The significance and mechanisms of action of different antithyroid antibodies in diffuse toxic goiter (Graves' disease) and chronic lymphocytic thyroiditis (Hashimoto’s disease) arc analyzed. Antibodies immediately decreasing the level of cAMP in isolated thyrocytes were revealed in the sera of adolescents with juvenile struma, often resulting from lymphocytic thyroiditis. Complement-fixing cytotoxic antibodies are heterogeneous in patients with Graves' diseases and Hashimoto's thyroiditis. Thyrocytes from the tissue of diffuse toxic goiter are resistant to the cytolytic effect of such antibodies from patients with Graves' diseases but not from patients with Hashimoto's thyroiditis. The causes and mechanisms of development of resistance of thyrocytes from diffuse toxic goiter to antibody-dependent complement-mediated cytotoxicity of sera from patients with Graves' disease and the possibility of using this phenomenon as a differential diagnostic test are discussed.

Lymphocytes isolated from diffuse toxic goiter (Graves' disease, GD) stimulate the proliferation of "normal" thyrocytes (isolated from euthyroid goiter) in primary culture, and give them the properties of GD-thyrocytes (loss of sensitivity to the growth-promoting factors of FCS and lesser capacity of binding antibodies from GD patients' serum). The complement-free sera of GD patients (but not the sera of patients with Hashimoto's thyroiditis, HT) induce the death of "normal" thyrocytes more rarely than full-complement sera do. Both types of serum cytotoxicity are manifested on GD-thyrocytes much more rarely than on "normal" cells. The Fas-receptor on GD-thyrocytes in situ is expressed less than on "normal" and especially on HT-cells. The level of soluble Fas-ligand in the serum of some complement-free patients was found to be increased. These sera induce apoptosis in "normal" thyrocytes, but not in GD-cells nor in human skin fibroblasts. In the authors' opinion, the proliferation of GD-thyrocytes in situ is stimulated by intrathyroid lymphocytes, which directly stimulate this process and induce the loss of receptors which mediate the cytotoxic effects of serum factors.

We studied the dependence of serum cytotoxic activity on the contents of soluble apoptosis receptor and its soluble ligand in patients with autoimmune thyroid diseases.

The primary cultures of thyrocytes isolated from the paranodal tissue of euthyroid nodal goiter indicated that the sera from patients with Hashimoto ’s thyroiditis and Graves’ disease had complement-independent cytotoxicity. This effect was found in about 40% of the sera from patients at different stages of drug compensation of autoimmune thyroid diseases. The cytotoxic effect of the sera was not shown in the primary cultures of human skin fibroblasts. The detection rate of complement-independent cytotoxicity in the sera from patients with Hashimoto ’s thyroiditis and Graves’ disease coincided with that of elevated levels of soluble FAS-receptor ligand in the respective sera. Thyrocytes isolated from patients with Graves’ disease turned out to be resistant to the action of 60% of the cytotoxic sera. This resistance may be associated with the lowered FAS-receptor expression on these cells, which has been revealed in special studies.

The capacity of lymphocytes isolated from diffuse toxic goiter (DTG) tissue to stimulate the proliferation of normal thyrocytes isolated from paranodular tissue adjacent to nodular euthyroid goiter was studied. Normal and DTG thyrocytes were incubated for 24 h with fetal calf serum (FCS) in various concentrations, DTG orparanodular lymphocytes, or both FCS and lymphocytes. The proliferation rate of normal thyrocytes in the presence of FCS alone increased with increase of the serum concentration, while the proliferation rate of DTG thyrocytes did not depend on the concentration of FCS. DTG lymphocytes, but not paranodular ones, stimulated the proliferation of normal thyrocytes. The growth-stimulating effect of DTG lymphocytes was paralleled by loss of normal thyrocytes sensitivity to growth factors (FCS). These data indicate a probable role of intrathyroid lymphocytes in increase of thyrocyte count characteristic of DTG and confirm a previous hypothesis on decrease in expression of surface antigens (receptors) on DTG cells under the effect of intrathyroid lymphocytes.

The significance and mechanisms of action of different antithyroid antibodies in diffuse toxic goiter (Graves' disease) and chronic lymphocytic thyroiditis (Hashimoto’s disease) arc analyzed. Antibodies immediately decreasing the level of cAMP in isolated thyrocytes were revealed in the sera of adolescents with juvenile struma, often resulting from lymphocytic thyroiditis. Complement-fixing cytotoxic antibodies are heterogeneous in patients with Graves' diseases and Hashimoto's thyroiditis. Thyrocytes from the tissue of diffuse toxic goiter are resistant to the cytolytic effect of such antibodies from patients with Graves' diseases but not from patients with Hashimoto's thyroiditis. The causes and mechanisms of development of resistance of thyrocytes from diffuse toxic goiter to antibody-dependent complement-mediated cytotoxicity of sera from patients with Graves' disease and the possibility of using this phenomenon as a differential diagnostic test are discussed.

