Graves disease

A 38 year old female presents to her primary care physician with a 3 month history of weight loss despite good appetite, palpitations, and insomnia. She also reports anxiety and a fine tremor in her hands. Vital signs show a heart rate of 110 beats per minute and blood pressure of 140/80 mm Hg. Examination reveals exophthalmos, a diffusely enlarged non-tender thyroid, and a fine tremor. Thyroid function tests show low TSH with elevated free T3 and free T4. Serology shows positive thyroid stimulating immunoglobulin. Radioactive iodine uptake shows diffuse increased uptake. Diagnosis?

Diagnosis is Graves disease.

1. Definition

Graves disease is an autoimmune disorder caused by TSH receptor stimulating antibodies, leading to excess thyroid hormone production.

It is the most common cause of hyperthyroidism, accounting for 60 to 80 percent of cases

2. Etiology and Risk Factors

1. Autoimmune loss of immune tolerance
2. Strong genetic predisposition
3. Environmental triggers such as smoking, stress, and vitamin D deficiency

3. Pathophysiology

1. TSH receptor antibodies stimulate thyroid hormone synthesis
2. Cause diffuse thyroid hyperplasia and goiter
3. Lead to hyperthyroidism
4. Orbital fibroblast activation
5. Deposition of glycosaminoglycans
6. Results in ophthalmopathy

4. Clinical Features

4.1 Hyperthyroid Features

1. Weight loss with increased appetite
2. Tachycardia and possible atrial fibrillation
3. Heat intolerance and sweating
4. Fine tremor
5. Hyperdefecation
6. Anxiety and insomnia

4.2 Thyroid Findings

1. Diffuse goiter
2. Thyroid bruit

4.3 Extrathyroidal Features

1. Ophthalmopathy, specific but not universal
2. Exophthalmos, lid lag, periorbital edema
3. Pretibial myxedema, uncommon

5. Diagnosis

1. Low TSH with elevated T3 and T4
2. TSH receptor antibodies confirm diagnosis
3. Diffuse increased RAI uptake distinguishes from thyroiditis
4. T3 toxicosis may occur early

6. Management

1. Beta blockers such as propranolol
• Control symptoms
• High doses reduce T4 to T3 conversion
2. Antithyroid drugs
• Methimazole is first line
• Propylthiouracil in first trimester and thyroid storm
3. Radioactive iodine therapy
• Causes thyroid ablation
• May worsen ophthalmopathy
• Contraindicated in pregnancy
4. Thyroidectomy
• Indicated in large goiter or refractory disease

7. Complications

1. Thyroid storm
2. Atrial fibrillation
3. Heart failure due to high-output state
4. Osteoporosis

8. Key Clinical Insight

Diffuse goiter, exophthalmos, low TSH, elevated T3 and T4, positive TSH receptor antibodies, and diffuse RAI uptake strongly indicate Graves disease

9. Exam Level Pearls

1. Graves disease is the most common cause of hyperthyroidism
2. Diffuse RAI uptake differentiates it from thyroiditis
3. Only common hyperthyroidism with ophthalmopathy
4. Methimazole is first line except in pregnancy and thyroid storm
5. Radioactive iodine is contraindicated in pregnancy and may worsen eye disease