The effect of 17 years of increased salt iodization on the prevalence and nature of goiter in Croatian schoolchildren

Introduction

Iodine is an essential element in thyroid hormonogenesis, and its adequate intake is critical for the prevention of iodine deficiency disorders. Epidemiological survey conducted after the World War II, demonstrated that in about two out of 17 million persons in the former state of Yugoslavia (which also included Croatia) had endemic goiter. In endemic regions, that were populated by six million inhabitants, there were 20,000 cases of endemic cretinism and 2000–4000 deaf mutes [1]. As a result of this investigation, former Yugoslavia introduced the first regulation on compulsory salt iodization with 10 mg potassium iodide (KI)/kg of salt in 1953. These measures resulted in a 3-fold decrease of goiter prevalence among schoolchildren 10 years after the introduction of iodine prophylaxis. Moreover, endemic cretinism was entirely eradicated [2]. In a survey conducted in 1991, nearly 40 years after the introduction of salt iodization in the district of Sibenik located on the Croatian coast, the goiter prevalence was found to be 2.8% among schoolchildren [3]. Another study carried out in 1995, among schoolchildren from different parts of Croatia discovered a goiter rate of 8–35% (with the highest rates in the continental parts of the country) and median urinary iodine concentration (UIC) of 68 μg/L [4], [5]. This finding led to a revision of salt iodization regulation with an increase from 10 to 25 mg KI/kg of salt in 1996.

The goal of this study was to establish an insight into the current situation of goiter prevalence and etiology 17 years after the last increase of salt iodization in Croatia. The study included 3594 schoolchildren from the district of Nasice located in the continental part of Croatia.

Materials and methods

This study was conducted in 2013 and included 3594 schoolchildren, who ranged in age from 10 to 18 years. There were 1777 girls (49.5%) and 1817 boys (50.5%). The investigation of goiter prevalence was the main goal of this study and the medical examination of schoolchildren was not a part of regular health monitoring. One experienced investigator (M.V., a pediatric endocrinologist) performed an inspection and neck palpation in the outpatient clinics of local schools in the Nasice district to determine the size of the thyroid gland in all 3594 participants. The size of the thyroid gland was determined according to the World Health Organization criteria [6]. The children diagnosed with goiter were advised to visit the University Hospital Zagreb for further examinations by one senior pediatric endocrinologist (JI), including re-examination by palpation of all these children. The following further studies were performed: thyroid ultrasound examination with Aloca ultrasound scanner equipped with 7.5 MHz linear transducer probe and plasma measurement of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-peroxidase antibodies (TPO ab) and anti-thyroglobulin antibodies (TGA ab) performed using standard biochemical methods.

Criteria for the diagnosis of autoimmune thyroiditis (AT) were increased titer of TPO ab (>100 IU/mL) and/or TGA ab (>100 IU/mL) and heterogeneous and hypoechoic parenchymal echo pattern.

Furthermore, a thyroid scan using Tc-99m was performed in two participants and a percutaneous fine needle aspiration of the thyroid in one participant.

The study protocol was approved by the Ethics Committee of the General Hospital Nasice, and informed consent was obtained from parents or guardians of children with goiter.

Statistical analyses included calculation of percentages and a chi-square (χ²) test for frequencies between the groups. All analyses were performed using a standard statistical package.

Results

Discussion

A high prevalence of goiter among schoolchildren was frequently reported in the 1980s by pediatricians and specialists in school medicine, particularly in the continental parts of Croatia. The first study to determine the actual prevalence and nature of goiter during mandatory iodine supplementation with 10 mg KI/kg of salt was carried out in 1991 on 5462 schoolchildren aged 11–18 years in the coastal district of Sibenik. In this study, goiter prevalence established by palpation was 2.8% (152/5462). SG was found in 126/152 (82.8%) and AT in 19/152 (12.5%) of goitrous patients [3]. A second study, initiated by the Ministry of Health in Croatia, was conducted in 1995 in different parts of Croatia. This study found the prevalence of goiter, assessed by palpation in 2856 schoolchildren aged 7–15 years, to be 8–35%. The lowest prevalence was observed in the coastal regions of the country, while in the northern continental region of Slavonia, where the city of Nasice is located, the prevalence estimated in 245 schoolchildren was 27%. It should be emphasized that in this study only the prevalence but not the etiology of goiter and thyroid function was investigated [4].

Because iodine deficiency was suspected as the primary cause of high prevalence of goiter, the iodine content in salt was measured in 1995 and an insufficient median content of 5.6 mg KI/kg of salt was established. It was also observed that the population with the lowest income used a low-cost, not regularly iodized salt for animal use. Additionally, the food industry also often obtained the salt from the same source. All of these factors contributed to insufficient iodine resulting in an increased goiter prevalence [7]. This was further confirmed by the measurement of UIC: the median UIC in schoolchildren from different parts of Croatia was 68 μg/L (range, 43–90 μg/L) [4], [5]. Evidence of iodine deficiency and its consequences on goiter morbidity in the population changed the mandatory regulation of salt iodization from 10 to 25 mg KI/kg of salt for both human and animal consumption in 1996.

