Mickiewiczologia – Tradycje I Potrzeby Słupsk 1999

Słupskie Prace Biologiczne

Nr 13 ss. 55-76 2016

ISSN 1734-0926 Przyjęto: 7.11.2016 © Instytut Biologii i Ochrony Środowiska Akademii Pomorskiej w Słupsku Zaakceptowano: 16.01.2017

FIFTEEN-YEAR FOLLOW-UP OF DIFFUSE GOITER PREVALENCE AMONG ADOLESCENTS IN ENDEMIC LVIV REGION (WESTERN UKRAINE)

Olha Kasiyan1 Halyna Tkachenko2 Jan Łukaszewicz3

1 Department of Hygiene and Preventive Toxicology Danylo Halytskyy Lviv National Medical University, Lviv, Ukraine e-mail: [email protected] 2 Pomeranian University in Słupsk Institute of Biology and Environmental Protection Department of Zoology and Animal Physiology Arciszewski St. 22b, 76-200 Słupsk, Poland 3 Faculty of Geographical and Geological Sciences Institute of Physical Geography and Environmental Planning Adam Mickiewicz University in Poznań

ABSTRACT

The aim of our study was the assessment of DG prevalence among adolescent (14- 18 years old) in Lviv region (western Ukraine) during 2000-2014. For assessment of the DG prevalence among adolescents (14-18 years old) of different districts (reions) in Lviv region during 2000-2014, the analysis of archival data from Lviv Regional Endocrinology Hospital was done. The research study covered by 20 districts (reions) of Lviv region (Brody, Busk, Horodok, Drohobych, Zhydachivskyi, Zhovkivskyi, Zolochivskyi, Kamianka-Buzka, Mykolaiv, Mostyska, Peremyshliany, Pustomyty, Radekhiv, Sambir, Skole, Sokal, Starosambirskyi, Stryiskyi, Turkivskyi, and Yavor- ivskyi Districts), as well as 6 towns of Lviv region (Lviv, Boryslav, Drohobych, Stryi, Truskavets, Chervonograd). A decrease of DG prevalence (I degree) among adolescents from 1747.72 to 1571.29 per 10,000 individuals during 2000-2014 was observed. A significant reduction of DG (I degree) prevalence among adolescents from towns of Lviv region was noted. It was 1971.74 per 10,000 individuals in 2000 and 1185.52 per 10,000 individuals in 2014. There was increased of DG (I degree) prevalence from 1591.92 to 1785.56 per 10,000 individuals among adolescents in Lviv region during 2000-2014. In 2014, the prevalence of disease among adolescents from districts was higher compared to the adolescents from towns (1785.56 compared to

55 1185.52 per 10,000 individuals, respectively). The decrease of DG (I degree) prevalence among adolescent population in the 6 districts (Zolochivskyi, Peremyshliany, Pustomyty, Radekhiv, Starosambirskyi, Stryiskyi) and all towns (except Chervo- nograd) in Lviv region was noted. Increased DG (II and III degrees) prevalence among adolescents of Lviv region was observed in Busk, Brody, Radekhiv, Skole, and Sokal districts in 2000, in Busk, Skole, Zolo-chivskyi, Turkivskyi, and Sokal districts in 2004, in Busk, Pustomyty, Skole, Sokal, and Turkivskyi districts in 2014. The decrease of DG (II and III degrees) prevalence among adolescents in the 11 districts (Brody, Busk, Horodok, Zhydachivskyi, Zolochivskyi, Mykolaiv, Peremyshliany, Radekhiv, Sambir, Starosambirskyi, Stryiskyi) and all towns (except Drohobych and Chervo- nograd) in Lviv region was noted. In our study, we also observed that DG prevalence among adolescents in altitude regions was higher compared to the plateau regions, a finding similar to trends in previous surveys that may be explained by deficiencies in natural iodine at high altitudes and limited educational and economic support for the people who reside there. According to the present information, the prevalence of DG also was differed in districts and towns. DG are more common in districts than in the towns, which may be explained by lifestyle choices. Furthermore, females were at greater risk for DGs and this difference was not changed when females were further divided into rural, mixed and urban groups. Our results indicate the need to clarify the relevant influencing factors of DG 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 DG incidence.

Key words: Iodine Deficiency Disorders, diffuse goiter, prevalence, adolescents, Lviv region, Ukraine

INTRODUCTION

Endemic goiter is one of the earliest and most visible sign of iodine deficiency (WHO, UNICEF and ICCIDD: Assessment of Iodine Deficiency Disorders and Monitoring Their Elimination). According to iodine deficiency level this response may be adequate to preserve euthyroidism, but at the cost of an enlarged thyroid and the attendant risks of neck compression and eventual hyperfunctioning autonomous nodules with hyperthyroidism. An insufficient adaptation in adults produces hypothyroidism with its usual clinical stigmata. The damage is greater when iodine deficiency provokes hypothyroidism during fetal or early postnatal life, because thyroid hormone is necessary for proper development of the central nervous system, particu- larly its myelination. Individuals who were hypothyroid at this critical period frequently have permanent mental retardation, which cannot be corrected by later administration of thyroid hormone or iodine. Most of the populations which live in areas of iodine deficiency are in developing countries, but many in the large indus- trialized countries of Europe are also affected (Delange 1994, Thyroid Disease in Adults 2011).

