Endocrine Abstracts

It is a clinical commonplace is that many other autoimmune conditions are associated with Hashimoto’s thyroiditis and Graves’ disease, but the breadth of these associations makes it clear that the classically defined spectrum of autoimmune diseases, ranging from organ- to non-organ-specific, does not in fact exist. All of these associations originate primarily in shared genetic predisposition. As well as HLA alleles, polymorphisms in CTLA-4, PTPN22 and CD25 are common to many autoimmune diseases, begging the question of why single autoimmune diseases occur. In some cases, this may be due to additional genetic factors: for instance, polymorphisms in the TSHR gene predispose to Graves’ disease rather than Hashimoto’s thyroiditis. Recently, a multinational consortium has identified several novel genetic polymorphisms associated with vitiligo and it will be important to determine if these too turn out to be disease-specific. In other cases, environmental factors have a clear role in determining organ-specificity, such as the strong association between smoking and ophthalmopathy, and the sudden recent rise in the prevalence of Hashimoto’s thyroiditis.

A further non-genetic mechanism to explain disease associations is the sharing of autoantigens, most clearly seen with the association between ophthalmopathy and thyroid disease. Nonetheless, characterisation of autoantigen(s) involved in this association has been slow and in other disorders commonly found with thyroid autoimmunity we still don’t know the autoantigenic basis: vitiligo is only infrequently associated with melanocyte autoantibodies (against tyrosinase, TRP1 and MCHR) and an absence of consistent ovarian autoantibodies is also a feature of premature ovarian failure, raising the question of whether these conditions have a more complex aetiology. Thyroid disease associations are clinically important, and developments in protein screening technologies mean that we will soon be in a position to screen for multiple autoantibodies in arrays, and thus able to offer more accurate disease predictions.

Partly supported by the Clinical Endocrinology Trust.