Vol 61, No 4 (2015)

Clinical endocrinology
The diagnostical importance of steroid profiles of biological fluids of patients with Cushing’s syndrome
Shafigullina Z.R., Velikanova L.I., Vorohobina N.V., Lisicyn A.A., Kuhianidze E.A., Strelnikova E.G., Povarov V.G., Talor N.F.
Abstract
Steroid profiles of 49 patients having Cushing’s syndrome were investigated. Differential diagnostic criteria of Cushing’s syndrome with adrenocortical adenoma and adrenocarcinoma and features of steroid hormones metabolism were established by combination of classical tests and steroid profiles investigation using HPLC and gas chromatography - mass-spectrometry. The adrenocarcinoma was diagnosed for 22,4% of patients having Cushing’s syndrome and the main biochemical criteria were the increasing of 11-deoxycortisol in blood (>20 ng/ml), the excretion of 18-OH-corticosterone and metabolites of glucocorticoids and pregnenes, 8,2% of patients having Cushing’s syndrome had additionally increased androgens metabolites excretion.
Problems of Endocrinology. 2015;61(4):4-8
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Trabecular bone score as one of the new methods of non-invasive evaluation of bone microarchitecture in patients with Cushing’s syndrome
Dragunova N.V., Belaya Z.E., Sasonova N.I., Sopodovnikov A.G., Tsoriev T.T., Rozhinskaya L.Y., Hans D., Melnichenko G.A., Dedov I.I.
Abstract
Objective - to evaluate the value of trabecular bone score and risk factors of fractures in patients with Cushing’s syndrome (CS). Material and methods. One hundred eighty two patients with laboratory-confirmed Cushing’s syndrome were enrolled. All patients underwent measurement of bone mineral density (BMD) at the lumbar spine (LI-LIV), femoral neck and total hip using DXA Prodigy (GEHC Lunar, Madison, WI, USA). Trabecular bone score (TBS) was assessed retrospectively on the basis of already existing DXA images using software TBS iNsight software v2.1 (Medimaps, Merignac, France). Each patient was interviewed for the presence of low-traumatic fractures during the active stage of the disease. A lateral X-ray of the thoracic and lumbar spine ThIV-LV was performed to estimate vertebral fractures. Twenty-four hours urinary free cortisol (24hUFC) was measured by imunochemiluminescence assay VITROS ECi with the preliminary extraction with diethyl ether (reference values 60-413 nmol/24 h). Results. Among 182 patients with CS (149 women, 33 men), Cushing’s disease was confirmed in 151 cases, 9 patients diagnosed with benign adrenal tumor and 22 - ACTH-ectopic syndrome. The median of age - 35 (Q25-Q75 27-49) years, body mass index - 29 (26-33) kg/m2, 24hUFC - 1760 (985-2971) nmol/24h. Fractures were confirmed in 80 (44%) cases, 70 patients suffered from vertebral fractures, which were multiple in 53 cases; 23 patients had non-vertebral fractures. Median of trabecular bone score was 1.205 (1.102-1.307), which is much lower than expected in healthy volunteers (>1.350), while the decrease in bone mineral density (BMD) did not correspond to the severity and prevalence of osteoporosis fractures: LI-LIV Z-score - 1.7 (2.5-0.73); femoral neck Z-score - 1 (-1.6- -0.4). However, when using binary logistic regression analysis (adjusted for sex, age, body mass index, bone mineral density, trabecular bone score and 24hUFC) revealed that the most significant predictor of fracture is high levels of 24hUFC (p=0.001) . The high prevalence of vertebral fractures in patients with CS most likely influenced the results of trabecular bone score and its ability to predict fractures. Conclusion. Patients with active CS have low trabecular bone score, rather than bone mineral density, which reflects deterioration in bone microarchitecture. The low-traumatic fracture occurrence depends on the severity of CS reflected in 24hUFC levels.
Problems of Endocrinology. 2015;61(4):9-16
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The state of the Sertoli cells in the children and adolescents presenting with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Chugunov I.S., Il’in A.V., Bogolyubov S.V., Kuznetsova E.S., Orlova E.M., Kareva M.A.