56 Knudsen and co-workers (2002) have demonstrated the risk factors for goiter and thyroid nodules. The major environmental factor that determines goiter prevalence is iodine status, but other environmental factors influencing entire populations have been identified such as goitrogens in food and drinking water (Knudsen et al. 2002). The environmental factors were also important for goiter development (increase in risk, smoking and pregnancy; decrease in risk, oral contraception and alcohol consumption), and the individual risk depended on the genetic background. Environ- mental factors also had only a minor influence on the prevalence of thyroid autoan- tibodies in the population (Laurberg et al. 2006). In iodine-deficient areas, a strong association between tobacco smoking and goiter prevalence is found, whereas the association is less pronounced in iodine-replete areas (Knudsen et al. 2002). The goiter prevalence is higher in certain groups in the population. The association with individual risk factors has been investigated in some studies, especially the association with tobacco smoking (Knudsen et al. 2002). Profound effects of even small differences in iodine intake level on the prevalence of goiter, nodules, and thyroid dysfunction was demonstrated by Laurberg and co-workers (2006). The variation in goiter prevalence between the genders is well known with a higher occurrence among women. The association with age is probably dependent on iodine status, because it seems that the zenith of goiter prevalence appears earlier in life the more severe iodine deficiency the population is exposed to (Knudsen et al. 2002). Mild and moderate iodine deficiency was associated with a decrease in serum thyroid- stimulating hormone (TSH) with age. There were more cases of overt hypothyroidism in mild than in moderate iodine deficiency caused by a 53% higher incidence of spontaneous (presumably autoimmune) hypothyroidism (Laurberg et al. 2006). On the other hand, there were 49% more cases of overt hyperthyroidism in the area with moderate iodine deficiency. Interestingly, the cautious iodine fortification program, aiming at an average increase in iodine intake of 50 μg/day has been associated with a 50% increase in incidence of hyperthyroidism in the area with the most severe iodine deficiency. The incidence is expected to decrease in the future, but there may be more cases of Graves’ hyperthyroidism in young people (Laurberg et al. 2006). Ukraine has generally been an area of mild-to-moderate iodine deficiency (Gerasi- mov 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 supple- mented 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 (Aghini-Lombardi et al. 1999). 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 Hashimoto’s thyroiditis after the therapeutic administration of iodized salt (Tronko et al. 2005). Shiraishi and co-workers (2006) have estimated daily iodine intake in Ukrainian subjects of northwestern regions in relation to the health effects on inhabitants after the Chernobyl accident. Total diets were collected from 106 locations for children and adult males by a duplicate portion study. Iodine was rapidly determined by in-

57 ductively coupled plasma mass spectrometry after chemical separation. Iodine concentration on a dry basis for Ukrainians was 0.11 µg and the daily iodine intake was in the range of 2.80-372 µg per person. The median, geometric mean, and standard deviation were 28.1, 32.7, and 2.51 µg, respectively. The yearly trend of the intake had almost no change. Regional differences would be expected to exist among the 10 areas of the Ukraine, but no clear differences appeared in the present findings. Daily iodine intake in Ukrainians was lower than the recommended dietary intake (RDI) allowance (150 µg), and its lack would be related to the high prevalence of goiter in the country (Shiraishi et al. 2006). The most important target groups to the effects of iodine deficiency from a public health point of view are pregnant mothers, fetuses, neonates, and young infants because the main complication of IDD, i.e., brain damage resulting in irreversible mental retardation, is the consequence of thyroid failure occurring during pregnancy, fetal, and early postnatal life. The main cause of endemic goiter and cretinism is an insufficient dietary supply of iodine. The additional role of naturally occurring goitrogens has been documented in the case of certain foods (milk, cassava, millet, nuts) and bacterial and chemical water pollutants. The mechanism by which the thyroid gland adapts to an insufficient iodine supply is to increase the trapping of iodide as well as the subse- quent steps of the intrathyroidal metabolism of iodine leading to preferential synthesis and secretion of triiodotyronine (T3). They are triggered and maintained by increased secretion of thyroid-stimulating hormone (TSH), which is ultimately responsible for the development of goiter. The acceleration of the main steps of iodine kinetics and the degree of hyperstimulation by TSH are much more marked in the pediatric age groups, including neonates, than in adults, and the development of goiter appears as an unfa- vorable side effect in the process of adaptation to iodine deficiency during growth. The most serious complication of iodine deficiency is endemic cretinism, a syndrome characterized by irreversible mental retardation together with either a predominant neurological syndrome or predominant hypothyroidism, or a combination of both syn- dromes (Delange 1994). Monitoring and adjustment of iodine intake in the population is an important part of preventive medicine. A number of environmental factors influence the epidemiology of thyroid disorders, and even relatively small abnormalities and differences in the level of iodine intake of a population have profound effects on the occurrence of thyroid abnormalities. Some epidemiology studies remain to be undertaken, and these are essential for comprehensive original data on the epidemiology and distribution of thyroid diseases (Laurberg et al. 2006). Correcting this public health problem is the goal of a massive global campaign that is showing remarkable progress so far (Dunn 1998). But despite its importance to most other countries, iodine deficiency receives high attention in the Ukraine. The iodination program also includes monitoring goitres and measuring the concentration of iodine in the urine in the population as quality assurance of the program. In- cidence of diffuse goitre (DG) in Ukraine is currently change during past decades. Therefore, the aim of our study was the assessment of DG prevalence among adolescents (14-18 years old) in Lviv region (western Ukraine) during 2000-2014.

MATERIALS AND METHODS

For assessment of the DG prevalence among adolescents (14-18 years old) of different districts (reions) in Lviv region during 2000-2014, the analysis of archival data from Lviv Regional Endocrinology Hospital was done. The research study covered by 20 districts (reions) of Lviv region (Brody, Busk, Horodok, Drohobych, Zhydachivskyi, Zhovkivskyi, Zolochivskyi, Kamianka-Buzka, Mykolaiv, Mostyska, Peremyshliany, Pustomyty, Radekhiv, Sambir, Skole, Sokal, Starosambirskyi, Stry- iskyi, Turkivskyi, and Yavorivskyi Districts), as well as 6 towns of Lviv region (Lviv, Boryslav, Drohobych, Stryi, Truskavets, Chervonograd). The obtained results were analyzed statistically using the STATISTICA 8.0 software package (StatSoft, Poland). In order to find significant differences (significance level, p < 0.05) between DG prevalence in different districts of Lviv region, Kruskal-Wallis test was applied to the data (Zar 1999).

