Słupskie Prace Biologiczne

Nr 12 ss. 93-110 2015

ISSN 1734-0926 Przyjęto: 15.10.2015 © Instytut Biologii i Ochrony Środowiska Akademii Pomorskiej w Słupsku Zaakceptowano: 25.02.2016

ASSESSMENT OF DIFFUSE GOITER PREVALENCE AMONG ADULTS IN ENDEMIC REGION (WESTERN )

Olha Kasiyan 1 Halyna Tkachenko 2 Jan Łukaszewicz 3

1Danylo Halytskyy Lviv National Medical University, Lviv, Ukraine e-mail: [email protected] 2Pomeranian University in Słupsk Institute of Biology and Environmental Protection Arciszewski St. 22b, 76-200 Słupsk, Poland 3Adam Mickiewicz University in Pozna ń Institute of Physical Geography and Environmental Planning

ABSTRACT

Even minor differences in iodine intake between populations are associated with differences in the occurrence of thyroid disorders. Both iodine intake levels below and above the recommended interval are associated with an increase in the risk of disease in the population. Optimally, iodine intake of a population should be kept within a relatively narrow interval where iodine deficiency disorders are prevented, but not higher. Monitoring and adjusting of iodine intake in a population is an im- portant part of preventive medicine (Laurberg et al. 2010). Incidence of diffuse goi- tre (DG) in Ukraine is currently higher than in past decades. Therefore, the aim of our study was the assessment of DG prevalence among adults (above 18 years old) in Lviv region () during 2000-2010. For assessment of the DG prev- alence among children, adolescents, and adults of different districts (reions) in Lviv region during 2000-2010, the analysis of archival data from Lviv Regional Endocri- nology Hospital was done. The research study covered by 20 districts of (, Busk, Horodok, , Zhydachivskyi, Zhovkivskyi, Zolochivskyi, Kamianka-Buzka, Mykolaiv, , , , , Sam- bir, , , Starosambirskyi, Stryiskyi, Turkivskyi, and Yavorivskyi Districts), as well as six towns of Lviv region (Lviv, , Drohobych, , , Chervonograd). A decrease of the DG prevalence (I degree) from 307.5 to 197.2 per 10,000 individuals during 2000-2010 was observed. A significant reduction in DG

93 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 de- cline of DG 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 indi- viduals, 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 prevalence in 7 districts (Brody, Zhydachivskyi, Mykolaiv, Peremyshliany, Rad- ekhiv, , 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 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 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) prevalence among adults of Lviv region was ob- served 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, Rad- ekhiv, 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, Zhydachivskyi, 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 influ- encing factors of DG prevalence among the population of Lviv region, the defini- tion 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 inci- dence.

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

INTRODUCTION

Iodine deficiency is a common cause of endemic goitre. Recently, the World Health Organization (WHO) calculated that about 740 million people, equivalent to 13% of the world’s population, have goiter due to an excessively low intake of iodine (Hetzel 1989, Thyroid Disease in Adults 2011). When the physiological require-