Abstract
Introduction. Compromised fertility is one of the main health-related problems encountered by men suffering from 21-hydroxylase deficient congenital adrenal hyperplasia (CAH). This condition can be attributed either to the disease itself or to the presence of the testicular adrenal rest tissue (TART). The dysfunction of the reproductive system can be diagnosed as early as the childhood and adolescence based on the reduced levels of anti-müllerian hormone (AMH) and inhibin B, i.e. the specific markers of Sertoli cell activity. Materials and methods. We have examined 53 patients at the age varying from 1 to 19 years presenting with the confirmed diagnosis of 21-hydroxylase deficient congenital adrenal hyperplasia and 21 children aged from 6 to 17 years free from endocrine pathology (the control group). Special attention was given to the elucidation of the relationship between the inhibin B and AMH levels, the clinical form of the disease, and the presence of TART. Results. The level of inhibin B in the patients with congenital adrenal hyperplasia at the onset of puberty turned out to be lower compared with that in the control group, regardless of the form of the disease. The presence of TART was documented in 9 patients (30%) with salt-wasting CAH (SW CAH) and in 1 patient (4.3%) having the simple virilizing form of CAH (SV CAH). The patients with TART had a lower level of inhibin B but not AMH. Conclusion. The excessive production of androgens does not exert a negative influence on the activity of the Sertoli cells in the boys suffering from congenital adrenal hyperplasia prior to puberty. The lowered level of inhibin B during the pubertal period, in the absence of reduction of the AMH level, suggests dysfunction of the Sertoli cells. The dysfunction during puberty is especially well apparent in the presence of TART.
Problems of Endocrinology. 2015;61(4):17-23
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Evaluating of the phosphodiesterase inhibitor type 5 effectiveness in treatment of neurogenic erectile dysfunction in patients with DM type 1
Kurbatov D.G., Galstyan G.R., Shvarts Y.G., Rozhivanov R.V., Dubskiy S.A., Lepetukhin A.E.
Abstract
Urogenital form of autonomous diabetic polyneuropathy is a specific lesion of the autonomic nervous system in patients with diabetes mellitus (DM) and is the main pathogenetic cause of sexual dysfunction in these patients. The most common form of the sexual dysfunction in patients with DM is an erectile dysfunction, the risk of which is at 3 times higher for patients with DM compared to the population without it. Considering that patients with DM are a special group because of the presence of specific complications, preferences in therapy is given to inhibitors of PDE-5 type inhibitors. Aim - optimization of diagnosis and treatment of neurogenic erectile dysfunction caused by urogenital autonomic diabetic neuropathy in patients with type 1 diabetes. Material and methods. The study included 40 patients with DM type 1 at the age of 25.7±6.1 years. The duration of the DM type 1 18±9.7 years. The average level of glycated hemoglobin at the time of inclusion of patients in the study 7.1±1.3%. All patients in addition to general clinical examination performed neuromyography of peroneal nerve and pudendal nerve (at baseline and after a course of therapy with sildenafil) and the analysis of endothelial function on the EndoPat ™ (baseline and after a course of therapy with sildenafil). Results. At baseline, all 40 men s complained on the quality of erection of varying severity. In 30 (75.0%) of men according to a survey on the unit EndoPat ™ determined endothelial dysfunction (RHI 1.45±0.16). In the range of the gray zone (RHI 1.79±0.13) IRG was detected in 7 (16.6%) men. RHI values, indicating normal functioning of the endothelium, were obtained in 3 (8.4%) cases. After 6 weeks, analisys of endothelial function after the course of treatment with sildenafil was repeated: endothelial dysfunction was found in 6 (16.6%) patients, in the range of the gray zone RHI was registered in 14 (33.4%). Evidence about normalized endothelial function were obtained from 20 (50.0%) patients. The results of neuromyomyographic test of n. peroneus and n. pudendus confirmed the presence of distal diabetic neuropathy and urogenital form of autonomic diabetic neuropathy baseline in all patients. Retest after treatment showed a significant positive trend in our patients. Conclusion. Our study showed the advisability of using inhibitiors PDE-5, in particular sildenafil, not only to improve erectile function in patients with DM type 1, but also to improve endothelial function and condition of the peripheral nerves. We are convinced that the examination of such patients should include both of these methods, because diabetic neuropathy in patients with DM directly linked with endothelial dysfunction
Problems of Endocrinology. 2015;61(4):24-28
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The quality of medical aid provided to the children with type 1 diabetes mellitus
Dedov I.I., Peterkova V.A., Karpushkina A.V., Vartapetova N.V., Shvabskiy O.R., Starovoytov M.L., Bashnina E.B., Vitebskaya A.V., Dedyukina E.S., Malievskiy O.A., Mikhaylova E.G., Samoylova Y.G., Filimonova A.Y., Khramova E.B., Pankratova M.S., Okorokov P.L., Chugunov I.S., Sozaeva L.S.