Clinicohormonal examinations of 19 patients with juvenile struma revealed in many of them signs of latent hypothyrosis (increased age-specific level of blood serum TTH level and hyperergic reaction to TRH). Incubation of thyro- cytes isolated from perinodular tissue of patients with euthyroid nodular goiter with IgG isolated from the blood serum of patients with juvenile struma resulted in a reliably lower content of cAMP in the cells than after thyrocyte incubation with IgG isolated from the blood serum of 9 healthy donors. This is indicative of the presence of thyroblocking antibodies in the blood serum of patients with juvenile struma. Though no correlation could be traced between the tested immunoglobulin activity, on the one hand, and blood serum TTH level and struma size, on the other, one may propose a contribution of thyroblocking antibodies to the pathogenesis of juvenile struma.

Clinico-hormonal examinations of 19 patients with juvenile struma revealed in many of them signs of latent hypothyrosis (increased age-specific level of blood serum TTH level and hyperergic reaction to TRH). Incubation of thyrocytes isolated from perinodular tissue of patients with euthyroid nodular goiter with IgG isolated from the blood serum of patients with juvenile struma resulted in a reliably lower content of cAMP in the cells than after thyrocyte incubation with IgG isolated from the blood serum of 9 healthy donors. This is indicative of the presence of thyroblocking antibodies in the blood serum of patients with juvenile struma. Though no correlation could be traced between the tested immunoglobulin activity, on the one hand, and blood serum TTH level and struma size, on the other, one may propose a contribution of thyroblocking antibodies to the pathogenesis of juvenile struma.

Blood sera of 46 patients with diffuse toxic goiter (DTG) and of 48 ones with Hashimoto's thyroiditis (HT) were tested for antibodies--complement-mediated cytotoxicity carriers (ACMMC). ACMCC targets were isolated DTG cells and cells of euthyroid nodular goiter (ENG) perinodular tissue. Antimicrosomal antibodies were assayed in the sera by indirect immunofluorescence and antibodies to all thyrocyte surface antigens isolated from both tissue samples were determined by solid-phase enzyme immunoassay. When DTG cells were targets, DTG patients' sera detected ACMCC in 36% of cases and HT patients' sera in 73% of cases (p < 0.001). In ENG cells the sera of patients of both groups detected ACMCC equally frequently (in more than 70% of cases). Of the 27 DTG patients' sera tested with both tissues approximately a half detected ACMCC in only ENG tissue. There was no difference in HT patients' sera effects on ACMCC detection in both tissue samples. This has brought the authors to a conclusion about DTG cells deficiency for ACMCC mediating antigens. Moreover, DTG cells bound much less antibodies from sera of patients with autoimmune thyropathies, than ENG cells (p < 0.001), this confirming a deficiency of surface antigen on DTG cells. No correlation between the presence in the sera of antimicrosomal cells and of ACMCC was detected. A conclusion has been made about heterogeneity of antimicrosomal antibody population and about the presence of ACMCC in blood sera of patients with autoimmune thyropathies, these antibodies not belonging to antimicrosomal ones. ACMCC also may be heterogeneous and differ in DTG and HT patients.

Blood sera of 46 patients with diffuse toxic goiter (DTG) and of 48 ones with Hashimotos thyroiditis (HT) were tested for antibodiescomplement-mediated cytotoxicity carriers (ACMMC). ACMCC targets were isolated DTG cells and cells of euthyroid nodular goiter (ENG) perinodular tissue. Antimicrosomal antibodies were assayed in the sera by indirect immunofluorescence and antibodies to all thyrocyte surface antigens isolated from both tissue samples were determined by solid-phase enzyme immunoassay. When DTG cells were targets, DTG patients' sera detected ACMCC in 36 % of cases and HT patients sera in 73% of cases (p0.001). In ENG cells the sera of patients of both groups detected ACMCC equally frequently (in more than 70% of cases). Of the 27 DTG patients sera tested with both tissues app. roximately a half detected ACMCC in only ENG tissue. There was no difference in HT patients sera effects on ACMCC detection in both tissue samples. This has brought the authors to a conclusion about DTG cells deficiency for ACMCC mediating antigens. Moreover, DTG cells bound much less antibodies from sera of patients with autoimmune thyropathies, than ENG cells (p0.001), this confirming a deficiency of surface antigen on DTG cells. No correlation between the presence in the sera of antimicrosomal cells and of ACMCC was detected. A conclusion has been made about heterogeneity of antimicrosomal antibody population and about the presence of ACMCC in blood sera of patients with autoimmune thyropathies, these antibodies not belonging to antimicrosomal ones. ACMCC also may be heterogenous and differ in DTG and HT patients.

Twenty-five patients with diffuse toxic goiter, investigated at various time of mercazolyl therapy, demonstrated the presence of thyrostimulating immunoglobulins in 100% before treatment, in 91% after 6 months and in 50% after 12 months of treatment. Specific therapy reduced considerably not only the frequency of detection but also the activity of thyrostimulating immunoglobulins. Clinical and hormonal remission of disease did not always coincide with immunological remission.

The blood level of antithyroid autoantibodies to TSH receptors was determined in patients with toxic goiter (TG) before and during antithyroid therapy using two biological methods (by the increment in the cAMP level in slices and primary monolayer culture of human thyroid cells) and a radioreceptor method (by inhibition of TSH binding with its receptors from the animal thyroid). Comparison of the results of these three methods has shown that all methods are almost equally valuable for diagnosis of new cases of TG. However the biological method was shown to be more sensitive and informative with regard to predicting the time of immunological remission during antithyroid therapy.