Vol 42, No 4 (1996)

Clinical endocrinology
The national register of diabetes mellitus: incidence of noninsulin-dependent diabetes and its complications (communication 1)
Dedov I.I., Suntsov Y.I., Kudryakova S.V., Ryzhkova S.G., Volkov V.S., Inyakina T.I., Lisitsyn V.Y., Baslerova Y.A., Gubanov N.V.
Abstract

The organizational structure of the National Register of Diabetes Mellitus (NRDM) is discussed, and results of the analysis for one of the territorial centers of NRDM in the Central Administrative District of Moscow are presented. The data indicate that the organization of NRDM appreciably improves the level and quality of medical statistical monitoring of the epidemiological situation as regards the above disease, extends the scope of available information needed for planning and economic validation of diabetologic service in public health, and helps develop the strategy of primary and secondary prophylaxis of diabetes and outline the main trends in epidemiological research. The register data may be used as the database for drug and food plants when planning antidiabetic agents and dietetic foodstuffs.

Problems of Endocrinology. 1996;42(4):3-9
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Lipid metabolism and hormonal status in patients with type I diabetes mellitus combined with subclinical hypothyroidism
Stroyev Y.A., Kasatkina E.P., Dmitriyeva N.V., Filimonova A.Y.
Abstract

Lipid metabolism and thyroid hormonal status were examined in diabetics with type 1 condition, subclinical hypothyroidism, and a combination of both. Lipid spectrum of the blood was assessed: total cholesterol, b-lipoproteins, triglycerides, a-cholesterol, total lipids, atherogenicity index, as well as the pituitary thyrotropic hormone, triiodothyronine, and thyroxin. Hyperlipoproteinemia was detected, which was particularly typical of atherogenic lipids in not only adult patients with type I diabetes, but in children as well, paralleled by an increase of the blood level of the pituitary thyrotropic hormone possessing a lipolytic activity. Atherogenic disorders in the lipid spectrum of children with subclinical hypothyroidism presenting as dyslipoproteinemia are considered to anticipate hyperlipoproteinemia in adult patients. A subclinical hypofunction of the thyroid is conducive to disorders of lipid metabolism when combined with type I diabetes and to boosting the atherosclerotic involvement of the vessels in children.

Problems of Endocrinology. 1996;42(4):9-11
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Enzymuria in diabetics with type ii condition and disordered purine metabolism
Gheorgadze Z.O., Balabolkin M.I., Mamayeva G.G., Lyudina L.I., Mischenko B.P.
Abstract

The authors compare enzymuria occurring in disorders of purine metabolism in patients with types I and II diabetes. Urinary enzymes (alkaline phosphatase, lactate dehydrogenase, N-acetyl-b-D-glucosaminidase, alanine aminopeptidase, cholinesterase, and b-galactosidase) were measured in 25 patients with noninsulin-dependent (NIDDM) and insulin-dependent diabetes mellitus (IDDM) with different disorders of purine metabolism (hyperuricemia and hyperuricosuria) and in 27 normal controls. The study revealed the syndrome of enzymatic insufficiency and syndrome of increased glomerular permeability (expressed increase of cholinesterase level in the urine) in patients with NIDDM; the latter syndrome was expressed similarly in patients with both NIDDM and IDDM. This syndrome was particularly severe in patients with IDDM complicated by diabetic nephropathy and disordered purine metabolism.

Problems of Endocrinology. 1996;42(4):12-14
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Adrenal steroids in the blood and urine and the immune status of women with age-associated disorders of glucose tolerance
Odin V.I., Poroshina T.E., Tsyrlina E.V., Berstein L.M.
Abstract

Dehydroepiandrosterone (DHA), hydrocortisone, and insulin are naturally occurring substances influencing the immune functions. The present paper is devoted to their combined effects on the mitogen-stimulated proliferation of lymphocytes (MSPL) with phytohemagglutinin-M (PHA-M) and Pokeweed mitogen used as stimulants. A positive correlation between blood insulin and urinary DHA levels (r=0.534; p<0.05) has been revealed. The level of DHA secretion was in a negative correlation with the values of MSPL stimulated by PHA-M (r=-0.651; p<0.01). Hence, age-associated hyperinsulinemia may be regarded as an important regulator of both, adrenal androgen production and the cellular immunity status.

