Hashimoto’s thyroiditis (HT) is the most prevalent autoimmune thyroid disorder. Intrathyroidal lymphocytic infiltration is followed by a gradual destruction of the thyroid gland which may lead to subclinical or overt hypothyroidism. Biochemical markers of the disease are thyroid peroxidase and/or thyroglobulin autoantibodies in the serum which are present with a higher prevalence in females than in males and increase with age. Although exact mechanisms of aetiology and pathogenesis of the disorder are not completely understood, a strong genetic susceptibility to the disease has been confirmed predominantly by family and twin studies. Several genes were shown to be associated with the disease occurrence, progression, and severity. Genes for human leukocyte antigen, cytotoxic T lymphocyte antigen-4, protein tyrosine phosphatase nonreceptor-type 22, thyroglobulin, vitamin D receptor, and cytokines are considered to be of utmost importance. Amongst endogenous factors for the disease development, the attention is focused predominantly on female sex, pregnancy with postpartum period and fetal microchimerism. Environmental factors influencing HT development are iodine intake, drugs, infections and different chemicals. Disturbed self-tolerance accompanied by the increased antigen presentation is a prerequisite for the HT occurrence, whereas proper interaction of thyroid cells, antigen presenting cells, and T cells are necessary for the initiation of thyroid autoimmunity. Secreted cytokines lead predominantly to T-helper type 1 (Th1) response as well as to Th 17 response which has only recently been implicated. Final outcome of HT is thyroid destruction which is mostly a consequence of the apoptotic processes combined with T-cell mediated cytotoxicity.

Thyroid disorders, especially Hashimoto's thyroiditis (HT), and polycystic ovary syndrome (PCOS) are closely associated, based on a number of studies showing a significantly higher prevalence of HT in women with PCOS than in controls. However, the mechanisms of this association are not as clear. Certainly, genetic susceptibility contributes an important part to the development of HT and PCOS. However, a common genetic background has not yet been established. Polymorphisms of the PCOS-related gene for fibrillin 3 (FBN3) could be involved in the pathogenesis of HT and PCOS. Fibrillins influence the activity of transforming growth factor beta (TGFb). Multifunctional TGFb is also a key regulator of immune tolerance by stimulating regulatory T cells (Tregs), which are known to inhibit excessive immune response. With lower TGFb and Treg levels, the autoimmune processes, well known in HT and assumed in PCOS, might develop. In fact, lower levels of TGFb1 were found in HT as well as in PCOS women carrying allele 8 of D19S884 in the FBN3 gene. Additionally, vitamin D deficiency was shown to decrease Tregs. Finally, high estrogen-to-progesterone ratio owing to anovulatory cycles in PCOS women could enhance the immune response. Harmful metabolic and reproductive effects were shown to be more pronounced in women with HT and PCOS when compared with women with HT alone or with controls. In conclusion, HT and PCOS are associated not only with respect to their prevalence, but also with regard to etiology and clinical consequences. However, a possible crosstalk of this association is yet to be elucidated.

No abstract

AimTo assess iodine supply and follow thyroid epidemiology for ten years after an iodine increase from 10 to 25 mg of potassium iodide per kilogram of salt in 1999.MethodsIn 2002 and 2003, we determined the thyroid size by palpation and ultrasound and measured urinary iodine concentration (UIC) in 676 schoolchildren from 34 schools throughout Slovenia. From 1999 to 2009, we followed the incidence of diffuse and nodular goiter, thyroid autonomy, Graves’ disease, and Hashimoto’s thyroiditis among adults in the stable catchment area of the University Medical Centre Ljubljana with 1 000 000 inhabitants.ResultsIn children, only 1% had a goiter grade 2 (visible and palpable thyroid gland), median thyroid volume was 5.8 mL, and median UIC was 148 µg/L. In adults, the incidence of diffuse goiter and thyroid autonomy decreased significantly (2009 vs 1999, rate ratio [RR], 0.16; 95% confidence interval [CI], 0.12-0.21 and RR, 0.73; 95% CI, 0.62-0.86, respectively), with a lower incidence in younger participants in 2009 (P < 0.001). The incidence of multinodular goiter and solitary nodule increased (2009 vs 1999, RR, 1.55; 95% CI, 1.35-1.79 and RR, 1.72; 95% CI, 1.49-1.99, respectively). No long-term changes were observed for Graves’ disease (2009 vs 1999, RR, 0.95; 95% CI, 0.81-1.13), while the incidence of Hashimoto’s thyroiditis increased strongly (2009 vs 1999, RR, 1.86; 95% CI, 1.64-2.12).ConclusionsThe change from mildly deficient to sufficient iodine supply was associated with a marked change in the incidence of thyroid epidemiology – a significant decline in the incidence of diffuse goiter and thyroid autonomy and a marked increase in the incidence of Hashimoto’s thyroiditis.

No abstract

No abstract

Strong genetic susceptibility to thyroid autoantibody (TAb) diathesis has been shown and one of the major genes involved is probably CTLA-4 gene. Our recent study of patients with Graves' disease has demonstrated that exon 1 CTLA-4 gene polymorphism influences higher TAb production. Here, we evaluated the influence of exon 1 and promoter CTLA-4 polymorphisms on TAb production in 109 newly diagnosed patients with Hashimoto's thyroiditis (HT). Serum TSH, thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) were measured. 49 A/G and -318 C/T polymorphisms were detected using polymerase chain reaction amplification of genomic DNA and restriction fragment length polymorphism analysis. Patients with AG and GG genotype had significantly higher TPOAb median values compared to patients with AA genotype (P < 0.003). Similarly, TgAb median value was significantly higher in AG patients and in the entire G-allele carrying group (P < 0.02). Compared to both T-allele carrying genotypes, CC genotype presented with significantly higher TPOAb median value (P < 0.02), whereas TgAb median values did not differ significantly between various genotypes. In conclusion, our results indicate that G allele influences higher TPOAb and TgAb production, whereas C allele affects especially TPOAb production in patients with HT. Therefore, our findings provide further evidence that CTLA-4 is a major TAb susceptibility gene.

Increasing evidence supports the genetic susceptibility for thyroid antibody (TAb) production in patients with autoimmune thyroid disease, and recently, it has been shown that the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene is most likely a major TAb susceptibility gene. To assess the relationship between exon 1 CTLA-4 gene polymorphism and TAb production, we genotyped 67 patients with newly diagnosed Graves' disease. Free thyroid hormones and TAb were measured, including thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb), and thyroid-stimulating antibodies (TSAb). AA genotype was found in 25 patients, AG genotype in 34 patients, and GG genotype in 8 patients. G allele carrying genotypes showed significantly higher frequency of positive TPOAb (p < 0.005) and TgAb (p < 0.05) compared to AA genotype. Furthermore, the median values of TPOAb were significantly higher in the group with G allele (p < 0.002). However, the median values of TgAb and TSAb did not differ significantly between both groups and similarly, CTLA-4 genotype showed no association with serum free thyroxine (T(4)) and Graves' ophthalmopathy. In conclusion, our findings suggest that G allele carrying genotype of the CTLA-4 gene influences higher production of TPOAb and TgAb, and therefore, support the hypothesis that CTLA-4 gene plays a major role in TAb production.