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Graves’ disease: Pathology, Morphology, Clinical features

gross of grave's disease
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Graves’ disease is an autoimmune disease & it is the most frequent cause of endogenous hyperthyroidism in the body. It is characterized by a triad of manifestations i.e.

  • Thyrotoxicosis, It caused by a diffusely enlarged, thyroid hyper-functional.
  • An infiltrative ophthalmopathy with resultant exophthalmos.
    • It is a localized, & infiltrative dermopathy sometimes designated pretibial myxedema, & more commonly present in a minority of cases.

Graves’ disease has a peak incidence between 20 to 40 years of age people, with women being highly affected up to seven times more commonly than men. Genetic factors are important in Graves’s disease such as HLA-DR3, CTLA-4, and tyrosine phosphatase PTPN22.

Pathogenesis of Graves’ disease

Many manifestations of Graves’ disease are caused by autoantibodies against the TSH receptor that binds to, and stimulates, thyroid follicular cells independent of endogenous trophic hormones.
Numerous autoantibodies are produced in Graves’ disease, that including the following autoantibodies listed below;

  • Thyroid-stimulating immunoglobulin (TSI)
  • Thyroid growth-stimulating immunoglobulins
  • TSH-binding inhibitor immunoglobulins

Thyroid-stimulating immunoglobulin (TSI)

  • This IgG antibody binds to the TSH receptors and then mimics the action of TSH, and stimulating adenyl cyclase, with resultant increased release of thyroid hormones.

Thyroid growth-stimulating immunoglobulins

  • It directed against TSH receptors & antibodies that proliferation of thyroid follicular epithelium in the gland of the body.

TSH-binding inhibitor immunoglobulins

  • These anti-TSH receptor antibodies prevent thyroid-stimulating hormone (TSH) from binding to its receptor present on thyroid epithelial cells and inhibit thyroid cell function.

In the Infiltrative ophthalmopathy conditions:

It is a T-cell mediated autoimmune phenomenon and in the Graves’ ophthalmopathy, and the volume of the retro-orbital connective tissues and extraocular muscles is increased due to the following condition,

  • Marked infiltration of the retro-orbital space by mononuclear cells, and T-cells (predominantly).
  • Inflammatory edema and swelling of extraocular muscles occurred.
  • Accumulation of extracellular matrix components such as specifically hydrophilic components called Glycosaminoglycans such as Hyaluronic acid and Chondroitin sulfate.
  • Increased numbers of adipocytes (fatty infiltration occurs).

These changes displace the eyeball forward, and potentially interfering with the function of the extraocular muscles.

Morphology of Graves’ disease


graves' disease

The thyroid gland becomes enlarged (usually symmetrically) due to diffused hypertrophy and hyperplasia of thyroid follicular epithelial cells and the weight of the thyroid gland is increased.
Cut section: The gland parenchyma is usually smooth and soft, resembling normal muscles and its capsule is intact.


Follicular epithelial cells are tall, columnar, more crowded resulting in the formation of small papillae, which projects into the follicular lumen. Such papillae that lack fibrovascular cores, in contrast with those of papillary carcinoma.

The colloid within the follicular lumen is a pale color, with scalloped margins present and then Lymphoid infiltrates, consisting predominantly of T-cells, and with fewer B-cells and mature plasma cells are present throughout the interstitium. This lymphoid aggregation more commonly shows germinal centers.

graves' disease


The tissues of the orbit are edematous due to the presence of large hydrophilic glycosaminoglycans and infiltration by lymphocytes, mostly T-cells. Initially, Orbital muscles are edematous but sometimes they may undergo fibrosis late in the course of the disease.


The thickening of the dermis in the body, as a result of deposition of glycosaminoglycans compounds & lymphocyte infiltration.

Clinical features of graves’ disease

  • Diffuse hyperplasia of the thyroid gland, ophthalmopathy, and dermopathy.
  • Features of thyrotoxicosis.
  • Sympathetic over-activity produces a characteristic wide, staring gaze and lid lag.
  • The ophthalmopathy results in abnormal protrusion of the eyeball (exophthalmos) that leads to corneal injury.
  • The infiltrative dermopathy involves the skin overlying the shins as scaly thickening present and induration of the skin (pretibial myxedema).

Graves’ disease has increased high risk for other autoimmune diseases such as:

  • The systemic lupus erythematosus(SLE)
  • Pernicious anemia
  • Type 1 diabetes
  • Addison disease.

Laboratory findings

  • Increases or elevated serum-free T4 & T3 levels in the body & depressed or decreased serum TSH.
  • Radioactive iodine uptake is increased diffusely.

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