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thyroiditis Dr.m.ghasemi Ped endocrinologist Kermanshah university of medical sciences LYMPHOCYTIC THYROIOITIS (HASHIMOTO THYROIDITIS, AUTOIMMUNE THYROIDITIS) • the most common cause of thyroid disease in children and adolescents • formerly designated "adolescent" or "simple“ goiter. • also the most common cause of acquired hypothyroidism, with or without goiter. • 1-2% of younger school-aged children • and 4-6% of adolescents • have positive antithyroid antibodies as evidence of autoimmune thyroid disease. Etiology • lymphocytic infiltration of the thyroid • About 60% of infiltrating lymphoid cells are T cells and about 30% express B-cell markers • Thyroid antiperoxidase antibodies (TPOAbs; formerly called antimicrosomal antibodies) and antithyroglobulin antibodies are demonstrable in the sera of 90% of children with lymphocytic thyroiditis and in many patients with Graves disease. • Thyrotropin receptor-blocking antibodies are often present, especially in patients with hypothyroidism, • Antibodies to pendrin, in 80% of children with autoimmune thyroiditis. Clinical Manifestations 2-4 times more common in girls than in boys • It can occur during the first 3 yr of life but becomes sharply more common after 6 yr of age and reaches a peak incidence during adolescence. • The most common clinical manifestations are goiter and growth retardation. • The goiter can appear insidiously and may be small or large. • In most patients, the thyroid is diffusely enlarged, firm, and nontender. • In about 30% of patients, the gland is lobular and nodular. • Most of the affected children are clinically euthyroid and asymptomatic; some may have symptoms of pressure in the neck, including difficulty swallowing and shortness of breath • Some children have clinical signs of hypothyroidism, but others who appear clinically euthyroid have laboratory evidence of hypothyroidism. • A few children have manifestations suggesting hyperthyroidism, but results of laboratory studies are not necessarily those of hyperthyroidism. • Occasionally, the disorder coexists with Graves disease. • The goiter might become smaller or might disappear spontaneously, • or it might persist unchanged for years while the patient remains euthyroid. • Most children who are euthyroid at presentation remain euthyroid. • In children who initially have mild or subclinical hypothyroidism, over several years: • about 50% revert to euthyroidism, • about 50% continue to have subclinical hypothyroidism, and a few develop overt hypothyroidism. • Thyroiditis is the cause of most cases of nongoitrous (atrophic) hypothyroidism. • incidence in siblings or parents of affected children may be as high as 25%. • The disorder has been associated with many other autoimmune disorders. • Autoimmune thyroiditis occurs in 10% of patients with type I autoimmune polyglandular syndrome (APS- 1), characterized by autoimmune polyendocrinopathy, • candidiasis, and • ectodermal dysplasia (APCED). • APS-1(HAM syndrome) consists of 2 of the triad of • hypoparathyroidism, • Addison disease • mucocutaneous candidiasis • APS-1 is autosomal recessive Caused by mutations in the autoimmune regulatory (AIRE) gene • Autoimmune thyroiditis occurs in 70% of patients with APS-2 (Schmidt syndrome). • APS-2 consists of the association of • Addison disease with • type 1 diabetes mellitus (TIDM) • or autoimmune thyroid disease. • The etiology is unknown, and it typically occurs in early adulthood. • Autoimmune thyroid disease also tends to be associated with pernicious anemia, vitiligo, or alopecia. • TPOAbs are found in approximately 20% of white and 4% of black children with TIDM. • Autoimmune thyroid disease has an increased incidence in children with congenital rubella. • Lymphocytic thyroiditis is also associated with Turner syndrome and Down syndrome. • In children with Down syndrome • one study reported that • 28% had antithyroid antibodies (predominantly anti-TPOs), • 7% had subclinical hypothyroidism, • 7% had overt hypothyroidism,and • 5% had hyperthyroidism. • In a study of girls with Turner syndrome: • 41% had antithyroid antibodies (again, predominantly anti-TPOs), • 18% had goiter • 8% had subclinical or overt hypothyroidism. Laboratory Findings • Thyroid function tests (free T4 and TSH) are often normal, • although the level of TSH may be slightly or even moderately elevated in some patients, termed subclinical hypothyroidism • goiter may be caused by the lymphocytic infiltrations or by thyroid growth-stimulating immunoglobulins. • Young children with lymphocytic thyroiditis have serum antibody titers to TPO, but the TG test for thyroid antibodies is positive in <50%. • Antibodies to TPO and TG are found equally in adolescents with lymphocytic thyroiditis. • When both tests are used, approximately 95% of patients with thyroid autoimmunity are detected. • Thyroid scans and ultrasonography usually are not needed. • thyroid scans reveal irregular and patchy distribution of the radioisotope, • and in about 60% or more, the administration of perchlorate results in a >10% discharge of iodide from the thyroid gland. • Thyroid ultrasonography shows scattered hypoechogenicity in most patients. • The definitive diagnosis can be established by biopsy of the thyroid; this procedure is rarely clinically indicated. Treatment • If there is evidence of hypothyroidism (overt or subclinical),replacement treatment with levothyroxine (at doses specific for size and age) is indicated. • The goiter usually shows some decrease in size but can persist for years. • In a euthyroid patient, treatment with suppressive doses of levothyroxine is unlikely to lead to a significant decrease in size of the goiter. • Antibody levels fluctuate in both treated and untreated patients and persist for years. • Because the disease is self-limited in some instances, the need for continued therapy requires periodic reevaluation. • Untreated patients should also be checked periodically. • prefer to treat Children with subclinical hypotyroidism until growth and puberty are complete, and then reevaluate their thyroid function • Prominent nodules, i.e. >1.0 cm, that persist despite suppressive therapy should be examined histologically using FNA, • because thyroid carcinoma or lymphoma has occurred in patients with lymphocytic thyroiditis