Vol 65, No 3 (2019)

Original Studies
The physical development of children born with the use of assisted reproductive technologies
Zyuzikova Z.S., Volevodz N.N., Shestakova M.V., Dedov I.I.

BACKGROUND. Today, about 0.1% of the world’s population is born using assisted reproductive technology (ART). According to the National Register of ART, in our country these children represent approximately 1.5% of all children born annually. Despite such a high percentage, data on the physical development of children born using ART is contradictory.

AIMS. The aim of the study is to compare the clinical and anthropometric measurements of children born with the help of ART with those of children conceived naturally, in different age groups.

MATERIAL AND METHODS. The study included 88 children born as the result of the use of ART (Group 1) and 117 children conceived naturally (Group 2). Statistical indicators were evaluated from birth to the onset of puberty. Anthropometric measurements for both groups were analyzed, factoring for multiple pregnancy: length/height, SDS length/height, body weight, SDS body weight, body mass index (BMI), and SDS BMI, at birth and at the times of examination of each child. The levels of insulin-like growth factor-1 (SDS IGF-1) in children of both groups were also determined.

RESULTS. SDS length and SDS weight at birth in children born to a singleton pregnancy were 0.82 [0.1; 1.83] and 0.17 [–0.53; 0.9] in Group 1, and 0.5 [–0.35; 1.75] and –0.11 [–0.94; 0.635] in Group 2 (p = 0.62 and 0.37, respectively). In children less than 1 year of age, 1 year to 3 years, and 3 to 11 years, there was no difference of SDS length/height and SDS BMI (p = 0.3 and 0.9; p=0.29 and 0.29; p=0.85 and 0.6, respectively).

CONCLUSION. Children born from a singleton pregnancy in both groups were comparable in terms of anthropometric measurements both at birth (adjusted for gestational age), and at different ages. The levels of IGF-1 in children born as a result of the use of ART did not differ from those in children conceived naturally.

Problems of Endocrinology. 2019;65(3):148-154
Case Reports
Autoimmune polyglandular disorders in myotonic dystrophy
Troshina E.A., Panfilova E.A., Panevin T.S.

Myotonic dystrophy (MD) is the most common muscle disorder in adults. MD is a hereditary disease with an autosomal dominant mode of inheritance, almost 100% penetrance and pronounced clinical polymorphism. The mechanism for the development of the disease is that a mutation of the DMPK (dystrophia myotonica protein kinase) gene disrupts the normal metabolism of RNA, which leads to a defect in the maturation and translation of mRNA. The disorder in the DMPK gene affects not only striated musculature, but also smooth myocytes and cardiomyocytes. The main clinical symptom that distinguishes MD from others is a spontaneous or provoked inability to relax muscles (myotonia phenomenon). Endocrine disorders arising from type 1 MD (MD1) with a higher than average frequency in the population include hypergonadotropic hypogonadism, impaired glucose tolerance with hyperinsulinism, and insulin resistance. Thyroid function may remain normal, although many cases of autoimmune thyroiditis resulting in hypothyroidism, as well as Graves’ disease, have been described. A description is given of a patient suffering from MD1 with a number of endocrine disorders, including hypergonadotropic hypogonadism, autoimmune thyroid disease, hyperinsulinism, and also impaired calcium-phosphorus metabolism. Important features are the absence of any significant complaints from the muscular system in the presence of an increase in creatine phosphokinase (CPK), which is characteristic of this disease, as well as the temporal dynamics of thyroid status and the nature of the autoimmune thyroid disease.

Problems of Endocrinology. 2019;65(3):155-160
Estrogen metabolism, lifetime methylation disorders, and breast cancer
Chagay N.B., Mkrtumyan A.M.

Oncogenesis can be caused by an increase in the activity of genes responsible for initiating tumor growth in stem or progenitor cells, as well as a reduction in the functioning of suppressor genes. Endogenous estrogen exposure is associated with an increased risk of breast cancer in both pre- and postmenopausal women.

