[Endocrine disorders in patients with transfusion-dependent hereditary anemias].

Often transfusions red blood cells in patients with hereditary anemias lead to iron overload, that can cause endocrine complications, such as growth retardation, hypothyroidism, hypogonadism, and disorders of carbohydrate metabolism.Clinical case 1. A boy with transfusion-dependent (TD) Diamond-Blackfan anemia at 16.3 years presented with impaired fasting glucose, growth hormone (GH) deficiency, hypogonadotropic hypogonadism; GH therapy was initiated. At the age of 16.8 years old secondary hypothyroidism, secondary hypocorticism and diabetes mellitus were diagnosed. At 17.2 years continuous glucose monitoring (CGM) detected glucose elevations up to 11.7 mmol/l. Therapy with GH and testosterone ethers was continued; levothyroxine and cortef were stopped by patient. At 17.9 years height was 163 cm; no data supporting hypothyroidism nor hypocorticism; glycaemia within goal range.Clinical case 2. A girl with TD beta-thalassemia major at the age of 11.5 years presented with GH deficiency; GH therapy has been conducted from 12.8 to 15.3 years of age. At 13.8 years retardation of pubertal development was diagnosed. At 15.0 hyperglycemia 7.2 mmol/l was detected; normal results of oral glucose tolerance test (OGTT) were observed; glycemia elevations were up to 9.5 mmol/l according to CGM data. At 16.0 height was 152 cm; because of pubertal development arrest hormone replacement therapy was prescribed.CONCLUSION. Growth, pubertal and carbohydrate metabolism disorders were diagnosed in patients with TD hereditary anemias, that confirms the necessity of regularly endocrine investigation. To detect impairment of carbohydrate metabolism investigation of fasting blood glucose, OGTT, and CGM is recommended; glycated hemoglobin measurement is not considered reasonable.

[Comparative study of glucagon and insulin tests for diagnostics of secondary adrenal insufficiency and growth hormone deficiency in children and adolescents].

BACKGROUND: Diagnostics of growth hormone deficiency (GHD) and secondary adrenal insufficiency (SAI) is based on estimation of peak GH and cortisol concentrations in provocation tests. Russian consensus on diagnostics and treatment of hypopituitarism in children and adolescences recommends to measure GH and cortisol concentrations in every time-point of insulin test (IT). Glucagon test (GT) is discussed in literature as alternative to IT. AIMS: To estimate the possibility to use provocation GT for diagnostics of SAI and GHD in children and adolescents. MATERIALS AND METHODS: We investigated blood and urine cortisol levels, IT, and GT in 20 patients 6.5-17.8 years (Me 13.0 (10.4; 15.3)) after surgery and/or radiology and/or chemical therapy of head and neck tumors; remission for 0.4-7.5 years (Ме 2.1 (1.5; 5.2)). RESULTS: With cut-off point 550 nmol/L sensitivity and specifity of IT was 100% and 60%, GT - 100% and 53% respectively. Minimal cortisol cut-off level for GT with sensitivity 100% was 500 nmol/L, maximal with specifity 100% - 400 nmol/L.Early morning cortisol levels did not exceed 250 nmol/l in 2 patients with SAI; and were above 500 nmol/l in 8 patients without SAI while primary or repeated examination.GHD was reviled by IT in all patients. Maximal GH concentrations in GT and IT did not differ significantly (p>0.05) but GT results of 4 patients exceeded or met cut-off for this test (7 ng/ml).GT was characterized by less severity compared with IT. CONCLUSIONS: For diagnostics of SAI by GT we can advise cut-off points of cortisol level 500 (sensitivity 100%, specifty 53%) and 400 nmol/L (sensitivity 80%, specifity 100%). Measuring of cortisol levels in 2-3 early morning blood samples allows to exclude or to suspect SAI in half of patients before tests. GH peaks in GT can exceed similarly data in IT that needs future investigation.

[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 therapy¼].

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 glycemia¼ (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. Aims: - 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 «minimum¼ 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).

[Insulin resistance in obese children: debate on assessment].

No age- and gender-adjusted criteria remain to be a main problem the investigators face when studying insulin resistance in children. This paper compares insulin resistance (IR) indices in 63 children and adolescents with simple (constitutionally exogenous) obesity. The authors demonstrated a low reproducibility of individual baseline values of insulin (not more than 26% as shown by Pearsons correlation analysis). Estimation of IR by means of the design indices calculated from the fasting concentration of immunoreactive insulin and glucose: 40% of obese children and adolescents had no fit of baseline IR indices with the results of an oral glucose tolerance test (OGTT), which may result in a diagnostic error - both hyperdiagnosis (in 12% of patients) and hypodiagnosis (18% of children). According to the results of this study, the values of stimulated insulin release and the Matsuda index, which were determined from the OGTT data, are of the highest diagnostic value in the assessment of insulin resistance in obesity in children and adolescents.

[Current trends in the diagnosis and treatment of idiopathic dwarfism].

The growth of a child has a significant impact on its development and adaptation in modern society. In various periods of life, the growth process depends on many exogenous and endogenous factors. Impaired development at any stage of life can lead to stunting, which affects up to 3% of the adult and children's population. What is the significance of stunting in a child's life? Does the quality of life of a child depend on his height? These issues are actively debated.

[Grelin: biological significance and prospects for use in endocrinology].

Ghrelin is a peptide consisting of 28 amino acid residues that is secreted in the stomach and to a lesser extent in other organs. It is a stimulant of growth hormone secretion (GHS), promoting the release of GH by activating the so-called GHS-receptors. These receptors are predominantly concentrated in the hypothalamic-pituitary region, but are also found in other tissues, which explains the wide range of effects of GHR, including stimulation of the secretion of GH, prolactin and adrenocorticotropic hormone (ACTH); effects on sleep and behavior, increased appetite and a positive energy balance; diabetic effect on carbohydrate metabolism, control of gastric secretion and peristalsis. In addition, the experiments have repeatedly shown the positive inotropic effect of ghrelin on the heart, vasodilation, and cell proliferation. The wide biological spectrum of action of ghrelin makes it promising to study and apply new knowledge in various fields of medicine: endocrinology, gastroenterology, immunology, oncology and cardiology.

[Diagnosis of insulin resistance in children and adolescents].

The high prevalence of obesity in children is one of the factors contributing to an increase in the frequency of development of the metabolic syndrome and related diseases. A key role in the development of the metabolic syndrome in both children and adults is played by insulin resistance - a violation of the biological effect of insulin and the reaction of insulin-sensitive tissues to it at the pre-, post- and receptor levels.