94 ments of iodine are not met in a given population, a series of functional and deve- lopmental abnormalities occur including thyroid function abnormalities and, when iodine deficiency is severe, endemic goiter and cretinism, endemic mental retarda- tion, decreased fertility rate, increased perinatal death, and infant mortality. These complications, which constitute a hindrance to the development of the affected popu- lations, are grouped under the general heading of iodine deficiency disorders (IDD) (Delange 1994). Iodine deficiency leads to hyperplasia of the thyroid epithelium. Over time, some follicles will become inactive and distended with colloid. This will lead to focal nodular hyperplasia and nodular changes that can assume grotesque proportions and be associated with a risk for hypothyroidism. Even in countries without iodine defi- ciency, goitre is a very common condition. The majority of patients with goitre have a multinodular nontoxic benign goitre. In some cases, a local change in thyroid folli- cles dominates so that the goitre behaves like a unilateral goiter or even as a palpable solitary lump (Thyroid Disease in Adults 2011). The clinical course of sporadic nodular goitre is highly varied. As a rule, younger or middle-aged individuals in the early phase of the pathophysiological process pre- sent with diffuse goitre, while the tendency with increasing age is a gradual deve- lopment towards the characteristics of multinodular goitre. In adults and the elderly, a slow but continuous further growth of the goitre is often observed. The rate of growth varies greatly from person to person. About 10% of cases with euthyroid multinodu- lar goiter progress to toxic multinodular goiter with sufficient availability of iodine, a diffuse enlargement of the thyroid can otherwise be caused by autoimmune thy- roiditis. From a global perspective, iodine deficiency is the most common cause of goitre in adolescents. Rarely occurring defects in enzymatic processes for synthesis of thyroid hormone or in the TSH receptor function can also cause dysfunction and/or increased size of the thyroid (Thyroid Disease in Adults 2011). Now, there is an ongoing global iodination program in a collaboration between the International Council for Control of Iodine Deficiency Disorders (ICCIDD), UNICEF and WHO, with the goal of eradicating iodine deficiency throughout the world. 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. The recommended dietary allowances of iodine are 100 micrograms/day for adults and adolescents, 60-100 micrograms/day for children aged 1 to 10 years, and 35-40 micrograms/day in infants aged less than 1 year (Delange 1994). Over the past decade, the number of countries that are iodine deficient has fallen from 54 to 30. The number iodine-sufficient countries has increased from 67 to 112, while the number with excessive iodine intake has increased from 5 to 10. In most coun- tries with excess intake, this is due to over iodization of salt and/or poor monitoring of salt iodization. Out of 128 countries with household coverage of adequately io- dized salt data, at least 90% of households in 37 countries consume adequately iodized salt, but in 39 countries, coverage rates are below 50%. Overall, about 70% of house- holds worldwide have access to iodized salt. There has been substantial recent progress in the global effort to control iodine deficiency. However, iodized salt pro- grams need to be carefully monitored to ensure adequate iodine intake while

95 avoiding iodine excess (Zimmermann 2013). Although international public health efforts over the past several decades have been highly effective, nearly one third of children worldwide remain at risk for iodine deficiency, and iodine deficiency is considered the leading preventable cause of preventable intellectual deficits (Pearce 2014). Endemic goiter is one of the earliest and most visible sign of iodine deficiency (WHO, UNICEF... 1999, 2001). 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 autono- mous 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 thy- roid hormone is necessary for proper development of the central nervous system, particularly 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 in- dustrialized countries of Europe are also affected (Delange 1994, Thyroid Disease in Adults 2011). Ukraine has generally been an area of mild-to-moderate iodine deficiency (Gerasimov 2002). The following territories in Ukraine are biogeochemical provin- ces with iodine deficiency: Zhitomir, Lviv, Ternopol, Volyn Oblast and other re- gions 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 prevent- ing 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 epi- demiologic 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 induc- tively coupled plasma mass spectrometry after chemical separation. Iodine concen- tration on a dry basis for 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 de- viation 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 ar- eas 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).

96 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 im- portance 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 dur- ing past decades. Therefore, the aim of our study was the assessment of DG preva- lence among adults (above 18 years old) in Lviv region (western Ukraine) during 2000-2010.

MATERIALS AND METHODS

For assessment of the DG prevalence among adults (above 18 years old) of dif- ferent districts (reions) in Lviv region during 2000-2010, 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, Zhy- dachivskyi, Zhovkivskyi, Zolochivskyi, Kamianka-Buzka, Mykolaiv, Mostyska, Pere- myshliany, Pustomyty, Radekhiv, Sambir, Skole, Sokal, Starosambirskyi, Stryiskyi, Turkivskyi, and Yavorivskyi Districts), as well as six towns of Lviv region (Lviv, Bo- ryslav, Drohobych, Stryi, Truskavets, Chervonograd). The obtained results were ana- lyzed statistically using the STATISTICA 10.0 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 AND DISCUSSION

The prevalence of diffuse goiter (I degree) (per 10,000 individuals) among the adults of Lviv region during 2000-2010 was presented in Tab. 1 and Fig. 1. Decrease of the DG prevalence from 307.5 to 197.2 per 10,000 individuals during 2000-2010 was observed (Tab. 1, Fig. 1). A significant reduction in DG 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 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 high- er compared to the adults from towns (197.2 compared to 99.6 per 10,000 individu- als, 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) (Fig. 1). The increase in the DG prevalence in 7 districts (Brody, Zhy- dachivskyi, Mykolaiv, Peremyshliany, Radekhiv, Sambir, Skole) among 20 districts

97 and in 1 town (Chervonograd) among 6 towns of Lviv region during 2000-2010 was observed (Tab. 1).

