The Effect of Mediterranean Diet on Thyroid Gland Activity.

The main goal of this research was to determine whether there is a correlation between adherence to the Mediterranean diet (assessed by the Mediterranean Diet Serving Score (MDSS)) and parameters indicating thyroid gland activity, such as concentration of thyroid-stimulating hormone (TSH), thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4)), thyroglobulin (Tg), antibodies to thyroid proteins (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)), and calcitonin (CT) in plasma and serum samples. An additional objective was to investigate whether there are differences in the values of the MDSS among clinical groups (euthyroid individuals, euthyroid individuals with positive TgAb and/or TPOAb, and hypothyroid and hyperthyroid participants). This cross-sectional study included 4620 participants over 18 years of age from the islands of Korcula and Vis, and the mainland city of Split. The MDSS was assessed from a food frequency questionnaire (FFQ). MDSS values were significantly higher in females compared to males and showed a positive association with the age of the participants. There was no significant difference in the MDSS values among the examined clinical groups. In the group of subjects with euthyroidism, a significant positive association was found between fT3 and the MDSS, while in the group of subjects with subclinical hypothyroidism, a significant positive association was observed between the MDSS and both fT3 and fT4. CT levels were also positively associated with the MDSS. Considering the significant positive association of the MDSS and both fT3 and fT4 levels in patients with subclinical hypothyroidism, the results of this study could be used to create guidelines for selecting an appropriate, potentially protective diet for these patients.

Role of ST6GAL1 in Thyroid Cancers: Insights from Tissue Analysis and Genomic Datasets.

Thyroid cancer is the predominant endocrine-related malignancy. ST6 ß-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers; however, the expression and function of ST6GAL1 in thyroid cancer has not been investigated so far. Previously, we conducted two genome-wide association studies and have identified the association of the ST6GAL1 gene with plasma thyroglobulin (Tg) levels. Since Tg levels are altered in thyroid pathologies, in the current study, we wanted to evaluate the expression of ST6GAL1 in thyroid cancer tissues. We performed an immunohistochemical analysis using human thyroid tissue from 89 patients and analyzed ST6GAL1 protein expression in papillary thyroid cancer (including follicular variant and microcarcinoma) and follicular thyroid cancer in comparison to normal thyroid tissue. Additionally, ST6GAL1 mRNA levels from The Cancer Genome Atlas (TCGA, n = 572) and the Genotype-Tissue Expression (GTEx) project (n = 279) were examined. The immunohistochemical analysis revealed higher ST6GAL1 protein expression in all thyroid tumors compared to normal thyroid tissue. TCGA data revealed increased ST6GAL1 mRNA levels in both primary and metastatic tumors versus controls. Notably, the follicular variant of papillary thyroid cancer exhibited significantly higher ST6GAL1 mRNA levels than classic papillary thyroid cancer. High ST6GAL1 mRNA levels significantly correlated with lymph node metastasis status, clinical stage, and reduced survival rate. ST6GAL1 emerges as a potential cancer-associated glycosyltransferase in thyroid malignancies, offering valuable insights into its diagnostic and prognostic significance.

Genome-Wide Association Analysis and Genomic Prediction of Thyroglobulin Plasma Levels.

Thyroglobulin (Tg) is an iodoglycoprotein produced by thyroid follicular cells which acts as an essential substrate for thyroid hormone synthesis. To date, only one genome-wide association study (GWAS) of plasma Tg levels has been performed by our research group. Utilizing recent advancements in computation and modeling, we apply a Bayesian approach to the probabilistic inference of the genetic architecture of Tg. We fitted a Bayesian sparse linear mixed model (BSLMM) and a frequentist linear mixed model (LMM) of 7,289,083 variants in 1096 healthy European-ancestry participants of the Croatian Biobank. Meta-analysis with two independent cohorts (total n = 2109) identified 83 genome-wide significant single nucleotide polymorphisms (SNPs) within the ST6GAL1 gene (p<5×10-8). BSLMM revealed additional association signals on chromosomes 1, 8, 10, and 14. For ST6GAL1 and the newly uncovered genes, we provide physiological and pathophysiological explanations of how their expression could be associated with variations in plasma Tg levels. We found that the SNP-heritability of Tg is 17% and that 52% of this variation is due to a small number of 16 variants that have a major effect on Tg levels. Our results suggest that the genetic architecture of plasma Tg is not polygenic, but influenced by a few genes with major effects.

