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Vol 39, No 5 (1993)

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Clinical endocrinology
Epidemic outbreaks of insulin-dependent diabetes mellitus
Lebedev I.В., Gubanov N.V., Smirnov V.V., Stroikova A.S., Bulgakova G.R., Korolyova N.P., Dedov I.I.

Analysis of annual and seasonal incidence of insulindependent diabetes mellitus in children living in 4 Russian cities in the 1980ies has shown only four rises of annual morbidity in three cities, but only one of them recorded in 1983 in Moscow conformed to the criteria of an epidemic outbreak of the disease. The incidence of the disease predominated by 29 % in autumn-winter, though there was no clear-cut correlation between diabetes incidence, on the one hand, and incidence of influenza and acure respiratory diseases, on the other.

Problems of Endocrinology. 1993;39(5):4-6
Hyperlipidemia: a factor contributing to diabetic nephropathy development and progress
Shestakova M.V., Dedov I.I., Neverov I.I., Severghina E.S., Dyuzheva T.G., Ponomaryov A.B.

Twenty-nine patients with insulin-dependent diabetes mellitus with similarly manifest renal involvement were examined to elucidate the role of dyslipidemia in diabetic nephropathy progress. Clinicolaboratory parameters (urinary albumin excretion, blood serum levels of total cholesterol, triglycerides, low, very low, and high density lipoprotein cholesterol) and morphologic changes in renal tissue biopsy specimens were analyzed. An increment of the number of large lipid incorporations was observed in various cells of renal glomeruli and interstitium, as well as a high prevalence of low density lipoprotein deposition in glomerular basal membranes and canaliculi as the renal process augmented in severity. Since lipids accumulating in glomerular structures may stimulate mesangial cell proliferation and mesangial matrix hyperproduction, the authors believe that dyslipidemia in diabetes mellitus may be conducive to a more rapid progress of renal disease.

Problems of Endocrinology. 1993;39(5):7-9
Some characteristics of the thyroid status in children and adolescents living in one of the Kaluga regions contaminated with radionuclides
Dedov I.I., Tsyb A.F., Matveyenko Y.G., Omelchenko V.N., Borovikova M.P., Peterkova V.A., Tyulpakov A.N., Kandror V.I., Goncharov N.P., Parshin V.S., Mischenko В.P., Semicheva T.V., Buraya T.L., Stepanenko V.F.

Thyroid status was examined in 9294 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 29.2 %, 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 94 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.

Problems of Endocrinology. 1993;39(5):10-13
Contribution of parotitis virus to the development of insulin-dependent diabetes mellitus
Severina T.I., Kolpakova V.Y., Venediktova N.Y., Ilyasova O.N., Akhmedyanova L.G., Balabolkin M.I.

Viral infection is one of the factors provoking the development of insulin-dependent diabetes mellitus (IDDM). Epidemic parotitis more frequently than other infections is connected with IDDM manifestations, but the results of examinations of convalescents after epidemic parotitis and of patients with newly diagnosed IDDM are contradictory. Parotitis viruses are believed to injure pancreatic p-cells and trigger on the autoimmune process in carriers of certain antigens. In none of the 200 cases of IDDM manifestation a relationship with epidemic parotitis was established and none of the 268 convalescents after epidemic parotitis developed IDDM. Screening for antibodies to epidemic parotitis virus carried out in 61 patients with newly detected IDDM revealed low antibody titers in the majority (83.3 %); HLA-B8 antigen was detected in 23 % of these examinees. In the group of subjects with persistent high antibody titers and their diagnostic increment or reduction HLA-BS antigen was found in only 12.5 %. These results do not permit a conclusion on the relationship between IDDM manifestation and parotitis infection.

Problems of Endocrinology. 1993;39(5):14-16
Azathioprin effect on immunologic parameters of patients with newly detected insulin-dependent diabetes mellitus
Shamkhalova M.S., Abugova I.A., Shishko P.I., Dedov I.I., Kozlov L.V., Alyoshkin V.A., Rozina M.N.

