Background. Obesity mainly caused by overeating is one of the most important risk factor of type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate eating behavior types of patients with T2DM and obesity.

Methods. We compared samples of patients with T2DM from the UK (N=113, 64 men) and Russia (N=200; 61 men) whom we asked to complete the Dutch Eating Behaviour Questionnaire (DEBQ). Mean age was 61.2±9.7 years old (range 39-85 years). Physical assessment included height, weight, body mass index and obesity degree according World Health Organization. Statistical analyses were performed using SPSS 21.0. Means (SD), 95% confidence interval (CI) were calculated.

Results. One hundred seventy-nine patients were classified as obese (range 30.0 – 53.9). Mean values for restraint, emotional and external eating for this obese group were 2.8±0.07 (95% CI 2.7-3.0), 3.3±0.08 (95% CI 3.2-3.5) and 3.0±0.05 (95% CI 2.9-3.2), respectively. Russian patients showed higher levels of external eating (p<0.0001) and emotional eating (p<.0001) than their UK counterparts, but levels of restraint eating did not differ by country (p=0.30). HbA1c was significantly lower in the Russian patients compared to the UK patients (p=0.04). Multiple regression analysis showed that emotional eating, but not restraint or external eating was a significant predictor of BMI even when controlling for age, sex, HbA1c and country (β = 0.56; p < 0.0001; 95%CI 1.03-3.0)

Conclusion. Present study has shown that emotional eating is an important correlate of BMI in patients with T2DM patients. However, eating behaviour styles may differ by country.

Background. The quality of life is very important and continuously medicine gives more weight to how one intervention can improve the quality of life of patients. Diabetes mellitus is a disease of modern lifestyle and is a chronic metabolic disease that affects the level of health and quality of life.

Aim of this study is to investigate the quality of life of patients with diabetes and the factors affecting it.

Materials and methods. The questionnaire used consists of two parts. The first concerns demographic questions for the patient and the condition of diabetes mellitus and the second questionnaire on diabetes-related quality of life ADDQoL 19. The study included 140 patients and was conducted from October to March 2015 the hospital Carl Thiem Klinikum of Cottbus, Germany. The statistical analysis will be done with statistical software «Statistical Package for the Social Science (SPSS) for Windows» and level of statistical significance was set to p = 0.05.

Results. Statistical significant difference showed in the present quality of life (Overview I) by gender of patients with p = 0,011. Based on the presence of complications of the disease there is a statistical significant difference in the average of responses for the 19 areas of life (AWI: Average Weight Impact) with p = 0,033. The diabetes school also shows statistical significant difference in the AWI with p = 0,018. Furthermore based on the type of diabetes and the treatment showed a statistical significant difference in quality of life (Overview I) for type 2 by treating with pills (Overview I: 1,117) than insulin treatment (Overview I: 0,471) with p = 0,008.

Conclusions. Educating patients appears to improve the quality of life of patients and the adoption of the Diabetes school should be followed by other countries. An important factor affecting the quality of life is the treatment followed and especially positive effect shows the use of treatment with pills which also support our results.

Introduction. Genetic susceptibility to Type 2 Diabetes (T2D) with a complex mode of inheritance is explained by the presence of multiple gene, each conferring a small moderate contribution the overall risk, as well as by alternative combinations of genes. Due to the success of Genome-Wide Association Study there has been rapid increase in the availability of genetic data for T2D. This allows the collection of large sets of genetic polymorphic loci, which could be key in the understanding of the genetic basis of T2D.

The aim of this study was to determine alleles and allelic combinations that are associated with T2D phenotype.

Methods. We assessed the associations of 96 single nucleotide polymorphisms (SNPs) linked with T2D different pathway components and carbohydrate metabolism abnormalities in 96 Russian patients and 96 normoglycemic controls using Illumina Golden Gate Genotyping Assay (low density DNA chip with 96 SNPs). T2D was defined according to the World Health Organization criteria, 1999. Data were analyzed with the free online statistical program named “Calculator for confidence intervals of odds ratio” (www.gen-exp.ru/calculator_or.php) and APSampler software (https://code.google.com/p/apsampler) for multi-locus association analysis.

Results. On the first stage of the study we detected ten SNPs that can be independently contributing to T2D risk in the Russian cohort, they are rs8050136 (p=0,05) and rs11642841 (p=0,04) in FTO gene, rs2943641 (p=0,02) and rs2943634 (p=0,03) in IRS1 gene, rs571312 in MC4R gene, rs1470579 (p=0,04) in IGF2BP2 gene, rs163184(p=0,03) in KCNQ1 gene, rs11924032 (p=0,04) in SLC2A2 gene, rs11634397 (p=0,03) in ZFAND6 gene, rs7172432(p=0,04) in C2CD4A gene. On the second stage we found a biallelic combination of A allele rs8050136 in FTO gene and A allele rs7172432 in C2CD4R gene that was associated with T2D risk. Remarkable, the combined effect (association) of rs8050136 and rs7172432 was stronger (OR=1,97; p=0.006) than that of each SNP alone.

