Słupskie Prace Biologiczne 11 ••• 2014
PREVALENCE OF HASHIMOTO’S THYROIDITIS AMONG ADOLESCENTS IN LVIV REGION (UKRAINE) DURING YEARS 2000-2010
Olha Kasiyan 1 Halyna Tkachenko 2 Jan Łukaszewicz 3 Natalia Kurhaluk 2
1 Danylo Halytskyy Lviv National Medical University, Ukraine Department of Hygiene and Preventive Toxicology 2 Pomeranian University in Słupsk Institute of Biology and Environmental Protection Department of Zoology and Animal Physiology Arciszewski Str. 22b, 76 200 Słupsk e mail: [email protected] 3 Adam Mickiewicz University Institute of Physical Geography and Environmental Planning Department of Hydrology and Water Management Dzięgielowa Str. 27, 61 680 Poznań
ABSTRACT
Incidence of autoimmune thyroid diseases (AITD) in Ukraine is currently higher than in past decades. In our previous study we demonstrated increase of AITD prevalence in Lviv region during 2000 2010 was mainly by the adult population in the greater urban area, less – among adults of rural areas (Kasiyan et al. 2009, 2010, 2013, 2014). Increase in the AITD prevalence among adults identified in 16 districts and 3 towns of Lviv region (Kasiyan et al. 2013). The aim of our study was the as sessment of Hashimoto’s thyroiditis (HT) prevalence among adolescents (14 18 years old) in Lviv region (western Ukraine) during 2000 2010. For assessment of the HT prevalence among adolescents of different districts (reions) in Lviv region during years 2000 2010, the analysis of archival data from Lviv Regional Endocrinology Hospital was done. The research study covered by 20 districts (reions) of Lviv oblast, as well as six towns of Lviv region. For assessment of the relative risk (RR) of HT among adolescents of Lviv region, retrospective study was used. Decrease of HT prevalence among the adolescent population in Lviv region during years 2000 2010 was observed. Increased HT prevalence among adolescents from towns during 2000 2004 years was found. The peak of disease prevalence was noted in 2000 and 2004. Among adolescents both in districts and towns, decrease of HT prevalence
77 from 2004 to 2010 was found. The decrease of HT prevalence among adolescents from rural areas during 2000 2004 years was observed, while its increase from 2004 to 2010 was noted. HT prevalence among adolescents was the highest in Brody, Turkivskyi, Sambir, Sokal, and Horodok districts during 2000 2010. Our results in dicate the need to clarify the reasons for the increased HT prevalence among the population of Lviv region, the definition of the risk of thyroid pathology in each dis trict of the region among the different age groups, which will propose measures to prevent further increase of HT incidence.
Key words: Hashimoto’s thyroiditis, Lviv region, adolescents, relative risk
INTRODUCTION
Autoimmune thyroid diseases (AITD), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are the most common organ specific autoimmune dis orders usually resulting in dysfunction (hyperfunction, hypofunction or both) of the thyroid gland (Trbojević and Djurica 2005). It is thought that autoimmune reactions against the thyroid can develop in various directions. In AIT, the immunological process is dominated be a lymphocyte mediated cell damaging processes, leading to destruction of follicular cells; in Graves’ disease the immunological process is dominated by synthesis and release of antibodies that stimulate the TSH receptor (Nystrom et al. 2011). The pathophysiological background of the development of AITD has not been entirely clarified. It’s likely that some individuals have a predisposition which, in conjunction with triggering factors, starts the process. In addition to genetic factors, predisposing factors can include reduced immunological tolerance, which could have arisen during maturation of the immune competent cells in the thymus (Nystrom et al. 2011). Epidemiological data support strong genetic influences on the development of AITD (Hasham and Tomer 2012). The importance of genetic factors is supported by the increased prevalence of autoantibodies in relatives of affected patients, and because several members of one family can be affected by autoimmune thyroid disease. In some way, certain changes in the MHC/HLA system are thought to be associated with these diseases. Twin studies have, however, demonstrated a higher occurrence of the disease in siblings than can be explained by the HLA system alone (Nystrom et al. 2011). In addition to the MHC class II genes, there are now several other confirmed gene loci associated with AITD, including immune regulatory (CD40, CTLA 4, PTPN22, FOXP3, and CD25) and thyroid specific genes (thy roglobulin and TSHR) (Hasham and Tomer 2012). The pathogenetic mechanisms leading to the development of autoimmune dis ease of the thyroid are based on several different factors (Schumm Draeger 2004). It is well established that a complex interplay of diverse environmental and genetic susceptibility factors interact in predisposing an individual to AITD. Significant progress has been made in understanding of the genetic and environmental triggers contributing to AITD. The major environmental triggers of AITD include iodine, medications, infection, smoking, and possibly stress (Tomer and Huber 2009).
