Increased Familial Clustering of Autoimmune Thyroid Diseases

Abstract

Data regarding familial prevalence and recurrence risk ratio of autoimmune thyroid diseases (AITD) in Germany are lacking. The data from 179 German families of AITD patients encompassing 1 229 relatives were collected using standardized clinical and laboratory diagnostic criteria. Of this large collective, 86 AITD index cases with their 139 children and 106 AITD index cases with their 157 siblings were included. The familial prevalence was estimated by the recurrence risk ratio. This quotient indicates whether first degree relatives display an increased risk for developing AITD, compared with the general population. AITD were present in 14% of children and 15% of siblings of patients with AITD. Female gender was frequently affected in both offspring (female:male ratio=3:1) and siblings (11:1). Daughters (19%) and sisters (24%) were more frequently affected than sons (7%) and brothers (3%). The risk for developing AITD was 16-fold and 15-fold increased in children and siblings, respectively, of patients with AITD. In particular, children and siblings of index cases with Hashimoto's thyroiditis had a 32-fold and 21-fold increased risk, respectively, for developing immunthyroiditis. In comparison, the risk for developing Graves’ disease was enhanced 7-fold in both children and siblings. The high prevalence of AITD in first degree, foremost female, relatives of patients with AITD demonstrates the importance of family history for developing AITD. Hence, regular screening of children and siblings of patients with AITD for presence of immunethyroiditis is recommended.

Key words

immunethyroiditis - recurrence risk ratio - siblings - children

References

• 1 Rallison ML, Dobyns BM, Meikle AW, Bishop M, Lyon JL, Stevens W. Natural history of thyroid abnormalities: prevalence, incidence, and regression of thyroid diseases in adolescents and young adults.  Am J Med. 1991;  91 363-370
• 2 Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW. Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review.  J Clin Endocrinol Metab. 2009;  94 1853-1878
• 3 Zimmermann J, Kahaly G. Erkrankungen der Schilddrüse [Diseases of the thyroid]. In: Dietel M, Dudenhausen J, Suttorp N (eds.) Harrison's Textbook of Internal Medicine, 15th ed. (German ed.). Berlin: McGraw-Hill/ABW Wissenschaftsverlag; 2003: 2255-2280
• 4 Laurberg P, Pedersen KM, Vestergaard H, Sigurdsson G. High incidence of multimodular goitre in the elderly population in a low iodine intake area vs. high incidence of Graves’ disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland.  J Int Med. 1991;  229 415-420
• 5 Huber A, Menconi F, Corathers S, Jacobson EM, Tomer Y. Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms.  Endocrine Rev. 2008;  29 697-725
• 6 Dultz G, Matheis N, Dittmar M, Bender K, Röhrig B, Kahaly GJ. The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes.  Thyroid. 2009;  19 143-148
• 7 Dittmar M, Kahaly GJ. Immunoregulatory and susceptibility genes in thyroid and polyglandular autoimmunity.  Thyroid. 2005;  15 239-250
• 8 Heward J, Gough SC. Genetic susceptibility to the development of autoimmune disease.  Clin Sci. 1997;  93 479-491
• 9 Dayan CM, Daniels GH. Chronic autoimmune thyroiditis.  New Engl J Med. 1996;  335 99-107
• 10 Dittmar M, Kahaly GJ. Polyglandular autoimmune syndromes: immunogenetics and longterm follow-up.  J Clin Endocrinol Metab. 2003;  88 2983-2992
• 11 Kahaly GJ, Dittmar M. Autoimmune polyglandular syndrome type 2.. In: Weetman AP (ed).Autoimmune Diseases in Endocrinology Totowa, NJ: Humana Press; 2007: 377-391
• 12 Tomer Y, Davies TF. Infection, thyroid disease, and autoimmunity.  Endocrine Rev. 1993;  14 107-120
• 13 Weetman AP, McGregor AM. Autoimmune thyroid disease: further developments in our understanding.  Endocrine Rev. 1994;  15 788-830
• 14 Ringold DA, Nicoloff JT, Kesler M, Davis H, Hamilton A, Mack T. Further evidence for a strong genetic influence on the development of autoimmune thyroid disease: the California twin study.  Thyroid. 12 647-653
• 15 Collins J, Gough S. Autoimmunity in thyroid disease.  Eur J Nucl Med Mol Imaging. 2002;  29 (S 02) S417-S424
• 16 Manji N, Carr-Smith JD, Boelaert K, Allahabadia A, Armitage M, Chatterjee VK, Lazarus JH, Pearce SHS, Vaidya B, Gough SC, Franklyn JA. Influences of age, gender, smoking and family history on autoimmune thyroid disease phenotype.  J Clin Endocrinol Metab. 2006;  91 4873-4880
• 17 Villanueva R, Greenberg DA, Davies TF, Tomer Y. Sibling recurrence risk in autoimmune thyroid disease.  Thyroid. 2003;  13 761-764
• 18 Hall R, Stanbury JB. Familial studies of autoimmune thyroiditis.  Clin Exp Immunol. 1967;  2 (Suppl) 719-725
• 19 Segni M, Wood J, Pucarelli I, Toscano V, Toscano R, Pasquino AM. Clustering of autoimmune thyroid diseases in children and adolescents: a study of 66 families.  J Ped Endocrinol Metab. 2001;  14 (S 05) 1271-1297
• 20 Vyse TJ, Todd JA. Genetic analysis of autoimmune disease.  Cell. 1996;  85 311-318
• 21 Tait KF, Marshall T, Berman J, Carr-Smith J, Rowe B, Todd JA, Bain SC, Barnett AH, Gough SCL. Clustering of autoimmune disease in parents of siblings from the type 1 diabetes Warren repository.  Diabetic Med. 2004;  21 358-362
• 22 Risch N. Linkage strategies for genetically complex traits. I. Multilocus methods.  Am J Hum Genet. 1990;  46 222-228
• 23 Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III).  J Clin Endocrinol Metab. 2002;  87 489-499
• 24 Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA. The Spectrum of thyroid disease in a community: the Whickham Survey.  Clin Endocrinol. 1977;  7 481-493
• 25 Jenkins RC, Weetman AP. Disease associations with autoimmune thyroid disease.  Thyroid. 2002;  12 977-988
• 26 Brix TH, Kyvik KO, Hegedüs L. What is the evidence of genetic factors in the etiology of Graves’ disease?.  A brief review. Thyroid. 1998;  8 727-734

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