Graves disease
- Lesion
In Graves disease an antibody switches the thyroid on permanently. The gland grows, the body speeds up, and the eyes can bulge.
What it is
Graves disease is the commonest cause of endogenous hyperthyroidism. Autoantibodies against the TSH receptor mimic TSH, so the gland becomes diffusely hyperplastic and overactive. The same autoimmune process inflames the orbit and the pretibial skin, producing the triad of thyrotoxicosis, ophthalmopathy and dermopathy. It is more common in women, peaks in young to middle adulthood, and shares genetic risk with other autoimmune diseases.
Structure
- Gross: symmetric, diffusely enlarged, soft, beefy-red gland with an intact capsule.
- Follicular cells are tall and crowded and fold into small papillae; colloid is pale with scalloped (resorption) edges.
- Lymphoid aggregates and occasional germinal centres in the stroma.
- Orbit: oedematous extraocular muscles with lymphocytes, glycosaminoglycans and later fibrosis.
- Dermopathy: thick dermis with glycosaminoglycans and lymphocytes over the shins.
Step by step
- Loss of tolerance to the TSH receptor in a genetically susceptible person.
- B cells produce TSI that bind and activate the receptor like TSH.
- cAMP rises in thyrocytes: growth (diffuse hyperplasia) and excess T4 and T3.
- High hormone suppresses pituitary TSH, but TSI keep driving the gland.
- Orbital and dermal fibroblasts with TSH receptor respond to the same immune attack: proptosis and pretibial myxoedema.
Clinical notes
- Exophthalmos, lid retraction and stare; severe cases risk corneal exposure and optic nerve compression.
- Smoking worsens orbitopathy; radioiodine can also worsen it.
- Thyroid storm is the life-threatening extreme.
Test yourself
Think of the answer, then tap the question to see it.
Why are there papillae without fibrovascular cores in Graves disease?
The hyperplastic, crowded follicular epithelium folds into the lumen; they lack cores, unlike true papillae of papillary carcinoma.
How does Graves ophthalmopathy develop?
Orbital fibroblasts and preadipocytes express the TSH receptor; autoreactive T cells and cytokines stimulate them to make glycosaminoglycans and fat, swelling the orbit.
Which type of hypersensitivity is Graves disease?
Type II (antibody-mediated), with stimulating rather than destructive antibodies.
Elsewhere in DurgiPedia
- Type II hypersensitivity (antibody against cells)
- Autoantibodies: the table to know
- Actions of thyroid hormones
- Hyperplasia: physiologic and pathologic
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Graves Disease (StatPearls (NCBI Bookshelf), 2025); Graves' disease (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.