Advances in Graves' disease, including a new mouse model

Sandra McLachlan, Ph.D. and colleagues from Cedars-Sinai Research Institute (Los Angeles, CA), have developed a new animal model of Graves' disease, a research tool that could lead to a better understanding of the underlying cause of Graves' disease and help in the development of a potential cure. In the presentation entitled "Development of a Unique Mouse Model for Graves' Disease that Spontaneously Develops Pathogenic TSH Receptor Antibodies," the authors report transgenic mice on a thyroiditis susceptible background that express a shed component of the human thyroid stimulating hormone receptor (TSHR) and spontaneously develop TSHR antibodies, as occurs in Graves' disease.

Theo Plantinga, Ph.D., Radboud University Medical Center, (Nijmegen, The Netherlands) and colleagues, used next-generation sequencing technology to perform whole exome DNA sequence analysis and look for a genetic cause of familial thyrostatic-induced agranulocytosis. Agranulocytosis is a rare side effect of thyrostatic treatment for Graves' disease. The authors identified five individuals in two different families in whom agranulocytosis developed after treatment with propylthiouracil or thiamazole. Among the 15 genes found to have mutations in all five individuals, the most likely gene to cause agranulocytosis was the NOX3 gene. In their presentation, "Mutations in NOX3 as Genetic Cause of Familial Agranulocytosis during Thyrostatic Treatment of Graves' Disease," the authors note that they did not find mutations in NOX3 in the member of one family who had Graves' disease and did not develop thyrostatic-induced agranulocytosis.

In the poster presentation "Can Thyroid Autoantibody Levels Aid In Treatment Decision-Making for Graves' Disease?" Dawn Elfenbein, M.D., Ph.D., University of Wisconsin, Madison, describes a retrospective review of more than 450 patients who underwent either radioactive iodine (RAI) therapy (71% of patients) or thyroidectomy (29% of patients) during a six-year period. The percentage of patients who underwent surgery increased significantly over the study period, from 14% to 52%. The authors state that a patient's decision whether to opt for treatment with RAI or surgery usually depends on the presence of clinical manifestations of Graves' disease such as eye disease or goiter. Based on their review of measurements of thyroid-specific autoantibodies for patients with and without ophthalmopathy or goiter, they conclude that the autoantibody measurements are not predictive of these clinical features and, though useful for diagnosis, cannot help patients decide between surgery or RAI.