Types of Parenchymal Changes Diagnosed on DMSA Scans of Kidneys Affected by Different Grades of Vesicoureteral Reflux.

BACKGROUND Renal parenchymal damage and scarring usually is associated with urinary tract infection (UTI), whereas the impact of vesicoureteral reflux (VUR) on the kidneys is unclear. We aimed to compare kidneys with all grades of VUR (grades Io-V) and those without VUR by using direct radionuclide cystography, voiding cystourethrography, and findings from 99mTc-DMSA scintigraphy (DMSA scan). MATERIAL AND METHODS The present analysis included 253 renal ureteral units (RUU) from 129 children with VUR and recurrent UTI and children with a single febrile UTI associated with abnormal ultrasonographic findings. The 6 grades of VUR (Io, I, II, III, IV, and V) and 35 RUUs without VUR were divided into 4 groups: 1. Non-dilated VUR (grades Io-II); 2. Mildly dilated VUR (grade III); 3. Dilated VUR (grades IV-V); and 4. The control group. RESULTS DMSA scanning showed significant differences between the groups with non-dilated VUR, grade III VUR, grades IV-V VUR, and the control group in kidney width (χ²=30.5; P<0.001); position and shape (χ²=30.6; P<0.001); intensity of activity (χ²=38.1; P<0.001); distribution of activity (χ²=34.5; P<0.001); and existence of scars (χ²=16; P<0.001). The probability of abnormalities on DMSA scans increased with the VUR grade. However, inside the groups of dilated and non-dilated VUR we found no significant statistical differences between those characteristics. CONCLUSIONS Our results indicate that kidneys without VUR or with non-dilated lateral VUR and dilated VUR on the contralateral side represent 2 different categories of parenchymal changes.

Genome-wide meta-analysis identifies novel gender specific loci associated with thyroid antibodies level in Croatians.

Autoimmune thyroid diseases (AITD) are multifactorial endocrine diseases most frequently accompanied by Tg and TPO autoantibodies. Both antibodies have a higher prevalence in females and act under a strong genetic influence. To identify novel variants underlying thyroid antibody levels, we performed GWAS meta-analysis on the plasma levels of TgAb and TPOAb in three Croatian cohorts, as well as gender specific GWAS and a bivariate analysis. No significant association was detected with the level of TgAb and TPOAb in the meta-analysis of GWAS or bivariate results for all individuals. The bivariate analysis in females only revealed a genome-wide significant association for the locus near GRIN3A (rs4457391, P = 7.76 × 10-9). The same locus had borderline association with TPOAb levels in females (rs1935377, P = 8.58 × 10-8). In conclusion, we identified a novel gender specific locus associated with TgAb and TPOAb levels. Our findings provide a novel insight into genetic and gender differences associated with thyroid antibodies.

Thyroid hormone levels are associated with metabolic components: a cross-sectional study.

AIM: To analyze the association of thyroid function and hormone levels with metabolic syndrome (MetS) and its components. METHODS: This cross-sectional population-based study involved 2183 Croatian individuals with no history of thyroid disease, hypertension, diabetes, and hyperlipidemia. MetS was diagnosed according to the National Cholesterol Education Program's Adult Treatment Panel III criteria. RESULTS: We found no association between thyroid function groups and the prevalence of MetS and its components. Clinically hypothyroid participants showed significantly higher triceps skinfold measurements than subclinically hypothyroid and euthyroid participants. Furthermore, clinically hypothyroid participants had higher abdominal skinfold thickness than subclinically hypothyroid participants. Otherwise, suprailiac and abdominal skinfold measurements were higher in the subclinically and clinically hyperthyroid group of participants compared with euthyroid and subclinically hypothyroid participants. A strong positive association of thyroid-stimulating hormone (TSH) and strong negative association of free triiodothyronine (fT3) and free thyroxine (fT4) levels with HOMA-IR and cholesterol levels were found. Furthermore, the fT4 level also showed a strong negative association with HDL and triceps skinfold thickness. CONCLUSIONS: This study supports the standing that TSH, fT3, and fT4 levels are important variables to determine the association of thyroid function with MetS.