78 Moreover, the contribution that each factor makes varies from patient to patient, and as yet there are no clear genotype phenotype correlations (Diseases... 2007). Children not only encounter a somewhat different range of environmental factors to adults, but also have overall a lower chance of encountering aetiological agents simply because of their shorter period of exposure. In turn, this has led to the sug gestion that genetic factors are likely to play a larger role in childhood thyroid auto immunity than in adults, while environmental factors would have an increasing role in adults as they age. Despite possible ascertainment artefacts, initial studies have certainly shown that children and adolescents with autoimmune thyroiditis have strik ingly strong family histories of thyroid and other autoimmune disease, including those in the non organ specific category (Diseases... 2007). HT is the most common cause of thyroid diseases in children and adolescents and it is also the most common cause of acquired hypothyroidism with or without goiter. Iodine and iodine containing drugs can precipitate HT in susceptible popula tions. There is an infiltration of lymphocytes and plasma cells between the follicles followed by their atrophy. The clinical course is variable and spontaneous remission may occur in adolescence. Goiter, menstrual disorders, short stature, constipation, nervousness and exophthalmos have been reported as the most recurrent clinical fea tures of HT (Lorini et al. 2003). In younger people, hypothyroidism requiring treatment is reported to occur in about 1 1.5/1,000 individuals. Autoimmune thyroiditis is the most common cause of hypothyroidism. This disease is more uncommon in children and adolescents than in adults. The disease can be diagnosed in small children but is uncommon before puberty and increased thereafter with age. Autoimmune thyroiditis is more common in girls than boys but the gender difference is less pronounced than in adults (Szymborska and Staroszczyk 2000). Probably the most frequent clinical presentation of thyroid autoimmunity in children and adolescents is with a small asymptomatic goitre typically appearing around 11 to 12 years of age and compris ing a mild lymphocytic thyroiditis. Patients are usually euthyroid (Diseases... 2007). Clinical observations indicate that autoimmune thyroiditis in children and adolescents is typically less severe than in adults, with lower levels of autoanti bodies and a more fluctuating course which includes spontaneous recovery (Dis eases... 2007). A careful follow up of children exposed to fallout after the Chernobyl nuclear re actor accident found a significantly higher frequency of thyroid antibodies in chil dren aged 7–14 years compared to unexposed controls (81 vs. 17%) and ultrasono graphic abnormalities compatible with lymphocytic thyroiditis were also increased (Vykhovanets et al. 1997). The dose of 131 I that the children had been exposed to correlated with thyroid antibody levels, up to a thyroid gland dose of 4Gy (Dis eases... 2007). Incidence of AITD in Ukraine is currently higher than in past decades. In our pre vious study we demonstrated increase of AITD prevalence in Lviv region during 2000 2010 was mainly by the adult population in the greater urban area, less – among adults of rural areas (Kasiyan et al. 2009, 2010, 2013, 2014). Increase in the AIT prevalence among adults identified in 16 districts and 3 towns of Lviv region (Kasiyan
79 et al. 2013). The aim of our study was the assessment of HT prevalence among adoles cents (14 18 years old) in Lviv region (western Ukraine) during 2000 2010.
