Sciences. V.I. Vernadsky Institute of Geochemistry and Analytical Chemistry of the Russian Academy of Sciences.

Email: val1910@mail.com
ORCID iD: 0000-0003-3308-8443
SPIN-code: 1778-9633

researcher

Russian Federation, 19 Kosygina St., Moscow, Russia, 119991

Valery Semyonovich Stupak

Federal State Budgetary Institution “Central Research Institute of Healthcare Organization and Informatization” of the Ministry of Healthcare of the Russian Federation

Email: stupak@mednet.ru
ORCID iD: 0000-0002-8722-1142
SPIN-code: 3720-1479

Doctor of Medical Sciences, Associate Professor, Head of the Department of Public Health and Demography

Russian Federation, 127254, Russia, Moscow, Dobrolyubova str., 11

Ekaterina Nikolaevna Yenina

Federal State Budgetary Institution “Central Research Institute of Healthcare Organization and Informatization” of the Ministry of Healthcare of the Russian Federation

Email: eninaen@bk.ru
ORCID iD: 0000-0002-9876-5102
SPIN-code: 7531-4051

senior researcher of the department of public health and demography

Russian Federation, 127254, Russia, Moscow, Dobrolyubova str., 11

References

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