The most important step in the understanding of the pathogenesis of breast cancer was the development of the theory of the switching of estrogen’s effect from hormonal to genotoxic, in which the main culprits of carcinogenesis are not chemical metabolites of estrogens, but their derivatives, corresponding to chemical procarcinogens according to their damaging characteristics. The origin of these substances and the formation of estrogen genotoxicity lies in the disruption of the inactivation process of catechol estrogens in methylation reactions.

The main epigenetic modification of the human genome is the methylation of cell DNA molecules. DNA methylation does not alter the primary sequence of nucleotides, but is necessary for the functional suppression of certain genes. The phenomenon of hypomethylation-hypermethylation underlies the long-term silencing of various genes, including tumor suppressor genes.

Nutrition and a lifestyle associated with smoking and the consumption of excessive quantities of alcohol determine estrogen metabolism and the availability of methyl groups in the body, as well as epigenetic changes in the DNA of the genome. The assessment of individual risk of breast cancer on the basis of an assay for the expression and methylation of the COMT gene responsible for estrogen metabolism seems relevant.

Problems of Endocrinology. 2019;65(3):161-173
The use of confocal microscopy in experimental studies and clinical practice of an endocrinologist: modern opportunities
Mokrysheva N.G., Kiselev S.L., Klementieva N.V., Gorbacheva A.M., Dedov I.I.

Confocal microscopy is a modern imaging method that provides ample opportunities for in vitro and in vivo research. The clinical part of the review focuses on well-established techniques, such as corneal confocal microscopy for the diagnosis of diabetic neuropathy or endocrine ophthalmopathy; new methods are briefly described (intraoperative evaluation of tissues obtained by removing pituitary adenomas, thyroid and parathyroid glands). In the part devoted to fundamental research, the use of confocal microscopy to characterize the colocalization of proteins, as well as three-dimensional intracellular structures and signaling pathways in vivo, is considered. Indicators of intracellular calcium are analyzed.

Problems of Endocrinology. 2019;65(3):174-183
The effect of vanadium compounds on carbohydrate and lipid metabolism disorders
Sidorova Y.S., Skalnaya M.G., Tinkov A.A., Mazo V.K.

At this stage in the development of nutriciological science, it has not been established if biologically active substances are essential to the human body; however, an explanation of the physiological role of minor biologically active substances is necessary to clarify the qualitative composition of Nutrioma. Of particular interest is the transition metal, vanadium. Adding vanadium to the diet of animals with induced or genetically determined type 2 diabetes mellitus normalizes glucose and blood insulin levels, reduces insulin resistance, promotes β-cell regeneration, and has a beneficial effect on lipid metabolism. Clinical studies of the effectiveness of vanadium are not convincing, in most part, because of their insufficient duration. The review briefly discusses the main mechanisms of the action of vanadium compounds. Therapeutic doses of vanadium compounds may overlap with toxic doses. Organic vanadium compounds could be used in significantly lower doses. The main problem with the possible use of vanadium compounds in antidiabetic therapy is the balance between their beneficial effects and the connected risks of side effects.

Problems of Endocrinology. 2019;65(3):184-190
Mechanisms for the development of arterial hypertension in overweight adolescents and young adults
Mustafayeva A.G.

In recent years, an increase in the number of young people with arterial hypertension (AH) has occurred together with the increased prevalence of obesity. It is generally recognized that obesity plays an important role in the pathogenesis of hypertension in adolescents and young adults. In adolescents of non-European ethnicity with a family history of disease, a low birth weight and sedentary lifestyle, and insufficient physical activity and poor sleep quality, excess weight is accompanied by a high probability of AH. High tolerance to cardio-respiratory exertion and a number of genetic polymorphisms can play a protective role against this pathology. Biochemical studies in young people with hypertension and excess weight display a number of features, including levels of hormones and enzymes of the renin-angiotensin system, associated with lipid metabolism and inflammation. Adolescents with hypertension can be included in the group of young people at high risk of damage to affected organs and the subsequent development of cardiovascular diseases, based on a number of characteristics: blood pressure readings, BMI, age, family history and ethnicity.