MATERIALS AND METHODS
For assessment of the HT prevalence among adolescents of different districts (reions) in Lviv region during years 2000 2010, the analysis of archival data from Lviv Regional Endocrinology Hospital was done. The research study covered by 20 districts (reions) of Lviv Oblast (Brody, Busk, Horodok, Drohobych, Zhydachivskyi, Zhovkivskyi, Zolochivskyi, Kamianka Buzka, Mykolaiv, Mostyska, Peremyshliany, Pustomyty, Radekhiv, Sambir, Skole, Sokal, Starosambirskyi, Stryiskyi, Turkivskyi, and Yavorivskyi Districts), as well as six towns of Lviv region (Lviv, Boryslav, Dro hobych, Stryi, Truskavets, Chervonograd). For assessment of the relative risk (RR) of HT among adolescents of Lviv region, retrospective study was used. Kamianka Buzka district as control district, as well as Drohobych as control town for RR as sessment in retrospective analysis was used. Assessment of air quality, water and soil quality, and food quality according to the hygienic indicators (the number of samples that not match to standards, %) in districts of Lviv region in 2000, 2002, 2004, 2006, and 2008 years was also done. The obtained results were analyzed sta tistically using the Statistica 10.0 software package (StatSoft, Poland). In order to find significant differences (significance level, p < 0.05) between Hashimoto’s thy roiditis prevalence in different districts of Lviv region, Kruskal–Wallis test was ap plied to the data (Zar 1999).
RESULTS AND DISCUSSION
Decrease of prevalence of HT among the adolescent population of Lviv region during years 2000 2010 was observed (Table 1, Figs 1 3). Increased prevalence of HT among adolescents from towns during 2000 2004 years was found. The peak of disease prevalence was noted in 2000 and 2004; it was 34.8 per 10,000 indi viduals among adolescents in districts in 2000, and 40.9 per 10,000 individuals among adolescents in towns in 2004. Among adolescents both in districts and towns, decrease of HT prevalence from 2004 to 2010 was found; it was 22.5 and 24.7 per 10,000 individuals in 2004 and 2010, as well as 8.0 per 10,000 individu als in 2010, respectively. The decrease of HT prevalence among adolescents from rural areas during 2000 2004 years was observed (34.8 to 22.5 per 10,000 indi viduals), while its increase to 24.7 per 10,000 individuals from 2004 to 2010 was noted. Increased HT prevalence among adolescents of Lviv region was observed in Brody, Horodok, Kamianka Buzka, Mostyska and Turkivskyi districts (increased by 15.18, 2.26, 1.13, 1.12 and 1.19 times, respectively). The decrease of HT preva lence among adolescent population in the other 15 districts and all towns in the Lviv region was noted (Table 1).
80 Table 1
Hashimoto’s thyroiditis prevalence (per 10,000 individuals) among the adolescents in Lviv region (Ukraine) in the years 2000, 2004 and 2010
2000 2004 2010 Districts of Lviv region Increased level Districts (reions) Brody 12.5 87.1 189.7 15.18 Busk 21.7 0.0 4.8 0.22 Horodok 31.6 24.5 71.4 2.26 Drohobych 6.1 0.0 0.0 0.0 Zhydachivskyi 45.9 7.4 5.5 0.12 Zhovkivskyi 11.1 5.6 3.3 0.30 Zolochivskyi 23.5 17.3 13.4 0.57 Kamianka Buzka 6.9 3.2 7.8 1.13 Mykolaiv 10.4 6.1 7.3 0.70 Mostyska 6.5 6.5 7.3 1.12 Peremyshliany 22.7 29.0 5.7 0.25 Pustomyty 26.9 35.4 6.8 0.25 Radekhiv 68 11.9 0.0 0.0 Sambir 94.4 31.1 29.2 0.31 Skole 24.0 35.9 9.2 0.38 Sokal 97.9 58.7 32.7 0.33 Starosambirskyi 12.5 5.1 0.0 0.0 Stryiskyi 6.7 6.1 3.9 0.58 Turkivskyi 110.7 111.8 131.4 1.19 Yavorivskyi 30.4 21.8 11.2 0.37 Total to Districts 34.8 22.5 24.7 0.71 Towns Lviv 28.5 52.6 5.6 0.20 Boryslav 30.0 46.8 6.6 0.22 Drohobych 19.1 4.2 10.2 0.53 Stryi 31.4 25.4 17.2 0.55 Truskavets 0.0 28.3 0.0 0.0 Chervonograd 19.1 15.5 14.8 0.77 Total to Towns 26.4 40.9 8.0 0.30 Summary 31.4 30.3 18.1 0.58
81
In 2000, the highest prevalence of HT among adolescent was found in Turkivskyi, Sokal, Sambir, Radekhiv, and Zhydachivskyi districts (110.7, 97.9, 94.4, 68.0, and 45.9 per 10,000 individuals, respectively), and in Lviv, Boryslav, and Stryi (28.5, 30.0, and 31.4 per 10,000 individuals, respectively) (Fig. 1).