Problems of Endocrinology. 1996;42(4):14-17
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Insulin content and arterial pressure in obese women
Ginzburg M.M., Kozupitsa G.S., Sergeyev O.V.
Abstract

The pathogenesis of hypertension developing in obesity is still to be studied. Hyperinsulinism and insulin resistance are believed to contribute to it. A relationship between the levels of basal and glucose-stimulated immunoreactive insulin (IRI) and arterial pressure (AP) has been studied in 36 women aged 18 to 37 suffering from obesity of the first-fourth degrees. Basal IRI level was appreciably increased and directly correlating with systolic and diastolic AP, but not related to body weight excess. AP directly depended on the degree of obesity and disease standing, but not on patient's age. These data permit us to conclude that insulin contributes to the pathogenesis of hypertension in obese women, but further studies are needed to elucidate the type and mechanisms of this contribution.

Problems of Endocrinology. 1996;42(4):17-19
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Pituitary prolactotropic function in patients with "inactive" pituitary adenoma
V. Vax V.V., Marova Y.I., Goncharov N.P., Kasumova S.Y., Kadashev B.A.
Abstract

Pituitary prolactotropic function was retrospectively analyzed in 23 patients with "inactive" pituitary adenoma (8 oncocytomas and 15 zero-cell adenomas) verified by electron microscopy. Before surgery basal prolactin level, prolactin concentrations in tests with thyrotropin-releasing hormone (TRH) and Parlodel, and daily fluctuations in prolactin levels in the blood were measured in all the patients. Moderate hyperprolactinemia was detected in 11 (47.8%) patients, which was often associated with galactorrhea-amenorrhea in women and with sexual dysfunction in men and was related to disturbed hypothalamo-pituitary relationships in cases with large adenomas. Irrespective of the basal level of prolactin, its secretion in response to TRH was abnormal: the reaction was reduced, particularly in patients in whom the tumors were associated with hyperprolactinemia. Acute loading with Parlodel led to a reliable reduction of prolactin concentration in the blood both in controls and in patients with normo- and hyperprolactinemia. A reduction of prolactin level by more than half in patients with inactive pituitary adenomas and moderate hyperprolactinemia in response to Parlodel loading, similarly as in normal subjects, confirms the functional type of hyperprolactinemia in such patients. Daily fluctuations of prolactin level were revealed in patients with large or giant adenomas.

Problems of Endocrinology. 1996;42(4):19-22
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The Shereshevsky-Turner syndrome: Spontaneous growth and growth-promoting effects of estrogen replacement therapy
Koledova Y.В., Semicheva T.V., Tyulpakov A.N., Yarovaya I.S., Peterkova V.A.
Abstract