Conclusion. The biallelic combination of A allele rs8050136 in FTO gene and A allele rs7172432 in C2CD4R gene can be used as a genetic marker of T2D.

Background. Chronic kidney disease is one of the most serious diabetic complications, which end-stage leads to a dramatic decline of renal function and needs for renal replacement therapy. Due to the progressive nature of CKD and the limited efficacy of treatment for advanced stages the prediction of risks and diagnostics on preclinical stage are of great importance. All of the above determines the high relevance of search for genetic markers predict the chronic kidney disease (CKD) development.

The aim of our study was to investigate association between polymorphic marker (PM) of gene involved in insulin secretion with development of CKD in type 2 diabetic (T2D) patients. Polymorphism of KCNJ11 gene is associated with different phenotypes of glycemic disorders: neonatal diabetes, hyperinsulinemia, reduced insulin secretion and increased risk of type 2 diabetes. This gene coding Kir6.2 subunit of ATP-dependent potassium channels. The pathogenesis of it’s involvement in renal damage development referred to the fact that this type of potassium channels found not only in the beta- cells, but also in smooth muscle cells of blood vessels, and therefore might have an effect on risk of vascular complications, including CKD.

Materials and methods. We enrolled 444 T2D patients. PM rs5219 in KCNJ11 gene was analysed among patients divided in 2 groups: with and without CKD (n=123/321) based on glomerular filtration rate (GFR) < and ≥ 60 ml/min/1,73m2 calculated by MDRD formula. PM studied using PCR. Differences in alleles/genotypes frequencies were assessed by χ² and odds ratio (OR) were calculated. The study was approved by local ethical committee; informed concern was obtained from all the patients.

Results. We studied the main clinical parameters: age, HbA1c, serum levels of cholesterol and triglycerides, BP between the groups. We observed significant differences in alleles/genotypes distribution of rs5219 in KCNJ11 gene between groups with and without CKD: the prevalence of allele C and genotype CC in patients without CKD: OR=0,53, 95%CI: 0,40-0,72 and OR=0,46, 95%CI: 0,27-0,79, respectively; while allele T and genotype TT did as risk factors: χ²=17,33; р=0,0002; OR=1,87, 95%CI: 1,39-2,53; genotype TT OR=2,39, 95%CI: 1,52-3,76.

Conclusions. We conclude that T2D patients might have genetic susceptibility to CKD development caused by polymorphism rs5219 of KCNJ11 gene with protective role of allele C and genotype CC and risk allelе/genotype is T/TT.

Background. Recently, as the therapy of diabetes mellitus, have been approved several members of a new class of drugs – SGLT2 inhibitors. SGLT2 inhibitors reduce glycemia and normalize renal perfusion. However renoprotective effect is still the subject of research.

The aim of this study was to evaluate the effect of SGLT2 inhibitors on renal tissue of rats with experimental type 1 diabetes (DM).

Materials and methods. This study was conducted on 22 white male rats at the age of 10 months with streptozotocin - induced diabetes. For the selection of the rats in the experiment were evaluated glycemia. The criteria for diabetes was blood glucose levels > 7 mmol / L and / or a positive glucose tolerance test. Rats were divided into 3 groups: 1 group (healthy control) - a group of 10 animals without DM, 2 group - (diabetic control) 6 animals with DM receiving insulin NPH; 3 -6 animals with DM receiving insulin NPH and dapagliflozin 0.1 mg / kg for 4 weeks. At the end of the study, animals were kept in metabolic cages and 24 hour urine was collected for estimation of albuminuria. Next animals were removed from the experiment, and kidney tissue was sampled for morphological evaluation. Sections were stained with haematoxylin and eosin (H&E), and PAS reaction stains for histopathological examination. Statistical significance of differences was assessed and linkages by standard methods of nonparametric statistics.