Effect of Methimazole Therapy on Thyroid Pathohistology That May Mimic Thyroid Malignancy.

Diffuse toxic goiter, as the most common cause of hyperthyroidism, is usually initially treated with thyrostatic drugs such as methimazole, followed by radioiodine therapy or surgery which may be indicated as definitive treatment. Radioactive iodine therapy has a known association with various histopathologic features including cytologic atypia, but herein we present a rare example of morphological thyrocyte changes induced by long-term pharmacological treatment with methimazole that mimicked thyroid malignancy in a pathohistological sample.

Treatment Approach to Follicular Thyroid Carcinoma Tumor Thrombus in the Internal Jugular Vein and Brachiocephalic Vein.

Thyroid gland carcinoma causing tumor thrombus in the great veins of the neck and mediastinum is a rare condition with poor prognosis. Invasion of the internal jugular vein by thyroid gland carcinoma has been occasionally reported, but tumor thrombi extending to the great veins of the mediastinum are reported extremely rarely. We present a treatment approach in a case of follicular thyroid carcinoma intravascular tumor thrombus in the left internal jugular and left brachiocephalic vein.

Genome-wide association meta-analysis for total thyroid hormone levels in Croatian population.

Thyroid hormones (THs) are key regulators of cellular growth, development, and metabolism. The thyroid gland secretes two THs, thyroxine (T4) and triiodothyronine (T3), into the plasma where they are almost all bound reversibly to plasma proteins. Free forms of THs are metabolically active, however, they represent a very small fraction of total TH levels. No genome-wide studies have been performed to date on total TH levels, comprising of protein-bound and free forms of THs. To detect genetic variants associated with total TH levels, we carried out the first GWAS meta-analysis of total T4 levels in 1121 individuals from two Croatian cohorts (Split and Korcula). We also performed GWAS analyses of total T3 levels in 577 individuals and T3/T4 ratio in 571 individuals from the Split cohort. The top association in GWAS meta-analysis of total T4 was detected for an intronic variant within SLC22A9 gene (rs12282281, P = 4.00 × 10-7). Within the same region, a genome-wide significant variant (rs11822642, P = 2.50 × 10-8) for the T3/T4 ratio was identified. SLC22A9 encodes for an organic anion transporter protein expressed predominantly in the liver and belongs to the superfamily of solute carriers (SLC), a large group of transport membrane proteins. The transport of THs across the plasma membrane in peripheral tissues is facilitated by the membrane proteins, and all TH transport proteins known to date belong to the same SLC superfamily as SLC22A9. These results suggest a potential role for SLC22A9 as a novel transporter protein of THs.

Evaluation of Correlations Between Food-Specific Antibodies and Clinical Aspects of Hashimoto's Thyroiditis.

