Chronic lymphocytic thyroiditis (hashimoto thyroiditis, autoimmune

Chronic lymphocytic thyroiditis (Hashimoto Thyroiditis ) The most common cause of thyroid disease in children and adolescents and the most common cause of acquired hypothyroidism, with or without goiter. Approximately 60% of infiltrating lymphoid cells are T cells, and approximately 30% express B-cell markers.A variety of different thyroid antigen autoantibodies are involved

1. Chronic Lymphocytic Thyroiditis (Hashimoto Thyroiditis, Autoimmune Thyroiditis ) Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital ,Sharjah, UAE [email protected]

2. Background Chronic lymphocytic thyroiditis The most common cause of thyroid disease in children and adolescents The most common cause of acquired hypothyroidism, with or without goiter. One to 2% of younger school-age children and 6-8% of adolescents have positive antithyroid antibodies as evidence of autoimmune thyroid disease. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 2

3. Etiology Inheritance of susceptible genes involved in immunoregulation ?? AND Environmental triggers ?? 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 3

4. Sequence of thyroid gland involvement Lymphoid follicle formation with germinal centers is almost always present T he degree of atrophy and fibrosis of the follicles varies from mild to moderate. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 4

5. Infiltrating cells Approximately 60% of infiltrating lymphoid cells are T cells , and approximately 30% express B-cell markers The T-cell population is represented by helper (CD4  + ) and cytotoxic (CD8  +  ) cells.  8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 5

6. Infiltrating cells (Cont.) Human leukocyte antigen ( HLA ) haplotypes: HLA-DR4 & HLA-DR5 : Are associated with an increased risk of goiter and thyroiditis HLA-DR3 : Are associated with the atrophic variant of thyroiditis. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 6

7. Thyroid antigen autoantibodies A variety of different thyroid antigen autoantibodies are also involved . Thyroid antiperoxidase antibodies ( TPO-Abs ) Antithyroglobulin antibodies ( anti- Tg Abs ) Are demonstrable in the sera of 90% of children with chronic lymphocytic thyroiditis 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 7

8. Thyroid antigen autoantibodies (Cont.) TPO-Abs are involved in: Activation of the complement cascade Antibody-dependent , cell-mediated cytotoxicity. Anti- Tg Abs do not appear to play a role in the autoimmune destruction of the gland. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 8

9. Cont. Thyroid-stimulating hormone (TSH) receptor–blocking antibodies Are related to the development of hypothyroidism and thyroid atrophy they have been demonstrated in 18% of patients with severe hypothyroidism (TSH >20  mU /L) caused by autoimmune thyroiditis . 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 9

10. Cont. Antibodies to pendrin , an apical protein on thyroid follicular cells have been demonstrated in 80% of children with autoimmune thyroiditis. Antibodies against the sodium–iodide symporter their pathogenic role is unclear. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 10

11. Clinical Manifestations The disorder is 4-6 times more common in girls than in boys . It can occur during the 1st 3  yr. of life B ecomes sharply more common after 6  yr . of age and reaches a peak incidence during adolescence . 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 11

12. Clinical Manifestations (Cont. ) 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. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 12

13. Clinical Manifestations (Cont. ) In approximately 30% of patients, the gland is asymmetric and can seem to be 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. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 13

14. Clinical Manifestations (Cont. ) 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, such as nervousness, irritability, increased sweating, and hyperactivity, but results of laboratory studies are not necessarily those of hyperthyroidism 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 14

15. Clinical course The clinical course is variable. The goiter might: Become smaller Disappear spontaneously Persist unchanged for years while the patient remains euthyroid. Most children who are euthyroid at presentation remain euthyroid, although a percentage of patients acquire hypothyroidism gradually within months or years . 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 15

16. Clinical course (Cont.) In children who initially have mild or subclinical hypothyroidism (elevated serum TSH, normal free thyroxine[T 4 ]level ), over several years approximately: 40% revert to euthyroidism 50% continue to have subclinical hypothyroidism, 10 % develop overt hypothyroidism (elevated serum TSH, subnormal free T 4 level). Chronic lymphocytic thyroiditis is the cause of most cases of nongoitrous (atrophic) hypothyroidism 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 16

