Riedel's thyroiditis pathophysiology
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The exact pathogenesis of Riedel's thyroiditis is not fully understood. The presence of thyroid autoantibodies and lymphoid infiltration of the thyroid gland resembling that of Hashimoto's thyroiditis might indicate an autoimmune etiology. It is considered that the infiltrating lymphocytes release cytokines which are responsible for the activation of fibroblasts responsible for the fibrosis. Riedel's thyroiditis is characterized by a replacement of the normal thyroid parenchyma by a dense fibrosis that invades adjacent structures of the neck and extends beyond the thyroid capsule. This makes the thyroid gland stone-hard and fixed to adjacent structures. A shared mechanism with retroperitoneal fibrosis and sclerosing cholangitis has been suggested.
|The control, synthesis, and release of the thyroid hormone is usually controlled by hypothalamus and pituitary gland.
The exact pathogenesis of Riedel's thyroiditis is not fully understood. The presence of thyroid autoantibodies and lymphoid infiltration of the thyroid gland resembling that of Hashimoto's thyroiditis might indicate an autoimmune etiology.
- It is considered that the infiltrating lymphocytes (CD4+ and CD8+) release cytokines which are responsible for the activation of fibroblasts responsible for the fibrosis.
- Riedel's thyroiditis is characterized by a replacement of the normal thyroid parenchyma by a dense fibrosis that invades adjacent structures of the neck and extends beyond the thyroid capsule.This makes the thyroid gland stone-hard and fixed to adjacent structures.
- Tissue eosinophilia and Major basic protein (MBP) identified in the thyroid gland on the histopathological analysis are also thought to play a role in the proliferation of fibroblasts.
- A shared mechanism with retroperitoneal fibrosis and sclerosing cholangitis is also suggested.
The following hypotheses regarding the pathogenesis of Riedel's thyroiditis have been proposed:
The Systemic Autoimmune Hypothesis
- It is proposed that the endothelial cells release oxidized low-density lipoprotein from atheromatous plaques following the injury resulting in an allergic hypersensitivity reaction.
- The natural consequence of this hypothesis is that the antigen initiating fibrosis is not localized within the thyroid but is affected secondarily by a systemic fibroinflammatory process.
- Thyroid follicular cells, peri-thyroid muscular cells, or intrathyroidal endothelial cells express antigens, cytokines, or adhesion molecules that might contribute to local activation of the disease. The evidence of a perivascular concentration of inflammatory cells in RT (occlusive phlebitis) might support the theory that the allergic process first involves blood vessels.
- Once the allergic reaction has started, a heavy inflammatory cell population such as B and T lymphocytes, plasma cells, monocytes, and eosinophils infiltrate tissues and produce several cytokines.
- The role of eosinophils in this context probably is central. When eosinophils migrate into the tissues involved by the disease, they degranulate and release cationic toxins into connective tissue including Major basic protein (MBP), eosinophil cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin.
- Eosinophils also release cytokines, the most important of which are transforming growth factor β, transforming growth factor α, and granulocyte-macrophage colony-stimulating factor. This stimulates fibroblast proliferation that finally causes fibrosis.
The Genetic Hypothesis
- The basis of this hypothesis was a report of multifocal fibrosclerotic disease in two brothers, whose parents were first cousins. They developed different combinations of the multifocal fibrosclerotic disease and a familial multifocal fibrosclerosis was hypothesized.
- It was thought that genetic factors might have played a partial role in an enzymatic defect in the tryptophan → serotonin → 5-hydroxyindolacetic acid pathway. However, such a relationship has never been proven, and the siblings described remain the only case of familial multifocal fibrosclerosis reported in the literature.
The Intrathyroidal hypothesis
- It is proposed that Riedel's thyroiditis might represent a late fibrotic stage of subacute or chronic thyroiditis. The fundamental concept of this theory is that the fibrosing process of RT is specific to the thyroid gland.
The Pharmacologic Hypothesis
This hypothesis is also proposed primarily for multifocal fibrosclerosis. As Riedel's thyroiditis is associated with multifocal fibrosclerosis this theory might explain the indirect association of Riedel's thyroiditis with drugs.
- The production of fibrosis by the drugs might be determined by an increased serum serotonin concentration through competitive inhibition at the serotonin receptor level and a reaction of hypersensitivity causing vasculitis and plasma exudation resulting in fibrosis.
- Although drugs have been found to cause multi organ fibrosis, there are no reports regarding medication induced Riedel's thyroiditis. This theory might explain the indirect association of Riedel's thyroiditis with drugs as Riedel's thyroiditis is associated with multifocal fibrosclerosis.
- Graves’ disease
- Hashimoto’s thyroiditis
- Multifocal idiopathic fibrosclerosis
- Addison’s disease
- Pernicious anemia
- Type 1 diabetes
On gross pathology the following findings are characteristic of Riedel's thyroiditis:
- Destruction of thyroid follicle by inflammatory cells
- Inflammatory cells including lymphocytes, plasma cells, and eosinophils in a dense matrix of hyalinized connective tissue
- Fibrous tissues and invasion of surrounding structures
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