Endemic goiter and iodine deficiency is an important public health problem parti-cularly in some areas of Turkey as it has been all over the world. We intended to evaluate this problem in Kayseri, where the goiter is endemic.
128 students aged between 10-13 years and 71 adults aged more than 15 years who were living in a rural area of Kayseri were included in the study.
Thyroid gland was evaluated with physical examination and ultrasonography (USG), blood samples were drawn to assess the levels of free T3 (fT3), free T4 (fT4), TSH, thyroglobulin (Tg), anti-microsomal antibody (anti-M) and anti-thyroglobulin (anti-Tg) and spot urine samples were collected from all participants.
Goiter prevalence was 54.8% with palpation and 48.7% with ultrasonography. Thyroid volumes were higher in females than males both in students and adults. fT3 levels were normal or slightly higher, fT4 levels were normal or slightly lower, TSH levels were high and thyroglobulin levels were extremely high.
Mean urinary iodine level was 11.1± 6.1 mg/dl and in 53.3% of the participants urinary iodine levels were below the normal level (10 mg/dl). Median urinary iodine level was 9.54 mg/dl indicating mild iodine deficiency.
In conclusion despite the high prevalence of goiter, median urinary iodine level was relatively high suggesting that measurement techniques of iodine level may affect the result. According to chronic iodine deficiency parameter such as thyroglobulin (Tg), it is obvious that the people living at this endemic area need iodine prophylaxis.
Keywords: Endemic goiter, Iodine deficiency, Thyroid function and Central Anatolia
Endemic goiter and iodine deficiency are important public health problems in many countries in the world [1,2]. Different nutritional and environmen-tal factors are responsible for the pathogenesis of goiter but iodine deficiency is the most important factor [2-5].
Recent studies in Turkey demonstrated a high pre-valence (up to 82%) of endemic goiter due to iodine deficiency [6-12]. Because of the geo-graphical characteristics of Kayseri, iodine defi-ciency is more common and goiter prevalence was reported as 30% in several studies [6,7,11]. But these results were obtained only with palpation of thyroid gland. Recently Erdoğan et al. investigated iodine status and goiter prevalence in school-age children in known endemic areas of Turkey inclu-ding Kayseri. After sonographic thyroid volume and urinary iodine concentration measurement, goiter prevalence and median urinary iodine level was reported as 33% and 25.5 mg/l, respectively [13,14]. Until now, such an extensive evaluation in both school-age children and adults, including thyroid gland USG (ultrasonography), measure-ments of urinary iodine level, thyroid fuction test and thyroid antibodies were not performed in this area previously. The aim of this study was to assess all these parameters in primary school students and adults who were living in Tomarza a town of Kayseri and Alakuşak village of Tomarza where goiter prevalence has been reported high.
This study was carried out in Tomarza where the altitude is higher than Kayseri and in Alakuşak (village of Tomarza) which is at the foot of mount Erciyes. Informed consent was obtained from the parents of students.
Heights of Tomarza and Alakuşak from sea level were 2250 meters and 2380 meters, respectively. Populations of Tomarza and Alakuşak were 10113 and 2110 persons, respectively. In Alakuşak pri-mary school students and adults over 15 year old were selected randomly. In Tomarza a school that could represent the town was selected and adults over 15 year old were selected randomly from the district near the school. Table 1 summarizes the age and genders of participants in Tomarza and Alakuşak.
Table 1: Classification of adults and primary school students in the study due to gender.
Physical examinations were done and PAHO (Pan American Health Organization) criteria  were used to evaluate the thyroid gland by the same endocrinologist (FB). Blood samples were drawn to assess the serum levels of free T3 (fT3), free T4 (fT4), TSH, thyroglobulin (Tg), anti-M (anti TPO) and anti-thyroglobulin (anti-Tg). Spot urine samples were collected. Blood samples were stored at 20 Co until they assayed. Urine samples were collected deionized tubes and after addition of acidic mate-rial stored at 20o. All blood and urine samples were studied at the same time.
Thyroid USG was applied, by the same radiologist (NE) with 7.5 mHz high resolution Toshiba sono-layer-L-SAL-77-A equipment and width-length-depth of both thyroid lobes were estimated. Volu-mes of both lobes of thyroid gland were estimated by the formula of widthXlengthX0.524 and isthmus was not included in the volume . Goiter prevalence was defined according to Gutekunsts criteria .
Serum fT3, fT4, TSH, Tg, anti-M and anti-Tg levels were measured with commercial kits (Amerlex-MAB-FT3 RIA, hsTSH Coated Tube Assey IRMA, Thyroglobulin DSL-2500 RIA, TMAb C.T. /BC 1005/IRMA, TGAb IRMA C.T. /BC1006). Normal levels and intra and interassay CV analyses and sen-sitivities were listed respectively; fT3 2.2-4.7 pg/ml, %4.4, %7.6, 0.7 pmol/l, fT4, 0.77-1.9 ng/dl, %4.4,% 6.1, 0.6 pmol/l, TSH 0.54-4.58 mIU/ml, %2.8, %6.0, 0.04 mIU/ml, Tg 7-38 ng/ml, %4.0, %5.5, 0.8 g/L, anti-M < 100 IU/ml, %6.3, %11.2, anti-Tg <100 IU/ml ,%5.8, 8.3.