Results. Sections of kidney from control group had classical structure of renal tissue. In contrast, histological sections from rats treated with insulin had showed cortical glomerulosclerosis, proliferation of mesangial cells and narrowed Bowman's spaces. In most of the proximal convoluted tubules was observed excessive hypertrophy, vacuolization and pyknotic nuclei. The kidneys of rats treated with dapagliflozin and insulin had a lower severity of degenerative processes compared with a group of rats treated with insulin. Many glomeruli had increased cellularity with normal Bowman’s spaces, while in the proximal convoluted tubules was observed weakly pronounced vacuolization and pyknotic nuclei and some less hypertrophy of tubular epithelium. Kidney sections of insulin-treated rats were showed signs of diffuse expansion of mesangial area with proliferation of mesangial cells and its PAS-positive matrix. While signs of mesangial expansion were absent in the dapagliflozin group. Analysis of the degree of glomerulosclerosis data was showed significant differences between the group of rats treated with dapagliflozin and insulin and the group of rats treated with insulin - 0.5 (0.4 - 0.6) and 1.1 (1.0 - 1.2), respectively ( p = 0.005). Furthermore, it revealed significant difference in percentage of mesangial area between group of rats treated with dapagliflozin and insulin and the group of rats treated with insulin - 28% (23 - 32) and 37% (33 - 41), respectively (p = 0.0082). Insulin-treated rats were showed significantly higher level of albuminuria compared with dapagliflozin-treated rats - 91.8 mg / 24h. (74.1 - 108.5) and 50.9 mg / 24 hr (41.3 - 60.2), respectively, (p = 0.012).

Conclusions. Administration of dapagliflozin slows the progression of glomerulosclerosis and reduces the degree of its severity and the level of albuminuria, which may suggest a renoprotective properties.

Background. Pancreatic β-cells failure and apoptosis in response to chronically elevated concentrations of saturated fatty acids in blood was considered as one of the main causes of type 2 diabetes mellitus development. Although precise molecular mechanisms of this process are still unclear, there are some indications that the p38 MAPK signaling pathway could be involved.

Aim, materials and methods. Therefore, we tested the role of p38 MAPK signaling pathway activation in apoptosis induction by SA in human pancreatic β-cells NES2Y. Crosstalk between p38 MAPK pathway activation and accompanying ERK pathway inhibition after SA application was also tested.

Results. We have found that saturated SA at apoptosis-inducing concentration (1 mM) activated the p38 MAPK signaling pathway MKK3/6→p38 MAPK→MAPKAPK-2 and inhibited the ERK signaling pathway c-Raf→MEK1/2→ERK1/2. The inhibition of p38 MAPK expression by siRNA silencing had no significant effect on cell viability or the level of phosphorylated ERK pathway members after SA administration. The inhibition of p38 MAPK activity by the specific inhibitor SB202190 resulted in noticeable activation of ERK pathway members after SA treatment but in no significant effect on cell viability. p38 MAPK overexpression by plasmid transfection produced no significant influence on cell viability or ERK pathway activation after SA exposure. The activation of p38 MAPK by the specific activator anisomycin led to apoptosis induction similar to application of SA (PARP cleavage and caspase-7, -8, and -9 activation) and in inhibition of ERK pathway members.

Conclusions. We demonstrated that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway and that this activation could be involved in apoptosis induction by SA in the human pancreatic β-cells NES2Y. However, this involvement does not seem to play a key role. Crosstalk between p38 MAPK pathway activation and ERK pathway inhibition in NES2Y cells seems likely. Thus, the ERK pathway inhibition by p38 MAPK activation does not also seem to be essential for SA-induced apoptosis.

Objective. To examine kidney transplant dysfunction markers in patients with diabetes mellitus type 1 (T1DM) after kidney transplantation (KT) and simultaneous kidney-pancreas transplantation (SPK).

Materials and methods. The study included 20 patients after successful SPK (group 1) and 41 patients after KT (21 received insulin pump therapy (group 2), 20 –multiple daily injections of insulin (group 3). Post transplantation period at the time of inclusion in the KT group was 8 months [7;8], in SPK-11 months [8;18]. The control group consisted of 15 patients with DM1 without diabetic nephropathy (group 4). Sex, age and duration of T1DM were comparable. Donors of SPK were younger than KT: 29 [25; 33] vs 46[30; 51] years p<0,01 and transplant cold ischemia time was less 8[7;10] vs 11,5 [1; 17] hours respectively, p<0,01. After 9 months of observation biomarkers of dysfunction of renal transplant: Cystatin C (serum, urine); NGAL, KIM-1, podocin, nephrin, IL-18, IP-10 (urine), TGF-β1, MMP-9, VEGF-A, Osteopontin – (OPN) (serum) were defined.

Results. the level of GFR in patients after transplantation was C2 stage, albuminuria A1 of chronic kidney disease. In the group of patients with T1DM after successful SPK and KT revealed a significant increase in markers of renal dysfunction (cystatin C (serum), NGAL, Podocin, OPN) compared with the control group despite of carbohydrate metabolism compensation (Tabl.1). High level and a negative associated of blood cystatin C with GFR (r = - 0,36, p<0.05) and positive with albuminuria (r=0,40, p<0,05), as well as a direct link of podocin urine-with blood creatinine (r = 0,35, p<0.05) and NGAL with albuminuria (r = 0,35, p<0.05) in recipients after transplantation were defined. Association between podocin with MMP-9 (r = 0,46, p<0,05) and NGAL (r = 0,33, p<0,05) indicated correlation of stress factors of renal microstructures in posttransplantation patients.

