TSH Receptor Antibody Heterogeneity in Children and Adolescents With Graves' Disease

NCT ID: NCT00335062

Last Updated: 2014-07-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 19 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2010-02-28

Brief Summary

Graves' disease, the most common form of hyperthyroidism in children, is caused by Thyrotropin (TSH) Receptor Antibodies (TRAbs) that mimic the action of TSH. The disease leads to significant morbidity in children both due to the prolonged course of antithyroid medication often required for sustained immunological remission and the high risk of relapse when medication is withdrawn. The ability to predict which patients are most likely to fail medical management would greatly improve the choice of therapy. In the past, large goiter size, age at diagnosis, increased biochemical severity, and decreased body mass index have all been associated with a poorer prognosis, but these clinical indicators lack sensitivity and specificity. Preliminary data suggest that the new TRAb assays are both sensitive and specific for the measurement of TRAbs in children with Graves' disease. In addition, variation in these antibodies over time is not the same in all patients. The goal of this proposal will be to prospectively follow children with newly diagnosed Graves' disease and use microarray technology to determine if there are genes whose expression differ in patients who respond to medical therapy versus those who will need more definitive therapy earlier in their disease.

Detailed Description

In the present grant proposal, we plan to utilize two new assays (binding and bioassay) in order to identify additional predictors of Graves' disease and apply them to a well characterized group of patients with Graves' disease followed prospectively. More specifically, we plan to further investigate the antibodies by measuring lambda: kappa light chain antibody ratios in pediatric patients. We will assess epitope heterogeneity by using novel chimeric proteins in which specific portions of the TSH receptor have been replaced with the closely related LH receptor. We will utilize microarray technology to determine if there are differences in gene expression profiles in responders versus non responders. It is hoped that these methods will lead to an improved ability to follow disease progression and to monitor efficacy of therapy.

Conditions

Graves' Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Age 2-21 years
• Suppressed Thyroid Stimulating Hormone (TSH)
• Elevated Triiodothyronine (T3), Thyroxine (T4)

Exclusion Criteria

• Pregnancy
• Toxic Nodule
• Currently receiving steroids or thyroid hormone replacement
• Bacterial, Viral, Radiation, or Autoimmune thyroiditis

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Rosalind Brown

Director of Clinical Trials

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rosalind S Brown

Role: PRINCIPAL_INVESTIGATOR

Children's Hosptial Boston/Harvard Medical School

Locations

Childrens' Hospital Boston

Boston, Massachusetts, United States

Countries

United States

Related Links

http://www.thyroidmanager.org

THYROID DISEASE MANAGER © offers an up-to-date analysis of thyrotoxicosis, hypothyroidism, thyroid nodules and cancer, thyroiditis, and all aspects of human thyroid disease.

Other Identifiers

S05-05-066

Identifier Type: -

Identifier Source: org_study_id