Our results suggest also that additional natural mutations (especially K183M, N, or Q) in position 183 of TSHr are expected to be found in gestational hyperthyroidism.
Thus, the main conclusions to be drawn from this case are 1) a search for mutations in cases of congenital nonautoimmune hyperthyroidism should not remain restricted to exon 10 of the TSHR gene, because germ-line gain of function mutations of the TSH receptor can be located outside of the transmembrane core of the receptor; and 2) this case illustrates the necessity for careful functional characterization of any novel mutation before a causal relationship to hyperthyroidism can be established.
These results confirmed that immunization with naturally expressed hTSHR in mammalian cells was able to induce functional TSHR autoantibodies that either stimulated or blocked the mouse thyroid gland and induced hyperthyroidism or thyroid failure.
Mice lacking murine MHC and expressing human HLA-DR3 develop thyrotropin receptor (TSHR) antibodies and sometimes hyperthyroidism after vaccination with TSHR-DNA.
Graves' disease, the production of thyroid-stimulating hormone receptor-stimulating antibodies leading to hyperthyroidism, is one of the most common forms of human autoimmune disease.
During pregnancy, the placental hormone human choriogonadotropin (hCG) can cause gestational hyperthyroidism through cross-reaction with the TSH receptor.
The amount of blocking and stimulating TSHRAb were measured in 200 patients with untreated hyperthyroid Graves' disease using several cell lines carrying different TSHR chimera.
A higher baseline TSH-receptor antibody titre corresponded to a greater improvement in exercise capacity (r=0.76, p<0.05) and physical quality of life (r=0.73, p<0.05) on resolution of the hyperthyroidism.
We report here that TSH and the pathogenic anti-TSHR antibodies that drive hyperthyroidism in GD induce IL-6 expression in fibrocytes and orbital fibroblasts.
TSH receptor antibody testing should be considered in pregnant women with any history of autoimmune thyroid disease and symptoms of fetal hyperthyroidism.
Cysteine 390 of the rat thyrotropin (TSH) receptor, when mutated to serine, results in a receptor with a reduced ability of TSH to bind and increase cAMP levels but a preserved ability of thyroid stimulating autoantibodies (TSAbs) from hyperthyroid Graves' patients to increase cAMP levels.
Graves' disease (GD) is an autoimmune thyroid disease defined by the production of stimulating autoantibodies to the thyroid-stimulating hormone receptor (TSHR) (TSAbs) that induce a sustained state of hyperthyroidism in patients.
Sequencing of all exons of the TSHR gene in one family with hyperthyroidism revealed a mutation in exon 10 (T6321), which was first identified in toxic adenomas and found to constitutively activate the TSHR.
A recent study on TSH receptor (TSHR) null mice suggested that skeletal loss occurring in hyperthyroidism is caused by the low TSH rather than high thyroid hormone levels.