Endocrine Abstracts

Thyroid autoimmune disorders comprise more than 30% of all organ-specific autoimmune diseases and are characterized by autoantibodies and infiltrating T cells. The pathologic role of infiltrating T cells is not well defined. To address this issue, we generated transgenic mice expressing a human T-cell receptor derived from the thyroid-infiltrating T cell of a patient with thyroiditis and specific for a cryptic epitope of thyroid-peroxidase. This humanized transgenic mouse mode...

Graves’ hyperthyroidism is caused by autoantibodies to the thyrotrophin receptor (TSHR) that mimic thyroid stimulation by TSH. The disease develops spontaneously in humans but not in animals and conventional immunization with purified TSHR protein and adjuvant fails to generate Graves’-like antibodies that stimulate the thyroid. However, antibody-mediated hyperthyroidism can be induced in mice or hamsters by novel approaches involving multiple injections of cells exp...

The dichotomy between hormone recognition, by the ectodomain containing leucine-rich repeats (LRR), and activation of the G protein, by the rhodopsin-like serpentine portion, is a well established property of glycoprotein hormone receptors (GpHRs). Extensive site-directed mutagenesis experiments and direct structural data have fully confirmed that high affinity recognition of the hormones by their receptors was built within the structure of the LRRs. It is possible to transfor...

The debate on the utility of TSH receptor (TSH-R) measurement in the management of Graves’ patients has a long history (see for instance J Clin Endocrinol Metab 1998; 83: 3777–3785), and despite advances in assay techniques, the use of TSH-R antibodies in clinical practice is determined more by local custom and practice than evidence base. The diagnosis of Graves’ disease itself is usually straightforward and surrogates for TSH-R antibody testing, such as thyroi...