Table 1

The prevalence of diffuse goiter (I degree) among adults during 2000-2010

The prevalence of diffuse goiter (I degree), per 10,000 individuals Districts of Lviv region 2000 2004 2010 Brody 48.0 43.4 88.8 Busk 1448.5 1001.3 489.1 Horodok 69.2 45.7 43.0 Drohobych 314.0 243.0 151.8 Zhydachivskyi 31.0 33.6 67.7 Zhovkivskyi 176.1 207.9 181.9 Zolochivskyi 195.4 137.1 88.0 Kamianka-Buzka 247.7 260.5 211.8 Mykolaiv 28.7 41.8 93.9 Mostyska 271.9 332.5 261.0 Peremyshliany 92.1 132.3 129.0 Pustomyty 766.0 303.4 282.4 Radekhiv 118.3 190.8 192.9 Sambir 100.1 177.6 231.9 Skole 201.1 293.8 368.2 Sokal 625.1 306.9 166.3 Starosambirskyi 776.2 882.8 359.6 Stryiskyi 133.7 144.7 104.0 Turkivskyi 518.3 510.5 443.4 Yavorivskyi 148.5 163.4 141.2 Total 307.5 260.1 197.2

Towns of Lviv region 2000 2004 2010

Lviv 133.2 122.2 111.1 Boryslav 160.7 113.4 96.3 Drohobych 218.2 87.0 61.2 Stryi 28.5 26.7 9.5 Truskavets 340.2 167.2 14.1 Chervonograd 38.2 84.8 145.0 Total in Towns 133.1 109.8 99.6 Total 231.8 195.1 155.3

98

Fig. 1. Prevalence of diffuse goiter (I degree) (per 10,000 individuals) among adults in districts (reions) of Lviv region in 2000 (A), 2004 (B) and 2010 (C)

Source: own research

The prevalence of diffuse goiter (II and III degrees) (per 10,000 individuals) among the adults of Lviv region during 2000-2010 years was presented in Tab. 2 and Fig. 2. Decrease of the DG prevalence from 31.4 to 29.6 per 10,000 individuals dur- ing 2000-2010 was observed (Tab. 2, Fig. 2). A significant increase in DG preva- lence among adults from districts of Lviv region was noted. 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 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) (Tab. 2). Increased DG (II and III degrees) prevalence 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, Rade- khiv, 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) (Tab. 2, Fig. 2). The decrease of DG prevalence among adults in the 15 districts (Busk, Horodok, Drohobych, Zhydachivskyi, Zolochivskyi, Sokal, Starosambirskyi, Stryiskyi) and all towns (except Drohobych and Chervonograd) in Lviv region was noted (Tab. 2, Fig. 2). As show our results, decrease of the DG prevalence from 307.5 to 197.2 per 10,000 individuals during 2000-2010 was observed. A significant reduction in DG 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

99 of DG 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 dis- tricts was higher compared to the adults from towns (197.2 compared to 99.6 per 10,000 individuals, respectively).