Urine samples were analyzed for urinary iodine content according to the method described by Garry PJ et al. . Briefly urine samples were incubated with arsenic acide for ten minutes and incubated with ceric ammonium phosphate for ten minutes at 550C heatingblock after dissolving the urine samples at room temperature. This material was analyzed with spectrophotometer at 410 nm compared with distillated water. Results were com-pared with standard levels and estimated as mg/dl. Urinary iodine levels higher than 10 g/dl were accepted normal, between 5-10 mg/dl mild, bet-ween 2-5mg moderate and lower than 2mg/dl were as accepted severe iodine deficiency.
Statistical analysis were performed by using paired and independent t-test for continuous variables, kappa test for agreement of diagnostic measure-ments (thyroid palpitation, thyroid USG), Chi-square test for categorical variables and linear regression test for relationships between continuous variables.
With thyroid palpation goiter prevalence was found as 57,1% in female students, 31.0% in male students and mean prevalence was 45.3%. Goiter prevalence was 86.3% in female adults, 35.0% in male adults and the mean prevalence was 71.8%. The mean goiter prevalence was 54.8% in all persons involved in the study (male 32.1%, female 69.4%).
Thyroid volumes measured with USG at the settlement areas were shown at Table 2. According to these findings thyroid volumes of students and adults in Alakuşak village were significantly higher than in Tomarza (students p<0.01, adults p<0.05). Despite the thyroid volumes (measured with USG) of female students were slightly higher than male students this data was not statistically significant (p>0.05), in adults thyroid volumes (measured with USG) of females were signi-ficantly higher than males (p<0.05).
Table 2: Thyroid volumes measured with USG at the settlement areas
With USG 55.7% of female students and 50.0% of male students (mean 53.1%) had goiter in iodine deficient areas . On the other hand, according to Kurtoğlus thyroid volume findings, 32.9% of female and 29.3 of males had goiter . According to Gutekunsts criteria the mean goiter prevalence in adults was 40.9% (female 52.9%, male 10.0%) . The mean goiter prevalence was 48.7% ( female 54.5%, male 39.74) in all persons involved in the study .
Students with nonpalpabl thyroid glands had significantly higher fT3, fT4 levels than students with palpable thyroid glands (p<0.05). Also we found that TSH, Tg levels and thyroid volumes were significantly higher in students with palpabl thyroid gland than students with nonpalpabl thyroid gland (p<0.05). Despite BMI, age, and anti-Tg were higher in students with palpable thyroid gland than in students with nonpalpable thyroid gland, no statistically significant difference was demonstrated (p>0.05) (Table 3). Adults with palpable thyroid glands had higher fT3, TSH , anti-M , anti-Tg levels, and adults with nonpalpable thyroid glands had higher BMI, and FT4 levels but these differences were not significant. Adults with palpabl thyroid glands had significantly higher thyroid volumes than nonpalpable thyroid glands (p<0.05) (Table 3).
Table 3: Comparison of some parameters (all students and adults) due to palpation of thyroid gland.
FT3, TSH , Tg, antiTg and thyroid volumes were significantly higher in students who have goiter with USG than normal students. FT4 levels were significantly higher in the students who have not goiter than students who have goiter (measured with USG) (p<0,001) (Table 4). It was demonstra-ted that in adult participants with goiter fT3 ,anti-M levels were slightly but not significant, but Tg, anti-Tg, thyroid volumes were significantly higher than adult participants without goiter. Although it did not reach a significant level some parameters such as BMI, fT4 and TSH were higher in adults with goiter (Table 4).
Table 4: Comparison of some parameters (all students and adults) due to thyroid gland USG.
FT3 levels were measured higher than upper limit in 7.34% of all participants and less than the lower limit in 3% of the same group. fT4 levels were measured higher than upper limit 19.1% of all participants and lower than lower limit in 5.5% of the same group and TSH levels of 22.1% of all participants were found as higher than upper limit but neither of the values were lower than lower limit. Tg, anti-M, anti-Tg levels were found higher than upper limit 64.8%, 0.,5%, 16.6% of all participants respectively.
In the diagnosis of goiter correlation between the palpation method and USG method was 76% in students (k=0.760) and 43% in adults (k=0.426).
Mean urinary iodine level was estimated as 11.1± 6.1 g/dl and in 53.3% of all participants urinary iodine levels were under the normal level (10 g/dl). Median urinary iodine level was estimated as 9.54 mg/dl. Table 5 summarizes the urinary iodine levels due to settlement areas.
