Autoimmune thyroid diseases (AITD) comprise two clinical phenotypes, Graves disease and Hashimotos thyroiditis. These conditions share distinct immunological features such as autoreactivity against the key thyroid autoantigens thyroglobulin and thyroid peroxidase. Considering Graves disease as well as Hashimotos thyroiditis, twin studies have revealed a higher concordance rate among monozygotic (MZ) as compared to dizygotic (DZ) twins, suggesting a relative strong genetic influence in the aetiology. According to the endophenotypic approach, it might be useful to subdivide a clinical phenotype into a set of variables thought to represent more basic processes. The presence of thyroid autoantibodies in euthyroid individuals can be regarded as a central phenotypic anchor point and, using the twin design, the relative contributions of genetic as well as environmental effects in the aetiology of AITD, at this early stage of the disease process, has been clarified as well.
The genetic contribution to autoimmune disease (AID) has been intensely investigated, and a slow progress towards identification of AITD susceptibility genes is seen. There is evidence of association and, in some cases, even linkage between AITD and several genetic loci. However, one problem is often the very pronounced discrepancy between the initial and subsequent reports. On the other hand, epidemiological studies aim at identifying specific measurable environmental exposures of importance for the development of AITD. So far only a few environmental factors (e.g. iodine intake and smoking habits), with a clear detectable effect on the disease, have been characterized. The underlying challenges in trying to understand a complex phenotype, such as AITD, will be discussed.
28 Apr - 02 May 2007
European Society of Endocrinology