OBJECTIVE: We have comprehensively evaluated an immunologic response to food antigens, mediated by immunoglobulin G (IgG) antibodies, on clinical aspects of Hashimoto's thyroiditis (HT). METHODS: IgG antibodies to 125 food antigens were measured in serum samples of 74 HT patients and 245 controls using microarray-based enzyme-linked immunosorbent assay (ELISA) test. We analyzed differences in IgG levels between two groups and evaluated correlations between food-specific IgG levels and HT-related clinical phenotypes (thyroid hormones/antibodies, symptoms of hypothyroidism, measures of body size and blood pressure) and food consumption in HT patients. RESULTS: We observed increased IgG levels to 12 different food antigens in either HT cases or controls, of which plum-specific IgG antibodies were significantly higher (p = 1.70 × 10-8), and almond-specific IgG antibodies were significantly lower (p = 8.11 × 10-5) in HT patients in comparison to controls, suggesting their possible roles in HT etiology or symptomatology. There was no significant correlation between any of 12 increased food-specific IgG antibodies, along with gluten-specific IgG, with clinically important phenotypes, such as thyroid hormones/antibodies or symptoms. Among other tested correlations, the most interesting is the negative correlation between coffee and tea combined IgG levels and number of symptoms, suggesting possible beneficial effect of tea and coffee on disease symptoms. We also found that food consumption is not correlated with IgG levels. CONCLUSIONS: Distribution of food-specific IgG antibodies is comparable between HT patients and controls, with the exception of plum and almond. There is no evidence that increased food-specific IgG antibodies are associated with clinical aspects of HT. Clarification of biology behind formation of these antibodies is needed.

Thyroglobulin Antibodies are Associated with Symptom Burden in Patients with Hashimoto's Thyroiditis: A Cross-Sectional Study.

BACKGROUND: Hashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid disorders characterized by lower production of thyroid hormones and positivity to autoantibodies to thyroglobulin (TgAb) and/or thyroid peroxidase (TPOAb). We performed a comprehensive phenotypic characterization of patients with HT, with specific focus on thyroid autoimmunity, to get better understanding of disease manifestation. METHODS: We collected information on thyroid-specific phenotypes (TSH, T3, T4, fT4, TgAb, TPOAb, thyroid volume) and other clinical phenotypes (age, body surface area, number of hypothyroidism symptoms, blood pressure) from 290 patients with HT without levothyroxine (LT4) therapy with the aim to test for correlations between thyroid-specific and clinical phenotypes. RESULTS: Our key and novel finding is the existence of significant positive correlation between TgAb levels and the number of symptoms (r = 0.25, p = 0.0001) in HT patients without LT4 therapy that remained significant after adjustment for TPOAb, T3, TSH levels and thyroid volume (ß = 0.66, SE = 0.3, p = 0.0299). Increased TgAb levels are significantly associated with fragile hair (p = 0.0043), face edema (p = 0.0061), edema of the eyes (p = 0.0293) and harsh voice (p = 0.0349). CONCLUSIONS: Elevated TgAb levels are associated with symptom burden in HT patients, suggesting a role of thyroid autoimmunity in clinical manifestations of HT. Based on these results, we recommend screening for TgAb antibodies in HT patients with symptom burden. We also suggest that further work on understandings of symptoms appearance due to their autoimmune or hypothyroid causation is needed.

The effect of multiple nutrients on plasma parathyroid hormone level in healthy individuals.

Although the effect of isolated nutrients on plasma parathyroid hormone (PTH) is somewhat familiar, the effect of multiple nutrients on plasma PTH level has not yet been studied. The aim of this study was to identify groups of food items that are associated with the plasma PTH level in healthy individuals. This cross-sectional study enrolled 1180 healthy individuals from Croatia with plasma PTH levels inside the referent values. A food frequency questionnaire containing 58 food items was completed to evaluate the dietary intake. We used principal component analysis to reduce food items into dietary groups, followed by linear regression analysis to test the association between dietary groups and the level of PTH. The results indicate that different sorts of vegetables (p = .006), sausages, salami, mushrooms, eggs (p = .033), as well as white bread (p = .009) are associated with the increase, while bran bread (p = .009) is associated with the decreased plasma PTH level.

Genome-wide meta-analysis identifies novel loci associated with parathyroid hormone level.