RESULTS

The prevalence of diffuse goiter (I degree) (per 10,000 individuals) among the adolescents of Lviv region during 2000-2014 was presented in Table 1 and Fig. 1 Extreme situation of DG prevalence among the adolescent populations in Lviv region was noted (Tables 1 and 2, Figs 1 and 2). DG prevalence among the adolescent population is higher by 7.5-9.7 fold (p < 0.05) compared to DG prevalence among adults (Tables 1 and 2). During years 2000-2014, decrease of DG I degree prevalence among the adolescent population of Lviv region was observed (1747.72 per 10,000 individuals in 2000 and 1571.29 per 10,000 individuals in 2014) (Table 1, Fig. 1). However, increased DG I degree prevalence among adolescents from districts during 2000-2014 years was found (1591.92 per 10,000 individuals in 2000 and 1785.56 per 10,000 individuals in 2014). The peak of disease prevalence was noted in 2014. Among adolescents from towns, decrease of DG I degree prevalence from 2000 to 2014 was found; it was 1971.74 and 1185.52 per 10,000 individuals, respectively (Table 1). Increased DG I degree prevalence among adolescents of Lviv region was observed in Pustomyty, Peremyshliany, Zolochivskyi, Busk, and Radekhiv districts in 2000 (5140.41, 4845.54, 3067.63, 2804.31, 2192.04 per 10,000 individuals, respectively), in Peremyshliany, Skole, Starosambirskyi, Pustomyty districts in 2004 (4871.91, 2675.72, 2156.84, 1840.04 per 10,000 individuals, respectively), in Zhovkivskyi, Busk, Turkiv- skyi, Skole, and Pustomyty districts in 2014 (3794.27, 3051.45, 3000.84, 2792.15, 2519.94 per 10,000 individuals, respectively) (Table 2, Fig. 2). The decrease of DG I degree prevalence among adolescent population in the 6 districts (Zolochivskyi, Pere- myshliany, Pustomyty, Radekhiv, Starosambirskyi, Stryiskyi) and all towns (except Chervonograd) in Lviv region was noted (Table 1, Fig. 1).

Table 1 The prevalence of diffuse goiter (I degree) among adolescents during years 2000-2014

The prevalence of diffuse goiter (I degree), per 10,000 individuals Districts of Lviv region 2000 2004 2014 Brody 703.12 917.92 2043.54 Busk 2804.31 1255.13 3051.45 Horodok 581.64 320.72 954.58 Drohobych 1003.01 1070.04 1112.19 Zhydachivskyi 691.92 717.71 822.96 Zhovkivskyi 850.01 1550.82 3794.27 Zolochivskyi 3067.63 1507.44 1460.69 Kamianka-Buzka 620.74 1175.04 1759.97 Mykolaiv 618.85 975.43 1446.84 Mostyska 900.02 821.42 913.14 Peremyshliany 4845.54 4871.91 1144.05 Pustomyty 5140.41 1840.04 2519.94 Radekhiv 2192.04 642.62 1378.84 Sambir 168.52 1660.05 2372.43 Skole 1020.01 2675.72 2792.15 Sokal 1487.54 799.41 1605.94 Starosambirskyi 1825.03 2156.84 1111.15 Stryiskyi 1873.32 1392.13 639.96 Turkivskyi 1935.74 1921.42 3000.84 Yavorivskyi 1237.71 0.0 1744.35 Total to Districts 1591.92 1277.84 1785.56

Towns of Lviv region 2000 2004 2014

Lviv 1528.52 1080.51 1153.65 Boryslav 10430.01 1283.13 425.55 Drohobych 2731.93 906.21 883.79 Stryi 2471.41 2127.52 936.88 Truskavets 4216.74 1112.24 3361.75 Chervonograd 80.92 514.94 842.78 Total to Towns 1971.74 1076.61 1185.52 Summary 1747.72 1193.32 1571.29

Source: own research

60 10,000 individuals) among adolescents in districts (reions) of Lviv region in 2000 (A), 2004

Prevalence of diffuse goiter (I degree) (per

Fig. 1. and(B), 2014 (C) ownSource: r

61 The prevalence of diffuse goiter of II and III degrees (per 10,000 individuals) among the adolescents of Lviv region during 2000-2014 years was presented in Ta- ble 2 and Fig. 2. Decrease of the DG II and III degrees prevalence from 115.54 to 82.46 per 10,000 individuals during 2000-2014 years was observed (Table 2, Fig. 2). A significant decrease in DG II and III degrees prevalence among adolescents from districts of Lviv region was noted. It was 140.82 per 10,000 individuals in 2000 and 124.08 per 10,000 individuals in 2014. There was a decline of DG II and III degrees prevalence from 79.03 to 21.81 per 10,000 individuals among adolescents from towns in Lviv region during 2000-2014. In 2014, the prevalence of disease among adolescents from districts was higher (124.08 compared to 21.81 per 10,000 individuals, in towns respectively) (Table 2). Increased DG II and III degrees prevalence among adolescents of Lviv region was observed in Busk, Brody, Radekhiv, Skole, and Sokal districts in 2000 (1608.71, 415.64, 324.05, 200.03, 147.91 per 10,000 individuals, respectively), in Busk, Skole, Zolochivskyi, Turkivskyi, and Sokal districts in 2004 (370.41, 339.53, 245.52, 173.03, 151.14 per 10,000 individuals, respectively), in Busk, Pustomyty, Skole, Sokal, and Turkivskyi districts in 2014 (567.05, 385.94, 354.24, 294.04, 266.85 per 10,000 individuals, respectively) (Table 2, Fig. 2). The decrease of DG II and III degrees prevalence among adolescents in the 11 districts (Brody, Busk, Horodok, Zhydachivskyi, Zolochivskyi, Mykolaiv, Peremyshliany, Radekhiv, Sambir, Starosambirskyi, Stry- iskyi) and all towns (except Drohobych and Chervonograd) in Lviv region was noted (Table 2, Fig. 2). As show our previous results among adults population (Kasiyan et al. 2014c), a decrease of the DG I degree prevalence from 307.5 to 197.2 per 10,000 individuals during 2000-2010 was observed. A significant reduction in DG I degree prevalence among adults from towns of Lviv region was noted. It was 133.1 per 10,000 individuals in 2000 and 99.6 per 10,000 individuals in 2010. There was a decline of DG I degree prevalence from 231.8 to 155.3 per 10,000 individuals among adults in Lviv region during 2000-2010. In 2010, the prevalence of disease among adults from districts was higher compared to the adults from towns (197.2 compared to 99.6 per 10,000 individuals, respectively). The highest prevalence of DG among adults was noted in Busk, Starosambirskyi, Pustomyty, Sokal, Turkivskyi districts (489.1-1448.5; 359.6-776.2, 282.4-766.0, 166.3-625.1, 443.4-518.3 per 10,000 individuals, respectively), and in Truskavets, Drohobych, and Boryslav (14.1-340.2, 61.2-218.2, 96.3-160.7 per 10,000 individuals, respectively). The increase in the DG I degree prevalence in 7 districts (Brody, Zhydachivskyi, Mykolaiv, Peremyshliany, Radekhiv, Sambir, Skole) among 20 districts and in 1 town (Chervonograd) among 6 towns of Lviv region during 2000-2010 was observed. Decrease of the DG prevalence II and III degrees from 31.4 to 29.6 per 10,000 individuals during 2000-2010 was noted. A significant increase in DG II and III degrees prevalence among adults from districts of Lviv region was demonstrated. It was 29.9 per 10,000 individuals in 2000 and 37.3 per 10,000 individuals in 2010. There was a decline of DG II and III degrees prevalence from 33.3 to 19.4 per 10,000 individuals among adults from towns in Lviv region during 2000-2010. In 2010, the prevalence of disease among adults from districts was higher compared to the adults from towns (37.3 compared to 19.4 per 10,000 individuals, respectively). Increased DG II and III degrees preva-