Short stature and ovarian failure are typical features of Turner's syndrome (TS). Although growth in TS has been intensively studied, few data are available concerning the influence of different karyotypes and estrogen replacement therapy on the growth of TS patients. This paper presents the first results of studying the growth of TS patients in Russia. Sixty-one girls aged 5 to 17 with TS were examined. Auxological data included parental height (Ht), target Ht, predicted Ht (1), spontaneous Ht, Ht SDS (Tanner), Ht SDS TS (1), birth length, birth length SDS, and Ht SDS for BA before and after estrogen therapy. The diagnosis of TS was confirmed by the identification of the karyotype from peripheral leukocytes. 45,X karyotype was detected in 69%, different types of mosaicism including X chromosome (45,X/46,XX; 45,X/46,X(r)x) in 16%, 46,Xi(q) and deletions of X chromosome in 10%; Y chromosome mosaicism (45,X/46,XY) in 5%. Estrogen replacement (dihydrostilbestrol orally in a daily dose of 1.0 mg) was started at BA>11.0 years if no signs of spontaneous puberty were observed. The mean duration of estrogen therapy was 0.96±0.15 years. A moderate growth delay was seen at birth (0.95±0.11 Ht SDS). There was no correlation between birth length and parental height (r=0.09 for maternal and r=-0.33 for parental height, respectively). The degree of postnatal growth retardation negatively correlated with CA (r=-0.647; p<0.01). Short stature was particularly evident at CA>9.0 yrs (-2.46±0.19 Ht SDS and -3.36±0.20 Ht SDS, CA<9.0 yrs vs. CA>9.0 yrs, respectively). The karyotype (45, X or mosaicism) did not influence growth retardation either at birth (49.32±0.28 cm vs. 48.61±0.56 cm; p=0.48) or in the postnatal life (p=0.8). Estrogen appreciably accelerated the growth (0.60±0.14 and 0.80±0.15 Ht SDS TS, before vs. after estrogen, p=0.006), followed by a decrease of SDS for BA (-1.43±0.23 vs. -1.80±0.34, p=0.2). Hence, spontaneous growth in Turner girls in Russia does not appreciably differ from European standards. Short stature progressed with age irrespective of the karyotype (45,X or mosaicism). Low estrogen doses, minimizing the unfavorable effects on BA maturation, are more appropriate for replacement therapy in TS.

Problems of Endocrinology. 1996;42(4):23-27
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For practitioners
Androgens: A lecture
Goncharov N.P.
Abstract

Androgens (Greek aner, andros - male and genesis - origin) - compounds with the properties of the male sex hormone testosterone (T). T (androst-4-en-17p-ol-3-one; molecular mass 288.41) is a derivative of androstane. In 1935, Laker from 100 kg of testes of bulls for the first time isolated 10 mg of a pure substance, which he called testosterone. Its biological activity was 10 times higher than that of androsterone known at that time. Based on a number of studies, it has been suggested that T is a 17-dihydro derivative of androstenedione. Soon, the hypothetical structure of T was deciphered and its synthesis was carried out. This was a prologue for the synthesis of dozens of derivatives of T with desired properties. Later, a large number of natural androgens secreted by the testes and adrenal glands, as well as their metabolic products excreted in the urine, were isolated from various biological environments of humans and animals. Biosynthesis and metabolism of androgens. Using various methods, including chemical-analytical, radioisotope, chromatographic, perfusion of testes, studying metabolic products excreted in the urine, it was possible to develop a conceptual scheme of androgen synthesis. Cholesterol ester, accumulated by Leydig cells of the testis, is a source of androgen formation.

Problems of Endocrinology. 1996;42(4):28-31
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General data on the hypothalamic-pituitary disorders (guidelines for patients)
Melnichenko G.A., Chernogolov V.A., Pavlova M.G.
Abstract

Most diseases of the hypothalamus and pituitary gland are relatively rare, and therefore not only patients, but many doctors are new to their manifestations, diagnostic methods, treatment tactics, and most importantly, rehabilitation methods (including psychological). The low incidence of such diseases, however, does not detract from the importance of the problems faced by a particular patient. Currently, schools for teaching methods of self-monitoring of patients with diabetes mellitus and a number of other chronic diseases have been created and are actively functioning. There is a need to create such schools for patients with hypothalamic-pituitary diseases, since competent replacement therapy, which the vast majority of patients need after various interventions on the pituitary gland, significantly improves their quality of life. And if we take into account that the age of most patients does not exceed 40 years, then the importance of such schools, as well as the need to create a comprehensive rehabilitation system for these patients, become obvious. Schools for patients with hypothalamic-pituitary diseases have already been established and are successfully functioning in Western Europe, in particular in the UK. These schools help patients with Itsenko-Cushing's disease, prolactinomas, acromegaly, diabetes insipidus, pituitary dwarfism, panhypopituitarism. During classes, patients get acquainted with the anatomical and physiological features of the hypothalamic-pituitary system, its relationship with peripheral endocrine glands, they explain the main clinical manifestations of their disease, methods for its diagnosis and treatment. Patients are told about the meaning of certain terms used by attending physicians to describe their disease, as well as the possible side effects of the medications they take.

