STUDY ON THE HETEROGENEITY OF TSH RECEPTOR ANTIBODIES IN THE PATHOGENESIS OF AUTOIMMUNE THYROID DISEASE

Objective To investigate the heterogeneity of TSH receptor antibodies ofpatients with autoimmune thyroid disease (AITD). Methods Six patients with heterogeneous TSH receptor antibodies were selected. The EBV-transformed B cell clones producing monoclonal anti-thyrotropin receptor antibodies were established from those selected patients. Results 125I-TSHbinding inhibiting immunoglobulin (TBII) values of the 6 patients ranged from 51 % to 89%. Thyroid stimulating antibody (TSAb) existed in patients No. 1,2, 4, 5 and 6 while only patients No. 1,2 and 3 had thyroid stimulation-blocking antibody (TSBAb ). After EBV-transformation of the peripheral B lymphocytes from those patients, we isolated and characterized 5 Bcell clones prepucing the TBII from patient No. 3 and 4 B cell clones prepucing TSAb from patient No. 6. Conclusion Autoantibodies against the us receptor are polyclonal and consist of heterogeneous populations with both stimulatory and inhibitory effects.

Protective effect of thyroid and restores of ovarian function of Buzhong Yiqi granule(补中益气颗粒)on experimental autoimmune thyroiditis in female rats

OBJECTIVE:To observe the effects of Buzhong Yiqi granule(补中益气颗粒)on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis(EAT).METHODS:EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine.Rats were randomly divided into normal control(NC)group,EAT model(EAT)group,selenium yeast(PC)group,low dose Buzhong Yiqi(BZYQ-L)group,medium dose Buzhong Yiqi(BZYQ-M)group and high dose Buzhong Yiqi(BZYQ-H)group.After two months of drug intervention according to dosage,enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of free triiodothyronine(FT3),free thyroxine(FT4),thyroid-stimulating hormone(TSH),antithyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb)in peripheral blood of rats.The pathological changes of rat thyroid tissues were observed under light microscope with HE staining;ELISA was used to determine estradiol(E2),follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),antimüllerian hormone(AMH),and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining.RESULTS:Compared with the NC group,BZYQ granule improved the thyroid and ovarian tissue morphology,and the levels of TPOAb,TGAb and TSH in the model group rats significantly increased(P<0.05),the thyroid tissue was severely destroyed,the levels of E2,FSH,LH,T,AMH significantly increased(P<0.05),and the ovary exhibited polycystic changes;Compared with the model group,TSH level in the BZYQ-L group rats decreased(P<0.05),FSH,T,AMH levels decreased(P<0.05),in the BZYQ-M group TPOAb,TSH levels decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),BZYQ-H group TPOAb,TGAb,TSH levels significantly decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),with the greatest improvement and significantly better than selenium yeast group(P<0.05).CONCLUSIONS:BZYQ granule could regulate the thyroid function of EAT rats,reduce thyroid antibody titers,then act on the ovarian function,regulate hormone disorders,and alleviate the pathological damage of rat's ovarian tissues.The effect of high dose Buzhong Yiqi granule is the best.

A comparative study of influential factors correlating with early and late hypothyroidism after ^131I therapy for Graves＇ disease