Conclusion. High levels of renal graft dysfunction biomarkers in the examined patients (including those after SPK) show the persistence of damage to the microstructures with stable graft function and demonstrate the need to control all factors in the preservation of renal function.

Table 1. Renal transplant dysfunction markers

Parametrs

Group 1

Group 2

Group 3

Group 4

TGF b1 (serum, pg/ml)

32999[24514;3917]

24473[21752;33330]

25139[11367;2862]

26986[17347;4266]

VEGF A (serum, pg/ml)

471,9[296;530,6]^#

407,6[301,6;522,2] ^#

226,6[177,8;367,4]

467,4[288,3;474,8]

CYS C, (serum, ng/ml)

1047[985;1295]*^∞

1252,9[1151;1540]^#∞

1113,32[986;1257] ^§

728,8[592,9;765,3]

Osteopontin (serum, ng/ml)

3,51[2,7;4,9] ^#∞

4,28[2,8;8,2] ^∞

4,71[3,6;12,7] ^§

2,86[2,2;3,1]

MMP-9 (urine, ng/ml)

1,15[1,1;1,7]

1,30[1,2;1,9] ^#

1,10[0,9;1,3]

1,22[1,0;1,3]

IP-10 (urine, ng/ml)

17,83[17,32;18,36]

17,83[17,32;18,36]

18,36[17,83;18,90]

18,36[17,83;18,90]

CYS C (urine, ng/ml)

10407[5812;16306]

15574[7518;28397]

13329[7006;24624]

14701[3643;26666]

Podocin (urine, ng/ml)

0,41[0,18;0,51] ^#

0,49[0,26;0,69]

0,56[0,38;0,79]^§

0,36[0,1;0,51]

Nephrin (urine, ng/ml)

0,0[0,0;0,1]

0,0[0,0;01]

0,0[0,0;0,07]

0,07[0,0;0,1]

KIM-1 (urine, ng/ml)

211,8[83,3;368,4]

314,9[152,1;508,6]

338,7[191,3;594,0]

359,2[204,4;494,5]

NGAL (urine, ng/ml)

2,4[1,7;6,7] ^*

7,8[2,8;14,5] ^∞

2,9[1,8;12,0]^§

2,3[1,7;7,3]

* р<0,01 (1-2); ^# р<0,01 (1,2-3); ∞ р<0,01 (1,2-4); § р<0,01 (3–4)

Distal sensorimotor polyneuropathy (DSPN) is a severe complication and the most common form of peripheral neuropathies in patients with type 2 diabetes (T2D). Nowadays, interest in the DSPN has increased significantly due to the increase of incidence of T2D, as well as the severity of its clinical manifestations.

This study aimed to assess the prevalence of DSPN in patients with T2D using Vibratip device as an alternative test for early diagnosis of vibration perception disorders.

Design and methods. This study was a cross sectional observational design. Height, weight, body mass index (BMI), systolic and diastolic blood pressure measured according to standard protocol. The information about T2D duration and treatment, diabetic complications, concomitant diseases and its treatment, data about laboratory parameters (level of HbA1c during the last six months, total cholesterol and triglycerides) collected from local database. All participants examined with Vibratip on both feet. Vibratip is new device using standardized vibration for DSPN detection. Vibratip is applied to the patients feet, testing two sites on both feet (1st metatarsal head on the plantar surface and hallux pump) - once whilst non-vibrating and once whilst vibrating and the patients (with their eyes closed) is asked to indicate when they feel the vibration.

Results. 2757 women and 1546 men aged 22-89 years selected from the six regions of the Republic of Belarus and Minsk-city. Among the 4303 subjects 7.78% (n=335) took place in this study aged less than 45 years (young patients), 65.4 % (n=2814) aged 45-65 years and 26.49 % (n=1140) aged more than 65 years old. Average age was 59 ±10.4; average body mass index (BMI) – 32.2±5.6 kg/m2. Participants with normal body mass index composed 9.02% (n=388), participants with superfluous body mass and obesity – 91% (n=3915). 710 (16.5%) participants were smoking, 2649 (61 %) suffered from high blood pressure. The most participants 1428 (33%) were treated by statins compared with fibrates 131 (3%). In patients with clinical symptoms of DSPN more often was pain (in 775 cases - 18.0%), burning (in 775 cases - 16.4%), numbness (in 1144 cases - 26.6%), feeling of pins and needles (in 921cases - 21.4%) and feeling of electric shock (in 235 cases - 5.5%). In patients with vibration sensitivity disorders were subjects with previous diagnosis of DSPN 1813 (42.13%) and subjects without previous diagnosis of DSPN 850 (19.75%). Amount subjects with asymptomatic vibration sensitivity disorder without clinical symptoms DSPN was 1640 (38.12%).

