**6. Infections**

Several infections have been implicated in the pathogenesis of HT including Helicobacter pylori, Borrelia burgdorferi, Yersinia enterocolitica, Coxsackie virus, and retroviruses. Furthermore, recent studies but not all have substantiated a strong association between HT and HCV (24,25).

Seasonal and geographic variations also support infection as a trigger of HT (11,23). Various mechanisms have been proposed to explain induction of autoimmunity by infection but it seems that three possibilities may be important in individuals susceptible to developing autoimmune disease: molecular mimicry (perhaps to retroviruses); polyclonal T cell activation (by an endogenous superantigen or an infecting organism); and MHC class II antigen induction (26). Although infections may promote HT, they can also be partially protective, as suggested by the hygiene hypothesis. According to this hypothesis, the immune system builds tolerance to repeated infectious exposures, and this may explain a lower prevalence of thyroid antibodies in those of lower socioeconomic class (27).

#### **6.1 Environmental toxins**

Many environmental pollutants, such as polyaromatic hydrocarbons, perfluorinated chemicals, phthalates, and bisphenol A, have been shown to be toxic to thyroid cells and promote the onset of HT (15). These chemicals are widely used in various industrial and consumer products and may specifically have thyroid-disrupting properties (28,29). Polyaromatic hydrocarbons, including polychlorinated biphenyls and polyhalogenated biphenyls, are organic compounds produced from coal and found in air and water, and they can possibly trigger thyroiditis. Polyhalogenated biphenyls are commonly used compounds in products including adhesives, lubricants, and flame retardants, while polychlorinated biphenyls are found in plasticizers. A high prevalence of hypothyroidism was observed in individuals exposed to polyhalogenated biphenyls with an associated elevation in antimicrosomal antibodies and anti-Tg antibodies (30). In view of the evidence that many of these chemicals can interfere with thyroid function, there is a growing concern about their effects on neurological development during embryonic life (15,29). Exposure during pregnancy, for example, which itself is a risk factor for HT, can have hazardous effects on the developing fetus in which normal thyroid hormone levels are crucial for normal growth

Hashimoto's Thyroiditis in Children and Adolescents 31

goiter during routine examination (38). Staii et al. reviewed 761 patients for which ultrasound guided thyroid fine needle aspiration biopsy were performed for nodule. The HT cohort consisted of 102 (13.4%) patients (659 out of 761 did not have cytological Hashimoto's diagnosis) for which 46 (6%) were identified as having clinical disease (i.e. diagnosed hypothyroid on thyroid hormone replacement and with cytological Hashimoto's diagnosis), 9 (1.2%) as having subclinic hypothyroidism and 47 (6.2%) as having euthyroid autoimmunity (36). Occasionally, the disorder may coexist with Graves's disease. Ophthalmopathy may occur in lymphocytic thyroiditis in the absence of Graves's disease. Hashimoto's encephalopathy is a rare condition and the estimation of incidence and prevalence is difficult. One prospective study examining cases of unexplained encephalopathy that had detectable antithyroid antibodies, estimated a prevalence of 2.1/100 000 subjects (39). Adequate information is not available about the frequency of Hashimoto's encephalopathy in children (40). The clinical picture of a relapsing and remitting encephalopathy in a female characterised by seizures, stroke-like episodes, neurological signs such as myoclonus and tremor, cognitive disturbance and hallucinations, and other psychotic symptoms is highly suggestive of Hashimoto's encephalopathy (41). Normal routine investigations, nonspecific neuroimaging and CSF findings (apart from elevated protein), and encephalopathic EEG can be supportive of the diagnosis. Thyroid hormone studies are not helpful, but may identify subclinical thyroid dysfunction (41). Detection of antithyroid (in particular anti-TPO) antibodies confirms the diagnosis. As anti-TPO antibodies are detected in as many as 10 % of the general population, (42) high titres (usually over 100-fold normal (43)) of these antibodies in conjunction with the clinical features of Hashimoto's encephalopathy are necessary before a diagnosis can be made. Thyroid antibody levels should be measured even in the setting of normal thyroid function and the diagnosis of Hashimoto encephalopathy has to be considered in patients with Down syndrome who present with rapid cognitive decline, particularly in association with myoclonus and an abnormal EEG result (44). Corticosteroid responsiveness can also support

HT may be the initial presentation of an autoimmune polyglandular syndrome, and the possibility of coexisting autoimmune diseases such as type I diabetes, celiac disease, Addison's disease, and pernicious anemia must be addressed by the past medical history (46). In a study performed on 268 children with type I diabetes mellitus, the percentage of those who presented with circulating thyroperoxidase and Tg antibodies was signicantly higher than those with celiac disease (47). In another study performed in Bratislava, 40-50% of patients with different types of diabetes had autoimmune thyroiditis (48). The incidence of histologic ndings of autoimmune thyroid disease in diabetic patients increases with age (49). Several other studies have conrmed the coincidence of autoimmune thyroiditis and latent or overt diabetes (50) and relatives of patients with type I diabetes have an increased incidence of HT (51). In a recent study, genetic susceptibility between autoimmune thyroiditis and diabetes was investigated among 448 individuals. Three loci in

Hashimoto's thyroiditis sometimes may be associated with connective tissue, cutaneous, hematologic (pernicious anemia, idiopathic thrombocytopenic purpura), gastrointestinal (autoimmune liver disease, celiac disease), genetic (autoimmune polyglandular syndrome

the diagnosis (45).

**9. Related disorders** 

chromosomes 2q, 6p and Xp were identied (52).

and brain development. It is important, therefore, to be aware of environmental triggers of HT and to monitor thyroid functions closely in susceptible women during pregnancy (15,23).