Fig. 1. Prevalence of Hashimoto’s thyroiditis (per 10,000 individuals) among adolescents (A), as well as assessment of air quality (B), water and soil quality (C), and food quality (D) (the number of samples that not match to hygienic standards, %) in districts (reions) of Lviv re gion (Ukraine) in 2000
82
In 2004, the highest prevalence of HT among adolescent was found in Turkivskyi, Brody, and Sokal districts (111.8, 87.1, and 58.7 per 10,000 individuals, respectively), and in Lviv, Boryslav, and Truskavets (52.6, 46.8, and 28.3 per 10,000 individuals, respectively) (Fig. 2).
Fig. 2. Prevalence of Hashimoto’s thyroiditis (per 10,000 individuals) among adolescents (A), as well as assessment of air quality (B), water and soil quality (C), and food quality (D) (the number of samples that not match to hygienic standards, %) in districts (reions) of Lviv re gion (Ukraine) in 2004
83 In 2010, the highest prevalence of HT among adolescent was found in Brody, Turkivskyi, Horodok, Sokal, and Sambir districts (189.7, 131.4, 71.4, 32.7, and 29.2 per 10,000 individuals, respectively), and in Stryi and Chervonograd (17.2 and 14.8 per 10,000 individuals, respectively) (Fig. 3).
Fig. 3. Prevalence of Hashimoto’s thyroiditis (per 10,000 individuals) among adolescents (A), as well as assessment of air quality (B), water and soil quality (C), and food quality (D) (the number of samples that not match to hygienic standards, %) in districts (reions) of Lviv re gion (Ukraine) in 2010
In our study, prevalence of Hashimoto’s thyroiditis (per 10,000 individuals) among adolescents was the highest in Brody, Turkivskyi, Sambir, Sokal, and Horodok dis tricts during 2000 2010. In these districts, high level of air and food samples that not match to standards was observed (Figs 1 3). Moreover, the number of water and soil samples that not match to standards in Zhydachivskyi district was also noted (Fig. 1). The high relative risk (RR) of HT among adolescents in Lviv region was noted in Turkivskyi district during 2000 2008 [3.84 291.70, increased in 16.05 39.99 fold, p < 0.001], in Brody district during 2002 2008 [2.89 223.10, increased in 12.25 30.37 fold, p < 0.001], in Pustomyty district during 2004 2008 [1.48 74.87, increased in 11.06 18.34 fold, p < 0.010], in Sokal district during 2000 2004 [4,32 18,34, increased in 4,32 18,34 fold, p < 0.05], and in Sambir district [0.93 109.70, increased in 4.07 14.65 fold, p < 0.001] compared to Kamianka Buzka as control district (Table 2). Low levels of RR of this pathology among adolescent population in districts of Lviv region during 2000 2008 were noted in Busk, Drohobych, Zhovkivskyi, Myko
84 laiv, Mostyska, Starosambirskyi, Stryiskyi districts; the incidence of AIT was absent or the value of RR occurrence were non significant (p > 0,05) (Table 2).