Conclusions. In 20% of patients T2D with impaired vibration sensitivity, established with the device Vibratip, defined pre-clinical stage of DSPN. Given the ease of use of the device Vibratip advisable its use as a screening method for early diagnosis of DSPN in clinical practice. 

Diurnal salivary and plasma cortisol variations are considered valid expression of circadian cortisol rhythmicity. The aim of this study was to assess the reliability of salivary and plasma cortisol evaluating if glycemia and glycemic oscillations may interfere with their concentration.

Methods: Forty-seven type 2 diabetic patients and 31 controls were studied for glycemic profile and diurnal salivary and plasma cortisol variations on two contemporary samples taken at 08:00 a.m. and 11:00 p.m (Late Night, LN). Glucose variability was evaluated in diabetic patients by considering the standard deviation of blood glucose (BGSD) readings, by calculating the mean amplitude of glycemic excursions (MAGEs) and continuous overlapping net glycemic action (CONGA).

Results: A significant correlation between LN serum cortisol and morning fasting glycemia (r = 0.78; p = 0.004) was observed in T2DM group but not in the control group (r = 0.09; p = 0.74). While LN serum cortisol significantly correlated with CONGA in diabetic patients (r = 0.50; p < 0.001), LN salivary cortisol did not correlate with any indices of glucose variability. Moreover, a highly significant correlation between LN salivary and LN serum cortisol concentrations was found in control group (r = 0.80; p < 0.001) but not in diabetic patients (r = 0.07; p = 0.62) .

Conclusions: This study shows for the first time that late night salivary cortisol may give more information than late night plasma cortisol on the dynamic of adrenal function of type 2 diabetic patients, as it is not significantly influenced by glycemic variations.

Background and aim. We planned this prospective cohort study in term newborn babies, with the objective to determine the incidence of vitamin D deficiency in infancy and to determine the level of vitamin D which triggers the physiological PTH axis of the body so as to differentiate truly deficient from sufficient vitamin D status.

Methods. 96 participants at birth were enrolled and followed up till 9 months of age. Serum25OHD was estimated in cord blood at birth and at 14 ± 1 weeks of life. 77 participants were followed up at 9 months for estimation of serum 25OHD, PTH, Alkaline phosphatase (ALP), calcium and phosphorus. Vitamin D deficiency was defined as serum 25OHD <15 ng/mL as per USIOM guidelines.

Results. Serum 25OHD levels at 9 months of age (15.78±8.97ng/mL) were significantly increased in comparison to the level of 3 months of age (14.04±7.10ng/mL) and at birth (8.94±2.24ng/mL).At birth all the participants (77) were deficient in 25OHD levels. It was found that 16/94 (17%)and 19/77 (24.7%) participants at 3 and 9 months of age respectively became vitamin D sufficient without any vitamin D supplementation. There was a significant inverse correlation between serum 25OHD and PTH concentration (r=-0.522, p<0.001), serum 25OHD and ALP(r=-.501, p<0.001). It was found that reduction in serum vitamin D level to below 10.25 ng/mL results in surge of serum PTH.

Conclusion: Vitamin D deficiency is common from birth to 9 months of age but incidence decreases spontaneously even without supplementation. Also large number of babies may be falsely labelled as vitamin D deficient with currently followed cutoffs. So a new cutoff for vitamin D deficiency needs to be established for neonates and infants.

Background. As a hormone, vitamin D is involved in a number of processes (normal brain formation, anticancer effect, cardioprotection effect, immune defense, etc.). In diabetes mellitus type 1 several genetic and epidemiologic factors have been recognized. There is some epidemiologic evidence that decreased vitamin D level in pregnancy or early childhood may be associated with diabetes risk, but the evidence is not yet conclusive. Low level of vitamin D has also been shown to have negative effect in beta-cells function. In our work the influence of vitamin D deficiency on the gravity of manifestation of type 1 diabetes in children was estimated.

Aim. To discover vitamin D deficiency and its effect on glycemic control in newly diagnosed type 1 diabetic children in Armenia.

Methods. Newly diagnosed type 1 diabetic children were investigated (n=74). In all children the level of vitamin D and glycohemoglobin on the 4th day of diagnosis were evaluated. Vitamin D normal range lies between 13-67ng/L.

