Objective and hypotheses. This study aimed at examining the effect of oxidative stress on amount and composition of major plasma carotenoids in prepubertal children with growth hormone deficiency (GHD).

Material and methods. Thirteen prepubertal treatment-naive children (2 girls, 11 boys; aged 3.5—12.0 yr, median 8.0 years; bone age 1.5—8.0 yr; median 6.0 years,) with GHD and 7 prepubertal health children (7 boys; aged 6—11 years; median 9.3 years) were included in the study. The levels and composition of carotenoids (lutein with zeaxanthin, lycopene isomers, β-cryptoxanthin, β- and α-carotene and ketocarotenoids) were measured using reverse phase HPLC. Activity of the antioxidant system was assayed via thiobarbituric acid reactive substances (TBARS), ceruloplasmin (CP) levels and total antioxidant capacity (TAC) of plasma. Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were also measured.

Results. The levels of TBARS, TC and LDL-C in the GHD children were higher than in healthy children (median 5.6 vs 3.8 µM/L, 4.00 vs 4.37 and 2.40 vs 2.70 mM/L, respectively). Total carotenoid level did not significantly differ between control and the GHD groups. However, contents of lutein and β-cryptoxanthin were significantly lower in the GHD children in comparison with control group (21.34 vs 6.97 and 25.23 vs 10.08 mg/l, respectively). In contrast, levels of lycopene, α- and β-carotene did not significantly differ in the GHD and control groups. At the same time, the level of ketocarotenoids in the GHD children increases (35.67 vs 114.9 mg/l).

Conclusions. We observed that the presence of mild oxidative stress leads to a changes in carotenoid profile of GHD children.

Aim — to compare the features of diastolic dysfunction (DD) with preserved left ventricular (LV) ejection fraction (EF) in patients with diabetes mellitus type 2 (DM2) with arterial hypertension (AH) and in patients with essential hypertension (EH) without diabetes.

Material and methods. The study involved 87 patients with DD with preserved LV EF: 53 patients with DM2 with AH and 34 patients EH without diabetes. Transthoracic echocardiography was performed by ultrasonic imaging system iE33 xMATRIX («Philips», USA). DD was determined in a complex: type on the basis of the ratio parameters of pulsed-wave (E/A) and tissue (e/a) Doppler; and severity on the Е/e values and pulmonary capillary wedge pressure (PCWP). Myocardial contractile function was assessed by traditional LVEF by Simpson and more exactly, in details on the basis of the longitudinal, radial and circular deformation of the LV myocardium by speckle-tracking echocardiography (using the program Q-lab 3.0 Advanced Ultrasound Quantification software).

Results. The groups were comparable in clinical characteristics. The average level of HbA1c in patients with DM2 was 8.2±1.7%. The average LV EF by Simpson in the EH group was 59.9±8.1, in DM2 — 58.3±6.7 (p=0.228). There were more severe disorders of LV Diastolic function in DM2 patients: the values of E/e (p=0.000) and PCWP (p=0.001) were significantly higher in diabetic patients (14,1±5,5 and 15,3±4,7 mm Hg) than in EH (9.7±2.3 and 11.9±1.3 mm Hg). Although that the LV EF (by traditional echocardiographic method of Simpson) was preserved in both groups , the LV global longitudinal strain (12.4±3.0) was significantly lower in DM2 (p=0.005), than patients with EH (16.6±2.0) by speckle-tracking echocardiography.

Conclusion. Severity of LV DD are harder in Patients with diabetes and hypertension, than in patients with EH with the similarity of clinical manifestations and data of traditional echocardiographic methods. There were found initial disorders of LV longitudinal myocardial fibers contraction by speckle-tracking echocardiography in patients with DM and preserved LV EF. The combination of impairment of systolic and diastolic function in diabetes is inseparable. Early development of combined systolic and diastolic dysfunction in DM2 is associated with a poor prognosis: a higher risk of early development of atrial fibrillation, ventricular arrhythmias and progressive heart failure.

The diagnosis of MODY should be verified by molecular genetic analysis. Recently the introduction of next-generation sequencing, allowing simultaneous analysis of several candidate genes, greatly facilitates the diagnosis of monogenic diseases including MODY. In addition, the simultaneous analysis of several candidate genes allows to identify cases with digenic and oligogenic inheritance. In this work we present the first description of MODY cases with digenic and oligogenic inheritance in our country.

Aim — to characterize MODY cases with digenic and oligogenic inheritance as defined by targeted next-generation sequencing.