Table 2 The prevalence of diffuse goiter (II and III degrees) among adults during 2000-2010

The prevalence of diffuse goiter (II and III degrees), Districts of Lviv region per 10,000 individuals 2000 2004 2010 Brody 6.6 5.2 8.8 Busk 51.5 130.2 27.0 Horodok 21.6 29.3 16.8 Drohobych 20.5 18.5 17.5 Zhydachivskyi 15.8 11.0 11.4 Zhovkivskyi 4.4 6.8 11.5 Zolochivskyi 27.9 34.3 9.5 Kamianka-Buzka 18.3 19.7 20.1 Mykolaiv 25.4 47.2 60.8 Mostyska 16.7 19.8 23.1 Peremyshliany 73.7 86.4 90.5 Pustomyty 35.6 42.1 58.5 Radekhiv 80.9 110.6 97.8 Sambir 22.0 32.1 28.4 Skole 63.7 67.5 79.4 Sokal 47.0 86.9 105.7 Starosambirskyi 25.8 23.9 12.5 Stryiskyi 24.2 21.9 17.9 Turkivskyi 62.5 62.7 71.0 Yavorivskyi 22.0 19.9 25.5 Total 29.9 39.3 37.3

Towns of Lviv region 2000 2004 2010

Lviv 38.9 26.7 20.8 Boryslav 74.8 30.3 10.1 Drohobych 5.4 10.1 18.0 Stryi 12.6 21.6 5.7 Truskavets 48.5 10.8 3.3 Chervonograd 3.5 17.0 20.1 Total 33.3 24.4 19.4 Total 31.4 32.9 29.6

100

Fig. 2. Prevalence of diffuse goiter (II and III degrees) (per 10,000 individuals) among adults in districts (reions) of Lviv region in 2000 (A), 2004 (B) and 2010 (C)

Source: own research

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 individu- als, respectively). The increase in the DG prevalence in 7 districts (Brody, Zhy- dachivskyi, 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 from 31.4 to 29.6 per 10,000 individuals during 2000-2010 was observed (Fig. 2). A significant increase in DG prevalence among adults from districts of Lviv region was noted. 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 prevalence from 33.3 to 19.4 per 10,000 individuals among adults from town 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) prevalence 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, Rade- khiv, 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) (Fig. 2). The decrease of DG prevalence among adults in the 15 districts (Busk, Horodok, Drohobych, Zhydachivskyi, Zolochivskyi, Sokal, Starosambirskyi, Stryiskyi) and all towns (except Drohobych and Chervo- nograd) in Lviv region was noted (Fig. 2).

101 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). 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 be- cause 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 insuf- ficient 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 subsequent steps of the intrathyroidal metabolism of iodine leading to preferen- tial synthesis and secretion of triiodotyronine (T3). They are triggered and main- tained by increased secretion of thyroid-stimulating hormone (TSH), which is ulti- mately 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 unfavorable side effect in the process of adaptation to iodine de- ficiency during growth. The most serious complication of iodine deficiency is en- demic cretinism, a syndrome characterized by irreversible mental retardation togeth- er with either a predominant neurological syndrome or predominant hypothyroidism, or a combination of both syndromes (Delange 1994). Goiter begins as an adaptation to iodine deficiency, probably mainly from increased stimulation by TSH. As the thyroid secretes inadequate amounts of hormone, the pi- tuitary responds by releasing more TSH, with all its various 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 TH, such as in pregnancy or adolescence, 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 autonomous and may even- tually hyperfunction and produce hyperthyroidism. This potential for excess hor- mone production is greatly increased if fairly large amounts of iodine suddenly be- come available. This iodine-induced hyperthyroidism (IIH) can be considered 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 longstanding goiter that has developed autonomous nodules. Previously, such a gland has avidly sought every available atom of iodine. If now sufficient iodine becomes available,

102 the nodular thyroid will react by synthesizing and secreting inappropriately large amounts of TH and causing hyperthyroidism (Stanbury et al. 1998). 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 correction of io- dine 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 mana- gement probably plays the most important role for disease progression, but iodine it- self may also affect the immunological processes. Thus, the prevalence of autoim- mune thyroiditis is higher in populations with a high intake of iodine than in popula- tions with a low intake. Other data indicate that iodine supplementation in populations with low iodine intake can increase the incidence of autoimmune Hashimoto's thy- roiditis. Our previous study confirm this thesis. The assessment of 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, 2013-2014, 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 dis- tricts 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 prevalence from 3.2 to 2.4 per 10,000 individu- als 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 dis- tricts, 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 popu- lation 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

