A 32-year-old woman presents with palpitations, tremor, and heat intolerance for 3 months. Clinical examination reveals a diffuse thyroid enlargement, exophthalmos, and pretibial myxedema. What is the most common cause of hyperthyroidism in this patient?

Explanation

## Most Common Cause of Hyperthyroidism: Graves' Disease ### Epidemiology **Key Point:** Graves' disease accounts for 60–80% of all hyperthyroidism cases worldwide and is the most common cause in iodine-sufficient regions like India. ### Clinical Features in This Case The patient presents with the classic triad of Graves' disease: 1. **Hyperthyroid symptoms**: palpitations, tremor, heat intolerance 2. **Diffuse thyroid enlargement** (goiter) 3. **Extrathyroidal manifestations**: exophthalmos and pretibial myxedema — pathognomonic for Graves' disease **Clinical Pearl:** Exophthalmos and pretibial myxedema are virtually diagnostic of Graves' disease and do NOT occur in other causes of hyperthyroidism (toxic nodule, thyroiditis). ### Pathophysiology - Autoimmune disorder with TSH receptor antibodies (TRAb) binding to TSH receptors on thyroid cells - Results in unregulated thyroid hormone synthesis and release - Antibodies cross-react with orbital fibroblasts → exophthalmos - Cross-reaction with dermal fibroblasts → pretibial myxedema ### Comparison with Other Causes | Feature | Graves' Disease | Toxic Multinodular Goiter | Thyroiditis | |---------|-----------------|---------------------------|-------------| | **Prevalence** | 60–80% | 15–20% | 5–10% | | **Age of onset** | 20–50 years (young adults) | >50 years (elderly) | Variable | | **Goiter** | Diffuse, smooth | Nodular | Small or absent | | **Exophthalmos** | Yes (30–50%) | No | No | | **Pretibial myxedema** | Yes (rare) | No | No | | **RAI uptake** | High | High (in nodules) | Low | | **TRAb positive** | Yes | No | No | **High-Yield:** The presence of exophthalmos or pretibial myxedema makes Graves' disease the diagnosis — no other cause of hyperthyroidism produces these signs. ### Diagnostic Confirmation - **TSH**: suppressed (<0.1 mIU/L) - **Free T4 and T3**: elevated - **TRAb (TSI)**: positive — confirms autoimmune etiology - **Thyroid ultrasound**: diffuse hypoechogenicity - **Radionuclide scan**: diffuse, homogeneous uptake [cite:Harrison 21e Ch 405]