Azathioprin immunosuppressive therapy prolongs remissions and stimulates residual p-cell function, suppresses insulin antibody production, reduces the activity of the complement and CH50 components, reduces initially increased cellular immunity parameters (total T and В cell counts, T helper to T inductor ratio, and the count of DR carrier cells) in patients with newly detected insulin-dependent diabetes mellitus; this makes this drug effective at the firts stages of the disease. When selecting patients for immunosuppressive therapy the following immunity parameters should be examined: complement status, total counts of T and В lymphocytes, T-helper-in- ductor/T-suppressor-cytotoxic immunoregulation index, DR carrier cell counts. Reduced levels thereof are a contraindication against immunosuppressant therapy. Male patients with insulindependent diabetes mellitus debut at the age of over 25 are particularly susceptible to immunosuppressive therapy with azathioprin.

Problems of Endocrinology. 1993;39(5):16-20
Therapy of diabetics with fatty hepatosis
Geller L.I., Gladkikh L.N., Gryaznova M.V.

A ten-day course of karsil (silimarin, legalon) or silibor therapy improved the absorption (as indicated by ueviridin test) and oxidative-antitoxic (as shown by antipyrin test) hepatocyte functions in patients with non-insulin-dependent diabetes mellitus with hepatosis. A similar ten-day course of Liv-52 did not change the studied liver parameters. lnductothermal exposure of the splenic area (a 20 min session daily for 5 days) improved the absorption and antitoxic functions of the liver in diabetics. A positive effect of splenic inductothermia persisted for at least two weeks. The peak values of ultrasonic amplitude histogram of the liver reflect the time course of liver status in the course of karsil and silibor therapy and splenic inductothermal exposure.

Problems of Endocrinology. 1993;39(5):20-22
Ultrasonographic assessment of thyroid palpation method in assessment of its size in children and adolescents
Kasatkina E.P., Shilin D.Y., Matkovskaya A.N., Pykov M.I.

The authors analyze the diagnostic value of thyroid palpation method (two modifications) comparing its results with those of ultrasonographic volumetry. The study involved 118 children aged 5 and 14 of both sexes living in regions endemic for goiter. The thickness of thyroid isthmus was found virtually the same no matter how greatly the gland was enlarged. The results proved the necessity of age-specific corrections in the criteria of current interpretation of palpation data: the first degree in preschool children was most often indicative of thyroid hypertrophy whereas in the pubertal age it was just a variant of normal size. Interpretation with due account of these amendments improved the reliability of diagnostic value of palpation, its sensitivity being 63±6, specificity 67±6, and accuracy 65±4%. When the results of palpation are adequately interpreted, the examinees’ age and sex and the method of examination proper do not influence the data accuracy. The sensitivity of palpation in detection of nodules up to 10 mm in diameter proved to be null (in 6 of the 81 examined adolescents sonographic signs of incapsulated formation were seen in the thyroid). Bearing all this in mind, the authors discuss differentiated approaches to management of children and adolescents with the first degree of palpated enlargement of the thyroid.

Problems of Endocrinology. 1993;39(5):22-26
Hormonal aspects in the pathogenesis of arterial hypertension in young obese patients in young obese patients
Tereschenko I.V., Vladimirskaya N.L.

Measurements of blood lipids and hormones (plasma renin, aldosterone, vasopressin, prolactin, atrial natriuretic peptide, 6-endorphine, thyrotropin, thyroid hormones) in two groups of patients suffering from obesity (group 1: 64 patients with arterial hypertension and group 2: 26 patients with normal arterial pressure) have brought the authors to a conclusion that arterial hypertension in young obese patients is an early manifestation of essential hypertension. Hormonal dysfunction in obese patients is conducive to early development of essential hypertension in cases when there is a hereditary predisposition to it.

Problems of Endocrinology. 1993;39(5):26-28
Niftolide tests used in the diagnosis of male hypogonadism
Reznikov A.G., Varga S.V., Demchenko V.N., Boyarskaya O.Y.

Comparative analysis with an antiandrogen niftolide and synthetic GnRF was carried out in 22 normal subjects, 14 patients with primary and 20 ones with secondary hypogonadism, and in 5 patients with clinical signs of gonadal insufficiency and obscure diagnosis in order to elucidate the pituitary gonadotropin reserves. Blood plasma and daily urine gonadotropin levels were measured. Changed gonadotropin excretion under the effect of niftolide in health and hypogonadism was in line with changed gonadotropin level in the blood after RF administration, this indicating a similar informative value of both tests for the differential diagnosis of various hypogonadism forms. In the first case measurements of blood gonadotropin were more informative, in the second daily urine analysis. Niftolide test, noninvasive and readily available, is recommended as an alternative test with RF administration.

