Autoimmune Diseases of the Endocrine System Flashcards
(38 cards)
What are the most common auto-immune endocrine disorders?
-Thyroid Gland (Autoimmune thyroiditis) –> Graves’ and Hashimoto
- Adrenal Gland –> Addisons
- Pancreas –> Type I Diabetes
- Polyglandular –> Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)
What is Hashimoto’s Thyroiditis?
chronic autoimmune hypothyroidism that creates thyroid-peroxidase antibodies and thyroglobulin antibodies
** most common cause of hypothyroidism in US and pregnancy
what are the manifestations of Hashimoto’s Thyroiditis?
- goiters
- enlarged tongue, thick lip, low salivary gland function, dysphagia
- kidney dysfunction
- Myxedema (severe, advanced hypothyroidism)
What are the key genetic risk factors for Hashimoto’s Thyroiditis?
- HLA-DR3: type of MHC class II molecule
- PTPN22 mutation: gene that regulates T cell responses causing over activation
- CTLA-4 mutation: “checkpoint” protein that helps turn off T cells
- FOXP3 mutation: control of regulatory T cells, which suppress overactive immune responses
What occurs during Pathogenesis in Hashimoto’s Thyroiditis?
- Innate cells start inflammation: macrophages and dendritic cells
- Helper T cells amplify it
- Regulatory T cells are suppressed
- Cytokines fuel destruction: IFN-y and TNF-a –> thyrocyte apoptosis
- Autoantibodies continue damage: antibodies against Thyroid peroxidase (TPO) and Thyroglobulin
- Bell Cells Present Auto-antigens: complement mediated cytotoxicity
What are the environmental triggers for Hashimoto’s Thyroiditis?
- Infections, Stress, Smoking
- Radiation
- Medications
- Nutrition
How are Iodine, Selenium, Iron and Vitamin D associated with Hashimoto’s Thyroiditis?
- Iodine: boosts immune visibility of thyroglobulin → triggers TPO antibodies → autoimmune flare ups
- Selenium: deficiencies ↑ T cells, Imbalances Th1/Th2 responses, reduces regulatory T cells
- Iron: deficiencies enhance recognition of thyroid proteins
- Vitamin D: deficiencies promote B cells into antibody producing plasma cells
What are the treatments for Hashimoto’s Thyroiditis?
- No Permanent Cure
- Thyroxine Replacement Therapy: main treatment → levothyroxine
- Supplementation: Selenium and Vit D
What is the treatment for serious cases of Hashimoto’s Thyroiditis with organ damage?
High doses of corticosteroids are used to reduce inflammation and are often combined with immune suppressants
- methotrexate, azathioprine, cyclophosphamide
What is the treatment for serious cases of Hashimoto’s Thyroiditis with brain or kidney involvement?
Plasmapheresis: Filters out harmful antibodies from the blood to rapidly reduce immune system activity in life-threatening situations
What is Graves’ Disease and the symptoms associated with it?
most common autoimmune cause of hyperthyroidism in iodine sufficient areas affecting women 5-10x more than men
- goiters
- proptosis (bulging eyes)
- hyperpigmentation and itchy skin on feet and legs
What is the autoantibody that causes graves’ disease and what is the mechanism?
TRAb = Autoantibody against TSH Receptor (IgG isotype)
- TRAb Mimics TSH → binds thyroid follicular cell receptor → T3/T4 production → autoantibody lacks feedback control → follicular hypertrophy → buildup of colloid droplets → overproduction of hormones
What are the genetic risk factors of Graves’ Disease?
- HLA genes are known risk factors
- TSHR gene polymorphism
- PTPN22 gene polymorphism
- CTLA-4 gene polymorphism
- FOXP3 gene polymorphism
- IL-2RA gene polymorphism
- CD40 gene polymorphism
What occurs during Pathogenesis in Graves’ Disease?
- Loss of Immune Tolerance: failed elimination of auto-reactive T and B cells
- Treg Dysfunction: Tregs not working properly
- Immune Cell Infiltration: T and B cells enter thyroid
- Cytokine Release: inflammation
- Abnormal Antigen Presentation: interferon forces follicular cells to express HLA class II antigens
- Activation of Auto-reactive T Cells
- Amplification → chronic inflammation → persistent damage
Why do symptoms of Graves’ Disease occur outside the thyroid?
TSH receptor (TSHR)—the same receptor that gets targeted in the thyroid—is also found in other parts of the body like:
- Eye region (retro-orbit)
- Skin (especially over the shins)
What is Graves’ ophthalmopathy and what causes it?
bulging of the eyes (proptosis) caused by TRAb stimulating TSH receptors on orbital fibroblasts, leading to inflammation, immune cell accumulation, and tissue expansion behind the eyes
What is pre-tibial myxedema and why does it happen?
skin thickening and swelling usually on the shins, caused by immune cell infiltration due to stimulation of TSHR in skin fibroblasts by TRAb
How can Yersinia enterocolitica trigger Graves’ disease?
antibodies may cross-react with thyroid tissue, activating autoimmunity
What viruses are linked to Graves’ disease through immune dysregulation?
Epstein-Barr Virus (EBV) and Hepatitis C Virus (HCV) can disrupt immune control
Which viruses may trigger autoimmunity via mimicry or bystander activation in Graves’ disease?
Herpes Simplex Virus (HSV) and Cytomegalovirus (CMV)
How does smoking impact Graves’ disease?
It increases risk and worsens eye symptoms (Graves’ ophthalmopathy)
How does excess iodine intake affect Graves’ disease risk?
Triggers or worsens Graves’ by increasing thyroid hormone production, especially in predisposed individuals
What is the link between celiac disease and thyroid autoimmunity?
Children with celiac disease have up to 10× greater risk of thyroid autoimmunity
What are the 3 main treatment options for Graves’ disease?
- Radioactive iodine (RAI) – destroys overactive thyroid tissue
- Anti-thyroid drugs – Methimazole (preferred) or PTU
- Surgery – Subtotal thyroidectomy for large goiters or treatment failure
