**4. TSHR-blocking autoantibody (TBAb)**

In Graves-Basedow's patients TRAb stimulates thyroid hormone synthesis by activating the TSH receptor (stimulating TRAb /TSAb/, TSHR agonist). TSHR antibodies that lack agonistic activity but are competitive inhibitors of TSH binding can cause hypothyroidism (blocking TRAb/TBAb/, TSHR antagonist). There is a wide variety of TSHR antibody assays employed in the past and nowadays. Depending on the underlying method, two types of assays are important for determination of circulating autoantibodies: Competition for ligand binding or measuring bio-response. A rare history of monozygotic 10-year-old twins was published who presented with hyper- and hypothyroidism, respectively [16]. Both girls had antibodies against thyrotropin receptors as measured by a radioreceptor assay. Analyzing further the sera in a functional bioassay, the TSH receptor antibodies of the hyperthyroid twin displayed stimulatory activity typical of Graves' Disease, while the antibodies of the hypothyroid twin acted as pure antagonists at the TSH receptor level. This is a proven pediatric case with hypothyroidism due to thyroid (or TSH)-blocking antibodies, where the pathogenesis was similar to GD. In the following 30 years an extensive work of research groups has led to significant improvements that has enabled bioassays to be employed routinely in clinical laboratories: 1, Two human monoclonal antibodies (MAbs) with TSHR agonist activity (M22 and K1-18), one human MAb with TSHR antagonist activity (K1-70) and one human MAb (5C9) with both TSHR antagonist and TSHR inverse agonist activity have been isolated [17]. 2, Currently available highly sensitive and specific assays to measure TRAbs use the human TSHR monoclonal antibody (Mab) M22 instead of the TSH [18]. Based on a research-use only service offered by RSR Limited, an adult case of woman with fluctuating hypo- and hyperthyroidism was published providing proof that a patient can produce a mixture of blocking and stimulating TSHR autoantibodies at the same time [19].

*Unusual Presentation and Rare Comorbidity of Graves-Basedow's Disease in Children DOI: http://dx.doi.org/10.5772/intechopen.97577*