Problems of Endocrinology. 1993;39(5):28-31
Case Reports
A combination of adrenocortical dysfunction and Icenko-Cushing’s disease in the same family
Brekhunenko T.F., Gabuniya A.R., Platovskaya R.G., Sazonova S.N., Yefuni S.S., Belchenko L.V.

The article is devoted to the review of the combination of adrenocortical dysfunction and Icenko-Cushing’s disease in the same family.

Problems of Endocrinology. 1993;39(5):32-33
For practitioners
Differential diagnosis of generalized lipodystrophy syndrome
Letova Y.K., Starkova N.T.

The article is devoted to the description of the differential diagnosis of generalized lipodystrophy syndrome.

Problems of Endocrinology. 1993;39(5):33-36
Clinical guidelines
Training of patients with hypothyrosis
Dlugach Y.A., Alexandrova G.F., Melnichenko G.A.

The article is devoted to the issue of training of the patients with hypothyrosis, which is associated with the need for lifelong replacement therapy, when the control over the adequacy without the active participation of the patient himself is impossible.

Problems of Endocrinology. 1993;39(5):36-37
Experimental endocrinology
Endocrinal function of the pancreas in rats with diabetes mellitus and specific features of this function adaptation to hypoxia
Kolesnik Y.M., Abramov A.V.

The present research was aimed at examination of the endocrinal system of the pancreas in diabetes mellitus, adaptation to hypoxia, and their combination in rats in order to elucidate the relationships between A, B, and D cells under various conditions. The status of Langerhans islet cells was assessed by radioimmunoassay, measurements of blood hormones, and by immunologic method for their quantitative detection in cells. Development of the early stages of diabetes mellitus was found to be associated with a marked restructuring of the total endocrinal system of the gland. Reduction of insulin level was parallelled by a compensatory activation of glucagon- and somatostatin-producing systems. Islet cell changes under such conditions were characterized by sexspecific features. Adaptation to hypoxia was found to have a favorable effect on the course of diabetes mellitus in rats, this manifesting by an increase of blood and В cell insulin levels, by inhibition of islet destruction process, and by reduced production of glucagon and somatostatin.

Problems of Endocrinology. 1993;39(5):37-40
Effect of a-tocopherol on the development of diabetic angiopathy, platelet aggregation, and prostacyclin-thromboxan system of rats with streptozotocin-induced diabetes
Zadkova G.F., Avakyan T.Y., Markov K.M.

Under study were effects of intravenous infusions of a new emulsion, α-tocopherol, on the development of diabetic microangiopathy, platelet α-tocopherol level, ADP-induced platelet aggregation level, exogenic (from 14C-arachidonic acid) thromboxan (TxA2) biosynthesis in suspension of washed platelets and of prostacyclin (Pgb) one in isolated aortic rings of rats with streptozotocin-induced diabetes. Six-week injections of α-tocopherol in a dose 100 mg/100 g b. w. with 48 h intervals immediately after development of streptozotocin-induced diabetes prevented the development of diabetic angiopathy but did not normalize platelet functional activity and Pgl2/TxA2 balance in vessels and platelets. Similar injections of α-tocopherol in the presence of developed angiopathy resulted in its regressive development and normalization of the before-said prostanoid balance and platelet characteristics.

Problems of Endocrinology. 1993;39(5):40-43
ATP-dependent K+ channels of pancreatic ß-cells under the effects of some sulfonylurea drugs
Babichev V.N., Ignatyev N.S., Balabolkin M.I.

The authors analyze the relationships between electrophysiologic processes taking place on (J-cell membranes under the effects of some second generation sulfonylurea drugs: glycaside, glybenclamide, and glypizine and their secretogenic effects on insulin secretion. All the tested drugs induced complete blocking of K+-ATP-dependent channels when administered in concentrations from 1 to 20 pM (physiologic doses). Glucose had a similar effect. The canal is closed very soon, within 30 sec, and is closed for approximately 10 min, rapidly opening after the drug is washed away. Reduced activity of the channels up to their closure is conducive to the onset of insulin secretion. Glybenclamide proved to be the most potent suppressor of individual channel activity, this being confirmed by its more potent hypoglycemic effect as compared to glyclaside or glypizine.

