Assessment of Iodine and Selenium Nutritional Status in Women of Reproductive Age in Latvia.

Background and Objectives: Adequate dietary intake of iodine and selenium is essential during pregnancy. While iodine is vital for maternal thyroid function and fetal development, selenium contributes to the regulation of thyroid function and thyroid autoimmunity. This study aimed to assess the consumption of iodine- and selenium-containing products by women of reproductive age and the iodine and selenium nutritional status of pregnant women in Latvia. Materials and Methods: Population health survey (2010-2018) data were used to characterize dietary habits in women of reproductive age. Additionally, 129 pregnant women in the first trimester were recruited; they completed a questionnaire and were tested for thyroid function, urinary iodine concentration (UIC), and serum selenium and selenoprotein P levels. Results: The use of some dietary sources of iodine (e.g., milk and dairy products) and selenium (e.g., bread) has decreased in recent years. Less than 10% of respondents reported the use of iodized salt. The use of supplements has become more common (reported by almost 50% of respondents in 2018). Dietary habits were similar in pregnant women, but the use of supplements was even higher (almost 70%). Nevertheless, most supplements used in pregnancy had insufficient contents of iodine and selenium. Thyroid function was euthyreotic in all women, but 13.9% of participants had a thyroid peroxidase antibodies (TPO-ab) level above 60 IU/mL. The median UIC (IQR) was 147.2 (90.0-248.1) µg/gCr, and 52.8% of pregnant women had a UIC below 150 µg/gCr. The mean selenium (SD) level was 101.5 (35.6) µg/L; 30.1% of women had a selenium level below 80 µg/L. The median selenoprotein P level was 6.9 (3.1-9.0) mg/L. Conclusions: Iodine nutrition in Latvian population of pregnant women was near the lower limit of adequate and a third of the population had a selenium deficiency. Supplements were frequently used, but most did not contain the recommended amounts of iodine and selenium.

Plasma levels of Th17-associated cytokines and selenium status in autoimmune thyroid diseases.

INTRODUCTION: The contribution of Th17 cytokines to autoimmune thyroid disease (AITD) is generally accepted. However, the roles of Th17 cells in the initiation and progression of Hashimoto's thyroiditis (HT) and Graves' disease (GD) remain unclear. Selenium deficiency, along with genetic predisposition and environmental factors, may have a role in thyroid autoimmunity. AIM: We aimed to assess (1) the Th17 immune response by measuring plasma levels of Th17- and Treg-associated cytokines and (2) the selenium status in treatment-naïve Latvian patients with newly diagnosed GD or HT. METHODS: Eleven GD patients, 41 HT patients, and 26 healthy subjects were recruited for this study. Plasma levels of IL-17a, IL-22, IL-23, IL-6, and IL-10 were detected by xMAP technology, while selenium was detected fluorometrically. RESULTS AND CONCLUSIONS: No significant differences in IL-17a, IL-22, IL-23, IL-6, or IL-10 levels were found among the HT patients, GD patients, and controls. In the HT patients, IL-17a levels were positively correlated with IL-22, IL-23, IL-6, and IL-10, while IL-22 was correlated with IL-6, IL-23, and IL-10. In the GD patients, IL-17a levels were positively correlated with IL-22, IL-23, and IL-10; IL-22 was positively correlated with IL-23, IL-6, and IL-10; FT3 was positively correlated with IL-17a, IL-23, and IL-10; and FT4 was positively correlated with IL-17a and IL-10 levels. Plasma selenium levels were negatively correlated with antithyroid peroxidase antibody titers in the HT patients. Although no difference in selenium levels was observed between the AITD patients and controls, the selenium status of the Latvian patients with GD or HT was at a suboptimal level.

Upregulated tissue expression of T helper (Th) 17 pathogenic interleukin (IL)-23 and IL-1ß in Hashimoto's thyroiditis but not in Graves' disease.

T helper (Th) 17 cells and interleukin (IL)-17 play a significant role in the pathogenesis of autoimmune thyroid disease (AITD). However, it has recently become clear that Th17 cells are more heterogeneous and exhibit two different phenotypes, whereas IL-23 and IL-1ß are crucial for the generation of pathogenic Th17 lymphocytes. We aimed to investigate the association between IL-17 and Th17-promoting cytokines in AITD by studying the immunoexpression patterns of IL-17, IL-23, and IL-1ß in thyroid tissue. Following thyroidectomy, 29 patients with AITD (21 cases of Hashimoto's thyroiditis (HT) and 8 cases of Graves' disease (GD)) and 18 patients with colloid goiter, as controls, were enrolled in this study, and immunohistochemistry was performed. The expression level of IL-17 in thyrocytes was significantly higher in HT and GD patients than in colloid goiter patients. Immunopositivity for both IL-23 and IL-1ß was significantly increased in HT patients compared to GD and colloid goiter patients. However, no difference was found between IL-23 or IL-1ß expression in patients with GD and colloid goiter. A positive correlation between IL-17 and IL-23 as well as IL-17 and IL-1ß expression was observed in HT patients (r = 0.574, p = 0.007 and r = 0.461, p = 0.036, respectively). In the GD group, IL-17 was positively correlated with IL-1ß (r = 0.817, p = 0.013) but not with IL-23 expression. We found increased IL-23 and IL-1ß expression in the HT group but not in the GD group. Furthermore, both interleukins were correlated with IL-17 immunopositivity in thyroid tissue, suggesting that pathogenic Th17-promoting cytokines may play a role in HT pathogenesis.