Problems of Endocrinology. 2019;65(3):191-196
Three ways to develop clinical guidelines. ADAPTE and AGREE GRS procedures
Rebrova O.Y.

Development of de novo clinical guidelines (CG) is a complex process that requires highly qualified personnel, an extended amount of time (from 1 to 3 years), and, consequently, substantial funding. In many countries there are limits to these resources, and so, as an alternative to the development of actual de novo CG, the expert community has developed simplified ways of preparing CG: adoption and adaptation. Adoption is the easiest option – it is simply translation of clinical guidelines developed by a credible foreign professional association into the native language. In this case, of course, translated guidelines should be attributed accurately as a translation, without claiming additional authorship by a local professional association. It may be stated that the local professional organization has discussed and approved the translated document. It is also possible to post comments. Another way – adaptation – is to adjust the CG, developed in one country, to the conditions and features of the healthcare system in another country. Adaptation is fundamentally more difficult than adoption. An adaptation procedure has been developed by ADAPTE, an international group of experts. Their detailed procedure, complete with commentaries, is freely available. The key stage of the multi-stage adaptation procedure is the assessment of the methodological quality of the adapted CG using the AGREE II questionnaire or its simplified version, AGREE GRS. An assessment of the relevance, consistency, acceptability and applicability of the CG is also performed. In situations of a pronounced shortage of resources, adoption of the CG is preferable, while under less constrained conditions – adaptation of the CG. Development of de novo CG in the context of an unlimited exchange of information seems inappropriate and unnecessarily costly. The compromise is an adaptation that serves, on the one hand, to significantly save various types of resources, and, on the other, to promote the methodology of evidence-based medicine in the national medical community.

Problems of Endocrinology. 2019;65(3):197-203
Clinical guidelines
Resolution on the results of the first working meeting of the Scientific Advisory Board «Actual problems of glycemic variability as a new criterion of glycemic control and safety of diabetes therapy»
Antsiferov M.B., Galstyan G.R., Zilov A.V., Mayorov A.Y., Markova T.N., Demidov N.A., Koteshkova O.M., Laptev D.N., Vitebskaya A.V., Alekseeva Y.G., Stavtseva S.I.

June 19, 2018 the meeting of the Scientific Advisory Board took place in Moscow, chaired by Professor G.R. Galstyan, (co-chair – A.V. Zilov) devoted to the discussion of the possibilities of improving the results of treatment of diabetes mellitus (DM) by consideration of «variability of glycemia» (VG) as an additional criterion of the glycemic control effectiveness (especially of insulin therapy) as well as one of the goals of treatment in patients with unstable glycemia.

The purpose of the working meeting was to develop a strategy for the introduction of VG as a predictor and an additional criterion in assessing the effectiveness and safety of hypoglycemic therapy to improve the pharmacotherapy of diabetes and reduce cardiovascular and total mortality.


– to conduct a comprehensive data analysis of the relationship between VG and adverse DM outcomes, such as hypoglycemia, micro-and macrovascular complications, cardiovascular and total mortality;

– to accumulate and analyze published data and the experience of decrease of VG and improving outcomes of diabetes on the background of different versions of insulin therapy;

– to compare existing methods of glycaemia monitoring and VG assessment, their validity and availability in real practice in the context of limited budget;

– to analyze the informativeness, clinical and prognostic significance of various parameters of VG assessment and determine their reasonable «minimum» for a comprehensive assessment of VG as a criterion for evaluating the effectiveness of treatment of DM and predictors of negative diabetes outcomes.

The following reports were heard during the discussion:

Glycemic variability: clinical and prognostic value. Types of glycemic variability. (Alexey V. Zilov, MD, PhD in Medicine, Assistant Professor).

Methods of assessment of variability of glycemia in clinical trials and routine practice (Tatiana N. Markova, MD, PhD in Medicine, Professor).

Current international and national recommendations on glycemic monitoring (Gagik R. Galstyan, MD, PhD in Medicine, Professor).

Peculiarities of glycemic variability and its evaluation among children and adolescents (Alisa V. Vitebskaya, MD, PhD in Medicine).

Problems of Endocrinology. 2019;65(3):204-211

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