Endocrine Abstracts

Introduction: Graves’ disease is an autoimmune condition with an estimated prevalence of about 2%, 5–10 times more frequent in females. A multifactorial nature is assumed, with genetic contribution accounting for up to 80% of the variability. Relevant genes includegeneral autoimmune risk loci, such as the HLA region, CTLA-4, PTPN22 and CD40, as well as thyroid-specific loci (thyroglobulin and TSH receptor genes). We report a particular case of Graves’ disease with a strong familial aggregation and speculate on possible immune mechanisms.

Case report: A possible founding effect occurred in the maternal grandmother with Graves’ disease, apparently in the sixth decade of life. Two of her three children, male and female, presented with Graves’ disease in the fourth decade of life. The clinically unaffected female child has two sons, both affected with Graves’ disease in the first two decades of life. In no case was there evidence of exophtalmus or pretibial mixedema. In every case, the initial treatment consisted of antithyroid drugs metimazol or propyltiouracil maintained for two years and was interrupted when TRAb titers became negative. Recurrences after the first episode occurring in every case required definitive treatment (radioiodine or surgery).

Discussion: This family is affected by Graves’ disease in three generations with no gender predominance suggesting a dominant autossomic pattern. It also appears to be genetic anticipation by means of a lower age of onset and an increase in severity with more rapid recurrences in succeeding generations. Accordingly, the clinically unaffected child in the second generation may also develop the disease. The fact that there is no evidence of other immune-mediated disorders or other immune processes directed against common target organs in Graves’ disease (exopthalmus or pretibial myxedema) points to a thyroid-specific antigen, most likely the TSH receptor. Genetic and molecular analysis of the TSH receptor is presently underway.