103 that mainly nutritive factors and environmental pollution by metals and chemicals 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 dise- ase 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 preva- lence 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 sam- ples 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 in- habitants 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 nature 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 in- creased 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. Some occurrences of this consequence are unavoidable, but their impact can be lessened by appropriate measures. These include careful monitoring of salt (or other iodine-supplementation sources), to ensure that its levels of iodine are not significantly above those recommended in the national program, and measuring of representative urinary iodine levels to see if they are in an appropriate range. If the estimates used to calculate the desired levels of iodine addition to salt were incorrect, they should be adjusted (Stanbury et al. 1998). Depending on the availability of iodine, the thyroid gland is able to enhance or limit the use of iodine for thyroid hormone production. When compensation fails, as in severely iodine-deficient populations, hypothyroidism and developmental brain damage will be the dominating disorders. This is, out of all comparison, the most se- rious association between disease and the level of iodine intake in a population. In populations with high iodine intake, the average serum thyroid-stimulating hormone (TSH) tends to increase with age. This phenomenon is especially pronounced in Cau- casian populations with a genetically determined high tendency to thyroid autoim- munity. A small tendency to higher serum TSH may be observed already when io- dine intake is brought from mildly deficient to adequate, but there is at present no evidence that slightly elevated serum TSH in elderly people leads to an increase in morbidity and mortality (Laurberg et al. 2010). Despite iodine repletion, the prevalence of goiter in the Ukraine remains at ap- proximately 20%, highlighting that iodine deficiency is not the only cause of goiter formation (Daniels 1996). Nontoxic goiter is more common in women than men. In

104 a population-based study in England, palpable goiters were identified in 10% of adult women and 2% of adult men (Vanderpump et al. 1995). Goiter development in iodine-replete populations is typically a disease of adulthood, whereas goiter develo- pment in areas of iodine deficiency is typically a disease of prepubertal children. No epidemiologic studies have suggested a relationship between race and the prevalence of goiter. Iodine deficiency is associated with goiter formation through activation of the hypothalamicpituitary-thyroid axis. Because iodine is required for the organifica- tion of thyroglobulin, iodine deficiency results in upregulation of thyroid-stimulating hormone (TSH) in the setting of decreased thyroid hormone release. The increased TSH stimulation of the thyroid gland results in gland enlargement, or goiter. In io- dine-replete populations, patients with nontoxic goiter are commonly euthyroid, thus suggesting additional causes for the development of goiter in addition to TSH stimu- lation. In these populations, the clinical phenotype of nontoxic goiter likely results from a number of genetic and environmental factors. The role of genetic factors in the development of goiter has been suggested by the aggregation of goiter within families (Heimann 1966). In 1999, Neumann and colleagues (1999) first identified a genetic locus associated with nontoxic goiter on chromosome 14q. In a study of twins in a nonendemic region, Brix and associates (1999) demonstrated a substan- tially higher heritability of goiter in monozygotic versus dizygotic twins. Multiple environmental factors have been identified as risk factors for goiter formation. Ex- amples include ingestion of goitrogens in the diet (e.g., soybeans, cabbage, turnips, Brussels sprouts, rutabagas, seaweed), administration of goitrogenic drugs such as lithium, environmental agents such as phenolic and phthalate ester derivatives found downstream from coal mines, and cigarette smoking (Orenstein et al. 1988, Bertel- sen and Hegedus 1994). Nontoxic goiter can also be observed in patients with an in- herited dyshormonogenesis, resulting in a defect in the thyroid hormone biosynthetic pathway. Finally, radiation exposure to the head and neck during childhood increases the likelihood of benign and malignant thyroid growth. The natural history of goiter is characterized clinically by thyroid growth, nodule formation, and the development of functional autonomy. This has been demonstrated in cross-sectional studies of pa- tients with nontoxic goiter by Vanderpump and co-workers (1995) and Berghout and colleagues (1990). Increased thyroid growth results from excessive cell replication, mainly of follicular cells. Whereas TSH stimulation contributes to the iodine- deficient goiter, in the euthyroid goiter additional growth factors, such as insulin- growth factor, epidermal growth factor, and fibroblast growth factor, are known to stimulate thyroid growth (Dumont et al. 1991). In addition to growth factors, growth inhibitors, released by the thyroid gland itself, are known to regulate thyroid mass size. The expression of transforming growth factor (TGF) was shown to be decreased in the nontoxic goiter compared with normal thyroid tissue (Grubeck-Loebenstein et al. 1989). In the setting of multiple growth factors and inhibitors, nodules are thought to arise because of heterogeneity of the growth responses among follicular cells. Follicu- lar cells with high growth potential are unequally distributed throughout a normal thyroid gland and, in the setting of replication, daughter cells remain clustered, caus- ing nontoxic goiters to become increasingly nodular over time (Peter et al. 1985). An additional mechanism contributing to nodule formation is hemorrhagic necrosis and subsequent fibrosis within areas of rapid growth, with newly formed, fragile, and in-