Table 2
The relative risk of Hashimoto’s thyroiditis occurrence among adolescents in districts (reions) of Lviv region (Ukraine) during 2000 2008
The relative risk of Hashimoto’s thyroiditis occurrence Districts of Lviv region 2000 2002 2004 2006 2008 1.81 12.25 3 27.22 3 30.37 3 20.65 3 Brody χ2 = 0.49 χ2 = 19.08 χ2 = 24.42 χ2 = 27.56 χ2 = 35.90 3.15 2.37 1.26 Busk – – χ2 = 2.09 χ2 = 1.06 χ2 = 0.05 4.58 1 5.48 1 7.66 1 8.16 1 7.49 2 Horodok χ2 = 4.81 χ2 = 6.37 χ2 = 5.22 χ2 = 5.72 χ2 = 10.16 0.88 – Drohobych – – – χ2 = 0.02 1.61 1.16 0.49 Zhovkivskyi – – χ2 = 0.35 χ2 = 0.01 χ2 = 0.53 6.65 2 4.66 1 2.31 3.49 2.18 Zhydachivskyi χ2 = 8.62 χ2 = 4.79 χ2 = 0.60 χ2 = 1.42 χ2 = 0.91 3.41 3.22 5.41 6.50 1.79 Zolochivskyi χ2 = 2.72 χ2 = 2.45 χ2 = 3.08 χ2 = 4.08 χ2 = 0.46 1.51 0.30 1.91 2.06 0.95 Mykolaiv χ2 = 0.24 χ2 = 1.11 χ2 = 0.29 χ2 = 0.37 χ2 = 0.0 0.94 1.0 2.03 3.0 2.43 Mostyska χ2 = 0.0 χ2 = 0.0 χ2 = 0.35 χ2 = 1.0 χ2 = 1.20 3.29 4.23 9.06 1 4.56 Peremyshliany – χ2 = 2.28 χ2 = 3.71 χ2 = 6.16 χ2 = 2.09 3.90 1.95 11.06 2 14.18 3 18.34 3 Pustomyty χ2 = 3.78 χ2 = 0.72 χ2 = 8.72 χ2 = 11.79 χ2 = 32.05 9.86 3 9.14 3 3.72 1.24 0.64 Radekhiv χ2 = 14.29 χ2 = 12.83 χ2 = 1.49 χ2 = 0.02 χ2 = 0.14 13.68 3 5.34 1 9.72 1 14.653 4.07 1 Sambir χ2 = 22.77 χ2 = 6.43 χ2 = 7.40 χ2 = 12.09 χ2 = 4.10 3.48 4.36 1 11.22 2 10.95 2 9.05 3 Skole χ2 = 2.65 χ2 = 4.03 χ2 = 8.39 χ2 = 8.15 χ2 = 12.68 14.19 3 10.83 3 18.34 3 4.32 1 Sokal – χ2 = 23.67 χ2 = 16.86 χ2 = 15.89 χ2 = 4.42 1.81 2.00 2.43 Starosambirskyi – – χ2 = 0.52 χ2 = 0.72 χ2 = 0.63 0.97 1.42 1.06 0.51 Stryiskyi – χ2 = 0.0 χ2 = 0.15 χ2 = 0.0 χ2 = 0.31 16.05 3 17.24 3 34.94 3 39.99 3 17.97 3 Turkivskyi χ2 = 26.66 χ2 = 28.96 χ2 = 32.10 χ2 = 37.19 χ2 = 30.47 4.41 1 3.41 8.65 1 8.27 1 1.43 Yavorivskyi χ2 = 4.82 χ2 = 3.0 χ2 = 6.43 χ2 = 6.05 χ2 = 0.20
Legend: 1 – changes is statistically significant compared to control Kamianka Buzka district, p < 0.05; 2 – changes is statistically significant compared to control Kamianka Buzka district, p < 0.010; 3 – changes is statistically significant compared to control Kamianka Buzka district, p < 0.001.
85 The high RR of HT among adolescent in towns of Lviv region was noted in Lviv in 2004 [3.11 50.49, increased in 12.54 fold, p < 0.001] and in 2006 [1.98 101.40, increased in 14.16 fold, p < 0.001], in Brody district during 2002 2008 [2.89 223.10, increased in 12.25 30.37 fold, p < 0.001], in Boryslav in 2004 [2.41 51.53, increased in 11.14 fold, p < 0.010] and in 2006 [1.60 116.70, increased in 13.64 fold, p < 0.010], in Chervonograd in 2006 [1.16 73.87, increased in 9.24 fold, p < 0.05], in Truskavets in 2004 [1.13 40.28, increased in 6.74 fold, p < 0.05], and in Stryi in 2004 [1.29 28.47, increased in 6.05 fold, p < 0.010] compared to Drogobych as control town (Table 3).
