[Genetic approaches to Itsenko-Cushing disease]. / O geneticheskikh podkhodakh k bolezni Itsenko--Kushinga.

107 patients with Itsenko-Cushing disease were examined for heredity: family history was analyzed in 75 cases, dermatoglyphics was assessed in 44 cases, I- and II-class HLA antigens were studied in 68 cases. The patients were found to have hereditary loading both by Itsenko-Cushing and other diseases (hypertension, atherosclerosis, autoimmune disorders). Clinico-genealogical evaluation made it possible to identify forms of the disease which are inherited autosome-recessively and autosome-dominantly. However, in the majority of patients the disease onset had multifactorial nature, as there were HLA-antigen associations by DR4, DR5, DR7, DRw53, DQw3. Pilot experience with genetic study of the disease showed its genetic determination in some forms, its association with hypertension and atherosclerosis, approaches to prevention, prognosis, classification. Practical recommendations on detailed family history collection in patients with Itsenko-Cushing disease have been developed.

[The importance of immunogenetic studies in Itsenko-Cushing disease combined with other endocrine diseases]. / Znachimost' immunogeneticheskikh issledovanii pri bolezni Itsenko--Kushinga v sochetanii ee s drugimi éndokrinnymi zabolevaniiami.

Ninety-seven patients suffering from Itsenko [correction of Icenko]-Cushing disease were examined. Analysis was made first of all of the clinical and laboratory signs pointing to the presence of other endocrine diseases to distinguish two groups of patients. The first group included subjects who did not manifest any concomitant diseases. The number of men and women was the same. The second group was made up of patients with associated Itsenko [correction of Icenko]-Cushing disease and other endocrine diseases. In this particular group, women were predominant. The first group patients demonstrated the predominance of the DR7 incidence, the second group that of the DR5. The method of estimating HLA associations identified is proposed. It allows distinguishing specific and nonspecific associations. In Itsenko [correction of Icenko]-Cushing disease, DR7 association is specific, whereas B8 and DR5 associations are unspecific. A specific polyendocrine autoimmune syndrome associated with Itsenko [correction of Icenko]-Cushing disease was revealed. A concept of the pathogenesis of Itsenko [correction of Icenko]-Cushing disease is advanced.

[Association of I and II class HLA antigens with Cushing's syndrome]. / Assotsiatsiia HLA-antigenov I i II klassov s bolezn'iu Itsenko- Kushinga.

Incidence of class I and II HLA antigens was studied in 69 patients suffering from Icenko--Cushing syndrome. Positive association was reported for antigens DRw53, DQw3, DR4, DR5, negative for antigen DR2. Antigen combinations DR5, DR7 and DR4, DR5 proved more prevalent. The risk to develop the disease rose 2-3-fold in case of HLA-DR5 phenotype occurrence with antigen DR4 or DR7. Association with DRw53 and DQw3 antigens showing wide specificity seemed most significant.

[The role of glucocorticoid receptors and HLA antigens in the pathogenesis of Cushing's syndrome]. / O roli gliukokortikoidnykh retseptorov i antigenov HLA-sistemy v patogeneze bolezni Itsenko-Kushinga.

Lymphocytic levels of glucocorticoid receptors were evaluated in 114 patients suffering from Icenko-Cushing's syndrome. Incidence of HLA antigens was determined in 94 of them. A significant rise of A10 and B27 antigen incidence compared to that in normal subjects allows these antigens to be considered genetic markers of Icenko-Cushing's syndrome. The levels of glucocorticoid receptors in lymphocytes of the patients are lower than in normal subjects both in the active stage of the disease and following bilateral total adrenalectomy. The patients carrying B27 antigen had lymphocytic receptor concentrations under the levels of such in patients free of the antigen carriage. Antigen B27 seems to be a cause of lower levels of glucocorticoid receptors in blood lymphocytes.

[Immunologic indices in Itsenko-Cushing disease]. / Immunologicheskie pokazateli pri bolezni Itsenko-Kushinga.

The status of the immune system was studied in 36 patients with the Itsenko-Cushing disease (10 at the initial stage, 12 in the period of recurrence, 14 during remission) and in 20 healthy persons comparing the corticotropin and hydrocortisone content in the plasma. The level of T lymphocytes was lowered at the initial stage of disease (40.6 +/- 3.4%) as well as during recurrence and remission (37.8 +/- 3.9 and 44.5 +/- 4.6%, respectively) as compared to this level in the healthy persons (60.5 +/- 3.6%). The content of B lymphocytes was lowered in all 3 groups (4.3 +/- 0.8,2.9 +/- 0.5 and 4.8 +/- 0.7%, respectively; in the group of healthy persons, it was 19.2 +/- 3.0%). The phagocytic activity of leukocytes was lowered at the initial stage of disease (39.0 +/- 7.6%) and during recurrence (36.7 +/- 4.5%) as compared to that of the healthy persons (44.6 +/- 1.5%). The hydrocortisone sensitive population of T lymphocytes was decreased 1.5-2 times. An increase in the corticotropin level (148.1 +/- 16.9 and 85.2 +/- 19.7 pg/ml, respectively; in health 47.9 +/- 3.8 pg/ml) and in the hydrocortisone level (142.5 +/- 11.1 and 181.3 +/- 20.5 ng/ml, respectively; in health 79 +/- 23 ng/ml) was marked simultaneously in the patients of these 2 groups. During remission (corticotropin and hydrocortisone normal levels), immunological indicators did not completely return to normal, thus suggesting a stable disorder of the cell immunity.

[The HLA system and Itsenko-Cushing disease]. / Sistema HLA i bolezn' Itsenko-Kushinga.

The determination of HLA antigens in 54 patients with Icenko-Cushing's disease demonstrated the high rate of AIO antigens (50.7%), B8 (27.3%) and B27 (26.2%) antigens. In the control group, the rate of the same antigens amounted to 17.8, 16.3 and 7.4%, respectively. Specific features were also revealed in the rate of individual HLA haplotypes. The rate of A X IO, B8; A X IO, B27 haplotypes occurring relatively rarely in normal subjects was high in patients with Icenko-Cushing's disease. The high rate of AIO, B8 and B27 antigens may attest to the high risk of the development of Icenko-Cushing's disease in subjects carrying these antigens.