Results. There were 51,35% (n=38) boys and 48,65% (n=36) girls by sex distribution. Distribution by age groups was as following : 0-4 years, n=14, 5-9 years, n=23, 10-14 years, n=32 and 15-17 years, n=5. Vitamin D deficiency was found in 58,11% patients (n=43). By age groups vitamin D deficiency was as following: 0-4 years - 78,55% (n=9), 5-9 years - 47,83% (n=11), 10-14 years - 62,5% (n=20), 15-17 years -60% (n=3). In 78,38% of cases (n=58) there was ketoacidosis on admission, and in 21,62% (n=16) -only ketosis. Moreover, vitamin D deficiency predominantly was met in the group of ketoacidosis cases (n=39, 67,24%), and in the ketosis group deficiency was seen only in 4 patients (25%). Average HbA1c was almost the same in the group of vitamin D deficiency and without (9,68% and 9,36%respectively).

Conclusion. Positive correlation between severity of manifestation of disease and vitamin D deficiency have been revealed, and probably vitamin D deficiency has an impact on the further course of diabetes. Therefore it can be suggested to see the level of 25 OH vit D in all cases of newly diagnosed DMT1, and include the management of vit D deficiency in the protocol of DMT1 treatment.

Introduction. Neonatal diabetes is a rare disease and it is frequently caused by a mutation in the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium channel. If the neonatal diabetes is associated with epilepsy and developmental delay, then the diagnosis is of DEND syndrome (developmental delay, epilepsy and neonatal diabetes).

Aim. To determine which are the best methods of diagnosis and treatment for a child with neonatal diabetes.

Methods and results. We present the case of a 9 years old girl, diagnosed with neonatal diabetes at age 3 months, who was first admitted to our clinic in December 2015 for frequent episodes of hyperglycemia at home and absence seizure lasting 2-4 minutes, suggesting minor epilepsy. The patient was treated with insulin from the moment of diagnosis until age 9 months, then with oral antidiabetic agents until January 2015, when she started again the insulin therapy in the context of persistent hyperglycemia and a level of glycated hemoglobin (HbA1c) of 10.6%. Her physical examination revealed height and weight according to age, with stable vital signs. The laboratory findings were all unremarkable, except for blood glucose values of 200-300 mg/dl and HbA1c level of 10.3%. The patient also had moderate mental delay, with an IQ of 66. The genetic testing for neonatal diabetes revealed a heterozygous mutation in KCNJ11 gene, so the diagnosis was of DEND syndrome. We initiated the treatment with glibenclamide 3.5 mg, 8 tablets/day and we recommended cognitive functions’ stimulation with exercises and reading 4-5 hours/day.

Conclusions. The genetic testing for the identification of a mutation in KCNJ11 gene has an important impact on the therapeutic approach in children with neonatal diabetes, as there is the possibility to replace the insulin therapy with antidiabetic oral agents, therefore improving the quality of life and possibly the epilepsy seizures.

Cornelia de Lange syndrome (CdLS) is a very rare genetic disorder that is apparent at birth (congenital). Since children with CdLS are often compared to a typical child’s grow rate, many are incorrectly diagnosed.

In the absence of the genotyping, the diagnosis would be clinical: a range of criteria would be required, such as the facial features and criteria related to at least one of the following : development, behaviour or growth. Short-stature associated with CdLS is usually due to GH deficiency or GH resistance. However the response to GH administration in patients with CdLS was reported in a limited number of cases.

We present the case of a female child 4,11 years old reffered for endocrinological evaluation of short stature. From her medical history we mention: language delay and a pulmonary valve regurgitation. At the time of evaluation, she presented short stature (-2,32 SDS) with a -3 SDS growth velocity during the past year, bone age was more than 2 years delayed compared to the chronological age (2,5 years), weight and head circumference below 5th percentile for age, synophrys, oral dystrophy, micrognathism and thin upper lip, down-turned corners of mouth, hypertrichosis, pulmonary systolic murmur, partial elbow extension.

Facial findings and criteria met for two major categories confirm the CdLS. The endocrinological evaluation revealed short-stature with GH deficiency based on two GH values below 10 ng/mL during two stimulation tests . The patient began treatment with somatropin 0,04 mg/kg/day and the patient grew 3,5 cm in 6 months (-2,7 SDS for height).

This case suggests that adequate evaluation of patients with CdLS and short stature could identify patients that are good candidate for GH treatment in order to improve final height. 

Background: Puberty is highly important for the accumulation of bone mass. Bone turnover and bone mineral density can be affected in transgender adolescents when puberty is suppressed by gonadotropin-releasing hormone analogues (GnRHa), followed by treatment with cross-sex hormone therapy (CSHT).