Table 3
The relative risk of Hashimoto’s thyroiditis occurrence among adolescents in towns of Lviv region (Ukraine) during 2000 2008
Towns of The relative risk of Hashimoto’s thyroiditis occurrence Lviv region 2000 2002 2004 2006 2008 1.49 3.52 2 12.54 3 14.16 3 0.44 Lviv χ2 = 1.35 χ2 = 8.70 χ2 = 21.11 χ2 = 12.15 χ2 = 2.12 1.57 2.60 11.14 3 13.64 2 Boryslav – χ2 = 0.75 χ2 = 2.46 χ2 = 15.13 χ2 = 9.77 1.64 2.10 6.052 1.56 1.25 Stryi χ2 = 1.25 χ2 = 1.78 χ2 = 6.75 χ2 = 0.10 χ2 = 0.09 1.86 6.741 Truskavets – – – χ2 = 0.56 χ2 = 5.87 1.0 1.11 3.69 9.24 1 1.17 Chervonograd χ2 = 0.0 χ2 = 0.03 χ2= 3.05 χ2 = 6.54 χ2 = 0.05
For legend – see Table 2
Increased RR and prevalence of Hashimoto’s thyroiditis in districts Turkivskyi, Brody, Pustomyty, Sokal and Sambir districts during 2000 2010 is connected with high level of environmental pollution. Indeed, such environmental pollutants as smoke, polychlorinated biphenyls, solvents and metals have been implicated in the autoimmune process and inflammation. Environmental factors have not yet, how ever, been sufficiently investigated to clarify their roles in pathogenesis, and there is a need to assess their effects on development of the autoimmune process and the mechanisms of their interactions with susceptibility genes (Duntas 2008). In our study, a significant impact of chemical pollution of water and soil on the RR of HT among residents of rural districts of the Lviv region was noted, while air pollution has impact on the RR of HT among urban residents. There is also increasing evi dence that mainly nutritive factors and environmental pollution by metals and chemicals are the main factors in the present day spread of AITD (Duntas 2011). There is a wide variety of synthetic chemicals that affect the thyroid gland or have the ability to promote immune dysfunction in the host. These chemicals are released into the environment by design, such as in pesticides, or as a by product of industry. Candidate pollutants include polyaromatic hydrocarbons (PAH), poly brominated biphenols (PBBs), and polychlorinated biphenols (PCBs), among oth
86 ers. Infections are also reputed to trigger autoimmunity and may act alone or in concert with environmental chemicals. Infections are also reputed to trigger auto immunity and may act alone or in concert with environmental chemicals (Burek and Talor 2009). The RR of Hashimoto’s thyroiditis among adolescent in districts of Lviv region can be connected with environment pollution. Indeed, Ukraine faces the same envi ronmental problems. The river’s contaminations are caused by two main types: on going sources of pollution, and industrial accidents that cause ecological catastro phes. The sources of the on going contaminations are factories near the river, or chemical fertilizers. Taking everything into account, the Carpathian rivers (e.g. Tisza, Laborec) often suffer from industrial contamination. There are many exam ples of recent chemical pollution (water and air), which are caused by industrial fa cilities from neighbouring countries (Dobák 2010). According to Report of Helsinki Commission Baltic Marine Environment Protection Commission (2005), approxi mately half of the diffuse nutrient pollution in Lviv region comes from livestock breeding, 30% from arable land and the rest from non sewered sanitation systems. Furthermore, only 46% of the population is connected to sewerage systems and chlorinated pesticides are still used in the area. There are 16 municipal wastewater treatment plants in the Ukrainian part of the Bug River basin, the main river in Lviv region, each with a processing capacity of more than 150 m 3/day. The plants were constructed during the 1970s and early 1980s, therefore the technology is outdated and the plants are in many cases overloaded. It is estimated that within 10 years nearly all of the existing plants will be unable to provide adequate treatment. Some 80% of the point source organic pollution load flowing into the Bug basin originates in Ukraine, particularly the Lviv region. Diffuse sources are the main contributors to nutrient pollution in the Bug River basin accounting for 84% of the total nitrogen pollution and 68% of the phosphorus pollution ( Evaluation of transboundary pollu- tion loads. Report of Helsinki Commission Baltic Marine Environment Protection Commission. Helcom – environmental focal point information 2005). Ukraine has generally been an area of mild to moderate iodine deficiency (Gera simov 2002). The following territories in Ukraine are biogeochemical provinces with iodine deficiency: Zhitomir, Lviv, Ternopol, Volyn Oblast and other regions of Ukraine, and some regions of the Crimea as well. It is necessary that food rations be supplemented with different iodine preparations with the view of preventing iodine deficiency (Gerasimov 2002). Preventative measures to eliminate iodine deficiency prior to 2001 had a negligible impact on the study population: only 5.4% of the population reported consuming iodinated preparations on an ongoing basis in the first round of screening. In relation to environmental factors, diffuse autoimmune thyroiditis and high levels of thyroid autoantibodies are rare in children in moder ately iodine deficient areas, although thyroglobulin and thyroperoxidase antibodies occur at low levels quite frequently (Aghini Lombardi et al. 1999). Supplemental iodine significantly elevated incidence of iodine induced hyperthyroidism in en demic goiter area. Over the years 2001 2003, an improvement in iodine nutrition of the population was noted. There are epidemiologic studies in endemic goiter areas in Ukraine that report an increase in AITD, particularly HT, after the therapeutic ad ministration of iodized salt (Tronko et al. 2005).