Material and methods. 256 subjects (age range, 0.3—25 yrs; males, n=149, females, n=107) were included in the study. The patients fulfilled the following MODY criteria: diabetes or intermediate hyperglycemia, absence of β-cell autoimmunity (ICA, GAD, IA2, IAA antibodies), preserved C-peptide secretion. Molecular genetic analysis was performed by next-generation sequencing using custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent). All mutations were confirmed by Sanger sequencing.

Results. 10 patients (8 probands, 1 sibling and 1 parent) showed digenic inheritance of MODY: 3 patients with combination of mutations in 2 candidate genes of MODY, 7 — in a candidate genes of MODY and another gene, associated with diabetes mellitus. In 1 case (sibling) showed oligogenic inheritance (mutations in GCK, HNF4A and INSR genes). Seven of the identified mutations were not previously described.

Conclusion. Next-generation sequencing is useful in identifying of MODY cases with digenic and oligogenic inheritance, which is extremely important with potentially modifying effect on the phenotype.

Multiple mutations in RET proto-oncogene are not common findings in patients with multiple endocrine neoplasia type 2A syndrome (MEN2A). Screening for RET mutation in MEN2A family members is usually limited by the known affected exon. However the second unrevealed mutation in RET proto-oncogene can coexist and modify the phenotype of MEN2 patients, including age of onset of medullary thyroid carcinoma, penetrance of pheochromocytoma etc. We here describe a family with MEN 2A syndrome with combination of three different germ-line RET mutations in its members (RET codon C634R, C634R+I852M, I852M+Y791F, Y791F). The earliest onset of medullary thyroid carcinoma was in a patient harboring the C634R+I852M double mutation at age 24 years. A 49-y.o.patient with C634R mutation has persistent medullary thyroid carcinoma after thyroidectomy at 35 years old. A carrier of Y791F mutation had no clinical evidence of disease at age of 28 years. In a child with compound I852M+Y791F mutation preventive thyroidectomy revealed C-cell hyperplasia at age of 4 years. The clinical significance of double RET mutation in the described family is not clear. Literature data of multiple germ-line RET mutations in patients with multiple endocrine neoplasia type 2A syndrome are presented.

Obesity is one of the 10 risk factors of death. Many epidemiological studies have shown that overweight and obesity are associated with 44% cases of diabetes type 2, and 23% of cases of coronary heart disease. The body mass index (BMI) is traditionally a diagnostic marker of obesity and overweight are considered. However, in the last 15 years, there has been work on the «paradox» of obesity. So the obese long-term prognosis and stroke are more favorable than individuals without excess weight and obesity. A deeper analysis of the data showed that the highest risk of developing cardiovascular disease and disorders of carbohydrate metabolism associated with visceral obesity. This is largely due to metabolic disorders occurring on the background of visceral obesity, such as insulin resistance, hyperglycemia, dyslipidemia, an imbalance of adipokines and markers of inflammation. These changes in individuals with visceral obesity can occur regardless of the value of BMI.

Primary hyperparathyroidism (PHT) is the third most common endocrine disorder in men and women after diabetes mellitus and thyroid disease and one of the most frequent causes of osteoporosis and fractures among the secondary osteopathy. PHT refers to socially significant problems in connection with involvement in the pathological process of the majority of organs and system In recent years, the conception of epidemiology, clinic and tactics of management of patients with PHT has changed due to significant increase of morbidity at the expense of identification of mild forms of disease. The modern management concept tactics depends on clinical manifestations. Bearing in mind the importance of the problem under consideration, the working group was set up for the development of federal recommendations on the treatment of PHT based on the principles of evidence-based medicine. The experience accumulated by the domestic and international experts was summarized in the federal clinical guidelines on PHT.

Hypogonadism in male patients defined as testosterone level decrease in serum associated with specific symptoms and/or signs (see the detailed description below) can be observed in case of abnormal changes in testes and/or pituitary such as Klinefelter syndrome, Kallmann syndrome and also in male patients with idiopathic, metabolic or iatrogenic disorders resulting in androgen deficiency. The Guidelines does not review all disorders conditioning development of testosterone deficiency (hypogonadism), but focusing on the options of the clinical conditions of hypogonadism generally observed in male patients. This article contains a supplement to the previously published draft of the guidelines: Dedov I.I., Mel’nichenko G.A., Rozhivanov R.V., Kurbatov D.G. The recommendations on diagnostics and treatment of male hypogonadism (deficit of testosterone). The project. Problems of Endocrinology. 2015;61(5):60-71. doi: 10.14341/probl201561560-71