Detection of macro-thyrotropinaemia in patients with Hashimotos thyroiditis and subclinical hypothyroidism

The level of thyroid stimulating hormone is one of the diagnostic indicators of thyroid function. In subclinical hypothyroidism, its concentration in the blood serum increases, while the level of thyroid hormones remains normal. One of the reasons for this is the phenomenon of macrotyrotropinemia, in which the macro isoforms of thyrotropin (a complex of thyrotropic hormone with immunoglobulin) are present in the blood. It is assumed that the biological activity of macrotyrotropin is low, and may accumulate in the circulation, causing a falsely elevated level of thyroid-stimulating hormone in serum. The aim of this study is to identify the nature and prevalence of the macrothyrotropinemia phenomenon among patients with subclinical hypothyroidism in presence of autoimmune thyroiditis and a group of healthy donors. Materials and methods: Fifty serum samples of venous blood served as the material for the study: 30 patients with subclinical hypothyroidism in presence of autoimmune thyroiditis; 10, with manifesting hypothyroidism, 10 conditionally healthy donors without thyroid gland pathology (control group). The group was derived from results of the clinical laboratory at the Clinical Hospital at the Kazan station railway. Patients’ blood serum was screened for the presence of macrotrorotropin by polyethylene glycol precipitation method, followed by analysis by gel filtration chromatography. Results of this study were as follows: screening of blood sera was performed by gel filtration and affinity chromatography. Polyethylene glycol was shown to precipitate 50 to 100% serum thyrotropin, of which true macrotrothropin makes 56-98%. In the patients with subclinical hypothyroidism with a thyroid-stimulating hormone level of more than 10 pIU/ml, a trend towards an increase in the level of macrothyrotrophinaemia has been shown. The content of macrotyrotropin complex in patients with subclinical hypothyroidism, in whom the level of antibodies to thyroperoxidase is > 500 U/L, is significantly higher if compared to the patients with manifesting hypothyroidism. Elevated levels of antibodies to thyroperoxidase can lead to the generation of macrotyropin. Our findings have shown that the phenomenon of macrothyrotropinemia is quite common in patients with subclinical and manifesting hypothyroidism with Hashimoto thyroiditis (53.3%) and in control group (25%). Macrotyrotropin complex probably consists of thyrotropin and IgG. Patients with a thyroid-stimulating hormone level of > 10 pIU/ml are candidates for screening for the presence of the macrotyrotropin complex.The activity of the autoimmune process may correlate with the phenomenon of macrothyrotropinemia. The results can be used to develop an additional tool when choosing therapy in clinical practice

ASSOCIATION OF IL-1β, IL-4 AND IL-6 GENES POLYMORPHISMS WITH GENETIC PREDISPOSITION FOR AUTOIMMUNE THYROIDITIS

Abstract.  Autoimmune  thyroiditis  (Hashimoto’s  thyroiditis,  HT)  still  represents  an  unresolved  problem of modern endocrinology, since its etiology and pathogenesis are yet unclear. Cytokines play an important role in the regulation of immune and inflammatory response, therefore, some gene variants encoding them, are considered as potential risk risk factors for autoimmune thyroid diseases. We have genotyped 298 women from the Republic of Tatarstan (RT, control group, 137 persons; HT patients, 161) for the following gene polymorphisms: interleukin-1 beta (IL-1β) +3953 C/T (rs 1143634); interleukin 4 (IL-4) -590C/T (rs 2243250), and interleukin 6 (IL-6) -174C/G (rs 1800795), using allele-specific PCR. The results showed a significantly increased frequencies of C allele (P  = 0.0003) and CT genotype (P  = 0.048, OR  = 6.05, 95%CI 2.59-2.97) of  +3953  C/T  of  IL-1β  in  patients  with  Hashimoto's thyroiditis, as compared with control group. The latter  group showed higher prevalence of T allele (P  = 0.0003) and TT genotype (P  = 4.95 Ч 6.10; OR  = 0.15, 95%CI 0.06-0.38). The 590C/T and -174C/G polymorphic variants in, resp., IL-4 and IL-6 genes are not associated with increased risk of this disease among women from RT. (Med. Immunol., 2011, vol. 13, N 6, pp 603-608

ASSOCIATION OF CTLA-4 AND PTPN-22 GENES POLYMORPHISMS WITH INCREASED RISK OF AUTOIMMUNE THYROIDITIS IN TATAR POPULATION

The aspects of autoimmune thyroiditis (AIT) remain quite actual, since many issues of etiology, pathogenesis, morphology, classification, diagnostics, therapy and prediction of this disorder are far from final solution. Since disturbances of fine molecular immune mechanisms underlie pathogenesis of either immune disorder, the genes coding its main components, are regarded as potential candidate genes predisposing for AIT, e.g., genes of surface antigen (CTLA-4) and protein tyrosine phosphatase non-receptor 22 (PTPN-22). We have performed genotyping of 298 Tatar women in Tatar Republic (Russia) with respect to age and biochemical parameters (control group, 137 persons; AIT group, 161 patients). The following gene polymorphisms were tested: +49 А/G, -318 С/Т, -1661 А/G of СТLA-4 gene, and 1858 С/Т polymorphism of PTPN-22 gene. Genotyрing was performed by PCR-RFLP method as described earlier. The data were analyzed using Chi-square test and 95% confidential interval (CI). The frequencies of CTLA-4 -1661 G allele and genotype A/G and +49 G/A G allele and genotype GG carriers were significantly higher in AIT patients than in controls (P = 0.04, OR 1.84, 95% CI 2.31-1.4; P = 0.001, OR 2,0 95% CI 1.62-2.31 respectively), with increased contents of serum antibodies to thyroglobulin (OR, 1.56, 95% CI 2.25-3.6; OR 1.12, 95% CI 1.9-2.75, respectively) and to thyroperoxidase (OR 1.3, 95% CI 1.5-4.1 for G/G genotype of +49 A/G polymorphism), independently of age (р < 0,05). We showed that the combinations of A/G, T/C and G/G genotypes of -1661 A/G, -318 T/C and +49 G/A polymorphisms is associated with increased risk of genetic predisposition to ITD in Tatar women (OR 7.87, 95% CI 2.03-3.25). A strong association was also observed between the increased level of antibodies to TPO (> 1000 ME/l) and GG genotype of +49 G/A polymorphism (OR 1.3, 95% CI 1.5-4.1) and antibodies to TG (> 100 ME/l) and genotypes A/G and G/G of CTLA-4 -1661 A/G and +49 G/A polymorphisms (OR 1.56, 95% CI 2.25-3.6; OR 1.12, 95% CI 1.9-2.75, respectively), independently of age. The genotypes -318 T/C and 1858 T/C of CTLA-4 and PTPN-22 genes, respectively, are not associated with AITD in Tatar women (p > 0.05). Our results suggest that polymorphisms of CTLA-4 and PTPN-22 genes may modify individual susceptibility to autoimmune thyroiditis in Tatar women