87 The apparent recent increase in prevalence may in part be owing to improved means of recognition and awareness, but may also be a result of an actual increased number of afflicted cases, probably owing to the increased iodine consumption that has characterized the world in the past 60 years (Volpe 1990, 1997, Weetman and McGregor 1994). A high intake of iodine can affect the progression of both Graves’ disease and autoimmune thyroiditis. Defective autoregulation of follicle cell iodine management probably plays the most important role for disease progression, but io dine itself may also affect the immunological processes. Thus, the prevalence of autoimmune thyroiditis is higher in populations with a high intake of iodine than in populations with a low intake. Other data indicate that iodine supplementation in populations with low iodine intake can increase the incidence of thyroiditis. Several different mechanisms have been proposed. Change configuration of thyroglobulin could possibly create new antigen epitopes. Another possibility is that TPO dependent oxidation of supplementary iodide releases oxidative molecules (free acid radicals), which can damage membranes thus exposing antigens. Finally, it has been pointed out that iodine can have direct effects on antigen presenting cells (Nystrom et al. 2011). Overall however the prevalence of thyroid antibodies in children in rela tion to iodine intake is not well established, although pilot data show equal preva lence of TPO antibodies in iodine replete and moderately iodine deficient patients (Kabelitz et al. 2003). Overall, therefore, the effect of dietary iodine on thyroid auto immunity appears, at best, modest (Diseases... 2007). In genetically predisposed individuals the iodine intake modulates autoimmune thyroid reactions. Especially with acute or chronic increase of iodine intake it leads to a significant increase in the incidence and intensity of AITD (Schumm Draeger 2004). There are epidemiologic studies in endemic goiter areas in Ukraine that re port an increase in AITD, particularly thyroiditis, after the therapeutic administration of iodized salt (Tronko et al. 2005). Lymphocytic infiltration of the thyroid is rarely found in patients from severe endemic goiter regions, yet there is a reversal of this observation after dietary iodine supplementation (Foley 1992). A threefold increase in the prevalence of autoimmune thyroiditis among schoolchildren was noted once iodine deficiency was eliminated in an area of endemic goiter in northwestern Greece (Zois et al. 2003). Concomitantly, iodine restriction in many patients with primary hypothyroidism restored normal thyroid function (Kasagi et al. 2003, Yoon et al. 2003).
CONCLUSIONS
1. In summary, decrease of HT prevalence among the adolescent population in Lviv region during years 2000 2010 was observed. Increased HT prevalence among adolescents from towns during 2000 2004 years was found. The peak of disease prevalence was noted in 2000 and 2004. 2. Among adolescents both in districts and towns, decrease of HT prevalence from 2004 to 2010 was found. The decrease of HT prevalence among adoles cents from rural areas during 2000 2004 years was observed, while its in crease from 2004 to 2010 was noted.
