HT is characteristic of hypothyroidism resulting from the destruction of the thyroid while GD is characteristic of hyperthyroidism due to excessive production of thyroid hormone induced by thyrotropin receptor-specific stimulatory autoantibodies.
The present study suggests that the TSHR A-subunit structure (possibly including posttranslational modification such as glycosylation) may explain, in part, why Graves' disease only develops in humans.
Cyclic peptides derived from some cylindrical loops of the leucine-rich repeat domain (LRD) of the thyrotropin receptor (TSHR) have been shown to treat disease manifestations in a mouse model of Graves' disease during a long-term protocol of four-weekly immunizations with adenovirus coding for the TSHR A-subunit (Ad-TSHR289).
Thyroid-stimulating hormone receptor antibodies during follow-up as remission markers in childhood-onset Graves' disease treated with antithyroid drugs.
Although TSH-receptor autoantibodies (TRAb) were negative, the persistence of hyperthyroidism, the hypervascular pattern at thyroid ultrasound, and the high uptake at thyroid scintigraphy were all features suggestive of Graves' disease.
However, no significant differences for rs2294025 and rs7005834 were observed, between the different clinical phenotypes of GD, including gender, Graves' ophthalmopathy (GO), and serum levels of thyrotropin receptor antibody, thyroid peroxidase antibody, and thyroglobulin antibody.
Circulating thyroid hormone levels, malondialdehyde concentrations, total antioxidant capacity, and the titer of GD-causing TSH receptor autoantibodies were not affected by Se.
Occurrence of the T gene allele of PTPN22 gene in GD manifestation in those under 40-year old was more frequent compared to individuals over 40, but the obtained difference was also not significant (p = 0.75).
It is important to identify patients with activating TSHR mutation due to treatment implication, but the overlapping clinical features with Graves' disease make it difficult to discriminate these two conditions without genetic testing.
It usually presents as a component of the syndrome known as Graves' disease where loss of immune tolerance to the thyrotropin receptor (TSHR) results in the generation of activating antibodies against that protein and hyperthyroidism.
Based on our earlier finding and on the large body of evidence here reviewed, we propose that DDT-induced formation of extracellular vesicles containing the TSH receptor could be directly involved in the development of autoimmune responses against the TSH receptor and that, therefore, their release could lead to the development of the Graves' disease.
The presence of such TSHR antibodies suggests that they may play an active role in the immune repertoire marshaled against the TSHR and may influence the Graves' disease phenotype.
M22 (P = 0.0082), bovine TSH (P = 0.0028), and sera of hyperthyroid patients with GD (P < 0.05) increased superoxide-specific 2-hydroxyethidium levels in HEK-293 TSHR cells after 48-hour incubation vs control subjects.
Overall, we show that mouse TSHR A-subunit plasmid immunization by electroporation overcomes tolerance to self-antigen to provide a faithful model of Graves' disease and GO.
The C allele of rs3789604 (PTPN22) was a significant risk factor for LD-associated hyperthyroidism in GD patients, whereas C allele of GPR174 rs3827440 and G allele of RNASET2 rs9355610 appeared to be a protective factor for this disease.