Table 5: Urinary iodine levels at the settlement areas
Iodine deficiency and its consequences are impor-tant public health problems in Turkey. Many studies had been done in Turkey and in Central Anatolia to evaluate this problem [1,2,4,5,20-22] but most of them did not establish the relation between urinary iodine level and the goiter prevalence.
Thyroid gland palpitation is noninvasive and easy, it has been used in many epidemiological studies. Although this method is reliable in adults, in children and newborns thyroid palpation method has limitations. In Turkey goiter prevalence had been reported between 30.5-82% in different studies [9,12]. The goiter prevalence was approxi-mately 40.2 % - 43.8% in Kayseri [7,11]. We found a higher prevalence of goiter (54.8% with palpation) than other studies. Female/male ratio was calculated as 2,17 in our study.
USG is recommended method in epidemiological studies for the diagnosis of goiter. Particularly for detecting goiters with small volumes, it is a reliable and accepted as a standard method for measuring thyroid volumes [21,16,23]. Aydın et al. reported that when compared with areas without iodine de-ficiency, all of the children had goiter and accor-ding to Kurtoğlus criteria goiter prevalence was found as 76.7% . In our study according to Gutekunsts thyroid volume findings 55.7% of female student and 50,0% of male student (mean 53.1%), according to Kurtoğlus thyroid volume findings from mild iodine deficient areas  32.9% of female students 29.3 of male students (mean %31.3) had goiter with USG. Recently by measuring sonographic thyroid volumes, Erdoğan et al. has reported goiter prevalence as 33% in school-age children living in our region. In this study, recommended normative values for thyroid volume in European schoolchildren, has been used to define goiter . The mean goiter prevalence in adults, with USG according to Gutekunsts criteria , was found as 40.9% (female 52.9%, male 10.0%). Thyroid volume measurements with USG reveals that female students had 1,1 times more goiter than males and this ratio was found 5,3 in adults; totally female/ male ratio was estimated as 1,37.
Various studies from our country and other count-ries with different results have been reported about the relation between gender and thyroid volumes [11,24-27]. In our study thyroid volumes in fe-males detected with USG were higher than males in students and in adults. In students (male and female) and in male adults right thyroid volumes were larger than left. In female adults left thyroid volumes were larger than right. These findings were correlated with some of the recent literatures [19,27,29].
85-90% of daily iodine intake is excreted via urine so urinary iodine level is one of the most important parameter that reflects iodine level of an area. To determine the iodine level of an area minimally 40-50 urine samples needed. Also to reflect the chronic iodine effect thyroid gland volumes and Tg levels are good criterias . In most European countries inverse ratio between urinary iodine level and goiter prevalence has been reported [29-31]. A study from our country showed the similar data , but another study has demonstrated that there were no differences between urinary iodine levels of pregnants with goiter, pregnants without goiter and normal females without goiter .
Aydın et al. showed that 94.6% of children had lower than normal urine levels in our region . We demonstrated 46.7% of adults had lower than normal urine levels. Furthermore we determined median urinary iodine as 9.54 mg/dl indicating mild iodine deficiency. Erdoğan et al. has reported moderate iodine deficiency (median urinary iodine level, 2.55 g/dl) . In our study, the median urinary iodine concentration was not comparable with the severity of goiter prevalence, and accor-ding to high goiter prevalence the median urinary iodine level was more than expected suggesting that measurement techniques of iodine level may interfere with the results. Moreover urinary iodine levels reflect iodine intake but thyroid volume and Tg level reflect chronic effects of iodine defi-ciency.
It is known that in iodine deficient areas fT3 levels are normal or high, fT4 levels are low-normal or low and TSH levels are generally normal or slightly high. Because of the adaptation mechanisms due to iodine deficiency TSH levels increase and thyroid volumes increase due TSH levels. Ando et al.  and Martino et al.  reported that fT4,TT4 and fT3,TT3 and TSH levels were not significantly different between endemic and control areas but in both studies its demonstrated that Tg levels were higher in endemic areas. Also anti-M and anti-Tg positivity were found 3% and 6.2% respectively. Hintze et al. showed that the persons with goiter had low TSH levels and high Tg levels . Many studies revealed different results between goiter prevalence and thyroid fuctions, TSH levels, thyroid antibody positivity and iodine levels [34-37]. In normal population Koloğlu reported that anti-M positivity as 2%, but in endemic areas this parameter was reported as 20.5% . Keleştimur et al. reported postpartum anti-M positivity as 0.2% . In our study we detected similar values as anti-M positivity as 0.5%, and high anti Tg level as 16,6%.
It is accepted that increase of Tg level is the most important parameter which shows chronic iodine deficiency and generally this is positively corre-lated with TSH levels [40,41]. In our study we detected positive correlation between increased Tg levels, TSH levels and goiter in students but in adults we could not demonstrate these relations.
In conclusion despite the high prevalence of goiter, median urinary iodine level was relatively high, suggesting that measurement techniques of iodine level may affect the results. According to chronic iodine deficiency parameter such as Tg, it is ob-vious that the people living at this endemic area need iodine prophylaxis.
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