Thyroid Autoimmune Diseases
Thyroid Autoimmune Diseases
Thyroid Autoimmune Diseases
Mechanism of development of Autoimmune endocrine disease: Two factors could be involved in development of human autoimmune disorders: 1-Expression of Class II HLA (human leukocyte antigen) on the surface of target endocrine cells.
Infectious agent (or Self-antigen) Inflammatory cells chemotaxis(INF)
Expression of HLA
Definition: -It is an autoimmune disease in which the thyroid gland is attacked by a variety of cell- and antibody-mediated immune processes. -The first disease recognized as autoimmune disease. -Described by the Japanese specialist (Hakaru Hashimoto) in Germany in 1912. -Hypothyroidism, large and lobulated thyroid gland. -Enlargement of thyroid due to lymphocytic infiltration and fibrosis.
General considerations: -Family history of thyroid disease and HLA gene polymorphism (DR4, DR5). -CTLA-4 (Cytotoxic T-Lymphocyte gene A-4) Polymorphism; results in reduced negative regulation of T-lymphocytes. -Studies on Monozygotic twins show: Anti-Thyroid Antibodies (Gene homology of 80%). Other Risk factors: -Infectious agents : Human Herpes Virus-6 (A, and B). -Chromosomal disorders: Turner ,Klinefelters, and Downs Syndrome. - Pollutants (Tobacco smoke).
-Most common in middle-aged and starts in adulthood. - 5-10 times more common in woman than in men. -Associated with other autoimmune diseases such as: Systemic lupus erythematosus, dermatitis, and scleroderma.
Pathogenesis: -Expression of MHC Class II-self epitope complex on the thyroid cuboidal cell surface. -Thyroid cell-CD4+ Lymphocyte interaction. -Cytokines production, and chemotaxis of CTL and Macrophage. -CTL-Thyroid cell interaction; Loss of T lymphocyte suppressor function due to CTL gene A mutation. -Killing of target cell by CTL; Apoptosis.
-Formation of Auto-reactive antibodies; Anti- thyroid peroxidase(90%), and Anti-thyroglobulin Antibodies(70%). -Sensitization of Thyroid tissue ( thyrocyte).
-ADCC for cuboidal cells lining the thyroid follicles by CD8+ and N.K cells.
Histologically:
-Diffuse parenchymal infiltration of lymphocyte; mainly Blymphocytes which can be seen as secondary lymphoid
Germinal center: lymphocyte infiltrate. Pink reactive dying thyroid cell : with cytoplasmic-acidophilic granules.
Clinical Features of Chronic thyroiditis: Primary stage: -Clinical hyperthyroidism due to inflammatory breakdown of thyroid follicles ( Silent, Painless inflammation). Late stage: -Hypothyroidism due to progressive destruction of thyroid tissue and cellular malfunction. -The most common outcome of Hashimotos disease is the hypothyroidism.
Clinical presentation of Chronic thyroiditis: -A consistent physical sign seen in Hashimotos disease is an enlarged thyroid gland (Goiter). (Rubbery-nodular thyroid).
- Lymph nodes surrounding the gland become enlarged. - Depression, Fatigue, Constipation, and dry skin.
-Rarely, Symptoms of generalized vasculitis with urticaria and nephritis could be seen due to presence of circulating immune complexes.
Graves Disease:
Definition: -It is an autoimmune disease where the thyroid is
General Considerations:
-Hyperthyroidism and thyrotoxicosis with a diffuse goiter. - About 30-50% of people with Graves' disease will also suffer from Graves' ophthalmopathy caused by inflammation of the eye muscles by attacking autoantibodies.
-Specific cross-reactivity between some microbes (Viruses; Coxsackievirus, and bacteria; Yersinia enterocolitica) and TSH-Receptor of thyroid follicular cells. -Strong association with DR3, DQ , and DQ genotype of MHC II haplotypes. -Family History:
The disease is associated with different types of generalized autoimmune susceptibility; such as Hashimotos disease and antibodies to gastric intrinsic factors.
Clinical presentation:
-Goiter, exophthalmos(30-50%), muscle weakness, weight loss,
diarrhea and frequent defecation, hyperactivity ,tachycardia, hair loss, and Oligomenorrhea.
Anti-thyroid antibodies could be detected by: 1-ELISA Test: Microtiter plate wells should be coated by recombinant Human TSH-receptors. 2-Tissue culture (Fisher Rat thyroid cell line 5): -It can be used to measure the presence and activity of Anti-thyroid antibodies ( IgG) in patient's sera. -Serum specimens should be incubated with cell line culture; then : The cAMP activity and the incorporation of radioactive thymidine are measured.