The production and iodization of salt in Croatia is under state supervision and control. Monitoring of salt produced in Croatian plants in 1999, confirmed that all samples contained equal or higher than 20 mg KI/kg salt as a result of the new regulation. Samples of imported salt that supplied a smaller part of the market, revealed that in 15.7% of the salt samples the KI content was below the recommended levels [8].

Following the change in the salt iodization policy in 1996, goiter prevalence (but not the nature of it) was determined in two small studies. The first study was conducted in 2001, comprising 378 schoolchildren in an endemic goiter region of Grobnik (in the north-west continental part of Croatia) and demonstrated a goiter prevalence of 6% [9]. This was significantly lower in comparison to the 61% found in 1961 in the same region [10]. In these two studies, goiter prevalence was determined by palpation and there is no data on the UIC. In the second study conducted in 2009, in the Croatian capital of Zagreb which is located in the central continental part of the country, the thyroid volume was measured by ultrasound in 101 schoolchildren 6–10 years of age. The findings were within the normal range in all participants and the median UIC was 288 μg/L [11]. At the same time, the median UIC measured in 386 schoolchildren, aged 6–10 years from different parts of Croatia, was 241 μg/L (range, 195–288 μg/L), and the authors concluded that iodine sufficiency had been reached in the population (goiter prevalence was not investigated) [11].

Our investigation conducted in 3594 schoolchildren from the Nasice district confirmed that the increase in salt iodization in Croatia resulted in a low goiter prevalence of 0.98%. This is in accordance with the results of other studies which demonstrated that the change from mildly deficient to sufficient iodine supply was associated with a marked decrease in the prevalence of goiter estimated by palpation or ultrasound examination [12], [13], [14], [15].

Nevertheless, some beneficial effects of other factors, besides increased salt iodization, which contributed to observed lower goiter rate, cannot be ruled out in this study. Thus, improved economic conditions resulted in certain changes in the nutrition of the population (consumption of more milk, dairy products and fish), as well as the elimination of non-iodized salt. Additionally, the use of “alternative-source” rock salts (e.g. red, pink, black, Himalayan) lost popularity after repeated warnings of health authorities through various media that these salts are iodine-deficient and thus a health hazard.

Higher prevalence of goiter in girls than in boys in our study corresponds to the results from other investigations carried out in the regions with a normal iodine intake, but we found no change in prevalence with age [3], [15], [16].

We demonstrated that the increase in salt supplementation also resulted in significant changes in the etiology of palpable goiter in our study in comparison to the Sibenik survey [3], conducted before the increase in salt iodization (the modes of diagnostic proceedings in these two studies were the same). The relative share of SG in patients with thyromegaly in our study is lower, and AT higher in comparison with the Sibenik study [3] (p<0.0001 and p=0.0009, respectively) (Table 4), resulting in a decrease in the SG/AT ratio from 6.8/1 in the Sibenik study [3] to 1.4/1 in this study.

In contrast to the Sibenik study, in which four patients with Graves’ disease were found in a population of 5462 schoolchildren [3], in this study, there were no cases of Graves’ disease among 3594 schoolchildren. Some authors reported increased prevalence of Graves’ disease as a result of an increase in iodine intake [17], but as Graves’ disease is uncommon in children, our investigated cohort of schoolchildren is small for a valid conclusion.

Although thyroid nodules are uncommon in childhood and adolescence, they require careful consideration because they can be malignant [18]. Only a few studies have estimated their prevalence in the general population of children, but the prevalence depends considerably on the method of detection and on the population evaluated (female gender, increasing age, iodine deficiency and previous radiation exposure, all increase the risk of thyroid nodules). Rallison et al. conducted a survey on 5179 schoolchildren in Utah and Nevada (states exposed to radioactive fallout) as well as in Arizona (using palpation as a screening method), and found 26 benign nodules and two malignant neoplasms [19]. Using the same method, in the general population of Michigan, Matovinovic et al., found exclusively benign nodules in 41/8141 adult participants (none were under 19 years of age) [20]. Furthermore, in the Sibenik study, nodular lesions were found in three of 5462 investigated children (two benign adenomas and one cyst) [3]. In our study, nodular lesions were detected in four of 3594 children (two thyroid cysts, one toxic adenoma and one papillary carcinoma). Only one nodular lesion, later diagnosed as toxic adenoma was detected by palpation. However, cysts and papillary carcinoma were detected by ultrasound examination of the thyroid performed after goiter was discovered by palpation. Before the time of our investigation, thyroid diseases were diagnosed in only two children with SG, two with AT and none with a nodular lesion.

As thyroid size and nodular lesions in our and previous studies conducted in Croatia were assessed by palpation and ultrasound and thyroid antibodies were measured only in children with established thyromegaly, we are aware that true prevalence of goiter, AT and nodules in this study on schoolchildren is probably underestimated.

In conclusion, in comparison with surveys conducted before increased salt iodization, the prevalence of goiter is decreased due to a smaller relative share of SG as a cause of thyromegaly in schoolchildren. As 0.89% of the children in this study had thyroid abnormalities and some of them required treatment, it is of the utmost importance to conduct a careful thyroid examination even in apparently healthy children in regions with adequate iodine supply.