Objective: To investigate the effect of GnRHa and CSHT on bone turnover markers (BTMs) and bone mineral apparent density (BMAD) in transgender adolescents.

Methods: Thirty four female-to-males (FtMs) and 22 male-to-females (MtFs) were divided into a young and old pubertal group, based on the bone age of 14 years in the FtMs and 15 years in the MtFs. All patients received GnRHa triptorelin. CSHT was prescribed in incremental doses from the age of 16 years. FtMs received testosterone ester mixture and MtFs were treated with 17-β estradiol. BTMs P1NP, osteocalcin and ICTP and the BMD of lumbar spine (LS) and femoral neck (FN) were measured at three time points. Furthermore, BMAD and Z-scores were calculated.

Results: P1NP and 1CTP decreased during GnRHa treatment, indicating decreased bone turnover. Osteocalcin showed an aberrant pattern. A low BMAD Z-score of both FN and LS was observed in the MtFs at start of GnRHa treatment. The decrease in bone turnover upon GnRHa treatment was accompanied by an unchanged BMAD of both FN and LS, however BMAD Z-scores of predominantly the LS decreased. Twenty-four months after CSHT the BTMs P1NP and ICTP were even more decreased. During CSHT BMAD Z-scores increased and returned towards normal, especially of the LS.

Conclusion: Suppressing puberty by GnRHa leads to a decrease of BTMs in transgender adolescents. The increase of BMAD and BMAD Z-scores predominantly in the LS as a result of treatment with CSHT is accompanied by decreasing BTM concentrations after 24 months of CSHT. Therefore, the added value of evaluating BTMs seems to be limited and DEXA-scans remain important in follow-up of transgender adolescents. 

Background. Hypercoagulation is one of the cardiovascular risk factors in patients with metabolic syndrome (MS). It results from various factors including hyperhomocysteinemia, endothelial dysfunction, non-enzymatic glycation of proteins etc.

The aim of this study was to assess clinical correlates of thrombodynamics in insulin resistant and non insulin resistant men with metabolic syndrome.

Methods. We investigated 79 patients with MS diagnosed in accordance with IDF criteria (2009). The main group consisted of 44 men with MS including insulin resistance. The control group consisted of 35 men with MS not including insulin resistance. In addition to routine clinical tests we performed thrombodynamics assay and measured serum levels of asymmetric dimethylarginine (ADMA) and homocysteine. Mann-Whitney U-test and Spearmen’s correlation coefficient (rs) were used for statistical analysis.

Results. There was no significant difference between thrombodynamics parameters, ADMA and homocysteine levels between the two groups. In both groups thrombodynamics parameters had no correlations with body mass index, hemoglobin level, platelet count and serum ADMA level. In patients with insulin resistance clot density correlated positively with serum level of C-reactive protein (rs=0.621, p=0.007); average and initial rates of clot growth correlated positively with homocysteine level (rs=0.539, p=0.017, and rs=0.554, p=0.014, respectively). In patients with insulin resistance clot density and rates of clot growth were not interrelated with the above mentioned parameters.

Background. Hypercoagulation is one of the cardiovascular risk factors in patients with metabolic syndrome (MS). It results from various factors including hyperhomocysteinemia, endothelial dysfunction, non-enzymatic glycation of proteins etc.

The aim of this study was to assess clinical correlates of thrombodynamics in insulin resistant and non insulin resistant men with metabolic syndrome.

Methods. We investigated 79 patients with MS diagnosed in accordance with IDF criteria (2009). The main group consisted of 44 men with MS including insulin resistance. The control group consisted of 35 men with MS not including insulin resistance. In addition to routine clinical tests we performed thrombodynamics assay and measured serum levels of asymmetric dimethylarginine (ADMA) and homocysteine. Mann-Whitney U-test and Spearmen’s correlation coefficient (rs) were used for statistical analysis.

Results. There was no significant difference between thrombodynamics parameters, ADMA and homocysteine levels between the two groups. In both groups thrombodynamics parameters had no correlations with body mass index, hemoglobin level, platelet count and serum ADMA level. In patients with insulin resistance clot density correlated positively with serum level of C-reactive protein (rs=0.621, p=0.007); average and initial rates of clot growth correlated positively with homocysteine level (rs=0.539, p=0.017, and rs=0.554, p=0.014, respectively). In patients with insulin resistance clot density and rates of clot growth were not interrelated with the above mentioned parameters.

Background and aims. It has been largely studied and proven that tight glycemic control is necessary for the favorable outcome of coronary artery bypass graft (CABG) as it is associated with less morbidity and mortality. Insulin is considered as the fastest and safest means to control blood glucose in patients with type 2 diabetes mellitus (T2DM) in perioperative period. The aim of our study was to assess the preoperative risk factors for hyperglycemia after CABG.

