[On the mechanisms of thyrocyte proliferation and death in autoimmune thyroid diseases].

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.

Increase in serum concentration of FAS ligand as a possible mechanism for antithyroid cytotoxicity during autoimmune thyroid diseases.

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.

Antibodies to pituitary surface antigens during various pituitary disease states.

Autoantibodies to cell surface antigens of human somatotropinoma (ASAS), human prolactinoma (ASAP) and rat adenohypophysis (ASARA) were assayed in the serum of patients with pituitary diseases associated with GH deficiency (GHD), such as pituitary dwarfism and primary empty sella syndrome (ESS), and in the serum of patients with hyperprolactinaemia of different etiologies: idiopathic hyperprolactinaemia, prolactinoma and ESS. The investigation was carried out with a cellular variant of an ELISA. Among children with GHD, the highest percentage of antibody-positive patients was found in the group with idiopathic isolated GHD (89% of ASAS(+) patients and 30% of ASARA(+) patients vs 33.3% and 0% respectively in the group with idiopathic combined pituitary hormone deficiency, and 33.3% and 9% in patients with pituitary hypoplasia associated with isolated GHD or combined pituitary hormone deficiency). Among hyperprolactinaemic patients, the highest ASAP and ASARA frequency was observed in patients with idiopathic hyperprolactinaemia (67.7% and 41.9% respectively) where it was twice as high as in the group of patients with prolactinoma. The proportion of ASAS(+) and ASARA(+) did not differ significantly between the groups of patients with ess with or without GHD. Similarly, there was no significant difference between the number of ESS ASAP(+) and ASARA(+) patients with or without hyperprolactinaemia. The data obtained suggested that autoimmune disorders may be primary, and responsible, at least in part, for pituitary dysfunction in the cases of idiopathic isolated GHD and idiopathic hyperprolactinaemia. At the same time, the autoimmune disorders in the patients with prolactinoma or ESS are probably secondary to the organic pituitary lesion and their significance in the development of the pituitary dysfunction is obscure.

[Blood serum immunoglobulins from patients with juvenile struma reduce the cAMP level in isolated human thyrocytes]. / Immunoglobuliny iz syvorotki krovi lits s iuvenil'noi strumoi snizhaiut uroven' tsAMF v izolirovannykh tireotsitakh cheloveka.

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.

[Interactions between serum antibodies of patients with autoimmune thyropathies and isolated cells of diffuse toxic euthyroid nodular goiter]. / Vzaimodeistvie antitel iz vyvorotok bol'nykh autoimmunnymi tireopatiiami s izolirovannymi kletkami diffuznogo toksicheskogo eutireoidnogo uzlovogo zoba.

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.

[Parameters of thyroid status in children and adolescents living in one of the Kaluga regions contaminated with radionuclides]. / Nekotorye pokazateli, kharakterizuiushchie sostoianie shchitovidnoi zhelezy u detei i podrostkov, prozhivaiushchikh v odnom iz zagriaznennykh radionuklidami raionov Kaluzhskoi oblasti.

Thyroid status was examined in 1214 children living in the Ulyanov district of the Kaluga region contaminated with radionuclides. Thyroid size and structure were assessed using ultrasonic examination, its function was characterized based on thyrotropin and free thyroxin measurements. Specific autoimmunity was evaluated from assays of antibodies to microsomal antigen and thyroglobulin. The resultant values were assessed with due consideration for the individual dose of 131I absorbed by the thyroid. Thyroid enlargement was detected in 21.2%, nodular goiter in 0.79% of the examinees. A reliable positive correlation was found between the degree of thyroid enlargement and 131I absorbed dose. Functional parameters (thyrotropin and free thyroxin) were within the normal range, no correlation was detected between hormonal parameters, thyroid size, and 131I absorbed dose. Antibodies to microsomal antigen were detected in 4.3%, to thyroglobulin in 7.2%, to both in 2.8% of the examinees, this being within the normal range in the population; but a relationship was detected between antibody production and absorbed dose of 131I. Hence, though no noticeable changes in the thyroid status were detected 5 years after the accident in the population examined, the revealed correlations between thyroid enlargement, presence of antithyroid antibodies, and 131I dose may be indicative of a possible growth of thyroid morbidity.

[Determination of autoantibodies to pancreatic beta-cells, non-islet endocrine cells and fibroblasts in patients with newly detected diabetes mellitus]. / Opredelenie autoantitel k beta-kletkam podzheludochnoi zhelezy, neostrovkovym éndokrinnym kletkam i fibroblastam u bol'nykh s vpervye vyiavlennym sakharnym diabetom.

The clinical onset of insulin-dependent diabetes (IDD) is characterized by the onset of circulation of autoantibodies to beta-cells. Thirty-three newly detected IDD patients and 14 newly detected patients with noninsulin-dependent diabetes mellitus were examined for autoantibodies to antigen P 64-69, to surface antigen of islet cells, to thyrocyte microsomal fraction, thyroglobulin, hypophysis, fibroblasts; the levels of circulating immune complexes were measured as well. IDD debut was found associated with the appearance of antibodies to pancreatic islet cells, thyroid, thyroglobulin, hypophysis, fibroblasts, this indicating a polyclonal activation of the immunity system. A relationship was revealed between antifibroblast antibody and anti-islet-cell antibody. Antihypophyseal antibodies were detected in 43% of patients with noninsulin dependent diabetes. Nine per cent of IDD patients and 24% of patients with noninsulin dependent condition were negative in the tests.