Problems of Endocrinology. 1996;42(4):31-32
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Experimental endocrinology
Interaction of nistranol with estradiol and progesterone receptors in the rat uterus cytosol in vitro and in vivo
Kareva Y.N., Fedotov V.P., Rzheznikov V.M., Solovyova Y.V., Pokrovskaya Y.V.
Abstract

Interactions between nistranol and estradiol and progesterone receptors in the cytosol fraction of the uterine tissue of oophorectomized rats and the relative competitive capacity of nistranol have been studied 24 h after a single injection of the drug. The results demonstrate the effects of nistranol on estradiol and progesterone binding. Nistranol boosting of uterine growth in rats is explained by its capacity to accelerate the translocation of hor- mone-receptor complexes into the nucleus. Investigations of the capacity of new estrogens to compete with estradiol for binding in the tissues of target organs in vitro and affect estradiol and progesterone binding in vivo permit a more effective screening of estrogens than use of only the classical in vitro method.

Problems of Endocrinology. 1996;42(4):33-34
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Functional activity of platelets in the early periods of angiopathy formation in rats with alloxane diabetes
Shestakova S.A., Stepanyan M.L., Titova V.A., Boikova N.V.
Abstract

Functional and metabolic activity of platelets and anti-aggregation activity of aortic wall, as well as the specific features in the structure of renal glomeruli were studied in rats at the early stages of alloxan diabetes development. A decrease of platelet disaggregation, an increase in the levels of malonic dialdehyde (MDA) in nonactivated platelets, and an expressed increase of MDA production by thrombin-activated platelets were observed in animals with 15-day diabetes mellitus. A depression of the anti-aggregation activity of the aorta was observed in the same period. In the renal glomeruli, the ultrastructure of the epithelium was changed (destruction of its fenestrae, vacuolization, and detachment from the basal membrane), and proliferation of the mesangial elements of a glomerulus observed. In later periods of diabetes mellitus (60 days) the maximal increase of platelet aggregation activity and a continuing decrease of their disaggregation were observed, which were not paralleled by higher production of MDA in nonactivated and activated platelets. Decrease of anti-aggregation activity of the aorta and changes in the renal glomeruli progressed by day 60 of the disease: degranulated platelets and aggregations thereof were found in the lumens of glomerular capillaries.

Problems of Endocrinology. 1996;42(4):34-37
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Reviews
Diabetic nephropathy: Pathogenesis and treatment
Vorontsov A.V., Shestakova M.V.
Abstract

Currently, diabetic nephropathy (DN) is the leading cause of disability and mortality in patients with diabetes mellitus (DM). Developing in 40–45% of patients, both insulin-dependent IDDM (type I) and non-insulin-dependent IDDM (type II) diabetes, this formidable complication leads to the development of chronic renal failure, and ultimately to the death of patients from uremia. The first kidney damage in diabetes was described by R. Kimmelstiel and C. Wilson in 1936. It is clinically characterized by the following manifestations: increasing proteinuria (with unchanged urinary sediment), hypertension, the formation of nephrotic syndrome (in about 30% of patients) and a progressive decrease in filtration kidney function. The insidiousness of this complication of diabetes lies in the fact that it develops gradually and remains unnoticed for a long time, since at the initial stages the patient does not cause discomfort. And in the later stages, when the presence of DN is no longer in doubt, preventing its further progression is extremely difficult, and often impossible. For many years in our country, the classification of DNs was used by V. R. Klyachko, according to which prenephrotic, nephrotic, and nephrosclerotic stages were distinguished. According to this classification, DN is diagnosed only from the moment when the patient develops proteinuria, registered by conventional laboratory methods, which indicates the severity and irreversibility of pathological changes in the kidneys. The modern classification, distinguishing stages at which clinical manifestations are still absent, and only functional disorders are detected, was proposed by S. Mogensen in 1983 (see table). In accordance with this classification, the first 3 stages are not detected by conventional clinical methods (preclinical stage of DN). The most informative marker of the early stages of DN is the determination of microalbuminuria (MAU), which means the excretion of albumin with urine in an amount of 30 to 300 mg / day. Identification of UIA in a patient with type I diabetes means that the probability of developing a clinical picture of DN in his next 10 years is 80%.

