Background. Absence of detectable MEN1 mutations in a patient with multiple endocrine neoplasia type 1 (MEN1) phenotype may disprove the hereditary predisposition and the necessity of a lifelong regular screening for detecting the remaining components of the syndrome, and the examination of the first-degree relatives. Nevertheless, there may be other genes involved in the co-occurrence of several MEN1-associated tumors. 

Aim — to determine the role of genes, associated with the development of familial pituitary adenomas (PA), and genes, presumably involved in pathogenesis of sporadic PA, in the development of MEN1 phenocopies with PA as one of components.

Material and methods. 23 patients with MEN1 phenocopy were included in the study. The patients underwent next-generation sequencing (NGS) (Ion TorrentTM PGMTM, Thermo Fisher Scientific — Life Technologies, USA) using a panel of candidate genes (MEN1, CDKN1B, PRKAR1A, AIP, SDHA, SDHB, SDHC, SDHD, GNAS, PRKCA, CDKN2A, CDKN2C, POU1F1, PTTG2).

Results. In 1 (4%) female patient with acromegaly and primary hyperparathyroidism (PHPT) a germline heterozygous change in exon 6 of AIP gene c.911G>A (p.R304Q) was revealed. In four female patients with acromegaly and PHPT we revealed polymorphisms whose pathological significance is not defined: heterozygous change in exon 1 of PTTG2 gene c.134G>A (p.R45H), heterozygous change in intron 1 of PRKAR1A gene (c.–10G>C), heterozygous change in exon 5 of SDHB gene c.487T>C (p.S163P), heterozygous change in 3’-UTR of CDKN1B gene g.3897G>T (c*8G>T).

Conclusions. The results of our study show that mutations in the majority of the examined genes associated with the development of hereditary and sporadic PA, do not cause the development of MEN1 phenocopies. The necessity to study AIP gene in all patients with MEN1 phenocopies needs further research. It is recommended to search for new genes, mutations in which could be the cause of the development of MEN1 phenocopies.

Background. Regardless of improvements in MRI, up to 20% of ACTH-secreting pituitary tumors are only identified at surgical exploration. 

Aim. Тo estimate whether there is any difference in blood vessels and the subsequent ability to uptake contrast agent in visualized microadenoma as compared to non-visualized on MRI ACTH-secreting pituitary tumors.

Material and methods. Retrospective evaluation of ACTH-positive pituitary tumors from patients with Cushing’s disease (n=39) with either non-visualized pituitary tumor on MRI (n=17) or pituitary tumor less then 25 mm (n=22). MRI was performed using Siemens Magnetom Harmony 1.0T with gadolinium. Selected tumors were stained with anty-СD34 antibody (clone QBEnd/10, RTU, Leica) and anty-D2-40 antibody (clone D2-40, RTU, Dako). We evaluated the microvessels density and measured the diameter of larger and smaller vessel.

Results. The microvessels density were not different in subject with visualized [123 (77; 136)] and non-visualized [112 (110,0; 126,5)] pituitary adenomas as well as number of slit-shaped vessels [32 (5; 50) in visualized vs 25 (5; 50) in non-visualized pituitary adenoma]. The diameter of these vessels also did not differ: the diameter of the largest vessels in patients without visualization 53 µm (32,5; 63,5) vs 33 µm (30,0; 51,5) the average diameter of the blood vessels 15 µm (14,5—26,0) against 13 µm (12; 14).

Conclusions. The diameter and microvessels density in ACTH-producing pituitary adenoma does not affect the visualization of adenoma on MRI in patients with Cushing ‘s disease.

Background. Growth hormone (GH) therapy for growth hormone deficient (GHD) children in Russia is funded by the state. This warrants the need for a full understanding of the disease and its treatment with recombinant GH (rGH) including its clinical, epidemiological and economical aspects. 

Aims — to estimate the incidence and the prevalence of GHD in children and adults in the Russian Federation.

Material and methods. In Russia, GHD patients are registered in both the official medical statistics (MS) and a special registry for patients suffering of «high expenditure dieseases». Both the official MS data and the GHD patients’ registry is used for analysis.