62 Table 2 The prevalence of diffuse goiter (II and III degrees) among adolescents during years 2000- 2014

The prevalence of diffuse goiter (II and III degrees), per 10,000 individuals Districts of Lviv region 2000 2004 2014 Brody 415.64 33.53 23.75 Busk 1608.71 370.41 567.05 Horodok 73.73 78.84 16.24 Drohobych 51.52 50.82 69.74 Zhydachivskyi 56.84 35.34 22.05 Zhovkivskyi 7.41 5.63 3.34 Zolochivskyi 338.24 245.52 164.24 Kamianka-Buzka 20.72 25.81 143.84 Mykolaiv 77.13 24.33 14.63 Mostyska 9.72 22.74 22.03 Peremyshliany 63.61 91.82 28.54 Pustomyty 7.74 55.91 385.94 Radekhiv 324.05 107.14 70.65 Sambir 44.42 29.32 8.35 Skole 200.03 339.53 354.24 Sokal 147.91 151.14 294.04 Starosambirskyi 57.52 2.62 25.75 Stryiskyi 40.03 44.91 30.86 Turkivskyi 125.02 173.03 266.85 Yavorivskyi 15.94 24.82 118.94 Total to Districts 140.82 80.24 124.08

Towns of Lviv region 2000 2004 2014

Lviv 83.13 33.52 17.12 Boryslav 300.04 72.73 25.22 Drohobych 21.32 29.74 25.95 Stryi 85.73 28.53 31.63 Truskavets 91.74 0.0 0.0 Chervonograd 2.15 24.34 35.86 Total to Towns 79.03 34.11 21.81 Summary 115.54 60.82 82.46

Source: own research

63 ) ) of Lviv region in 2000

lescents lescents in districts (reions

Prevalence Prevalence of diffuse goiter (II and III degrees) (per 10,000 individuals) among ad

Fig. 2. 2004(A), 2014(C) and (B), ownSource: research

64 lence among adults of Lviv region was observed in Radekhiv, Peremyshliany, Skole, Turkivskyi, and Busk districts in 2000 (80.9, 73.7, 63.7, 62.5, 51.5 per 10,000 individuals, respectively), in Busk, Radekhiv, Sokal, Peremyshliany, Skole, and Turkivskyi districts in 2004 (130.2, 110.6, 86.9, 86.4, 67.5, 62.7 per 10,000 individuals, respectively), in Sokal, Radekhiv, Peremyshliany, Skole, and Turkivskyi districts in 2010 (105.7, 97.8, 90.5, 79.4, 71.0 per 10,000 individuals, respectively). The decrease of DG prevalence among adults in the 15 districts (Busk, Horodok, Drohobych, Zhy- dachivskyi, Zolochivskyi, Sokal, Starosambirskyi, Stryiskyi) and all towns (except Drohobych and Chervonograd) in Lviv region was noted. Our results indicate the need to clarify the relevant influencing factors of DG 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 DG incidence. Compared to adults population (Kasiyan et al. 2015), DG prevalence among the adolescent population is higher by 7.5-9.7 fold (p < 0.05). During years 2000-2014, decrease of DG I degree prevalence among the adolescent population of Lviv region was observed (1747.72 per 10,000 individuals in 2000 and 1571.29 per 10,000 individuals in 2014) (Table 1, Fig. 1). However, increased DG I degree prevalence among adolescents from districts during 2000-2014 years was found (1591.92 per 10,000 individuals in 2000 and 1785.56 per 10,000 individuals in 2014). The peak of disease prevalence was noted in 2014. Among adolescents from towns, decrease of DG I degree prevalence from 2000 to 2014 was found; it was 1971.74 and 1185.52 per 10,000 individuals, respectively (Table 1). Decrease of the DG II and III degrees prevalence from 115.54 to 82.46 per 10,000 individuals during 2000-2014 years was observed (Table 2, Fig. 2). A significant decrease in DG II and III degrees prevalence among adolescents from districts of Lviv region was noted. It was 140.82 per 10,000 individuals in 2000 and 124.08 per 10,000 individuals in 2014. There was a decline of DG II and III degrees prevalence from 79.03 to 21.81 per 10,000 individuals among adolescents from towns in Lviv region during 2000-2014. In 2014, the prevalence of disease among adolescents from districts was higher compared to the adults from towns (124.08 compared to 21.81 per 10,000 individuals, respectively) (Table 2).