105 sufficient capillary networks. Within these populations of rapidly dividing follicular cells, it has also been observed that functional autonomy develops, because follicles have varying sensitivities to TSH stimulation for iodine metabolism (Studer and Gerber 1995). Because of the greater number of follicular cells metabolizing iodine autonomously, patients with nontoxic goiter can progress to subclinical and then overt thyrotoxicosis, particularly in the setting of excessive amounts of iodine (e.g., iodinated contrast dye) (Studer et al. 1989).

CONCLUSIONS

1. A decrease of the DG prevalence (I degree) from 307.5 to 197.2 per 10,000 individuals during 2000-2010 was observed. A significant reduction in DG 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 prevalence from 231.8 to 155.3 per 10,000 individuals among adults in Lviv region during 2000-2010. In 2010, the prevalence of dis- ease among adults from districts was higher compared to the adults from towns (197.2 compared to 99.6 per 10,000 individuals, respectively). 2. 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 DG prevalence in 7 districts (Brody, Zhydachivskyi, Mykolaiv, Peremyshliany, Radekhiv, Sambir, Skole) among 20 districts and 1 town (Chervonograd) among 6 towns of Lviv region during 2000-2010 was observed. Decrease of the DG prevalence from 31.4 to 29.6 per 10,000 individuals during 2000-2010 was noted. A significant in- crease in DG 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 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). 3. Increased DG (II and III degrees) prevalence among adults of Lviv region was observed in Radekhiv, Peremyshliany, Skole, Turkivskyi, and Busk dis- tricts in 2000 (80.9, 73.7, 63.7, 62.5, 51.5 per 10,000 individuals, respective- ly), 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, respective- ly), 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 de- crease of DG prevalence among adults in the 15 districts (Busk, Horodok, Drohobych, Zhydachivskyi, Zolochivskyi, Sokal, Starosambirskyi, Stryiskyi) and all towns (except Drohobych and Chervonograd) in Lviv region was not- ed.

106 4. 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

The aim of our study was the assessment of DG prevalence among adults (above 18 years old) in Lviv region (western Ukraine) during 2000-2010. For assessment of the diffuse goitre (DG) prevalence among children, adolescents, and adults of differ- ent districts (reions) in Lviv region during 2000-2010. For assessment of the DG prevalence, the analysis of archival data from Lviv Regional Endocrinology Hospi- tal was done. The research study covered by 20 districts 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, Drohobych, Stryi, Truskavets, Chervo- nograd). A decrease of the DG prevalence (I degree) from 307.5 to 197.2 per 10,000 individuals during 2000-2010 was observed. A significant reduction in DG preva- lence among adults from towns of Lviv region was noted. There was a decline of

109 DG prevalence from 231.8 to 155.3 per 10,000 individuals among adults in Lviv re- gion during 2000-2010. In 2010, the prevalence of disease among adults from dis- tricts was higher compared to the adults from towns (197.2 compared to 99.6 per 10,000 individuals, respectively). The increase in the DG prevalence in 7 districts (Brody, Zhydachivskyi, Mykolaiv, Peremyshliany, Radekhiv, Sambir, Skole) among 20 districts and in one 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 in- crease in DG prevalence among adults from districts of Lviv region was demonstrat- ed. 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 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). Our results indicate the need to clarify the relevant influencing factors of DG prevalence among the popula- tion 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.

110