BACKGROUND: Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis. Although serum PTH level is mostly accounted by genetic factors, genetic background underlying PTH level is insufficiently known. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels. METHODS: We performed GWAS meta-analysis within two genetically isolated Croatian populations followed by replication analysis in a Croatian mainland population and we also combined results across all three analyzed populations. The analyses included 2596 individuals. A total of 7,411,206 variants, imputed using the 1000 Genomes reference panel, were analysed for the association. In addition, a sex-specific GWAS meta-analyses were performed. RESULTS: Polymorphisms with the lowest P-values were located on chromosome 4 approximately 84 kb of the 5' of RASGEF1B gene. The most significant SNP was rs11099476 (P = 1.15 × 10-8). Sex-specific analysis identified genome-wide significant association of the variant rs77178854, located within DPP10 gene in females only (P = 2.21 × 10- 9). There were no genome-wide significant findings in the meta-analysis of males. CONCLUSIONS: We identified two biologically plausible novel loci associated with PTH levels, providing us with further insights into the genetics of this complex trait.

RET EXPRESSION AND ITS CORRELATION WITH CLINICOPATHOLOGIC DATA IN PAPILLARY THYROID CARCINOMA.

- The purpose of this study was to analyze the possible prognostic value of RET mutation in papillary thyroid carcinoma and its incidence in the past few decades in our population, due to the increasing incidence of papillary thyroid carcinoma. The present study included 180 patients operated for papillary thyroid carcinoma. The clinical and histopathologic characteristics were analyzed. Paraffin sections of the selected histologic slides were cut again and immunohistochemically stained by the Clone 3F8 P (HIER) from Novocastra (Vision Bio Systems Europe, Newcastle upon Tyne, UK) monoclonal antibody to RET oncoprotein. Univariate analysis indicated sex (p=0.01), histologic subtype (p=0.075) and capsular invasion (p=0.010) to be statistically significant predictors of lymph node metastases, whereas age (p=0.796), tumor size (p=0.556) and intraglandular dissemination (p=0.131) showed no such correlation. The presence of RET mutation (p=0.704) was not a statistically significant predictor of the tumor metastasizing potential. RET mutation (p=0.500) showed no statistically significant correlation with papillary thyroid carcinoma classifed into prognostic groups according to clinicopathologic features either. RET mutation was detected in 30% of 180 papillary thyroid carcinomas. This is the first large study demonstrating that RET mutation incidence in papillary thyroid carcinoma in Croatian population is consistent with the classic distribution of sporadic cases, despite the increased prevalence of papillary thyroid carcinoma in the past few decades.

Association of Established Thyroid-stimulating Hormone and Free Thyroxine Genetic Variants with Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT), the most frequent autoimmune thyroid disease (AITD), is characterized by chronic inflammation of the thyroid gland that usually results in hypothyroidism. Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels are used as clinical determinants of thyroid function. The main aim of this study was to explore the association of established TSH and FT4 genetic variants with HT. We performed a case-control analysis using 23 genetic markers in 200 HT patients and 304 controls. Additionally, we tested the association of selected variants with several thyroid-related quantitative traits in HT cases only. Two genetic variants showed nominal association with HT: rs11935941 near NR3C2 gene (p = 0.0034, OR = 0.57, 95% CI = 0.39-0.83) and rs1537424 near MBIP gene (p = 0.0169, OR = 0.72, 95% CI = 0.55-0.94). Additionally, three SNPs showed nominal association with thyroglobulin antibody (TgAb) levels: rs4804416 in INSR gene (p = 0.0073, ß = -0.51), rs6435953 near IGFBP5 gene (p = 0.0081, ß = 0.75), and rs1537424 near MBIP gene (p = 0.0117, ß = 0.49). GLIS3 genetic variant rs10974423 showed nominal association with thyroid peroxidase antibody (TPOAb) levels (p = 0.0465, ß = -0.56) and NRG1 genetic variant rs7825175 was nominally associated with thyroid gland volume (p = 0.0272, ß = -0.18). All detected loci were previously related to thyroid function or pathology. Findings from our study suggest biological relevance of NR3C2 and MBIP with HT, although these loci require additional confirmation in a larger replication study.

