title: Mechanisms in endocrinology: autoimmune thyroid disease: old and new players.
abstract: The last 10 years have seen some progress in understanding the etiology of autoimmune thyroid disease (AITD). The female preponderance can now be explained - at least in part - by fetal microchimerism and X-chromosome inactivation. The number of identified susceptibility genes for AITD is increasing (among others now including TSHR, TG, HLA, CTLA4, PTPN22, CD40, FCRL3, IL2RA, and FOXP3), but these genes together probably do not explain more than about 10% of the heritability of AITD. As twin studies indicate that genes contribute for 70% of AITD, it follows that there must be many more loci, each of them contributing a little. While the genetic studies have clarified why various autoimmune diseases so often cluster in the same patient, the molecular mechanism of action of these genetic polymorphisms (frequently located in introns) has hardly been explained. Polymorphisms in AITD susceptibility genes may become helpful in clinical practice, e.g. in assessing risk of recurrent Graves' hyperthyroidism (GH) after a course of antithyroid drugs. Moderate alcohol intake decreases the risk on overt GH and overt Hashimoto's hypothyroidism. Current smokers - as well known - are at increased risk for Graves' disease, but - surprisingly - at diminished risk for Hashimoto's thyroiditis. Low selenium and low vitamin D levels might increase the risk of developing AITD, but data are still inconclusive. Current options for preventive interventions in subjects at risk to develop AITD are very limited.
authors.affiliation: Department of Endocrinology and MetabolismAcademic Medical Center, Room F5-169, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands.
authors.forename: Grigoris
authors.initials: G
authors.lastname: Effraimidis
authors.affiliation: Department of Endocrinology and MetabolismAcademic Medical Center, Room F5-169, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands w.m.wiersinga@amc.uva.nl.
authors.forename: Wilmar M
authors.initials: WM
authors.lastname: Wiersinga
mesh_terms: D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D012307:Risk Factors; D013315:Stress, Psychological / Q000150:complications / Q000453:epidemiology / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D049951:X Chromosome Inactivation / Q000502:physiology