DISCUSSION

The present study confirmed that after the increase in salt iodization in Ukrainian there was a prevalence of diffuse goiter (I degree) below to 1193.32 per 10,000 individuals in 2004 and increased to 1571.29 per 10,000 individuals in 2014. The ten- year follow-up showed a marked change in thyroid epidemiology in adolescents, with a gradual decrease in the incidence of diffuse goiter in 2000-2014, an increase in the incidence of Hashimoto’s thyroiditis (Kasiyan et al. 2009, 2010, 2013-2014, Tkachenko et al. 2014). In our study, we also observed that DG prevalence among adolescents in altitude regions was higher compared to the plateau regions, a finding similar to trends in previous surveys that may be explained by deficiencies in natural iodine at high altitudes and limited educational and economic support for the people

65 who reside there. According to the present information, the prevalence of DG also was differed in districts and towns. DG are more common in districts than in the towns, which may be explained by lifestyle choices. Furthermore, females were at greater risk for DGs and this difference was not changed when females were further divided into rural, mixed and urban groups. The large differences in thyroid disease prevalence between populations may be caused by genetic and environmental factors. Among the latter, iodine deficiency seems by far to be the most important risk factor. Thus, nodular goitre is a condition predominantly seen in iodine deficient areas of the world. On the other hand, few studies have shown that abundant iodine intake may lead to development of diffuse goiters, but world-wide this has been a minor problem compared with development of nodular goiters (Carlé et al. 2014). Severe iodine deficiency causes hypothyroidism that results in impaired somatic growth and motor development in children. Mild and moderate iodine deficiencies cause multifocal autonomous growth of thyroid, which results in thyrotoxicosis. On the other hand, iodine excess is associated with the development of hypothyroidism and thyroid autoimmunity. In areas of iodine deficiency, a sudden increase in iodine intake is associated with transient hyperthyroidism (Chung 2014). Increased iodine intake in an iodine-deficient population is associated with a small increase in the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether these increases are also transient is unclear. Variations in population iodine intake do not affect risk for Graves’ disease or thyroid cancer, but correc- tion of iodine deficiency might shift thyroid cancer subtypes toward less malignant forms (Zimmermann and Boelaert 2015). The apparent recent decrease in prevalence of DG may in part be owing to improved means of recognition and awareness, but may also be a result to the increased iodine consumption that has characterized the world in the past 60 years (Volpe 1990, 1997, Weetman and McGregor 1994). On the other hand, a high intake of iodine can affect the progression of both Graves’ disease and Hashimoto’s thyroiditis (HT). Defective autoregulation of follicle cell iodine management probably plays the most important role for disease progression, but iodine 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 autoimmune Hash- imoto’s thyroiditis (Kasiyan et al. 2009, 2010, 2014a-d). Our previous study confirm this thesis. The assessment of Hashimoto’s thyroiditis (HT) prevalence, as well as relative risk (RR) of HT among children (0-14 years old), adolescents (14-18 years old), and adults (above 18 years old) in Lviv region (western Ukraine) in years 2000-2010 was done (Kasiyan et al. 2009, 2010, 2013- 2014a-d, Tkachenko et al. 2014). 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, 2004 and 2010 years was also performed. Decrease of the HT prevalence from 4.7 to 2.7 per 10,000 children during 2000-2010 years was observed. A significant reduction in HT prevalence among children from large cities was noted. It was 7.1 per 10,000 individuals in 2000 and 2.1 per 10,000 individuals in 2010. There was a decline of HT preva-

66 lence from 3.2 to 2.4 per 10,000 individuals among children population from districts during 2000-2004, and its increase to 3.1 per 10,000 individuals from 2004 to 2010 years. The increase of the prevalence of HT in 8 of the 20 districts and 2 of the 6 towns of Lviv region during 2000-2010 was observed. The increase of the HT prevalence in the Lviv region during 2000-2010 was mainly in the Brody, Peremyshliany and Turkivskyi districts. In these districts, high level of samples that not match to standards according to the air and food quality was observed. Moreover, the high relative risk of HT among children population in Lviv region during 2000-2010 years was also noted in Brody and Turkivskyi districts in 2000-2010 years, and Peremyshliany district during 2000-2004 years compared to Kamianka-Buzka as control district. Our study confirmed that mainly nutritive factors and environmental pollution by metals and chemi- cals are the main factors in the present-day spread of HT. 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 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. 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. The increase of HT prevalence in the Lviv region during 2000-2010 years was mainly due to the adult population from urban areas, and less – by inhabitants of rural areas. Increased HT prevalence among adults were found in 16 districts and 3 towns in Lviv region; among adolescents – in 5 districts; among children – in 8 districts and 2 towns. The risk of HT prevalence among adults living in more polluted areas is higher compared with the inhabitants from relatively clean areas of Lviv region. On the risk of HT prevalence among inhabitants of agricultural districts has a significant impact of chemical pollution of water and soil, among inhabitants of towns – air pollution. The observed pattern will determine the differentiated na- ture of preventive and therapeutic measures for the decrease of HT prevalence in regions with varying degrees of chemical pollution of environmental objects. 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. We suggest that the epidemiology of thyroid disorders is significantly associated with iodine supply. Indeed, goiter begins as an adaptation to iodine deficiency, probably mainly from increased stimulation by TSH. As the thyroid secretes inadequate amounts of hormone, the pituitary responds by releasing more TSH, with all its vari- ous effects including thyroid enlargement. Goiter, then, is one of the first signs of iodine deficiency. Initially, the goiter is diffuse and reflects generalized hyperplasia, so- called “simple goiter.” At first, the compensation may be adequate, but with continued iodine deficiency or renewed demand for increased TSH, such as in pregnancy or ado- lescence, the cycle may begin anew, with increased TSH and further thyroid enlargement. Over years or decades, the hyperplasia becomes more focal, and nodules or adenomas develop, resulting in a multinodular goiter. The nodules may be adenomas, cysts, collections of colloid, or, less commonly, follicular cancer. Some adenomas are