17. Other associated autoimmune disorders The disorder is associated with many other autoimmune disorders . Autoimmune thyroiditis occurs in: 10% of patients with type I autoimmune polyglandular syndrome ( APS-1) 70 % of patients with APS-2 Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome Associated with pernicious anemia, vitiligo, or alopecia Children with congenital rubella. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 17

18. Associated with chromosomal disorders Chronic lymphocytic thyroiditis also is associated with certain chromosomal disorders, particularly Turner syndrome and Down syndrome. In children with Down syndrome: 28 % had antithyroid antibodies (predominantly anti-TPOs ) 7 % had subclinical hypothyroidism 7 % had overt hypothyroidism, 5 % had hyperthyroidism 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 18

19. Associated with chromosomal disorders (Cont.) 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. Autoimmune thyroid disease increased from the 1st (15%) to the 3rd (30%) decade of life . Boys with Klinefelter syndrome appear to be at risk for autoimmune thyroid disease 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 19

20. Laboratory Findings Thyroid function tests (free T 4 and TSH) are often normal I n some patients , the level of TSH may be slightly or even moderately elevated which is termed subclinical hypothyroidism . Many children do not have elevated levels of TSH (indicates that the goiter is caused by: L ymphocytic infiltrations or T hyroid growth-stimulating immunoglobulins . 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 20

21. Laboratory Findings (Cont.) In young children with chronic lymphocytic thyroiditis have serum TPO-Abs and t he anti- Tg Abs are positive in <50 %. In adolescents with chronic lymphocytic thyroiditis, TPO-Abs and anti- Tg Abs are found equally. When both tests are used, approximately 95% of patients with thyroid autoimmunity are detected . 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 21

22. Laboratory Findings (Cont.) Levels in children and adolescents are lower than those in adults with Hashimoto thyroiditis, In adolescent females with overt hypothyroidism, measurement of TSH receptor–blocking antibodies may identify patients at future risk of having babies with transient congenital hypothyroidism. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 22

23. Laboratory Findings (Cont.) Thyroid scans and ultrasonography usually are not needed. The definitive diagnosis can be established by biopsy of the thyroid; this procedure is rarely clinically indicated. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 23

24. Histopathology 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 24 http:// www.pathologyoutlines.com/topic/thyroidhashimotosthyroiditis.html

25. Treatment If there is evidence of overt hypothyroidism (elevated TSH, low T 4 or free T 4) , 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. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 25

26. Treatment (Cont.) Antibody levels fluctuate in both treated and untreated patients and persist for years . T he disease is self-limited in some instances, so the need for continued therapy requires periodic reevaluation . 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 26

27. Treatment (Cont.) Untreated patients should also be checked periodically . Concerning subclinical hypothyroidism (elevated TSH, normal T 4 or free T 4 ), It is preferable to treat such children until growth and puberty are complete, and then reevaluate their thyroid function. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 27

28. References Brown RS: Autoimmune thyroiditis in childhood. J Clin Res Pediatr Endocrinol 2013; 5: pp. 45-49 . de Vries L, Bulvik S, Phillip M: Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child 2009; 94: pp. 33-37 . Fava A, Oliverio R, Giuliano S, et. al.: Clinical evolution of autoimmune thyroiditis in children and adolescents. Thyroid 2009; 19: pp. 361-367 . Zimmermann MB, Hess SY, Molinari L, et al., New reference values for thyroid volume by ultrasound in iodine-sufficient schoolchildren: a World Health Organization/Nutrition for Health and Development Iodine Deficiency Study Group Report. Am J Clin Nutr 79 (2004) 231-237 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 28

29. 8/29/2017 Chronic lymphocytic thyroiditis Prof. Dr. Saad S Al Ani 29 http://www.presentermedia.com