Problems of Endocrinology. 1996;42(4):37-42
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Muscle capillarization, their morphology and pathogenesis of metabolic syndrome
Krotkiewski M.
Abstract

Morphological changes in muscles associated with a decrease in the number of fast, oxidizing muscle fibers of type IIA and an increase in the number of fast, glycolytic muscle fibers of type IIB, as well as a violation of the blood supply to muscle tissue, were considered by us in many pathological conditions associated with insulin resistance. Violation of tissue blood supply, closely associated with a decrease in sensitivity to insulin and the degree of hypertension, occurs at a relatively early stage, while an increase in the number of muscle fibers of type IIB occurs later and is associated with an increase in the concentration of atherogenic factors and hyperlipidemia. Type IIB muscle fibers (MF) are the most insulin-insensitive type MF and are not adapted to fat oxidation during muscle work. This contributes to the further development of insulin resistance and obesity; while the excess of fatty acids is sent to the liver, again violating its function. Excessive insulin also inhibits the liver. Hyperinsulinemia leads to inhibition of the synthesis of specific proteins such as the protein transporting testosterone (a sex hormone-binding globulin). As a result, an increased concentration of free testosterone leads to virilization of women and the further development of insulin insensitivity. In contrast to the previously existing concept, which assigned the main role to intra-abdominal adipose tissue, muscles and liver should also be considered as organs involved in the pathogenesis and development of the metabolic syndrome.

Problems of Endocrinology. 1996;42(4):42-46
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Peer-REVIEW
V. N. Babichev. Neuroendocrine Regulation of the Reproductive System
Goncharov N.P.
Abstract

The problems raised by V. N. Babichev in this monograph on deciphering the central mechanisms of regulation of the pituitary gonadotropic function occupy one of the main places among other issues of neuroendocrinology. To study the sequence of events in neuroendocrine processes that contribute to the preovulatory release of luteinizing hormone is a very complicated but necessary task. In the last decade, neuroendocrinologists are no longer satisfied with a fairly well-studied system of the relationship between gonadaliberin - gonadotropins and sex steroids. The essential role of monoamines of central origin in the regulation of the synthesis and secretion of pituitary gonadotropins, which show their function through luliberins, is shown. Experimenters and clinicians now have rich material that deepens and significantly changes our understanding of the neuroendocrine control of the reproductive system. These literature data in combination with prof. V.N. Babicheva demanded their generalization, which was perfectly done in the peer-reviewed monograph. A comprehensive approach to the study of the entire reproductive function control system, carried out in the laboratory of physiology of the endocrine system of the Russian Academy of Medical Sciences, starting from the period of early ontogenesis, made it possible to specify the role of neurotransmitters such as norepinephrine, dopamine and serotonin in the regulation of the pituitary gonadotropic function, to determine the point of their application in the hypothalamus , the direction of the response from gonadotropins depending on the level of sex hormones in the blood. The starting role of norepinephrine in the mechanism of ovulatory release of gonadotropins has been established, while the main point of its application is the preoptic region. The main point of application of dopamine is the area of ​​the mediobasal hypothalamus, or rather, the arcuate core.

Problems of Endocrinology. 1996;42(4):46-47
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