Causes of diffuse toxic goiter

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

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

Sensitized B-lymphocytes under the influence of corresponding antigens form specific immunoglobulins that stimulate the thyroid gland and imitate the action of TSH. They are united under the general name TSI. The supposed reason for the secretion of immunoglobulins is a deficiency or decrease in the functional activity of T-suppressors. TSI is not a strictly specific sign of diffuse toxic goiter. These antibodies are found in patients with subacute thyroiditis, Hashimoto's thyroiditis.

Along with TSI antibodies to the receptor of cytoplasmic membranes of thyrocytes (possibly the TSH receptor), antibodies to other thyroid antigens (thyroglobulin, the second colloid component, microsomal fraction, nuclear component) are often detected in patients with diffuse toxic goiter. A higher frequency of detection of antibodies to the microsomal fraction is observed in patients who received iodine preparations. Considering the fact that they have a damaging effect on the follicular epithelium of the thyroid gland, it is possible to explain the development of Jod-Basedow syndrome (iodine-based) with long-term use of iodine preparations in patients with diffuse toxic goiter or endemic goiter. Damage to the follicular epithelium leads to a massive influx of thyroid hormones into the bloodstream and the clinical picture of thyrotoxicosis or its exacerbation after previous remission against the background of taking iodine preparations. Iodine Basedowism does not differ in clinical picture from true Basedow's disease. A distinctive feature of hyperthyroidism caused by iodine intake is the absence or low absorption of iodine isotopes by the thyroid gland.

Previously, it was believed that hyperthyroidism develops with increased production of thyroid-stimulating hormone. It turned out that the level of TSH in this disease is unchanged or more often reduced due to suppression of the pituitary gland function by high concentrations of thyroid hormones. In rare cases, there are patients with TSH-producing pituitary adenoma, while the TSH content in the plasma is significantly increased, there is no reaction of TSH to TRH. In some forms of the disease, an increased content of TSH and thyroid hormones in the blood is detected simultaneously. It is believed that there is partial resistance of thyrotrophs to thyroid hormones, resulting in the development of symptoms of thyrotoxicosis.

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Pathological anatomy

Diffuse toxic goiter is classified as primary thyroid hyperplasia and hypertrophy. The surface of the gland is smooth, on the section its substance is dense, homogeneous structure, grayish-pink color, sometimes shiny or colloidal. Small-point whitish inclusions (lymphoid infiltrates), foci or layers of fibrous tissue may be encountered. Histologically, we distinguish three main variants of diffuse toxic goiter (Graves' disease):

1. hyperplastic changes combined with lymphoid infiltration;
2. without lymphoid infiltration;
3. colloidal proliferating goiter with morphological signs of increased thyroid epithelial function.

The first variant is classical. It is characterized by increased proliferation of the 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 to varying degrees and is focal. When it is weakly expressed, 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 titer of antithyroid antibodies, as well as the severity of the oncocytic-cellular reaction. In such glands, the development of focal autoimmune thyroiditis is sometimes noted. In some cases, the outcome of diffuse toxic goiter (Graves' disease) into autoimmune thyroiditis is observed.

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

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

In case of relapse of diffuse toxic goiter (Graves' disease), the structure of the thyroid gland often repeats the structure of the thyroid tissue that was removed for the first time, but subcapsular and interstitial fibrosis and a tendency to nodule formation are often observed in it.

In recent years, there has been an increase in the incidence of primary thyroid cancers associated with diffuse toxic goiter (Graves' disease). These are usually microcancers, predominantly highly differentiated: papillary, such as Graham's adenocarcinoma, follicular, or mixed, the removal of which usually results in recovery. We have not observed any relapses or metastases in these cases.

In individuals with diffuse toxic goiter (Graves' disease) who died of heart failure, the heart is moderately enlarged with atrial dilation and mild hypertrophy and dilation of both ventricles. In the myocardium of the left ventricle, foci of necrosis and fibrosis are found. Enlargement of the thymus, cervical lymph nodes and even tonsils is often noted. Fatty dystrophy develops in the liver. In the bones, there is sometimes increased osteoclast activity with bone resorption. Thyrotoxic myopathy is characterized by atrophy of skeletal muscles with fatty infiltration.