Immunological Aspects of Thyroid Disorders

Study Notes

Immunological Basis of Endocrine Disorders

Hashimoto Thyroiditis (Chronic Lymphocytic Thyroiditis):
- The most common cause of goitrous hypothyroidism.
- Most common cause of hypothyroidism in iodine-sufficient areas.
- Typically affects middle-aged women.
- Associated with certain HLA types (e.g., HLA-DR3).
- Increased risk for other autoimmune diseases (e.g., Graves' disease, type 1 diabetes, SLE, non-Hodgkin lymphoma).
- Target antigen unknown, but CD8 cells directly destroy thyroid tissue and CD4-attracted macrophages destroy thyroid tissue, releasing components into the bloodstream (like thyroglobulin and thyroid peroxidase).
- The immune system attacks these components as if they were foreign.
- The net result is destruction of the thyroid tissue.
Graves' Disease (Toxic Diffuse Goiter):
- Most common cause of hyperthyroidism.
- Typically affects women younger than 50 more than men.
- Associated with certain HLA types (e.g., HLA-B8).
- Increased risk for other autoimmune diseases (e.g., type 1 diabetes, SLE).
- Possible triggers include infectious agents (like Yersinia enterocolitica), stress, pregnancy, and environmental factors (like smoking, radiation, drugs).
- Stimulating immunoglobulins (IgG) bind to and activate TSH receptors, overproducing thyroid hormones.
- This leads to hyperthyroidism and a goiter.
- Thyroid-associated ophthalmopathy can occur: Inflammatory response in retro-orbital space leading to increased orbital fat and muscle tissue and myxedema (in the skin).
Type 1 Diabetes Mellitus (Insulin-Dependent Diabetes Mellitus):
- Onset typically before age 30.
- Associated with certain HLA types (e.g., HLA-DR3/4).
- Increased risk for other autoimmune diseases.
- Possible triggers include viral infections.
- Autoantibodies (e.g., anti-GAD, islet cell antibodies) target and destroy insulin-producing beta cells in the pancreas.
- This results in the body's inability to produce enough insulin.

Clinical Pictures and Diagnoses

Hashimoto Thyroiditis:
- Early stages: asymptomatic, gradual goiter (painless, nontoxic), possible transient hyperthyroidism ("hashitoxicosis").
- Late stages: hypothyroidism, possible small, fibrotic thyroid.
- Laboratory Diagnosis: anti-thyroid peroxidase (TPO) antibodies, antithyroglobulin (Tg) antibodies, and thyroid function tests (TSH, T3, T4.)
Graves' Disease:
- Clinical Presentation: Manifestations of hyperthyroidism (e.g., rapid heartbeat, bulging eyes (exophthalmos), goiter, pretibial myxedema).
- Laboratory Diagnosis: Measure thyroid antibodies (TRAbs, specifically TPO and Tg antibodies), but TRAbs are more specific. Thyroid function tests (TSH, T3, T4).
Type 1 Diabetes:
- Laboratory Diagnosis: measuring specific autoantibodies (like anti-GAD antibodies), detecting high blood glucose and other related measures/tests (Hyperglycemia, random, fasting, glycosylated hemoglobulin A1c (HbA1c), urine tests).