**8. Conclusions**

It is now established that patients with type 1 diabetes are at increased risk of other autoimmune diseases as compared to general populations (Michels & Eisenbarth, 2010). Besides islet-cell autoantibodies, other antibodies against numerous non -cell antigens have been frequently reported. Clinically-evident diseases are rarely observed in young patients with type 1 diabetes, and can be considered as the tip of the iceberg. Latent forms of these autoimmune-associated diseases, characterized by the presence of circulating autoantibodies with mild or no symptoms, are more frequent. Early detection of antibodies and latent organ-specific dysfunction are advocated to alert physicians to take appropriate actions aimed to prevent full-blown disease. Moreover patients and their relatives should be instructed to recognize subclinical signs and symptoms attributable to these autoimmune-associated diseases. Several risk factors have been identified for a group of autoimmune diseases like genetic background, gender, age, age at clinical onset and duration of diabetes.

#### **9. References**

20 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights

disease in early childhood; other endocrine and non-endocrine disorders can be associated: thyroiditis, autoimmune hypogonadism, hypophysitis, chronic active hepatitis, atrophic gastritis, pernicious anemia, alopecia, vitiligo and ectodermal dystrophy (Mazza et al., 2011). The disease results from the inheritance of recessive genes (AIRE gene) mapping to 21q22.3 and it is not linked to genes within the HLA-DR/DQ genetic region of chromosome 6. **Type II APS** is more common than type 1 APS, the prevalence is 1/20,000 with a female preponderance (male/female ratio = 1/3) and has a peak incidence between the ages of 20 and 60 years, mostly in the third or fourth decade (Van den Driessche et al., 2009). It is defined by the association of Addison's disease with thyroid autoimmunity, type 1 diabetes and sometimes pernicious anemia, vitiligo and hypogonadism. Type II APS is HLAassociated (DQB1\*0302/0201), while Hashimoto's thyroiditis itself is associated with HLA-DQB1\*0301. Multiple antigens have now been identified for the component disease of type II APS ie: thyroperoxydase and thyroglobulin in Hashimoto's thyroiditis; TSH receptors I Graves' disease; insulin, GAD and IA-2 and IA-2B in type 1 diabetes mellitus; 21 hydroxylase in Addison's disease; 17 hydroxylase and SCC (all p450 enzymes) in hypogonadism; tyrosine in vitiligo; H+K+ATPase an intrinsic factor in pernicious anemia and the calcium sensing receptor (CaSR) in hypoparathyroidism. Indeed the autoantibody that reacts to CaSR does so through its external domain, suggesting that the respective autoimmunity (hypoparathyroidism) may be antibody dependent. In mice, such immune responses proceeded through a T cell helper-2 (Th2) pathway; whereas those that results in cell mediated pancreatic β-cell loss are though to occur through a Th1 pathway. It could be that APS I results from an inherited defective Th1 responsiveness resulting in uninhibited Th2 overactivity. On the other hand, APSII/III appears to results from Th1 autoimmunity,

perhaps explaining why APS-I does not co-exist with APS-II or III.

upon their cytokine phenotypes.

**8. Conclusions** 

duration of diabetes.

CD4+ T helper (Th) cells play important roles in regulating immune responses including that of immunological tolerance to self. When these regulatory processes go away, one or more organ-specific autoimmune disease may develop. One prevailing theory developed in the mice is that immunoresponsiveness follows at least two polarized pathways. While one track (Th1) promotes cellular immune responses, the other (Th2) pathway favours antibody or allergic immunoresponsiveness. Such differentiated Th cells can be distinguished based

It is now established that patients with type 1 diabetes are at increased risk of other autoimmune diseases as compared to general populations (Michels & Eisenbarth, 2010). Besides islet-cell autoantibodies, other antibodies against numerous non -cell antigens have been frequently reported. Clinically-evident diseases are rarely observed in young patients with type 1 diabetes, and can be considered as the tip of the iceberg. Latent forms of these autoimmune-associated diseases, characterized by the presence of circulating autoantibodies with mild or no symptoms, are more frequent. Early detection of antibodies and latent organ-specific dysfunction are advocated to alert physicians to take appropriate actions aimed to prevent full-blown disease. Moreover patients and their relatives should be instructed to recognize subclinical signs and symptoms attributable to these autoimmune-associated diseases. Several risk factors have been identified for a group of autoimmune diseases like genetic background, gender, age, age at clinical onset and


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**2** 

*Turkey* 

**Hashimoto's Thyroiditis in** 

**Children and Adolescents** 

Erkan Sar, Abdulbaki Karaoglu and Ediz Yeşilkaya

*Gülhane Military Medical Academy Department of Pediatric Endocrinology, Ankara,* 

Hashimoto's thyroiditis (HT) is an autoimmune disease with genetic background. It is also named as autoimmune thyroiditis or chronic lymphocytic tiroiditis. Hashimoto's thyroiditis is the most common cause of thyroid diseases in children and adolescents and it is also the most common cause of acquired hypothyroidism with or without goiter. Hashimoto's thyroiditis was rst described in 1912 by Hakura Hashimoto in a series of patients with diffusely enlarged, rm thyroid glands with distinct pathologic features, classied as chronic lymphocytic thyroiditis (1). The characteristic histologic features include diffuse lymphocytic inltration, atrophic follicles, well-developed germinal centers, and brosis. Hashimoto's thyroiditis is the most important cause of hypothyroidism in children and adolescents. In an American population with age between 11 and 18 years, five new cases were detected out of 1,000 adolescents screened every year. It is more common among girls, varying from 4:1 to 8:1 depending on the geographical region. Although the disease can be seen before three years of age, it is usually seen after six years of age and its peak ages are 10 and 11 years (2). The prevelance of Hashimoto's thyroiditis between 6-18 years old is 3% in Japan. Thirty-40% of the cases have familial history of thyroid disease. It occurs far more often in women than in men (between 10:1 and 20:1), and is most prevalent between 45 and 65 years old. Autoimmune thyroid disease (AITD) has two clinical forms: a goitrous form more common in young age groups, in whom goiter may be the only clinical expression (3), often referred to as classical Hashimoto's disease, and an atrophic one often called atrophic thyroiditis (4). Both are characterized by circulating thyroid autoantibodies and varying degrees of thyroid

The prognosis is not known very well, and studies reporting about long-term outcome of the disease are scarce (3,5). Thyroid function tests show variations at the time of diagnosis; mostly euthyroid or hypothyroid and rarely hyperthyroid. Hypothyroidism is thought to be a permanent sequelae of HT. Patients with overt hypothyroidism may have been recommended lifelong levothyroxine (LT4) therapy but it should be checked after puberty if

Hashimoto's thyroiditis is inuenced by both genetic and environmental factors (6). Family and twin studies support the evidence for genetic susceptibility (7-9). Dittmar et al. (10) have

dysfunction, differing only by the presence or absence of goiter.

LT4 therapy is still necessary or not.

**2. Etiology** 

**1. Introduction** 

