Causes of diffuse toxic goiter

Currently, diffuse toxic goiter (DTZ) is considered as an organ-specific autoimmune disease. Its hereditary nature is confirmed by the fact that family cases of goiter are observed, thyroid antibodies are detected in the blood of relatives of patients, a high incidence of other autoimmune diseases among family members (type I diabetes, Addison's disease, pernicious anemia, myastenia gravis) and the presence of specific HLA antigens (HLA B8, DR3). The development of the disease often provokes emotional stress.

The pathogenesis of diffuse toxic goiter (Graves' disease) is caused by a hereditary defect, apparently by a deficit of T-lymphocyte suppressors, which leads to mutation of the forbidden clones of T-lymphocyte helper cells. Immunocompetent T-lymphocytes, reacting with autoantigens of the thyroid gland, stimulate the formation of autoantibodies. The peculiarity of immune processes in diffuse toxic goiter is that autoantibodies exert a stimulating effect on cells, lead to hyperfunction and hypertrophy of the gland, whereas in other autoimmune diseases, autoantibodies exert a blocking effect or bind an antigen.

Sensitized B-lymphocytes under the action of the corresponding antigens form specific immunoglobulins, stimulating the thyroid gland and mimicking the effect of TSH. They are united under the general name TSI. The expected cause of secretion of immunoglobulins is deficiency or decrease in the functional activity of T-suppressors. TSIs are not strictly specific signs of diffuse toxic goiter. These antibodies were found in patients with subacute thyroiditis, Hashimoto's thyroiditis.

Along with TSI antibodies to the receptor of cytoplasmic thyrotoxic membranes (possibly the TSH receptor), patients with diffuse toxic goiter often have antibodies to other thyroid antigens (thyroglobulin, the second colloid component, the microsomal fraction, the nuclear component). A higher incidence of antibodies to the microsomal fraction is observed in patients receiving iodine preparations. Given the fact that they have a damaging effect on the follicular epithelium of the thyroid gland, one can explain the development of the syndrome Jod-Basedow (iodobazedov) with prolonged use of iodine preparations in patients with diffuse toxic goiter or endemic goiter. Damage to the follicular epithelium leads to massive admission to the bloodstream of thyroid hormones and the detection of a clinical picture of thyrotoxicosis or its exacerbation after a previous remission with iodine preparations. Iodine-based monodism according to the clinical picture does not differ from the present Graves' disease. A distinctive feature of hyperthyroidism caused by iodine intake is the absence or low absorption of iodine isotopes by the thyroid gland.

Previously believed that hyperthyroidism develops with increasing production of thyroid-stimulating hormone. It turned out that the level of TSH in this disease is not changed or is more often reduced due to suppression of the pituitary gland by high concentrations of thyroid hormones. In rare cases, there are patients with TTG-producing adenoma of the pituitary gland, while the plasma TSH content is significantly increased, there is no TSH reaction to TRH. In some forms of the disease, high levels of TSH and thyroid hormones are found simultaneously. It is believed that there is a partial resistance of thyrotrophs to thyroid hormones, as a result of which the symptoms of thyrotoxicosis develop.

[1], [2], [3], [4], [5], [6], [7], [8]

Pathanatomy

Diffuse toxic goiter is classified as primary thyroid hyperplasia and hypertrophy. The surface of the gland is smooth, on the cut its substance is dense, of a homogeneous structure, grayish-pink in color, sometimes glistening or colloidal. There may be small-scale whitish inclusions (lymphoid infiltrates), foci or interlayers of fibrous tissue. Histologically, we distinguish three main variants of diffuse toxic goiter (Graves' disease):

1. Hyperplastic changes in combination with lymphoid infiltration;
2. without lymphoid infiltration;
3. colloid proliferating goiter with morphological signs of increasing the function of thyroid epithelium.

The first option is classic. It is characterized by increased proliferation of thyroid epithelium with the formation of papillary outgrowths in the follicle, which gives them a stellate appearance. The follicular epithelium is usually low, cylindrical or cubic. Lymphoid infiltration of the stroma is expressed in different degrees, is focal. With its weak expression, foci of lymphoid cells are localized mainly under the capsule. There is a direct relationship between the degree of manifestation of lymphoid infiltration and the titre of antithyroid antibodies, as well as the severity of the oncocyte-cell response. In such glands, the development of focal autoimmune thyroiditis is sometimes noted. In a number of cases, the outcome of diffuse toxic goiter (Graves' disease) is observed in autoimmune thyroiditis.

The second variant of the disease occurs mainly in young people. Hyperplasia of thyroid epithelium is particularly pronounced. Proliferation of thyroid epithelium is accompanied by neoplasm of small follicles lined with cylindrical and rarely cubic epithelium. The bulk of such follicles contains small amounts of liquid intensively resorbed colloid or is devoid of it. The follicles are located close to each other. This is the so-called parenchymal type of the structure of the gland.

Colloid proliferating goiter, in contrast to endemic colloid goiter, is characterized by increased proliferation of follicular epithelium with the formation of either papillate outgrowths or Sanderson pads. The follicular epithelium is mostly cubic, with morphological signs of increasing its functional activity. The colloid in the bulk of the follicles is liquid, intensively resorbed.

With the relapse of diffuse toxic goiter (Graves' disease), the structure of the thyroid gland often repeats the structure of the first removed thyroid tissue, but it often observes subcapsular and interstitial fibrosis, a tendency to nodal formation.

In recent years, there has been an increase in the incidence of primary thyroid cancers on the background of diffuse toxic goiter (Graves' disease). Usually these are microrakies, mostly highly differentiated: papillary, such as Graham adenocarcinoma, follicular, or mixed, the removal of which, as a rule, results in recovery. We did not observe any relapse, nor a metastasis in these cases.

In people with diffuse toxic goiter (Graves' disease), those who died from heart failure, moderately increased heart with atrial dilatation and mild hypertrophy and dilatation of both ventricles. In the myocardium of the left ventricle, foci of necrosis and fibrosis are found. Often there is an increase in the thymus, cervical lymph nodes and even tonsils. The liver develops fatty degeneration. In the bones, sometimes the increased activity of osteoclasts with the phenomena of bone resorption. Thyrotoxic myopathy is characterized by the atrophy of skeletal muscles with fat infiltration phenomena.