Download Thyroid Autoimmune Diseases:

Endocrine 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
Inflammatory cells chemotaxis(INFγ)
Expression of HLA
Presentation of own
cellular proteins; reactive
T and B cell response.
N
2-The antigen Cross-reactivity:
external organic material
or infectious agents epitopes
Show
antigenic crossreactivity with
target tissues.
formation of
Auto-reactive
Humoral immune response
antibodies.
Tissue destruction.
Thyroid Autoimmune Diseases:
Chronic Thyroiditis: (Hashimoto’s thyroiditis):
Definition:
It is an autoimmune disease in which the thyroid gland is
attacked by a variety of cell- and antibody-mediated
immune processes.
General considerations:
-Family history of thyroid disease and HLA gene
polymorphism (DR4, DR5).
-Most common in middle-aged and elderly patients.
-Females make up the vast majority of patients (85%).
N
Major Immunologic features of Hashimoto’s thyroiditis:
1-The lymphocytic infiltration of the thyroid gland.
2-The Antibodies against thyroid antigens are present.
3-The cellular sensitization to thyroid antigens.
Germinal center: lymphocyte infiltrate.
Pink reactive dying thyroid cell :
with cytoplasmic-acidophilic granules.
Immunohistochemistry for P63.
:Positive in Germinal center (H.T).
N
Pathogenesis mechanism in Hashimoto’s thyroiditis:
-Various Autoantibodies are present against thyroid
peroxidase, and thyroglobulin.
-Sensitization of Thyroid tissue
( thyrocyte).
-CD8 and NK cell hyperactivity
by ADCC (Antibody-Dependent
Cell-Mediated Cytotoxicity )
mechanism.
-Apoptosis of thyrocyte.
-CD4 response, and chemotaxis
of macrophage.
Clinical Features of chronic thyroiditis:
Primary stage:
-Clinical hyperthyroidism due to inflammatory breakdown
of thyroid follicles.
Late stage:
-Hypothyroidism due to progressive destruction of thyroid
tissue and cellular malfunction.
-The most common outcome of Hashimoto’s disease is
the hypothyroidism.
Signs and Symptoms of Chronic thyroiditis:
-A consistent physical sign seen in Hashimoto’s disease is
an enlarged thyroid gland (Goiter).
-Often, lymph nodes surrounding
the gland become enlarged.
-Rarely, Symptoms of generalized vasculitis with urticaria
and nephritis could be seen due to presence of circulating
immune complexes.
Differential diagnosis of Chronic thyroiditis:
-The hallmark of the diagnosis of this disease is the
presence of circulating Autoantibodies:
1-Anti-thyroglobulin antibodies.
2-Anti-thyroid peroxidase antibodies.
-These antibodies show a sensitivity of 90% and detected
by:
1-Immunofluorescence assay.
2-ELISA.
3-Agglutination assay.
-In patients without serum antibodies, autoantibodies are
localized in intrathyroidal lymphoid follicles.
Graves’ Disease:
Definition:
-It is an autoimmune disease where the thyroid is
activated by anti-TSH receptor autoantibodies to produce
excessive amount of thyroid hormones.
-The most common cause of hyperthyroidism (60-90% of
all cases).
-It has a powerful hereditary component, affects up to 2%
of the female population, and is between five and ten
times as common in females as in males.
n
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.
Graves’ Goiter: hyperthyroidism
The orbit around the eye: upper eyelid
retraction, edema, erythema, and
conjunctivitis.
N
-Specific cross-reactivity between some microbes (Viruses;
Coxsackievirus, and bacteria; Yersinia) and TSH-Receptor
of thyroid follicular cells.
-Strong association with DR3, DQα , and DQβ genotype of
MHC II haplotypes.
-Family History:
The disease is associated with different types of generalized
autoimmune susceptibility; such as Hashimoto’s disease and
antibodies to gastric intrinsic factor.
N
Major Immunologic features of Graves’ disease:
1-Antibodies against thyroid antigen are present; that
stimulate thyroid cell function.
2-Class II HLA expression on the surface of thyroid cells.
3-Associated autoimmune ophthalmopathy.
Pathogenesis mechanism of Graves’ disease:
-Autoantibodies present against TSH-receptor:
1- Thyroid-stimulating immunoglobulins (TSI):
Activate TSH-receptor; elevated thyroid hormones.
2- Thyroid growth immunoglobulins( TGI) :
Growth of thyroid follicles.
3-Thyroid binding-inhibiting immunoglobulins (TBII) :
Inhibits TSH binding.
-No Cellular immune response; Histology show no destruction
of thyroid tissues.
-Colloid suspension show lymphocytic infiltration: CD4, CD8,
and B lymphocytes.
Pathogenesis mechanism of Graves’ disease:
N
Diagnosis of Graves’ disease:
-Clinically: Signs and symptoms of hyperthyroidism.
-Radiology: Increased uptake of radioactive iodine.
-Serology:
A-Elevated Total and free T4, and T3.
B-Identification of Anti-thyroid antibodies in patient’s sera:
1-Antibodies that activate cellular cAMP ; Thyroid
stimulating Immunoglobulin (TSI).
2-Thyroid growth stimulating immunoglobulins (TGI).
3-Antibodies that displace the binding of TSH from its
receptor (TBII).
N
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.