67 autonomous and may eventually hyperfunction and produce hyperthyroidism. This po- tential for excess hormone production is greatly increased if fairly large amounts of iodine suddenly become available. This iodine-induced hyperthyroidism (IIH) can be con- sidered as another IDD, because it occurs chiefly in subjects who were initially iodine- deficient (Stanbury et al. 1998). It typically involves an older subject having a longstand- ing goiter that has developed autonomous nodules. Previously, such a gland has avidly sought every available atom of iodine. If now sufficient iodine becomes available, the nodular thyroid will react by synthesizing and secreting inappropriately large amounts of TSH and causing hyperthyroidism (Stanbury et al. 1998). The reports on goiter in adolescents are limited and conflicting. Our data showed a significantly lower incidence of diffuse goiter after improved iodization, which is in accordance with a other observational study, as well as with two interventional studies that showed a significant decrease in thyroid volume in patients with eu- thyroid diffuse goiter (Kahaly et al. 1997, 1998). On the other hand, high prevalence of subclinical hypothyroidism was not corre- lated with either thyroid autoimmunity or iodine intake, as reflected in urinary iodine excretion in study of Marwaha and co-workers (2012). They have found the impact of two decades of universal salt iodization on the prevalence of goiter, thyroid autoimmunity and thyroid dysfunction in Indian adults. The subject population included 4409 adult members of resident welfare associations of 5 residential colo- nies, from 18-90 years of age, who participated in general health check-up camps. The subjects underwent a detailed evaluation including history, anthropometry, goiter grading, USG thyroid, thyroid auto-antibodies and thyroid function tests. All these subjects were regularly consuming iodized salt. Overall, 9.6% of subjects had clinical goiter (13.3% women and 3.3% in men). Prevalence of nodules on palpation was found to be in 1.6% which was lower in men. The nodule prevalence increased to 4.6% in men and 5.6% in women on ultrasonography. Thyroid hypoechogenicity was seen in 30.6% of subjects with severe hypoechogenicity higher in women (5.7% men and 15.5% women). Thyroid peroxidase (TPO) antibody was positive in 13.3% adults and it showed a positive correlation with age, female sex and hypothyroidism. Subclinical hypothyroidism was the commonest abnormality encountered and affected 19.3% subjects (15.9% men; 21.4% women). Thyroid dysfunction showed a rising trend with age in both genders (Marwaha et al. 2012). The data on the incidence of thyroid disorders after increased ionization are scarce. Slovenia increased iodine content in kitchen salt from 10 mg to 25 mg of potassium iodide per kg of salt from 1999. According to the WHO criteria, Slovenia shifted from a mildly iodine-deficient country to a country with adequate iodine intake. Ten years after the increase in iodine intake, the incidence of diffuse goitre and thyroid autonomy decreased. Now patients with diffuse goitre and thyroid autonomy reach older age than the patients before the increase in iodine intake. In addition, patients with thyroid autonomy are less frequently hyperthyroid than ten years ago and iodine-induced hyperthyroidism is less severe. The incidence of highly malignant thyroid carcinoma has also dropped. However, the incidence of Hashimoto’s thyroiditis increased, most probably in genetically predisposed individuals (Gaberšček and Zaletel 2016). The change from mildly deficient to sufficient iodine supply was associated with a marked change in the incidence of thyroid epidemiology – a significant decline in

68 the incidence of diffuse goiter and thyroid autonomy and a marked increase in the incidence of Hashimoto's thyroiditis. Zaletel and co-workers (2011) have assessed iodine supply and follow thyroid epidemiology for ten years after an iodine increase from 10 to 25 mg of potassium iodide per kilogram of salt in 1999. In 2002 and 2003, they have determined the thyroid size by palpation and ultrasound and meas- ured urinary iodine concentration (UIC) in 676 schoolchildren from 34 schools throughout Slovenia. From 1999 to 2009, they followed the incidence of diffuse and nodular goiter, thyroid autonomy, Graves’ disease, and Hashimoto’s thyroiditis among adults in the stable catchment area of the University Medical Centre Ljublja- na with 1 000 000 inhabitants. In children, only 1% had a goiter grade 2 (visible and palpable thyroid gland), median thyroid volume was 5.8 ml, and median UIC was 148 μg/l. In adults, the incidence of diffuse goiter and thyroid autonomy decreased significantly (2009 vs 1999, rate ratio [RR], 0.16; 95% confidence interval [CI], 0.12-0.21 and RR, 0.73; 95% CI, 0.62-0.86, respectively), with a lower incidence in younger participants in 2009 (P < 0.001). The incidence of multinodular goiter and solitary nodule increased (2009 vs. 1999, RR, 1.55; 95% CI, 1.35-1.79 and RR, 1.72; 95% CI, 1.49-1.99, respectively). No long-term changes were observed for Graves’ disease (2009 vs. 1999, RR, 0.95; 95% CI, 0.81-1.13), while the incidence of Hashimoto’s thyroiditis increased strongly (2009 vs 1999, RR, 1.86; 95% CI, 1.64-2.12) (Zaletel et al. 2011). Moreover, Mao and co-workers (2013) have also evaluated the status of diffuse goiter of population in Zhejiang Province (China) and to analyze the relevant influencing factors. A total of 18188 subjects were recruited in the cross sectional survey, by multistage stratified cluster random sampling method. B ultrasound measurement were carried among the subjects to detect the thyroid volume, and the basic information and life styles were interviewed by questionnaires. Then, Mao and co- workers (2013) have analyzed the distribution and its influencing factors of diffuse goiter. The ratio of diffuse goiter among the surveyed population was 2.2%, the difference showed statistical significance (χ2 = 267.11, P < 0.05). The ratio among the group aged 6-7 years old and 8-10 years old was comparatively high, separately 10.3% and 9.8%. The ratio among women (2.9%) was higher than it among men (1.3%) (χ2 = 55.55, P < 0.05). The residents from inland areas had the highest prevalence (3.2%), followed by residents from sub-coastal areas (2.0%), coastal areas minimum (1.8%) (χ2 = 24.31, P < 0.05). The content of water iodine and salt iodine among people with symptoms of goiter had statistical difference with it among ordinary population (water iodine: χ2 = 4.95, P = 0.026; salt iodine: χ2 = 11.03, P < 0.01). The median (quartile) of water iodine in ordinary population was 2.41 (1.96-6.15) µg/l and among people with symptoms of goiter was 1.88 (1.49-5.15) µg/l. The median (quartile) of salt iodine in ordinary population was 30.18 (24.69-32.65) mg/kg and among people with symptoms of goiter was 29.1 (24.70-31.95) mg/kg. The in- fluential factors of goiter were as follows: the family income, the education degree, the job and profession status, the diet character, the habitual sea food consumption, the alcohol intake status (χ2 were separately 8.08, 37.85, 98.78, 68.69, 10.91, 12.21, 26.94, P < 0.05). Multi-factor analysis showed the results as follows: female (OR = 0.27, 95%, CI: 0.18-0.39), school students (OR = 8.05, 95%, CI: 3.87-16.73), vege- tarian (OR = 1.60, 95%, CI: 1.15-2.22) took a higher risk of getting pathogenic goi-

