Thyroid autoimmunity Flashcards
What is the most common cause of hypothyroidism in countries with sufficient iodine?
Hashimoto’s thyroiditis
Mutations in which genes have been shown to be associated with Hashimotos?
HLA DR-3 and HLA DR-5
What is the pathophysiology of Hashimotos thyroiditis?
- Genes have been associated with hashimotos (HLA-DR3 and HLA-DR5)
- These genes cause immune cells to lack the ability to differentiate between thyroid antigens and foreign antigens as they look similar (molecular mimacy)
- Host protein triggers an immune response (autoantigens)
- Autoantigens are picked up by APC’s and taken to nearby lymph nodes
- In the lymph nodes, they activate CD4+ T helper cells which stimulate B cells to start proliferating and differentiating into plasma cells
- Plasma cells then produce specific auto-antibodies against self-antigens
- Once at the thyroid, plasma cells make antibodies against thyroid peroxidase, thyroglobulin or TSH receptors which are tagged and destroyed by NK cells
- Inflammatory cytokines are also produced by CD4 T helper cells which attract macrophages and directly damage the follicles and cytokines also attract CD8 cytotoxic cells which target and destroy the follicular cells
Why is there a transient hyperthyroid state in hashimotos?
The initial destruction of follicular cells leads to T3 and T4 being spilled over into the blood causing transient hyperthyroid state (hashitoxicosis)
What causes the thyroid gland to enlarge?
Chronic inflammation and build up of connective tissue and immune infiltration causes the thyroid gland to enlarge
What are the clinical signs and symptoms of Hashimoto’s?
- Brain fog
- Depression
- Fatigue due to decreased met rate
- Exercise intolerance due to dec met rate
- SOB
- Goitre
- Weight gain
- Constipation
- Cold intolerance
- Dry skin and brittle nails
Increased prolactin secretion due to increased TRH can lead to what symptoms/signs?
- Menstrual abnormalities
- Galactorrhea
- Infertility
- Myxedema in severe cases (usually around eyes, hands and feet)
Lab tests to diagnose hashimotos?
- Low serum free thyroid hormones
- High levels TSH
- High levels associated antibodies (anti-thyroid peroxidase and anti-thyroglbulin)
- Fine needle aspiration to get biopsy if suspected thyroid lymphoma
Treatment of hashimotos
Life long thyroid hormone replacement with levothyroxine
Large goiter or lymphoma may need to be surgically removed
Pathophysiology of Graves disease
- B cells produce different types of antibodies against thyroid proteins - most common in thyroid stimulating immunoglobulin which imitates TSH
- This binds to thyroid receptors on follicular cells and stimulates the release of more T3 and T4
What effect does Graves disease have on the thyroid gland?
- Thyroid stimulating immunoglobulin causes hypertrophy and hyperplasia of the follicular cells causing the thyroid to enlarge
- Follicular cells change shape and become taller as more cells are present
- As a response to thyroid stimulating antibodies, follicular cells express molecules which attract T cells
- T cells then bind to follicular cells and infiltrate into the interstitium of the thyroid tissue
What are the clinical signs and symptoms of graves?
Triad: hyperthyroidism, opthalmopathy and dermopathy
- Goiter
- Anxiety
- Insomnia
- Restlessness
- Hand tremors
- Heart palpitations
- Sweating
- SOB
- Muscle weakness
- Heat intolerance
- Weight loss despite increase in apetite
What is graves ophthalmopathy and why does it occur?
- Build up of glycosaminoglycans causes inflammation and swelling around eyes
- This causes exophthalmos (bulging of eye)
- Weakens muscles of upper eyelid movement
- Damage cornea (corneal ulcers) due to bulging eye & drying out of eye
What dermopathy can be seen in Graves?
Glycosaminoglycan build up can cause pretibial myxedema which can lead to non-pitting oedema and skin thickening (usually over the shins)
What is a thyroid storm?
- Life threatening complication of hyperthyroidism where the body enters a state of severe hypermetabolism
- It can develop if someone stops their treatment, develops an infection or has surgery
- All of the symptoms of hyperthyroidism are exaggerated - high fevers, cardiac arrhythmias