Cyclin D1, Ret and P27 Expression in Papillary Thyroid Microcarcinoma

Th e aim of the study was to determine the influence of RET, p27 and cyclin D1 on regional lymph node metastases in papillary microcarcinoma. The analysis included 70 patients with papillary thyroid microcarcinoma that underwent surgery at Split University Hospital Center between 1999 and 2001. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue by the RET, p27 and cyclin D1 antibodies. Quantification was based on the intensity and distribution of nuclear staining, dividing tumors into those that showed expression (expressors) and those that showed no expression (non-expressors). Univariate analysis using χ²-test and Fisher exact test was performed with the level of statistical significance set at p<0.05. There was no statistically significant difference in the incidence of metastases according to the expression or non-expression of RET mutation (χ²-test: p=0.459; Fisher exact test: p=0.672). Among 25 cases with cyclin D1 expression, 6 had metastases, whereas only 2 of 45 cases with no cyclin D expression had metastases (χ²-test: p=0.014; Fisher exact test: p=0.021), indicating that the expression of cyclin D1 is not crucial for the development of metastases in lymph nodes. In contrast, analysis of p27 expression showed it to be significantly associated with lymph node metastasis because 3 of 45 patients with p27 expression had metastases, indicating a statistically significant correlation between p27 expression and lymph node metastases (χ²-test: p=0.093; Fisher exact test: p=0.124). This study confirmed the importance of the evaluation of RET, p27 and cyclin D1 expression and demonstrated the validity of their application in the assessment of microcarcinoma behavior.

Associations between vitamin D levels and dietary patterns in patients with Hashimoto's thyroiditis.

Introduction: Vitamin D insufficiency is a global health problem affecting healthy and diseased individuals, including patients with Hashimoto's thyroiditis (HT). Identifying dietary factors that may affect vitamin D levels and providing dietary guidelines accordingly can alleviate this problem. We therefore aimed to identify still unknown associations of dietary patterns, assessed through the Food Frequency Questionnaire (FFQ) with vitamin D blood levels. Materials and methods: FFQ was collected from 459 patients from Croatian Biobank of Patients with Hashimoto's thyroiditis (CROHT), while total 25(OH)D was measured from their stored serum samples. We performed linear regression analysis between vitamin D levels and weekly intake of 24 food groups in 459 patients with HT (ALL), and in two disease-severity groups (MILD and OVERT). Results: The main results of our study are observations of: (1) an inverse association between vitamin D levels and coffee consumption (ALL: ß = -0.433, p = 0.005; OVERT: ß = -0.62, p = 0.008); (2) an inverse association between vitamin D levels and sweets consumption (ALL: ß = -0.195, p = 0.034; OVERT: ß = -0.431, p = 0.006); (3) positive association between vitamin D levels and vegetable consumption (ALL: ß = 0.182, p = 0.019; OVERT, ß = 0.311, p = 0.009). Importantly, effect sizes of all three associations were more prominent in HT patients with prolonged and more severe disease (OVERT). Conclusion: Further research into the functional and causal relationships of the observed associations is important to provide guidance regarding coffee/sugar intake on vitamin D status. A well-balanced diet can help prevent vitamin D deficiency and improve the quality of life of patients with HT, especially those in later stages of disease characterized by greater metabolic imbalance.

An unusual cause of the ileus: non-specific stenosing ulceration of the small intestine.

Non-specific ulcerations of the small intestine are very rare. The cause and pathogenesis of these lesions remain obscure. The diagnosis of primary ileal ulcer is commonly overlooked and infrequently is established intraoperatively. Here we described a case of a 73-year-old woman who was presented to the emergency surgical department with the five days history of vomiting, distension, constipation, and abdominal pain. On physical examination abdomen was mildly distended and diffusely painful on palpation. Bowel sounds were present and active. Plain abdominal x-ray film showed ileus of the small intestine. Multislice computed tomography showed stenosing process of the ileum. Patient underwent exploratory laparotomy. Approximately 60 cm from the ileocecal valve ileum was inflamed and hypertrophic with a point of obstruction. Grossly, it appeared as a small intestine carcinoma. Involved segment of ileum including the point of obstruction was resected. Pathological examination showed ulceration of the ileum. After the surgery the patient made rapid recovery and was discharged from the hospital on the tenth postoperative day.