69 ter; while the group of those who had university degree or above (OR = 0.84, 95%, CI: 0.73-0.97), ate sea food frequently (OR = 0.62, 95%, CI: 0.44-0.88) took a lower risk (Mao et al. 2013). Defective autoregulation of follicle cell iodine management probably plays the most important role for disease progression, but iodine 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 autoimmune Hashimoto’s thyroiditis. Zhang and co-workers (2007) have studied the prevalence of goiter associated with some factors in Guangzhou (China) after the implementation of universal salt iodization. The prevalence of goiter was got by thyroid palpation, and the relationship between the prevalence and factors mentioned above was analyzed. Chi-square test was used to test the difference of the rates, and Logistic regression model was used to do multi-factors analysis. Overall, 442 cases of thyroid large were found, including I grade 330, formed 74.7%, and II grade 112, formed 25.3%. The prevalence in total, female and male were 4.3%, 5.1% (369 cases) and 2.4% (73 cases) respectively. The prevalence was significantly higher in the female than that in the male. The results of multi-Logistic regression showed that gender, history of thyroid diseases and education were the main impact factors. The risks suffered from goiter in the female, in those who had ever suffered from thyroid diseases and in those who were middle school education and higher were more 1.81 times, 5.43 times and 1.25 times than those in the male in those who had never suffered from thyroid diseases and in those who were primary school education and lower respectively. The iodine nutrition of Guangzhou elderly population was fairly moderate. Female and those who had ever suffered from thyroid diseases got a higher risk suffering from goiter (Zhang et al. 2007). Zhao and co-workers (2014) comprehensively estimated the prevalence of goiter and thyroid nodules (TNs) before and after the implementation of the Universal Salt Iodization (USI) program in mainland China and provided information for creating effective health policies. They examined 52 epidemiological research studies cover- ing 14 provinces, municipalities and autonomous regions in China. They also sys- tematically analyzed the prevalence of goiter and TNs prior to and after 1996, when China implemented the USI program. Research indicates that the prevalence of goiter in children 8-10 years-of-age is an indicator of local iodine consumption. The analysis was focused on the general population, to provide epidemiological information concerning the disease itself. Iodine nutrition is certainly an important factor for goiter, and the association between iodine intake and goiter prevalence has been investigated extensively. In subgroup analyses, both before and after 1996, the prevalence of goiter significantly changed with iodine status, with data suggesting hormesis – emphasizing that overdoses of iodine, as well as deficiencies may be associated with high prevalence of goiter (Zhao et al. 2014). Zhao and co-workers (2014) also reported that the USI program in China successfully reduced the prevalence of goiter after 1996. However, the program might cause excesses iodine intake that may be associated with a high prevalence of goiter (Zhao et al. 2014).

CONCLUSIONS

A decrease of DG prevalence (I degree) among adolescents from 1747.72 to 1571.29 per 10,000 individuals during 2000-2014 was observed. A significant reduction of DG (I degree) prevalence among adolescents from towns of Lviv region was noted. It was 1971.74 per 10,000 individuals in 2000 and 1185.52 per 10,000 individuals in 2014. There was increased of DG (I degree) prevalence from 1591.92 to 1785.56 per 10,000 individuals among adolescents in Lviv region during 2000-2014. In 2014, the prevalence of disease among adolescents from districts was higher compared to the adolescents from towns (1785.56 compared to 1185.52 per 10,000 individuals, respectively). The highest DG prevalence (I degree) among adolescents of Lviv region was observed in Pustomyty, Peremyshliany, Zolochivskyi, Busk, and Radekhiv districts in 2000 (5140.41, 4845.54, 3067.63, 2804.31, 2192.04 per 10,000 individuals, respectively), in Peremyshliany, Skole, Starosambirskyi, Pustomyty districts in 2004 (4871.91, 2675.72, 2156.84, 1840.04 per 10,000 individuals, respectively), in Zhovkivskyi, Busk, Turkivskyi, Skole, and Pustomyty districts in 2014 (3794.27, 3051.45, 3000.84, 2792.15, 2519.94 per 10,000 individuals, respectively). The decrease of DG (I degree) prevalence among adolescent population in the 6 districts (Zolochivskyi, Pere- myshliany, Pustomyty, Radekhiv, Starosambirskyi, Stryiskyi) and all towns (except Chervonograd) in Lviv region was noted. Increased DG (II and III degrees) prevalence among adolescents of Lviv region was observed in Busk, Brody, Radekhiv, Skole, and Sokal districts in 2000 (1608.71, 415.64, 324.05, 200.03, 147.91 per 10,000 individuals, respectively), in Busk, Skole, Zolochivskyi, Turkivskyi, and Sokal districts in 2004 (370.41, 339.53, 245.52, 173.03, 151.14 per 10,000 individuals, respectively), in Busk, Pustomyty, Skole, Sokal, and Turkivskyi districts in 2014 (567.05, 385.94, 354.24, 294.04, 266.85 per 10,000 individuals, respectively). The decrease of DG (II and III degrees) prevalence among adolescents in the 11 districts (Brody, Busk, Horodok, Zhydachivskyi, Zolochivskyi, My- kolaiv, Peremyshliany, Radekhiv, Sambir, Starosambirskyi, Stryiskyi) and all towns (except Drohobych and Chervonograd) in Lviv region was noted. In our study, we also observed that DG prevalence among adolescents in altitude regions was higher compared to the plateau regions, a finding similar to trends in previous surveys that may be explained by deficiencies in natural iodine at high altitudes and limited educational and economic support for the people who reside there. According to the present information, the prevalence of DG also was differed in districts and towns. DG are more common in districts than in the towns, which may be explained by lifestyle choices. Furthermore, females were at greater risk for DGs and this difference was not changed when females were further divided into rural, mixed and urban groups. Our results indicate the need to clarify the relevant influencing factors of DG 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 DG incidence.

