Causes and pathogenesis of autoimmune chronic thyroiditis

The study of the HLA system showed that Hashimoto's thyroiditis is associated with the DR5, DR3, B8 loci. The hereditary genesis of the disease (thyroiditis) Hashimoto is confirmed by data on frequent cases of the disease among close relatives. Genetically determined defect of immunocompetent cells leads to a breakdown of natural tolerance and infiltration of the thyroid gland by macrophages, lymphocytes, plasma cells. Data on subpopulations of peripheral blood lymphocytes in patients with autoimmune diseases of the thyroid gland 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, which are assigned the role of a resolving factor in the breakdown of natural tolerance. It has been proven that the production of antibodies occurs in the thyroid gland, is carried out by derivatives of beta cells, is a T-dependent process. Formation of antibodies to thyroglobulin (ATA), microsomal antigen (AMA), TSH receptor leads to the appearance of immune complexes, release of biologically active substances, which ultimately causes destructive changes in thyrocytes and leads to a decrease in thyroid function. The outcome of chronic thyroiditis is hypothyroidism. Subsequently, pathomorphological changes can be hypertrophic or atrophic.

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

The atrophic form is characterized by the clinical picture of hypothyroidism without an enlarged gland even with a high level of TSH in the blood. This situation suggests insensitivity of the thyroid epithelium to the hormone. There were reports in the literature, the authors of which explained this phenomenon by the effect of thyroglobulin released into the blood on membrane receptors of TSH. At the same time, an inverse relationship was noted between the concentration of thyroglobulin and the sensitivity of the receptors.

T. Feit, using the cytochemical method, demonstrated that patients with thyroid atrophy may have immunoglobulins G, capable of blocking TSH-induced growth of thyroid tissue. The same antibodies were found in thyrotoxicosis without enlargement of the gland. It was noted that patients with thyroid atrophy sometimes give birth to children with a familial form of congenital hypothyroidism. Another feature of rare types of Hashimoto's thyroiditis is an atypical variant of clinical manifestations, when the hyperthyroid phase is replaced by a hypothyroid one, and then hyperthyroidism develops again. However, to date, the causes of such a course of chronic thyroiditis are not precisely known. But the fact that thyroid-stimulating immunoglobulins are occasionally determined in the blood of patients with chronic thyroiditis allows us to assume that the hypo- and hyperthyroid phases reflect the ratio of thyroid-stimulating and thyroid-blocking antibodies.

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

Pathological anatomy

In Hashimoto's thyroiditis, the thyroid gland is enlarged to 50-150 g or more; dense, sometimes woody, with a bumpy surface. In section, its substance is often white-marbled or whitish-pink, sometimes yellowish, with a large-lobed structure. Against this background, nodes of various sizes and types are common. The gland is not fused with the surrounding tissues. The stroma of the gland is abundantly infiltrated with lymphoid elements, including plasma cells. The formation of typical lymphoid follicles of various sizes with light centers and a clear mantle zone is observed. In rare cases, infiltration is diffuse and is caused either by the accumulation of small lymphocytes or predominantly by plasma cells. Infiltrates cause separation of thyroid follicles, sometimes large lobules are preserved, in which follicles with morphological signs of increased functional activity (phenomena of hasitoxicosis) are found. In other areas, the follicles are small, lined with either compacted or hypertrophied epithelial cells transformed into Hürthle-Ashkenazi cells. Colloid is thick or absent. In degeneratively altered follicles, deflated follicular and giant multinucleated cells formed from follicular epithelium are found. Lymphoid elements are sometimes located in the follicle wall, compressing follicular cells, but destroying their membrane and preserving their own. Transformation of follicular epithelium into Hürthle-Ashkenazi cells also occurs in surviving follicles; These cells often have giant, ugly nuclei, binuclear, etc. The stroma of the gland is often fibrotic, especially in the interlobular septa. The degree of fibrosis is early. It can give the gland a dense, sometimes woody consistency. Then the gland is difficult to distinguish from Riedel's thyroiditis. This is a fibrous variant of Hashimoto's disease. There is a point of view that changes in the thyroid gland with this disease, if they progress over time, then very slowly.

In the plasmacytic-cell variant of the disease, infiltration is diffuse, predominantly by plasma cells. In these cases, the transformation of thyrocytes into Hürthle-Ashkenazi cells is particularly intense, as is the destruction of the gland parenchyma, but fibrosis of the stroma occurs rarely.

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