Graves' Disease

Graves' disease is an organ-specific autoimmune disorder. Thyroid-stimulating immunoglobulins, also called TSH-receptor antibodies (TSHR-Ab or TRAb), bind to and activate the TSH receptor on thyroid follicular cells. Unlike pituitary TSH, these antibodies are not controlled by the normal negative-feedback loop. The thyroid therefore continues to enlarge and synthesize and release excessive T4 and T3. The excess hormones accelerate cellular metabolism and increase beta-adrenergic receptor sensitivity. That combination explains the characteristic picture: heat intolerance, sweating, weight loss despite increased appetite, tremor, anxiety, weakness, and a fast pulse. The patient may feel restless but still be profoundly fatigued because the body is consuming energy faster than it can replace it. The eye findings are part of the same autoimmune process, not simply a consequence of a large thyroid. Orbital fibroblasts are stimulated, causing inflammation, glycosaminoglycan deposition, and oedema around the extraocular muscles and retro-orbital tissues. The result may be dry or gritty eyes, lid retraction, proptosis, diplopia, pain, or impaired vision. Pretibial myxedema develops through a similar fibroblast-mediated process in the skin. Smoking increases the risk and severity of ophthalmopathy.