Problems of Endocrinology. 1993;39(5):43-46
Immobilization stress effect on thyroid hormone secretion
Turakulov Y.K., Burikhanov R.B., Patkhitdinov P.P., Myslitsksya A.I.

Analysis of blood flowing from the rat thyroid has shown that an acute immobilization stress enhanced thyroid hormone secretion with an increase of the T3/T4-100 index. The most marked response to stress was observed after repeated 2 min immobilization with a 3 min interval: Such increase of secretion was arrested by injection of prasosin, an α-adrenoblocker. Propylthiouracil injected an hour before the experiment reduced T4 thyroid conversion index. These results permit a conclusion that short-term repeated immobilization enhanced thyroid hormone secretion via α-adrenergic system stimulation, this being paralleled by increased production of hormonally more active T3.

Problems of Endocrinology. 1993;39(5):47-48
Thyroid regeneration in various localizations of the resected fragments of the organ
Pavlov A.V., Doborzhginidze T.R., Miro T.L., Alexandrov Y.K.

Structure and function of the regenerating thyroid fragment were studied in 18 adult white rats 30 days after partial resection of centromedial or peripheral fragments of the lobes similar in size using quantitative methods (organometry, his- tometry, measurements of blood serum hormones). The volume of glandular tissue removed in two series of experiments was 40 and 75 % of the total thyroid mass of experimental animals. Centromedial portions of the thyroid of intact rats were characterized by greater follicular epithelium volume (by 10 %) and C-cell content per section area (six-fold), as well as by a lesser mean diameter of the follicles (by 26 %) and colloid volumic fraction (by 40 %) in comparison with the peripheral segments. No reliable differences in the quantitative structural parameters (mass, tissue component volumic fractions, mean follicular diameter and follicular epithelium height) and hormonal activity of the regenerated tissue in the two variants of surgery were observed. The results indicate that thyroid parenchyma of various portions of the organs is similarly capable of full-value regeneration.

Problems of Endocrinology. 1993;39(5):49-51
Present-day concepts of insulin-dependent diabetes mellitus immunopathogenesis
Zlobina Y.N., Dedov I.I.

The article is devoted to the review of the present-day concepts of insulin-dependent diabetes mellitus immunopathogenesis.

Problems of Endocrinology. 1993;39(5):51-58
Current notions on the contribution of growth factors to the system of intratissue reproduction regulators
Potin V.V., Vorobyova O.A.

The article is devoted to the review of the current notions on the contribution of growth factors to the system of intratissue reproduction regulators.

Problems of Endocrinology. 1993;39(5):58-62
In memory to Professor D. Ya. Shuryghin

The article is devoted to the memorable date, the 70th anniversary of the birth of Professor Dorofey Yakovlevich Shurygin, one of the prominent endocrinologists of the country, honored scientist of the RSFSR.

Problems of Endocrinology. 1993;39(5):62-62
Clinical use of DNA recombinant human growth hormone
Dedov I.I.

The article is devoted to the issue of the clinical use of DNA recombinant human growth hormone.

Problems of Endocrinology. 1993;39(5):65-67
KIGS demographic studies
Albertson-Wikland K.

The eighth kigs report (international growth study by Kabi Pharmacy) is based on an analysis of the treatment outcomes of 7,083 children from 18 countries. Of these, 3380 had idiopathic growth hormone deficiency (IGN), 1111 - IGN due to organic lesions and 2592 - other causes of stunting. All the children were at different schemes of injection of growth hormone. The duration of treatment in idiopathic DISEASE averaged 3.5 years, in organic disorders-4 years, with other types of stunting-3.3 years. At the beginning of treatment, all children had low growth: -2.7 SDS (Tanner standards) in idiopathic GAMES, -2.2 SDS in organic GAMES (-1.75 SDS in brain tumors, -1.8 SDS in leukemia), -2.9 SDS with other types of stunting. The average age of children in all groups before treatment was about 10 years. The growth rate before treatment was low compared to healthy children of the same age. In most cases (95 %) growth hormone treatment was carried out daily or 6 times a week, while the dose of the hormone administered in different countries varied significantly (from 0.4 to 0.7 u/kg per week). Subsequent analysis of the KIGS database will help to see how these differences will affect growth rates and the end result of treatment.