Current status of iodine intake in Croatia--the results of 2009 survey.

In 1996, due to persistence of mild to moderate iodine deficiency, new law on obligatory salt iodination with 25 mg of potassium iodide (KI) per kg of salt was implemented in Croatia. Along with a new law, a new program for monitoring of iodine prophylaxis was implemented. Investigations of goiter and iodine intake performed in 2002, demonstrated sufficient iodine intake in Croatia with overall median of urinary iodine concentration (UIC) for schoolchildren in Croatia of 140 microg/L. In 2002, thyroid volumes (TV) measured by ultrasound in schoolchildren from all four geographic regions of Croatia were for the first time within the normal range according to ICCIDD reference values. Nowadays, Croatia is internationally recognized as iodine sufficient country. The aim of the present study was to assess current status of iodine intake in Croatia. The investigation was carried out in 2009. A total of 386 schoolchildren aged 7-10 years from all four major geographic regions of Croatia, 103 euthyroid pregnant women and 36 women of child-bearing age from Zagreb, the capital, were included in the survey. Urinary iodine concentration (UIC) was measured in all participants. Thyroid volumes were measured by ultrasound in schoolchildren from the capital of Zagreb (N = 101) and the village of Rude (N = 56). In the time period 2002-2009, the content of KI was analyzed in 384 salt samples from Croatian salt plants and samples of imported salt. An overall median UIC for schoolchildren in Croatia was 248 microg/L. Median UIC in pregnant women was 159 microg/L, with 50% of samples below and under 150 microg/L. Median UIC in women of child-bearing age was 136 microg/L. Thyroid volumes in schoolchildren were within the normal range according to the new reference values. Mean value of KI/kg of salt in samples from Croatian salt plants was 25.5 mg/kg and 24.9 mg/kg in samples of imported salt. A total of 72/384 (18.8%) of salt samples didn't corresponded to the Croatian law on obligatory salt iodination. Presented data indicate sufficient iodine intake of the Croatian population. Current medians of UIC in schoolchildren in Croatia are significantly higher than medians measured in 2002. This indicates that other potential sources of iodine are present in Croatian diet that may contribute to overall iodine intake. Due to rising medians of UIC in schoolchildren in Croatia, it is important to conduct nutrition studies to identify potential sources of "silent prophylaxis" in order to avoid iodine excess.

Epidemiology of Hypothyroidism, Hyperthyroidism and Positive Thyroid Antibodies in the Croatian Population.

Thyroid dysfunction appears to be the leading endocrine disorder. We conducted a cross-sectional study on 4402 individuals from three Croatian cohorts. The aim of this study was to analyse the prevalence of diagnosed and undiagnosed hypothyroidism, hyperthyroidism (subclinical and clinical) and positive thyroid antibodies in the Croatian population. The results of the study indicated that 17.6% of participants were euthyroid with positive antibodies. The prevalence of clinical and subclinical hypothyroidism was 3% and 7.4%, respectively, while the prevalence of clinical and subclinical hyperthyroidism was 0.2% and 1.1%, respectively. Among them, 92.6% subclinical hypothyroid, 93.9% clinical hypothyroid, 83% subclinical hyperthyroid and 71.4% clinical hyperthyroid participants were undiagnosed. Finally, the prevalence of undiagnosed subclinical and clinical hypothyroidism in our population was 6.9% and 2.8%, respectively, while the prevalence of undiagnosed subclinical and clinical hyperthyroidism was 0.9% and 0.1%, respectively. Women showed a higher prevalence of thyroid disorders; 1.57 times higher odds of euthyroidism with positive antibodies, 2.1 times higher odds of subclinical hyperthyroidism, 2.37 times higher odds of clinical hypothyroidism and 1.58 times higher odds of subclinical hypothyroidism than men. These results indicate an extremely high proportion of undiagnosed cases, and therefore require investments in a prevention programme.