We have investigated the possibility of application of the direct mass-spectrometric analysis of plasma metabolites for diagnostics of impaired glucose tolerance (IGT). The plasma samples obtained from the control group of patients showing no disturbances of carbohydrate metabolism (n=30) and those with IGT (n=20) were treated with methanol to precipitate proteins and the residual fractions were analysed on a quadrupole flight-of-time mass-spectrometer. A total of 230 metabolites were identified the levels of which were attributable to IGT. The accuracy of diagnostics using the mass-spectrometric analysis was 92% (specificity 94%, sensitivity 89%, area under the Roc-curve 0.94, reproducibility 85%). The detected metabolites included endocanabioids, cresol, ornithine, phospholipids, and fatty acids the presence of which was related to the previously described risk factors of diabetes mellitus. It is concluded that the direct spectrometric analysis of plasma metabolites can be used in routine clinical practice as a more rapid and better reproducible alternative method in comparison with the glucose tolerance test .

This paper reports the results of the year-long treatment of 46 patients presenting with active phase of acromegalia (39 (85%) women and 7 (15%) men, at the age varying from 22 to 76 years) using the long-acting somatostatin analog octreotide-depo. The treatment was started using a dose of 20 mg with the measurement of GH and IGF-1 levels each 3 months; the dose was titrated as appropriate. The maximum dose of octreotide-depo amounted to 40 mg. The effectiveness of therapy was evaluated from the severity and frequency of the principle symptoms of acromegalia, viz. facial, hand, and leg soft tissue oedema, fatigue, excessive sweating, headache, arthralgia, elevated blood GH and IGF-1 levels. The target GH levels were considered to be below 2.5 ng/ml and those of IGF-1 within the normal age-specific concentration range. The most well-apparent regression of clinical symptoms was observed within the first 3 months after the onset of the treatment, concurrently with the maximum reduction of blood GH and IGF-1 levels. The values reached during the first 3 months remained unaltered up to the end of the study. Simultaneous normalization of the blood GH and IGF-1 levels was documented in 55% of the patients. The clinical symptoms most frequently disappeared in the patients with normal IGF-1 levels. The adverse reactions of octreotide-depo therapy included short-term diarrhea (45.6%), meteorism (25.1%), abdominal pain (26%), nausea (13.4%), constipation (10.8%). These conditions were not serious and did not require the withdrawal of the preparation.

The state of the guanylate cyclase activity of myocytes was evaluated from the increment in the diameter of the brachial artery in response to the exogenous administration of nitroglycerin (#D^NO) in 64 samples obtained from 44 patients. A total of 23 studies were carried out during thyrotoxicosis decompensation, 28 ones in the phase of medicamental thyrotoxicosis, and 13 within 5-6 days after thyroidectomy. The guanylate cyclase activity of myocytes was found to correlate with the production of vascular endothelium factors. Thyroidectomy in the patients with toxic goiter and reduced guanylate cyclase activity of myocytes was associated with the statistically significant increase of endothelium-independent vasodilatation.

The non-classical form of 21-hydroxilase deficiency (21-OHD) has up to now been fairly well studied only in the patients of prepubertal and pubertal age as well as in the women of reproductive age. The advent of neonatal screening for congenital adrenal hyperplasia (CAD) made it possible to more frequently detect 21-OHD in the children during the first year of life. The domestic literature proposes no clinical and laboratory criteria for 21-OHD in the young children. The results of neonatal screening of 50 children presenting with elevated 17-hydroxyprogesterone (17-OHP) levels carried out in the period from 2011 to 2013 were used to form two groups of patients, one comprised of 20 children with verified 21-OHD (group 1), the other containing 30 "healthy" children showing the false-positive elevation of 21-OHD levels. All the patients underwent the comprehensive clinical and hormonal examination supplemented by the molecular-genetic analysis. The main criterion for the inclusion of children in group 1 was the presence of mutations in the CYP21 gene It was shown that determination of 21-OHD by tandem mass-spectrometry (TMS) including that in the framework of multisteroid analysis yields the most specific and accurate data in the children below one year of age; such analysis is indicated to all patients in whom the neonatal screening for congenital adrenal hyperplasia reveals the slightly elevated 17-OHP levels. The analysis for the group of patients with verified 21-OHD has demonstrated the absence of clinical and laboratory signs of adrenal insufficiency and/or hyperandrogenism in the children aged below 1 year.

