| The research program is focused on thyroid diseases, both on prevention, etiology and pathogenesis as well as on diagnosis and treatment. The research questions originate from clinical practice. To answer these questions it is often necessary to carry out fundamental research in the laboratory. The characteristic of our research group is the very close collaboration between clinical scientists and basal scientists, optimal for translational on research. The research program for the next few years has four major lines on investigation: 1. GRAVES OPHTHALMOPATHY Graves Ophthalmopathy is frequently seen in patients with Graves hyperthyroidism; it is cosmetically disfiguring and functionally very often invalidating in nature. The treatment results are still disappointing, and patients suffer from a substantial loss of quality of life. We try to improve treatment outcome by applying new forms of immunosuppressive treatment, preferably in the setting of randomized clinical trials. The pathogenesis of Graves Ophthalmopathy is largely unknown. Elucidation of the pathogenesis is studied using orbital fibroblasts in culture taking from orbital fat and extraocular eye muscles during surgery. 2. AUTOIMMUNE THYROID DISEASES Graves hyperthyroidism and Hashimoto hypothyroidism are very prevalent diseases which often run in families. Female relatives of patients with autoimmune thyroid disease are at risk to contract the disease themselves, and we are doing a preventive intervention study in this respect. Also we study in detail genotype-phenotype relationships in Graves hyperthyroidism. 3. NON THYROIDAL ILLNESS Illness in general results in a low serum T3, a slightly high, normal or sometimes decreased free T4, and despite these changes mostly a normal TSH. These changes are known as the nonthyroidal illness syndrome or the thyroid adaptation syndrome. We investigate the biologic relevance and the pathogenesis of this very basic syndrome, in particular the rule of cytokines. 4.THYROID HORMONE RECEPTOR We have demonstrated specific zonal distribution of thyroid hormone receptors in the liver (e.g. strict pericentral localization of the isoform form of TRß1). We now do functional studies in aiming at the biologic relevance of the isoform specific distribution of TRs. We also have demonstrated differential distribution of TRa1 and TRß1 in the heart, and we are trying to learn about their functional significance with the help of TR knock outs. TRs traditionally have been thought to reside in the nucleus a clear only, but our very recent results clearly show isoform form specific distribution among various cellular compartments, especially mitocondria. This is being further investigated, together with our recent finding that amiadarone acts as a antagonist for both TRa1 and TRß&1, whereas dronedarone acts only as a selective TR&1 antagonist. |
