This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HYPOTHESES AND SPECIFIC OBJECTIVES: The objectives of this proposal will be to: 1) Prospectively follow a group of children and adolescents with newly diagnosed Graves' disease 2) Measure thyroid function tests (T4, Free T4, Total T3, and TSH), TSH receptor antibodies (by both ELISA and bioassay), and TSH receptor antibody oligoclonality (as assessed by lambda/kappa ratio) at diagnosis, 6 months, and 12 months 3) Determine whether initial severity of hyperthyroidism (as determined by both clinical and hormonal parameters) is related to initial TSH receptor Ab potency and/or oligloclonality or both 4) Determine whether TSH receptor Ab titer at 6 months and at 12 months is related to: a) initial severity of hyperthyroidism (as determined by both clinical and hormonal parameters) b) initial TSH receptor Ab potency (by both ELISA and bioassay) c) initial TSH receptor Ab oligoclonality, as well as TSH receptor Ab oligoclonality at 6 months and 12 months 5) Characterize the course of TSH receptor Ab heterogeneity at diagnosis, 6 months and 12 months in individual patients; We hypothesize that: 1) Amongst children with Graves' disease, 75% will have TSH receptor Abs that are polyclonal as assessed by lambda/kappa ratio and 25% will have oligoclonal Abs 2) Oligoclonal Abs are more potent and affected patients have more severe disease and are less likely to remit 3) Those patients who have the most severe disease at diagnosis will have the highest TSH receptor Ab titers and will be less likely to remit on medical therapy 4) 25% of patients will have a change in clonality with disease progression.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
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National Center for Research Resources Initial Review Group (RIRG)
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Children's Hospital Boston
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