88 3. In our study, HT prevalence among adolescents was the highest in Brody, Turkivskyi, Sambir, Sokal, and Horodok districts during 2000 2010. In these districts, high level of air and food samples that not match to standards was observed. Moreover, high relative risk of HT among adolescents in Lviv re gion was noted in Turkivskyi district during 2000 2008, in Brody district dur ing 2002 2008, in Pustomyty district during 2004 2008, in Sokal district dur ing 2000 2004, and in Sambir district compared to Kamianka Buzka as con trol district. Low levels of relative risk of HT among adolescent population in districts of Lviv region during 2000 2008 were noted in Busk, Drohobych, Zhovkivskyi, Mykolaiv, Mostyska, Starosambirskyi, Stryiskyi districts. 4. Our results indicate the need to clarify the reasons for the increased HT prevalence among the population of Lviv region, the definition of the risk of thyroid pathology in each district of the region among the different age groups, which will propose measures to prevent further increase of HT inci dence. Although approximately 80% of the risk for developing AIT is attrib utable to genetic background (Sgarbi and Maciel 2009), environmental trig gers are thought to play a role in the development of AITD in susceptible in dividuals in endemic goiter Lviv region.
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90 SUMMARY
Autoimmune thyroid diseases (AITD), including Graves’ disease (GD) and Hashi moto’s thyroiditis (HT), are the most common organ specific autoimmune disorders usu ally resulting in dysfunction (hyperfunction, hypofunction or both) of the thyroid gland (Trbojević and Djurica 2005). The pathogenetic mechanisms leading to the development of autoimmune disease of the thyroid are based on several different factors (Schumm Draeger 2004). It is well established that a complex interplay of diverse environmental and genetic susceptibility factors interact in predisposing an individual to AITD. certain changes in the MHC/HLA system are thought to be associated with these diseases. The major environ mental triggers of AITD include iodine, medications, infection, smoking, and possibly stress (Tomer and Huber 2009). Moreover, the contribution that each factor makes varies from patient to patient, and as yet there are no clear genotype phenotype correlations (Dis eases... 2007). Children not only encounter a somewhat different range of environmental factors to adults, but also have overall a lower chance of encountering aetiological agents simply because of their shorter period of exposure. Incidence of AITD in Ukraine is cur rently higher than in past decades. In our previous study we demonstrated increase of AITD prevalence in Lviv region during 2000 2010 was mainly by the adult population in the greater urban area, less – among adults of rural areas (Kasiyan et al. 2009, 2010, 2013, 2014). Increase in the AIT prevalence among adults identified in 16 districts and 3 towns of Lviv region (Kasiyan et al. 2013). The aim of our study was the assessment of HT prevalence among adolescents (14 18 years old) in Lviv region (western Ukraine) during 2000 2010. For assessment of the HT prevalence among adolescents of different districts (reions) in Lviv region during years 2000 2010, the analysis of archival data from Lviv Re gional Endocrinology Hospital was done. The research study covered by 20 districts (reions) of Lviv oblast, as well as six towns of Lviv region. For assessment of the relative risk (RR) of HT among adolescents of Lviv region, retrospective study was used. Kamianka Buzka district as control district, as well as Drohobych as control town for RR assessment in retro spective analysis was used. Assessment of air quality, water and soil quality, and food qual ity according to the hygienic indicators (the number of samples that not match to standards, %) in districts of Lviv region in 2000, 2002, 2004, 2006, and 2008 years was also done. In order to find significant differences (significance level, p < 0.05) between Hashimoto’s thy roiditis prevalence in different districts of Lviv region, Kruskal Wallis test was applied to the data (Zar 1999). Decrease of HT prevalence among the adolescent population in Lviv region during years 2000 2010 was observed. Increased HT prevalence among adolescents from towns during 2000 2004 years was found. The peak of disease prevalence was noted in 2000 and 2004. Among adolescents both in districts and towns, decrease of HT preva lence from 2004 to 2010 was found. The decrease of HT prevalence among adolescents from rural areas during 2000 2004 years was observed, while its increase from 2004 to 2010 was noted. HT prevalence among adolescents was the highest in Brody, Turkivskyi, Sambir, Sokal, and Horodok districts during 2000 2010. Our results indicate the need to clarify the reasons for the increased HT prevalence among the population of Lviv region, the definition of the risk of thyroid pathology in each district of the region among the different age groups, which will propose measures to prevent further increase of HT incidence. Although ap proximately 80% of the risk for developing AIT is attributable to genetic background (Sgarbi and Maciel 2009), environmental triggers are thought to play a role in the develop ment of AITD in susceptible individuals in endemic goiter Lviv region.
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