Results. According to MS the prevalence of GHD in Russia among children is 14,38 per 100 000. Including the adult population and adult patients with GHD, the prevalence is calculated at 4,94 per 100 000 total population. Calculations based on the registry show similar, yet not identical results: 14,57 per 100 000 children and 4,56 per 100 000 total population. The incidence of GHD among children results at 2,45 per 100 000 children/year according to MS, according to the registry — 2,06 per 100 000 children/year. Several regions of Russia demonstrate an extremely high or low prevalence/incidence of GHD among children. The prevalence of GHD among adults is much lower (statistics — 2,68 per 100 000 adults, registry — 2,16 per 100 000 adults). These circumstances warrant closer investigations and possible corrections of both diagnostics of GHD and patient monitoring.

Conclusions. The differences between the MS and the registry revealed here show the necessity for correcting the rules of conducting the registry. Today there are no clear exclusion criteria. Considering the epidemiology of GHD shown by the official MS, the dependence of GH therapy outcome on a timely diagnosis we suggest to widen the functional use of the federal registry, which has the potential to become a useful tool in GH therapy control and patient monitoring.

Aim — to investigate serum level of fibronectin in obese and non-obese women with polycystic ovary syndrome (PCOS) as a marker of endothelial dysfunction, and the relationship of that factor to the endothelium-dependent dilatation and other risk factors for cardiovascular disease.

Material and methods. We study 62 women: 45 — with PCOS (23 obese women, 22 — non-obese) and 20 — a control group. Serum level of fibronectin was determined by ELISA. Endothelium-dependent dilatation was measured by test of Celermajer. Data was presented as mean ± SD.

Results. We found an elevation of serum level of fibronectin in obese women with PCOS compared to control (258,12±48,47 and 196,34±46,68 pmol/ml respectively; р<0,05), in non-obese women compared to control (227,62±35,36 and 196,34±46,68 pmol/ml respectively, р<0,05). Serum level of fibronectin in obese was higher than non-obese women (258,12±48,47 и 227,62±35,36 pmol/ml respectively, р<0,05). Also, there are a correlation between the serum levels of fibronectin and BMI, HOMA index, lipid metabolism, androgens in PCOS women obese and non-obese (p<0,05).

Conclusion. Serum level of fibronectin is elevated in obese and non-obese women with PCOS. Hyperandrogenemia, dyslipidemia, insulin resistence, obesity appears to be significant factor to contributing elevation of fibronectin. The revealed change of fibronectin could reflect an endothelial dysfunction in PCOS.

Background. GPR119 receptor is a promising target for novel antidiabetic drugs development because of its agonists in addition to hypoglycemic effects have cytoprotective effect on beta cells.

Aim — to assess the effect of the novel GPR119 receptor agonist and sitagliptin on carbohydrate metabolism and morphological structure of the pancreas in animals with experimental type 2 diabetes.

Material and methods. The study was performed in Wistar rats with streptozotocin-nicotinamide-induced diabetes. Serum insulin was determined by ELISA (Rat Insulin, (INS) ELISA Kit, 96 CSB). Immunohistochemical studies were performed using mouse monoclonal antibodies to insulin (clone 1G4, GeneTex) with determination of the absolute and relative area of immunopositive material (beta-cells) of the pancreatic islets.

Results. 28-day treatment of animals with diabetes by GPR119 receptor agonist — ZB-16 (dipiaron) (1 mg/kg, per os, daily) and an inhibitor of the DPP-4 (sitagliptin) led to a reduction of fasting hyperglycemia and improve its glucose tolerance and enhance basal and stimulated insulin secretion relative to the control without treatment. Morphometric assessment of islets revealed that animals treated with the ZB-16 and sitagliptin have significantly higher absolute and relative islets area, as well as the perimeter of the insulin-positive material compared to islets of rats without treatment.

Conclusion. Course administration of GPR119 receptor agonist to animals with streptozotocin-nicotinamide-induced diabetes has a pronounced antidiabetic effect consists in reducing fasting plasma glucose, improve glucose utilization, increase basal and stimulated insulin secretion, as well as increasing the area of the insulin-positive material in islets. Antidiabetic action of novel GPR119 receptor agonist, was comparable to that of sitagliptin.

