Other Autoimmune Disorders

Thyroid Factor

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Probably the bulk of immunologically related studies in children and adolescents with autoimmune thyroid disease have addressed the frequency of association with other autoimmune disorders, especially type 1 diabetes melli-tus. Although there are few lessons to be gleaned from such reports in a narrow immunological sense, given the fact that all such disorders share similar genetic susceptibility factors, there are clear implications for screening, which in turn frequently leads to questions over the utility of TG and TPO antibody testing. The effectiveness of screening strategies for measuring non-thyroid autoantibodies in autoimmune thyroid disease has been reviewed recently [49]. Major difficulties in such association studies concern adequate population size and inclusion of suitably matched contemporary controls. In attempting to establish baseline frequencies for thyroid antibodies in the healthy population it is clear that age is crucial, since in females, but not males, the prevalence of thyroid antibodies increases at puberty and there is unexplained geographical heterogeneity which is not related to goitre prevalence or iodine intake [50].

Type 1 Diabetes Mellitus and Thyroid Autoimmunity

It is clear that thyroid autoimmunity is more frequent than expected in type 1 diabetes. However, the frequency of autoantibodies in diabetic patients which are directed against glutamic acid decarboxylase (65-kDa isoform) and IA-2 does not differ between those with or without other autoimmune disorders, including thyroid disease [51]. In a series of 216 diabetic children (mean age 13 years), 10% had TPO antibodies, 8.7% had TG antibodies and 5.9% had both autoantibodies [52]. Around half of those with thyroid antibodies had an elevated TSH and/or echographic features of thyroiditis on ultrasound, or developed these within a mean of 3.5 years of follow-up, and there was an increased risk in those with the highest antibody levels. A similar set of findings have come from a 3-year follow-up of 105 diabetic children with a mean age of 12.7 years at the beginning of the study; the prevalence of thyroid dysfunction rose from 5 to 8%, while the prevalence of TPO antibodies remained constant at 13% and TG antibody positively declined from 14 to 7% [53]. An even higher figure for thyroid autoantibody positivity (25%) was reported in 109 children with a mean age of 13, and the frequency in their first-degree relatives was 27% compared to half the prevalence in controls [54]. Another series found that 18.4% of 197 diabetic children had thyroid antibodies, compared to 7.8% of first-degree relatives and 3.2% of controls [55].

Both series also make clear that these patients are at a significantly increased risk of coeliac disease as well, and support the case for consideration of screening for both coeliac disease and thyroid disease in children with type 1 diabetes mellitus. Parietal cell antibodies are also found in around 20% of diabetic patients, but occur in a somewhat older patient population; those with concurrent thyroid autoantibodies are at 50% greater risk of developing parietal cell antibodies [56].

Other Diseases

Many other diseases are associated with autoimmune thyroid disease in adults but rather few studies have examined these specifically in children [57]. Pernicious anaemia is rare in the young, but in 129 children, mean age 9.7 years, with autoimmune thyroid disease, parietal cell antibodies were present in 30%, and almost half of these had elevated gastric levels [58]. In 80 Kuwaiti children aged less than 12 years with alopecia areata, 17.5% had some evidence biochemical evidence or positive thyroid autoantibodies [59]. Thyroid autoim-munity is also more common than expected in juvenile rheumatoid arthritis, and 25% of the relatives of such patients have autoimmune thyroid disease [60].

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