Graves disease
Graves disease is an autoimmune disorder in which thyrotropin receptor antibodies stimulate the thyroid, causing hyperthyroidism, and is the most common cause of thyrotoxicosis in iodine-sufficient regions. Diagnosis rests on a suppressed thyroid-stimulating hormone with elevated free thyroxine and positive thyrotropin receptor antibodies, and first-line treatment is a thionamide, most often methimazole, with radioactive iodine or thyroidectomy reserved for recurrence or patient preference.
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What this article covers
- Overview
Autoimmune thyroid stimulation: Graves disease is an autoimmune disorder in which T lymphocytes become sensitized to thyroid antigens and drive B lymphocytes to produce thyrotropin (TSH) receptor…
- Epidemiology
Most common cause of thyrotoxicosis: hyperthyroidism affects about 1.3% of the United States population, and Graves disease is the dominant cause in iodine-replete regions.
- Risk factors
Family history of thyroid autoimmunity: clusters in families, paralleling the risk pattern seen with Hashimoto thyroiditis.
- Pathophysiology
TRAb activates the TSH receptor: stimulating antibodies bind the TSH receptor on thyroid follicular cells, driving continuous hormone synthesis and release independent of pituitary feedback.
- Clinical features
Biochemical thyrotoxicosis with a diffusely enlarged gland: the thyroid is diffusely enlarged, may have a bruit, and has a firm, smooth texture; cervical lymphadenopathy can also occur.
- Differential diagnosis
Toxic multinodular goiter: autonomously functioning thyroid tissue in an asymmetric, nodular gland, unlike the diffusely smooth gland of Graves disease, and TRAb is negative.
- Diagnosis
The diagnosis is established biochemically and immunologically: a suppressed TSH with elevated free T4 or total/free triiodothyronine (T3) confirms thyrotoxicosis, and a positive TRAb (TSI) test…
- Management
First, confirm the diagnosis and start a thionamide.
- Complications
Thyroid storm: a life-threatening exacerbation of thyrotoxicosis, often precipitated by infection, surgery, trauma, or abrupt thionamide discontinuation, presenting with fever, tachyarrhythmia, and…
- Prognosis
Good with appropriate treatment: most patients achieve euthyroidism with thionamide therapy, definitive ablation, or surgery.
- Prevention
Smoking cessation reduces the risk and severity of Graves ophthalmopathy, the single most modifiable risk factor identified for this complication.
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Related articles
- Hyperthyroidism
Hyperthyroidism is the clinical syndrome of thyroid hormone excess, produced by a range of causes from Graves disease and autonomously functioning nodules to destructive thyroiditis and exogenous hormone ingestion. Diagnosis begins with a suppressed thyroid-stimulating hormone and elevated free thyroxine, followed by radioactive iodine uptake testing or antibody measurement to identify the cause, and first-line treatment is a beta blocker for symptom control while the underlying cause directs thionamide, radioactive iodine ablation, or thyroidectomy therapy.
- Thyroid storm
Thyroid storm is a rare, life-threatening exaggeration of thyrotoxicosis with multiorgan dysfunction and mortality up to 30%, most often precipitated by discontinuation of antithyroid drugs, infection, surgery, or trauma in a patient with underlying hyperthyroidism. It is a clinical diagnosis treated emergently in the ICU with intravenous beta-blockade, a thionamide (propylthiouracil transitioning to methimazole), potassium iodide given only after the thionamide, and high-dose glucocorticoids.
- Hashimoto thyroiditis
Hashimoto thyroiditis is a chronic autoimmune process in which lymphocytic infiltration destroys the thyroid, and is the most common cause of hypothyroidism in iodine-sufficient regions such as the United States. Diagnosis rests on an elevated thyroid-stimulating hormone with a low or normal free thyroxine, and first-line treatment is lifelong levothyroxine replacement dosed to normalize thyroid-stimulating hormone.
- Thyroid nodules
A thyroid nodule is a discrete structural lesion within an otherwise normal thyroid gland, found on ultrasound in about 40% of the United States population though palpable in far fewer, and malignant in roughly 5%. Evaluation begins with a thyroid-stimulating hormone (TSH) level and thyroid ultrasonography, and management is surveillance for benign or low-risk nodules, with lobectomy or total thyroidectomy reserved for cytology suspicious for or diagnostic of malignancy.