Causes and pathogenesis of autoimmune chronic thyroiditis

A study of the HLA system showed that Hashimoto's thyroiditis is associated with loci DR5, DR3, B8. Hereditary genesis of the disease (thyroiditis) of Hashimoto is confirmed by data on frequent cases of the disease among close relatives. Genetically caused defect of immunocompetent cells leads to a breakdown of natural tolerance and infiltration of the thyroid gland by macrophages, lymphocytes, and plasma cells. Data on subpopulations of peripheral blood lymphocytes in patients with autoimmune thyroid diseases are contradictory. However, most authors adhere to the point of view of the primary qualitative antigen-dependent defect of T-suppressors. But some researchers do not confirm this hypothesis and suggest that the immediate cause of the disease is an excess of iodine and other drugs that play the role of a resolving factor in a breakdown of natural tolerance. It is proved that the production of antibodies occurs in the thyroid gland, is carried out by the derivatives of beta-cells, is a T-dependent process. The formation of antibodies to thyroglobulin (ATA), microsomal antigen (AMA), TSH receptor leads to the appearance of immune complexes, the release of biologically active substances, which ultimately causes destructive changes in thyroid cells and leads to a decrease in thyroid function. The outcome of chronic thyroiditis is hypothyroidism. In the future, pathomorphological changes may be hypertrophic or atrophic.

A decrease in the concentration of thyroid hormones in the blood contributes to an increase in the pituitary thyroid stimulating hormone, which stimulates the growth of the preserved thyrotropic epithelium (with subsequent infiltration by lymphocytes) by forming antigen-antibody complexes and destroying the follicular epithelium. The cytotoxic effect depends on the effect of K-cells in a complex with autoantibodies. Thus, the gradual increase in symptoms of hypothyroidism is accompanied by an increase in the size of the gland and ultimately the formation of goiter.

Atrophic form is characterized by a clinic of hypothyroidism without enlarging the gland even at a high level of TSH in the blood. This situation assumes insensitivity of the thyroid epithelium to the hormone. In the literature there were reports, the authors of which explained this phenomenon by action on the membrane receptors of TSH of the released thyroglobulin. In this case, there was an inverse relationship between the concentration of thyroglobulin and the sensitivity of the receptors.

T. Feit using the cytochemical method, demonstrated that patients with thyroid atrophy can have immunoglobulins G, capable of blocking the TTG-induced growth of thyroid tissue. The same antibodies were detected in thyrotoxicosis without enlargement of the gland. It is noted that in patients with thyroid atrophy, children with a family form of congenital hypothyroidism are sometimes born. Another peculiarity of rare types of thyroiditis Hashimoto is an atypical variant of clinical manifestations, when the hyperthyroid phase is replaced by a hypothyroid phase, and then hyperthyroidism again develops. However, until now, the causes of this course of chronic thyroiditis are not known exactly. But the fact that thyroid stimulating immunoglobulins are rarely detected in the blood of patients with chronic thyroiditis suggests that the hypo- and hyperthyroid phases reflect the ratio of thyostimulating and tyreoblocking antibodies.

[1], [2], [3], [4], [5], [6], [7]

Pathanatomy

When thyroid Hashimoto thyroid gland is increased to 50-150 g or more; dense, sometimes woody, with a bumpy surface. On a cut, its substance is often white-marble or whitish-pink, sometimes yellowish in color, large-lobed structure. Against this background, nodes of different sizes and types are frequent. The iron is not soldered to the surrounding tissues. The stroma of the gland is abundantly infiltrated by lymphoid elements, including plasma cells. Formation of typical lymphoid follicles of various sizes with bright centers and a clear mantle zone is observed. In rare cases, infiltration is diffuse and is caused either by accumulation of small lymphocytes, or mainly by plasma cells. Infiltrates cause the dissociation of thyroid follicles, sometimes large lobules are preserved, in which follicles with morphological signs of increasing functional activity (the phenomenon of hasitoxicosis) are found. In other areas, the follicles are small, lined either compacted or hypertrophied, transformed into Gurtle-Ashkenazi cells by epithelial cells. The colloid is thick or absent. In the degenerate-altered follicles, the downtrodden follicular and giant multinucleate cells are formed, which are formed from the follicular epithelium. Lymphoid elements are sometimes located in the wall of the follicle, they squeeze the follicular cells, but destroy their membrane and preserve their own. The transformation of the follicular epithelium into the cells of Gurtle-Ashkenazi occurs also in the surviving follicles; these cells are often with giant ugly nuclei, binuclear, etc. The stroma of the gland is often fibrotic, especially in interlobular septa. The degree of fibrosis is early. It can give the gland a dense, sometimes woody consistency. Then the iron is difficult to distinguish from the thyroiditis of Riedel. This is a fibrous variant of Hashimoto's disease. There is a point of view that changes in the thyroid gland with this disease in time, if they are progressing, are very slow.

In the plasmocyte-cell variant of the disease, infiltration has a diffuse character mainly by plasma cells. In these cases, the transformation of thyrocytes into Gurtle-Ashkenazi cells is particularly intense, as does the destruction of the parenchyma of the gland, but fibrosis of the stroma is rare.

At atrophic form the gland mass does not exceed 5-12 g, in its significant part the parenchyma is replaced by a hyalineized connective tissue containing lymphoid elements with an admixture of plasma cells. In the surviving follicles, either the transformation of thyrocytes into Gurtle-Ashkenazi cells or squamous cell metaplasia is noted.