Graves Disease
Graves’ disease is the most common cause of hyperthyroidism. It is an autoimmune disorder where autoantibodies stimulate the thyroid gland to produce excess hormone.
1. Pathophysiology
- Mechanism: Thyroid-stimulating immunoglobulin (TSI/TSIg) binds to and activates the TSH receptor, bypassing normal regulatory feedback loops.
- Autoimmunity: Often associated with HLA-DR3 and HLA-B8.
2. Clinical Manifestations
| Finding | Pathophysiology |
|---|---|
| Exophthalmos | Retro-orbital fibroblast activation (TSH receptors) leads to increased hyaluronic acid deposition and swelling. |
| Pretibial Myxedema | Dermal fibroblast activation causes localized thickening of the skin. |
3. Exam Must-Knows
- Histology: Thyroid follicles show scalloped colloid and tall, crowded follicular epithelial cells.
- Labs: Elevated T4/T3, suppressed TSH, and the presence of anti-TSH receptor antibodies (TSI).
- Diffuse Goiter: The gland is uniformly enlarged due to constant TSH-receptor stimulation.
Pathology Board Hint: For board exams, distinguish Graves from other causes of hyperthyroidism: the presence of exophthalmos and pretibial myxedema is virtually pathognomonic for Graves disease. If the thyroid is painful, it’s subacute thyroiditis; if there are nodules, think toxic multinodular goiter.