Modern nutrition has clear evidence of the involvement into the metabolism of many minor food components, which were not previously discussed as factors necessary for life support of health and ill human. One of the innovative approaches to the creation of a new generation of specialized food products for the dietary treatment of type 2 diabetes is a targeted use in their composition plant minor biologically active food substances with proven significant hypoglycemic, cholesterol-lowering and antioxidant action as a «micro-ingredients». Promising sources of natural functional food ingredients for the dietary treatment and prevention of type 2 diabetes and its attendant complications are plant extracts with a high content of natural polyphenolic compounds. The natural polyphenolic compounds include flavonoids, obligate food antioxidants what is the reason of their hypoglycemic and/or lipid-lowering effects. However, we consume no individual flavonoids, but their mixtures, with plant food. Data about antidiabetic properties of plant extracts containing various combinations of flavonoids are very important in the framework of the problem of dietary correction and prevention of type 2 diabetes from the position of clinical nutrition. The review briefly discusses the effect of green tea, bilberry leaves and bean coats plant extracts on disorders of carbohydrate and lipid metabolism in laboratory animals with experimentally or genetically determined diabetes. The presented analysis of publications shows that the results of experimental studies in vitro and in vivo confirm the antioxidant, hypoglycemic and/or hypolipidemic effect of polyphenolic plant extracts. It was concluded that the inclusion of plant extracts of flavonoids in the specialized food products for targeted nutritional correction and/or prevention of metabolic disorders of type 2 diabetes is a promising direction.

Medullary thyroid cancer with ectopic ACTH production - the disease is extremely rare. The literature describes only a few cases of this disease. Rare ectopic ACTH syndrome caused by medullary thyroid cancer, and the diversity of the clinical picture are responsible for numerous diagnostic errors leading to ineffective treatment. In this regard, we consider it expedient to share our own experience in this area.

Traditionally the Cushing’s disease (CD) is considered a rare disease. Since 2012 СD has the official status of an orphan disease in the Russian Federation. Now prevalence of this disease in the world are from 1,5 to 3,9 cases of CD on 1 million people of the population. The reason of CD is the adenoma of a hypophysis (сortiсotropinoma). The “gold” standard of therapeutic tactics of patients with CD is the transsphenoidal surgery. However in 20% of cases after the radical treatment  fail to achieve remission of pathological process. Now in an arsenal of the neuroendocrinologist we have various methods of  therapy, including various methods of drug therapy. The focus of  preparations are central type action:  analogs of a somatostatin. The representative of this group of preparations is Pasireotid who has proved the efficiency by results of the multicenter clinical trials. This review  focuses of the current   state of knowledge about methods of treatment of CD, about new therapeutic opportunities with application of analogs of a somatostatin.

Polycystic ovary syndrome (PCOS) is the most common cause of hyperandrogenism in women. The criteria for diagnosis in women of reproductive age at present are subject to dispute. At the same time, diagnosis in adolescent girls is associated with even greater challenges, since many of the manifestations of the disease are a manifestation of normal puberty. In the absence of clear criteria for diagnosis in adolescence, more attention is paid to the search for new markers PCOS, one of which may be anti-Müllerian hormone. However, data on its diagnostic value is currently controversial, which calls for more extensive research in order to develop specific criteria for the diagnosis PCOS in teenagers.

Background. Adequate intake of vitamin D and its concentration in serum is important for the health of bones and calcium-phosphorus metabolism and for the optimal functioning of many organs and tissues. Most epidemiological studies have shown that vitamin D deficiency is widespread among the population in Russian Federation.

Material and methods. We reviewed relevant literature on the epidemiology of insufficiency and deficiency, skeletal and extraskeletal effects of vitamin D and summarized recommendations for the diagnosis, prevention and treatment of vitamin D deficiency in the general population, which were subsequently discussed and amended in conjunction with leading endocrinologists of the Russian Federation who are experts in this subject.

Results. The optimal concentration of 25(OH)D in the serum as the best indicator of vitamin D body stores is recognized as 30—100 ng/ml (75—250 nmol/l), insufficiency — from 20 to 30 ng/ml (50 to 75 nmol/l), deficiency — less than 20 ng/ml (less than 50 nmol/l). In prevention and treatment it is recommended to stick to the target serum levels of 25(OH)D in the range of 30—60 ng/ml (75—150 nmol/l). We’ve developed a general practice recommendations for the prevention, diagnosis and treatment of vitamin D deficiency in adults, including pregnant and lactating women, persons over 50 years old and subjects suffering from various diseases affecting the metabolism of vitamin D.

Conclusions. Increased sufficiency of vitamin D in the population should be included as one of the priorities of modern healthcare due to proven preventive health effects on the musculoskeletal system and the potential positive impact on many socially significant diseases. This publication is a detailed version of the Federal Guideline.