Problems of Endocrinology. 1993;39(5):68-73
Classification of growth hormone idiopathic insufficiency: Clinical features and efficacy of therapy with growth hormone
Price D.A.

In 3,226 patients with idiopathic growth hormone (GH) deficiency included in the KIGS study, a comparative analysis of epidemiological factors and the effectiveness of treatment with recombinant GH depending on the presence or absence of birth trauma was performed. The relative frequency of gluteal presentation, instrumental AIDS in childbirth, reduced Apgar score, neonatal hypoglycemia and occurrence of microfallos was higher in the group with birth trauma, which was manifested later by more severe hypopituitarism and earlier manifestations of the disease. Both groups had almost the same reaction to GH therapy. A similar study was conducted in a group of children with GH deficiency in combination with empty Turkish saddle syndrome, septooptic dysplasia, cleft palate, neurosecretory dysfunction and secretion of biologically inactive GH. The comparative analysis was carried out with a group of children with idiopathic insufficiency of GH. Despite the differences in the clinical picture between the groups, the effectiveness of treatment of GH was the same. The study confirms the concept of multifactorial etiology of idiopathic gr insufficiency. Comparison with other groups of congenital insufficiency of GH indicates that complications in the perinatal period may occur secondary to hypopituitarism.

Problems of Endocrinology. 1993;39(5):74-82
Growth hormone level during stimulation test and efficacy of growth hormone therapy of idiopathically undersized children with this hormone insufficiency
Ranke M.B., Gilbod O.

For the first time, a broad study of the effectiveness of treatment with growth hormone (GH) in patients with varying degrees of impaired secretion of GH is undertaken. In this work, 885 patients of pre-pubertal age who received treatment for 1 year were examined. All children were given 2 standard tests with stimulation of the secretion of GH. The following diagnoses were established: idiopathic insufficiency of GH (classification number 1.1) or idiopathic stunting (3.1). Patients were divided into groups depending on the maximum release of GH during sampling: A - in both samples <5 ng/ml, B - in one sample <5 ng/ml, in another - 5-10 ng/ml, C - in both samples 5-10 ng/ml, D - in one sample 5-10 ng/ml, in another - >10 ng/ml, E - in both samples >10 ng/ml.anthropometric indicators, main parameters of therapy and results of treatment of GY were evaluated in all developed model (expected RESULTS). According to the study, patients with the most severe GH deficiency (group A) had better treatment outcomes, while the other groups were almost identical. The division of group A into a subgroup with isolated GH deficiency and a subgroup with deficiency of other tropic hormones (hypopituitarism) showed that in the first subgroup the growth of parents was significantly lower. Thus, despite the fact that standard samples with stimulation of GH can be used to diagnose the insufficiency of GH, the results of these samples do not always allow to predict the effectiveness of treatment of GH for 1 year. It should also be noted that the shortness of the parents, especially the growth of the mother, may indicate the presence of an additional hereditary factor in the Genesis of shortness in these patients.

Problems of Endocrinology. 1993;39(5):82-85
A second KIGS communication on side effects of growth hormone therapy
Chatlein P.J., Wilton P.

By March 25, 1992, among the 16,604 patients included in the KIGS database who had been treated with growth hormone (GH) for at least one year, 135 had serious side effects (SE). Among the most frequent SE are relapses of craniopharyngioma (17) and other brain tumors (11). Changes in bone tissue, joints and muscles were more rarely observed. 7 patients had convulsive syndrome. More information is needed to assess the effect of GH therapy on these complications.

Problems of Endocrinology. 1993;39(5):85-88
Pressing problems of dwarfism in children and adolescents: Classification, specificities in the clinical course of the disease variants
Kasatkina E.P.

The article is devoted to the pressing problems of dwarfism in children and adolescents, classification, specificities in the clinical course of the disease variants.

Problems of Endocrinology. 1993;39(5):90-93
Genotropin therapy of children with growth hormone deficiency
Kasatkina E.P., Sokolovskaya V.N., Mursankova N.M., Ibraghimov G.V.

The article is devoted to the issue of the genotropin therapy of children with growth hormone deficiency.

Problems of Endocrinology. 1993;39(5):94-96

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