The present study was designed to measure pre- and postprandial ghrelin secretion in the children presenting with Prader-Willi syndrome (PWS). The clinical, hormonal, and metabolic characteristics of 17 prepubertal children with the genetically verified diagnosis of PWS, 15 patients with exogenous-constitutional obesity, and 10 healthy children are presented. The children suffering PWS were found to exhibit pre- and postprandial hyperghrelinemia.

We have studied the state of the mitochondrial permeability transition pore (MPTP), respiration, and oxidative phosphorylation in mitochondria of the liver and pancreas of the rats with streptozotocin-induced diabetes. In addition, we considered the approaches to the correction of membraneous lesions with the help of glycorazmulin, a hypoglycemic preparation based on mumiyo (Jew's tar) and an extract from rhodiola roots and tubers (Rhodiola Semenovii A.). The mitochondria swelling rate in the liver and pancreas of the rats with experimental diabetes mellitus is known to be lower than in the unaffected animals; in other words, hepatic and pancreatic megapores in case of pathology remain open. Glycorazmulin normalizes their state and thereby eliminates the effect of spreptozotocin on mitochondria. The mitochondrial respiration rate in the liver and pancreas of the rats with experimental diabetes inceases at states V3 and V4 which results in a significant decrease of respiratory and ADP/O coefficients compared with the control values. The results of the study suggest decoupling of respiration from oxidative phosphorylation in the rats with experimental diabetes. Glycorazmulin administered per os at a dose of 50 mg/kg b.w. during 8 days eliminated functional disorders of mitochondria in the liver and pancreas of the rats, presumably by virtue of its antioxidative properties.

At present, four main types of autoimmune polyglandular syndromes (APS) are distinguished. Type 1 APS is associated with candidiasis, primary hypoparathyroidism, and primary adrenal insufficiency developing in the childhood as a result of mutations in the AIRE gene. Type 2 APS involves primary adrenal insufficiency in combination with autoimmune thyroid diseases and/or type 1 diabetes mellitus. Type 3 APS is characterized by the combination of autoimmune thyroid diseases with other endocrine and non-endocrine autoimmune pathologies in the absence of adrenal cortical dysfunction and hypoparathyriodism. Type 4 APS is presented by the combinations of autoimmune diseases other than the aforementioned ones. The above syndromes usually manifest themselves at the age between 20 and 60 years; they are of the polygenic type and associated with the genetic markers, such as HLAII-complex haplotypes, CTLA-4, PTPN22, FOXP3 genes, etc. In addition, the latent forms of APS have been described that occur in the populations much more frequently than the manifest disorders. These latent diseases can exert strong influence on the compensation and risk of complications of the underlying pathology. Of great importance in this context is the timely identification of the groups of patients at risk of developing clinical forms of APS among the subjects presenting with a single endocrine pathology.

Graves' disease is rather rare occurrence in the childhood, with the girls being the most frequently affected gender. The draft clinical guidelines on diagnostics and treatment of Graves' disease in the children and adolescents are proposed for the extensive discussion. The guidelines are intended for pediatric endocrinologists, pediatrists, surgeons, and specialists in radioisotope therapy.

Hypoparathyroidism is a rare etiologically heterogeneous condition that manifests itself in the children in the first place as hypocalcemia. The purely hypocalcemic convulsions are usually interpreted as manifestations of epilepsy which leads to the prescription of an inadequate treatment. The early diagnostics and correct therapy ensure the normal development and social adaptation of the affected child. The present clinical guidelines developed at the Institute of Pediatric Endocrinology, Endocrinological Research Centre, highlight the diagnostic problems pertaining to hypoparathyroidism, as well as its clinical and genetic variants. In addition, the algorithm of diagnostics of hypocalcemic syndrom is proposed in conjunction with the schemes for its treatment.