Heterogeneity of tissue IL-17 and tight junction proteins expression demonstrated in patients with autoimmune thyroid diseases.

Th17 cells together with their hallmark cytokine interleukin (IL)-17 were identified as crucial contributing factors in the pathogenesis of thyroid autoimmunity. The cytokine-regulated tight junction (Tj) disruption is thought to be essential in the initiation and/or development of several diseases. Still, the role of IL-17 maintaining Tj integrity in autoimmune thyroid diseases (AITDs) has not yet been evaluated. We aimed to investigate integrity of the thyroid follicle by studying immunoexpression of cellular Tj - zonula occludens (ZO)-1 and claudin-1 proteins coupled to IL-17A and CD68 detection in AITD patients compared with controls.Thirty-five adult patients undergoing thyroidectomy and presenting 18 cases of Hashimoto thyroiditis (HT), 7 of Graves' disease (GD) as well as 10 subjects of colloid goiter without autoimmune component served as controls were enrolled in this study. An immunohistochemical analysis including IL-17A, ZO-1, claudin-1, and CD68 detection was performed in each case. The correlation of IL-17A with Tj and CD68 in patients with AITD was also analyzed.Apart from inflammatory cells, we evidenced a stronger expression level of IL17A in the thyroid follicular cells in HT patients when compared with GD or colloid goiter. A significant reduction of ZO-1 immunoreactivity was observed in the thyrocytes in HT patients, whereas no significant differences were found in claudin-1 expression in HT and GD compared with colloid goiter patients. A significantly higher number of thyroid follicles with CD68-positive cells was found in HT patients than that in patients with GD or colloid goiter. In HT patients, the expression of IL-17A in the follicular cells was positively correlated with CD68 immunopositivity, whereas no association with claudin-1 or ZO-1 expression was found. GD patients did not reveal any significant correlation of IL-17A with Tj and CD68.Strong overexpression of IL-17A observed in the thyroid epithelial cells is associated with the presence of intrafollicular CD68-positive cells in HT patients. We evidenced the changes in molecules of thyrocyte junctional complexes highlighting impairment of the thyroid follicle integrity in HT, but no association with IL-17A was found.

Novel Variant of the Androgen Receptor Gene in a Patient With Complete Androgen Insensitivity Syndrome and Polyorchidism.

Introduction: Complete androgen insensitivity (CAIS) in 65-95% cases is caused by pathogenic allelic variants (mutations) in the gene encoding androgen receptor (AR gene) and is characterized by female phenotype development with a male karyotype (46, XY). Patients are usually diagnosed during puberty and undergo gonadectomy due to increased testicular germ cell tumor risk. Only a few outcomes have been reported in older individuals with postponed gonadectomy. Case presentation: A 48-year-old CAIS patient presented with polyorchidism (four testes) without gonadal malignancies. Genetic testing identified a novel allelic variant in the AR gene [c.2141T>G (p.Phe805Cys)] causing the clinical symptoms. Conclusion: We have described a unique patient with CAIS and polyorchidism without malignancies in her late 40's bearing a novel likely pathogenic variant in the AR gene.

Iodine deficiency during pregnancy: a national cross-sectional survey in Latvia.

OBJECTIVE: Low iodine intake during pregnancy may cause thyroid dysfunction, which results in inadequate fetal brain development. In the absence of a universal salt iodization programme, we conducted a nationwide survey of iodine deficiency in pregnant women in Latvia. DESIGN: A countrywide twenty-cluster survey, with at least twenty women per cluster. Participants completed a questionnaire on dietary habits concerning iodine intake (n 739). Thyroid function (thyroid-stimulating hormone, free thyroxine and thyroperoxidase antibodies) was measured (n 550). Urinary iodine was measured using the ammonium persulfate method (n 696). SETTING: The survey was performed in all regions of Latvia during the spring and autumn seasons in 2013. SUBJECTS: Pregnant women (n 829). RESULTS: The median creatinine (Cr)-standardized urinary iodine concentration (UIC) was 80·8 (interquartile range (IQR) 46·1-130·6) µg/g Cr or 69·4 (IQR 53·9-92·6) µg/l during pregnancy, and 81% of pregnant women had UIC levels below the WHO recommended range of 150-250 µg/g Cr. The UIC was lowest during the first trimester of pregnancy, 56·0 (IQR 36·4-100·6) µg/g Cr, reaching higher concentrations of 87·5 (IQR 46·4-141·7) µg/g Cr and 86·9 (IQR 53·8-140·6) µg/g Cr in the second and third trimesters, respectively. Women taking supplements containing ≥150 µg iodine (6·8% of respondents) had non-significantly higher UIC than did women without supplementation (96·2 v. 80·3 µg/g Cr, respectively, P=NS). Thyroperoxidase antibody concentration did not correlate significantly with UIC: Spearman's ρ=-0·012, P=0·78. CONCLUSIONS: The median UIC indicates iodine deficiency in pregnant women in Latvia. Iodine supplementation (150 µg daily) and regular UIC monitoring should be suggested to overcome iodine deficiency and to reach the recommended levels without inducing autoimmune processes.