[Determination of autoantibodies to thyrotropin receptors in patients with diffuse toxic goiter]. / Opredelenie autoantitel k retseptoram tireotropnogo gormona u bol'nykh diffuznym toksicheskim zobom.

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.

[Dynamics of thyrostimulating immunoglobulin levels during treatment of diffuse toxic goiter]. / Dinamika urovnia tireostimuliruiushchikh immunoglobulinov v protsesse lecheniia diffuznogo toksicheskogo zoba.

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 relationship of endocrine ophthalmopathy to the thyroid status and to the indices of an autoimmune lesion of the thyroid]. / Sviaz' éndokrinnoi oftal'mopatii s tireoidnym statusom i pokazateliami autoimmunnogo porazheniia shchitovidnoi zhelezy.

The paper is devoted to a study of the pathogenetic relationship of endocrine ophthalmopathy with thyroid diseases. Altogether 76 patients with endocrine ophthalmopathy combined with various thyroid lesions (diffuse toxic goiter, Hashimoto's disease, primary hypothyrosis) and without thyroid diseases were investigated. The serum level of thyroid hormones, the content of Ig A, M, G, thyroglobulin and the presence of antithyroid antibodies were analyzed. HLA typing by A, B, C, D2 loci was done for a group of patients. The results did not show correlation of the origin and gravity of ophthalmopathy either with thyroid function or with the factors determining thyroid affection. Some differences in the genetic markers of endocrine ophthalmopathy and autoimmune thyroid diseases were also established.

[Characteristics of the endocrine function of the pancreas in diffuse toxic goiter in children]. / K kharakteristike éndokrinnoi funktsii podzheludochnoi zhelezy pri diffuznom toksicheskom zobe u detei.

The examination of 28 children with diffuse toxic goiter showed disturbance of glucose tolerance with a significant decrease in the level of C-peptide in the blood serum and its response to glucose. The concentration of immunoreactive insulin (IRI) and its increment under the influence of a glucose tolerance test in children was much above the normal. At the same time the molar C-peptide/IRI ratio in the patients' sera both on an empty stomach and during the glucose tolerance test showed a dramatic decrease indicating the reduction of insulin extraction by the liver as a cause of peripheral hyperinsulinemia. Distortion of the plasma immunoreactive glucagon reaction to a glucose tolerance test was observed in children with diffuse toxic goiter.

[Reflexometry: an early prognostic test for assessing postoperative hypothyroidism]. / Refleksometriia: rannii prognosticheskii test otsenki posleoperatsionnogo gipotireoza.

The serum content of thyroxin (T4) and the duration of Achilles reflex was studied in 23 patients with toxic goiter 1-3 months after subtotal thyroidectomy. Concentration of T4 assessed in the serum revealed 9 euthyroid subjects and 14 patients with hypothyrosis. But as the duration of Achilles tendon reflex was within the norm in all 14 hypothyrosis patients reflexometry technique turned to be inconsistent in distinguishing between hypo- and euthyroidism. However the high prognostic value of this method for differential diagnosis of transient or long-standing forms of the disease was shown. Six months after the surgery hypothyrosis disappeared spontaneously, i.e. turned to be transient, in 5 patients whose Achilles tendon reflex parameters were normal, though in all 9 hypothyrosis patients with the reflex parameters higher than 350 m/s clinical and biochemical signs of thyroid under-activity were detected. The data obtained give evidence in favour of reflexometry to be used for early prognostic assessment of post-operative hypothyrosis.

[TRH test after subtotal thyroid resection for diffuse toxic goiter]. / TRG-test posle subtotal'noi rezektsii shchitovidnoi zhelezy po povodu diffuznogo toksicheskogo zoba.

Altogether 25 patients were examined one month after subtotal resection of the thyroid for diffuse toxic goiter. A wide spectrum of the TSH to TRH reaction was detected. The nature of this reaction made it possible to single out 4 groups of patients with a progressively decreasing and even paradoxical response of TSH to TRH. There were no correlations between the nature of the TSH to TRH reaction and the patients' thyroid status in the pre- and postoperative period, time-period of disease and the expression of autoimmune processes. Profound changes in function of the pituitary-hypothalamo-thyroid system were found in most of the patients at the above mentioned time after operation.

[Mechanisms of hormonal regulation of blood glucose in thyrotoxicosis]. / Mekhanizmy gormonal'noi reguliatsii glikemii v dinamike tireotoksikoza.

Rabbits with thyrotoxicosis develop at the early stages of this pathology hyperglycemia, and, as the disease persisted and grew more severe, hypoglycemia. The insulin level in the peripheral blood decreases progressively in the time course of thyrotoxicosis; insulin response to glucose, a specific stimulus, also weakens. The idea of glucose utilization by muscles regardless of the insulin effect is postulated basing on analysis of the authors' and literature data. Its main physiological function in the body is supposed to be the inhibition of glucose production by the liver and free fatty acids by the adipose tissue.