**9. Related disorders**

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

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

Hashimoto's Thyroiditis in Children and Adolescents 33

diagnosis but it is recommended to conrm the presence of a thyroid nodule, solitary or multiple nodule can be detected both hypothyroid or euthyroid patients. During disease progression, reduced echo levels develop gradually, reflecting either reduction of colloid content and increased intrathyroidal blood flow or lymphocytic tissue infiltration, which induces diffuse fibrosis (64). The appearance of thyroid gland on ultrasonography may be normal at diagnosis, but characteristic changes evolve over time. Vlachopapadopoulou et al. studied 105 children, the time needed for 30%, 50%, and 70% of children to demonstrate an abnormal thyroid sonographic pattern has been detected 4, 7, and 14 months, respectively. Important factors accelerating sonographic changes have been demonstrated as goiter, hypothyroidism, and seropositivity for both anti-TPO and anti-Tg autoantibodies (67).

Hashimoto's thyroiditis is diagnosed based on findings of seropositivity for Tg autoantibodies and/or TPO autoantibodies, accompanied by at least one of the following: abnormal thyroid function; enlarged thyroid gland; morphological changes on thyroid ultrasound. If anti-TPO antibodies are absent, less common etiologies of primary hypothyroidism should be considered for example transient hypothyroidism due to postsubacute thyroiditis, hypothyroidism related to external irradiation (69) and consumptive hypothyroidism due to the inactivation of thyroid hormone by the paraneoplastic expression of type III iodothyronine deiodinase, mostly in vascular tumors

The typical patient with hypothyroidism secondary to HT has an elevated TSH, a low fT4, and positive anti-TPO antibodies. In early stages of the disease, TSH may be normal and anti-TPO antibodies may be positive with or without goiter. Later, TSH elevation becomes modest (5-10 IU/mL) with a normal fT4 (biochemical or subclinical hypothyroidism). Up to 90% of patients with hypothyroidism secondary to HT have positive anti-TPO antibody (46). If HT is suggested and thyroid autoantibodies are negative, they should be controlled later.

Most of these patients are asymptomatic, but studies in the adult population suggest that individuals with the combined risk factors of TSH level above the normal limit and positive thyroid antibodies (anti-Tg or anti-TPO) are at high risk for progression to overt hypothyroidism. For this reason, thyroid hormone replacement is recommended in all patients with TSH values >10 IU/mL or with TSH values >5 IU/mL in combination with goiter or thyroid autoantibodies (71). Levothyroxine is the replacement therapy of choice. There are almost no adverse reactions; its good intestinal absorption and its long half life of 5-7 days allow oral administration once a day. Although very rare, the development of pseudotumor cerebri associated with the initiation of LT4 has been described in a few school-age children (72). Alternatively, a starting dose can be estimated based upon the patient's age and ideal body weight (73). The medication's long half-life insures a gradual equilibration over the course of 5 – 6 weeks, and dosing should be individualized based on biochemical monitoring (73). TSH normalization (0.5-2 micro IU/mL) is the goal of replacement. This will usually be associated with an fT4 in the upper half of the normal range. Thyroid function tests should be obtained about 6-8 weeks after the beginning or next

**12. Diagnosis** 

It is possible to raise in follow-up.

**13. Treatment** 

(70).

type II/III, ovarian failure, Down syndrome, Klinefelter's syndrome, Turner's syndrome), infectious (Hepatitis C infection), neurologic (Miller Fisher syndrome, Guillain-Barre´ syndrome, multiple sclerosis, myasthenia gravis) and renal diseases (minimal change glomerular disease) (53).

The coexistence of papillary thyroid carcinoma and HT is not known exactly, but it is reported to range from 10% to 58% in various studies (54,55). The prevalence of HT in patients with papillary thyroid carcinoma has been reported to be signicantly higher than with benign thyroid tumours (56). Patients with HT are suggested to be at higher risk for papillary thyroid carcinoma compared with patients without HT (57)