Abstract
This paper reports the results of the study designed to estimate the quality of medical aid provided to the children with type 1 diabetes mellitus in six regions of the Russian Federation. The primary objective of the study was to improve the quality and to enhance the availability of the medical assistance for the children suffering from endocrine diseases in the framework of the “Alpha-Endo” program
Problems of Endocrinology. 2015;61(4):29-42
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Experimental endocrinology
Features of molecule expression markers of insulin resistance in experimental Alzheimer’s disease
Gorina Y.V., Komleva Y.K., Lopatina O.L., Volkova V.V., Gersog G.E., Popova N.N., Salmina A.B.
Abstract
Alzheimer’s Disease (AD) is characterized by a significant loss of neurons and synapses, especially in the hippocampus and cortex, the extracellular β-amyloid accumulation and formation of neurofibrillary tangles. Insulin resistance plays important role in neurodegeneration and cognitive disorders in the central nervous system, especially AD. However, the cellular and molecular mechanisms that connect insulin resistance and Alzheimer’s pathogenesis remain largely unexplained. Therefore, great importance is the identification of molecular markers that allow to define new approaches to targeted pharmacological correction of neurodegeneration. This article describes the study of the expression of molecular markers, namely, IRAP, GLUT4, and IL-18 in different brain regions (hippocampus, olfactory bulb) rats with experimental AD
Problems of Endocrinology. 2015;61(4):43-48
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Reviews
Role of stress proteins and hormones in bioregulation of ontogeny
Goudochnikov V.I.
Abstract
In this short review article we tried to overview diffusely spread data on the role of stress proteins and hormones in ontogeny. The work presented here is a product of our long-term studies beginning from the middle of eighties of the last century and performed both in Russia and Brazil. It involves the results obtained with the use of experimental models on laboratory animals in vivo and in vitro, as well as later theoretical research in world literature databases. In experimental studies we used laboratory rats of different age groups and primary cultures of pituitary and liver cells for evaluating respectively body and organ growth and production of immunoreactive growth hormone (GH) and serum albumin (SA), as well as biosynthesis of DNA, total RNA and protein. The results obtained, showing important role of glucocorticoids (GC) in regulation of perinatal pituitary and liver functions and postnatal growth, were reinterpreted by us recently in the frame of DOHaD concept and as related to perinatal imprinting/programming phenomena. It is concluded that the present moment is quite appropriate for the widening of our studies both to the side of early embryonal development and in direction to aging, thus completing the whole cycle of life history / course research, as referred to stress proteins and hormones.
Problems of Endocrinology. 2015;61(4):49-53
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Continuous glucose monitoring technologies: state of the art and future perspectives in view of artificial pancreas
Tarasov Y.V., Philippov Y.I., Borisova E.A., Fedorova E.A., Mayorov A.Y., Shestakova M.V.
Abstract

Continuous glucose monitoring (CGM) - a relatively new and rapidly developing technology of optimization glycemic control in patients with diabetes. The efficiency of the use of CGM for improving glycemic level in many clinical situations (asymptomatic hypoglycemia, high blood glucose variability, etc.). In the long term, CGM treated as a mandatory component of the «artificial pancreas» - an insulin pump with a closed-loop control infusion of insulin depending on the concentration of glucose in the blood. However, the modern technology such as CGM could not be used, as a data source to control closed-loop insulin pump (artificial pancreas), because of the significant limitations and lack of precision. In further development of technologies CGM, obviously, will address three main objectives: increased service life of sensors for the detection of glucose, improving the accuracy of measurement results and ease of use for patients. This article describes the main technological solutions of modern devices for CGM and promising directions for further developments in this field, their potential advantages and disadvantages, including in the light of the prospects for further integrating them into an «artificial pancreas».

Problems of Endocrinology. 2015;61(4):54-72
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