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SUMMARY

Correcting this public health problem is the goal of a massive global campaign that is showing remarkable progress so far (Dunn 1998). But despite its importance to most other countries, iodine deficiency receives high attention in the Ukraine. The iodination program also includes monitoring goitres and measuring the concentration of iodine in the urine in the population as quality assurance of the program. Incidence of diffuse goitre (DG) in Ukraine is currently change during past decades. Therefore, the aim of our study was the assessment of DG prevalence among adults (above 18 years old) in Lviv region (western Ukraine) during 2000-2014. For assessment of the DG prevalence among adolescents (14-18 years old) of different districts (reions) in Lviv region during 2000-2014, the analysis of archival data from Lviv Regional Endo- crinology Hospital was done. The research study covered by 20 districts (reions) of Lviv region (Brody, Busk, Horodok, Drohobych, Zhydachivskyi, Zhovkivskyi, Zolo- chivskyi, Kamianka-Buzka, Mykolaiv, Mostyska, Peremyshliany, Pustomyty, Rad- ekhiv, Sambir, Skole, Sokal, Starosambirskyi, Stryiskyi, Turkivskyi, and Yavorivskyi Districts), as well as six towns of Lviv region (Lviv, Boryslav, Drohobych, Stryi, Truskavets, Chervonograd). A decrease of DG prevalence (I degree) among adolescents from 1747.72 to 1571.29 per 10,000 individuals during 2000-2014 was observed. A significant reduction of DG (I degree) prevalence among adolescents from towns of Lviv region was noted. It was 1971.74 per 10,000 individuals in 2000 and 1185.52 per 10,000 individuals in 2014. There was increased of DG (I degree) prevalence from 1591.92 to 1785.56 per 10,000 individuals among adolescents in Lviv region during 2000-2014. In 2014, the prevalence of disease among adolescents from districts was higher compared to the adolescents from towns (1785.56 compared to 1185.52 per 10,000 individuals, respectively). The highest DG prevalence (I degree) among adolescents of Lviv region was observed in Pustomyty, Peremyshliany, Zolochivskyi, Busk, and Radekhiv districts in 2000 (5140.41, 4845.54, 3067.63, 2804.31, 2192.04 per 10,000 individuals, respectively), in Peremyshliany, Skole, Starosambirskyi, Pustomyty districts in 2004 (4871.91, 2675.72, 2156.84, 1840.04 per 10,000 individuals, respectively), in Zhovkivskyi, Busk, Turkivskyi, Skole, and Pus- tomyty districts in 2014 (3794.27, 3051.45, 3000.84, 2792.15, 2519.94 per 10,000 individuals, respectively). The decrease of DG (I degree) prevalence among adolescent population in the 6 districts (Zolochivskyi, Peremyshliany, Pustomyty, Radekhiv, Starosambirskyi, Stryiskyi) and all towns (except Chervonograd) in Lviv region was noted. Increased DG (II and III degrees) prevalence among adolescents of Lviv region was observed in Busk, Brody, Radekhiv, Skole, and Sokal districts in 2000 (1608.71, 415.64, 324.05, 200.03, 147.91 per 10,000 individuals, respectively), in Busk, Skole, Zolochivskyi, Turkivskyi, and Sokal districts in 2004 (370.41, 339.53, 245.52, 173.03, 151.14 per 10,000 individuals, respectively), in Busk, Pustomyty, Skole, Sokal, and Turkivskyi districts in 2014 (567.05, 385.94, 354.24, 294.04, 266.85 per 10,000 individuals, respectively). The decrease of DG (II and III degrees) prevalence among adolescents in the 11 districts (Brody, Busk, Horodok, Zhydachivskyi, Zolochivskyi, My- kolaiv, Peremyshliany, Radekhiv, Sambir, Starosambirskyi, Stryiskyi) and all towns (except Drohobych and Chervonograd) in Lviv region was noted. In our study, we also

74 observed that DG prevalence among adolescents in altitude regions was higher compared to the plateau regions, a finding similar to trends in previous surveys that may be explained by deficiencies in natural iodine at high altitudes and limited educational and economic support for the people who reside there. According to the present information, the prevalence of DG also was differed in districts and towns. DG are more common in districts than in the towns, which may be explained by lifestyle choices. Furthermore, females were at greater risk for DGs and this difference was not changed when females were further divided into rural, mixed and urban groups. Our results indicate the need to clarify the relevant influencing factors of DG 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 DG incidence.