Background 131Ⅰ therapy is recognized as the simplest, safest, least expensive, and most effective treatment, and accepted by more and more patients. However its curative effect is influenced by many factors, therefore there are some difficulties for doctors to establish individual treatment strategy. The aims of this study were to determine the incidence of early and late hypothyroidism after 131Ⅰ treatment for Graves＇ disease （GD） and to compare their correlation, to observe and analyze the influential factors and to understand the predictabilities of them.Methods Five hundred GD patients （144 males, 356 females; age （41.2±12.3） years） received 131Ⅰ treatment for the first time. The therapeutic procedure was carried out as the following： undergoing 131Ⅰ uptake test to obtain maximum of thyroid uptake value and effective half-life （EHL） time; estimating the thyroid＇s weight by ultrasonography; determination of thyroid hormones and correlative antibodies; pre-therapy physical examination; thyroid imaging; calculating 131Ⅰtherapeutic dosage; per os uptake of the determined 131Ⅰ dosage; follow-up appraisal of curative effect. The observing parameters included age, gender, thyroid weight, GD duration, condition of onset, state of disease, course of treatment, EHL time, maximum of thyroid uptake value, 131Ⅰ dosage and titer of correlative antibodies. We sorted out the data and used both univariate and multivariate analysis to evaluate them statistically.Results The incidence rates of early and late hypothyroidism were 33.2% and 6.6% respectively after 131Ⅰ treatment and approximately 22.2% cases of late hypothyroidism developed from early hypothyroidism. The influential factors of early hypothyroidism included course of GD, the highest thyroid uptake ratio of 131Ⅰ, EHL time and thyroid microsome antibody （TMAb）, etc. A multivariate analysis on late hypothyroidism showed that female patients, with recurrence after anti-thyroid drug treatment and higher thyroid weight, had lower possibility of late hypothyroidism after 131Ⅰ therapy.Conclusions The incidence of early hypothyroidism is higher than that of late hypothyroidism. The highest thyroid uptake ratio of 131Ⅰ, EHL and TMAb will increase the possibility of early hypothyroidism, while GD course is the protective factor. Higher 131Ⅰ dosage, longer EHL and higher TMAb titer will also increase the possibility of late hypothyroidism. The multi-perspective and multi-factor analysis has the benefit to establish individualized treatment strategy.

Thyroid peroxidase antibody positivity and triiodothyronine levels are associated with pediatric Graves'ophthalmopathy

Background:Graves'ophthalmopathy(GO)occurs commonly in children with Graves'disease(GD).However,there are limited studies on the clinical manifestations and thyroid autoantibodies in pediatric GO.The aim of this study was to investigate the prevalence and risk factors of GO in childhood GD.Methods:Clinical and biochemical data from children and adolescents with GD were retrospectively reviewed.Eighty patients under 19 years of age were included in the present study.We compared the clinical and biochemical differences between patients with and without GO.Results:Thirty-nine percent of the patients had GO,and 81%of the GO patients were females.Of these,two patients showed unilateral GO.Triiodothyronine(T3)levels were higher in GO patients than in those without GO.Anti-thyroglobulin antibody and thyroid stimulating hormone receptor antibody titers were not significantly different between the two groups.Anti-thyroid peroxidase antibody(TPO Ab)positivity was 68%in the patients with GO and only 47%in the patients without GO.In multivariate regression analysis,high T3 levels and TPO Ab positivity were related to the presence of GO.Conclusion:In children and adolescents with GD,TPO Ab positivity and high T3 levels could act as predictive factors for the presence of GO.

Association between serum levels of TSH and free T4 and per- and polyfluoroalkyl compounds concentrations in pregnant women

Many per-and polyfluoralkyl substances(PFASs)may disrupt maternal thyroid hormone homeostasis in pregnancy.Concerns should be raised regarding the PFASs exposure in pregnant women because thyroid hormones are involved in the early development of the fetus.In this study,we measured the concentrations of 13 PFASs,including five novel shortchain PFASs,in serum from 123 pregnant women in Beijing,China.Linear regression models were used to investigate the association between thyroid-stimulating hormone(TSH)or free thyroxine(FT4)levels and PFASs concentrations under consideration of the impacts of pregnancy-induced physiological factors.We found that perfluorobutanoic acid(PFBA)(β=0.189,95%CI=-0.039,0.417,p=0.10)and perfluorodecanoic acid(PFDA)(β=-0.554,95%CI=-1.16,0.049,p=0.071)were suggestive of significant association with TSH in thyroid peroxidase antibody(TPOAb)negative women.No association was observed between all PFASs and FT4 levels after controlling for these confounding factors,such as BMI,gestational weight gain and maternal age.These findings suggest that it should pay more attention to the association between thyroid hormone levels and short-chain PFASs concentrations.Future studies could consider a greater sample and the inclusion of other clinical indicators of thyroid function,such as free T3 and total T3.