Materials and methods. 70 insulin-naive T2DM patients undergoing CABG were included in the study. Anthropometric, biochemical and hormonal examinations were performed before the operation. Hyperglycemia was managed with insulin. Continuous intravenous insulin infusion was used according to the Portland Protocol until the third postoperative day (target serum glucose concentration < 180 mg/dl). Patients were switched to subcutaneous insulin injections using intermediate and fast acting insulin after moving to the ward (Insulatard 100 IU/ml, Actrapid 100 IU/ml, Novo Nordisk A/S) until the day of discharge. All patients had 3-4 times daily capillary blood glucose check in the ward and mean daily glucose value was calculated.

Results. The postoperative blood glucose values correlated significantly with the preoperative HbA1c values (p<0.05). The daily dose of insulin required to correct hyperglycemia correlated more with HbA1c values (p<0.005) than with patients’ weight (p<0.05).

Conclusion. The preoperative good metabolic control in necessary for the patients awaiting CABG. The value of HbA1c should be considered to estimate the daily dose of insulin.

Introduction. Atherosclerotic processes are more pronounced at diabetes mellitus (DM). Chronic hyperglycemia activated pathological mechanisms of restructuring the connective tissue, including the vascular wall. Fibroblasts are the main cellular components. Activation of the transforming growth factor (TGFß1), basic fibroblast growth factor (ß-FGF), produced by fibroblasts, inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor (α-TNF), advanced glycation endproducts (AGE) and their receptors (rAGE), may have important prognostic value.

Objective. To investigate the level AGE, TGFß1 and ß-FGF in patients with severity atherosclerosis coronary artery disease (CAD), to compare with normal blood glucose and DM.

Material and methods. The study involved two groups of patients with CAD: 56 patients of the first group had normal blood glucose and 78 patients suffered from DM type 2. The degree of coronary atherosclerosis was determined by coronary angiography (CAG) in all patients. The blood samples were collected from the aorta during CAG and cubital vein simultaneously, immediately centrifuged (15000g*min), supernatants were stored at –70*C until analysis were done. Serum was analyzed by ELISA (IFA). The critical significance level (p) for statistical hypothesis testing was set at <0.05.

Results. Average β-FGF, TGF-ß1, AGE, RAGE in the second group was significantly higher than in the first (p<0.005). Increased level of the AGE, RAGE and TGFß1 was positive correlated with low-density lipoprotein and triglycerides (R=0,049, p<0.005). IL-6 was significantly higher in the second group. There was the significant correlative relationship between the levels AGE, RAGE, TGFß1, ß-FGF and IL-6 with DM duration (R=-0,120; p=0.009), direct association with HbA_1C (R=0,429; p=0.006). There were significantly higher level of the AGE, TGFß1 and ß-FGF in aortic blood than in peripheral venous blood p<0,005). IL-6 level had opposite features: serum IL-6 was higher in venous than arterial blood. The patients with DM had three-vessel disease often (73%) then the patients without DM (R = 0,021, p<0.005), which was direct correlated with level TGFß1 (R = 0,03, p<0.005). There weren`t any differences in α-TNF level between two groups.

Discussion. High AGE, TGFß1 level and positive correlation with atherogenic lipids may indicate the role of the connective tissue remodeling in pathogenesis of the coronary atherosclerosis. As the longer DM duration led to increasing AGE, TGFß1 and IL-6 levels the chronic hyperglycemia can restructure the vascular wall. Higher AGE, TGFß1 and ß-FGF levels in aorta then in peripheral blood may show the involvement of the cardiomyocytes in these growth factors metabolism.

Conclusion. DM existence with CAD was characterized by higher AGE, RAGE, TGFß1 and IL-6 levels, which was direct correlated with the atherogenic lipids. Patients with type 2 DM and CAD had more severe coronary artery disease. 

Aim. The present study was designed to evaluate the prognostic value of platelet reactivity, initial level of inflammation markers and endothelial dysfunction, as well as CYP2C19*2 allele carriage in clinical outcome after percutaneous coronary interventions (PCI) in patients with stable coronary artery disease (SCAD) on dual antiplatelet therapy (DAPT).

Methods. A prospective, single-center study included 94 patients with SCAD who underwent PCI with DES implantation, 20% had diabetes mellitus. Platelet reactivity was determined in all patients using light transmission aggregometry induced with 5μmol/L ADP (LTA-ADP) and VerifyNow before PCI, as well as CYP2C19 genotyping. In 74 patients were determined baseline levels of high-sensitivity C-reactive protein, soluble P-selectin, soluble CD40 ligand, highly sensitive IL-6, plasminogen activator inhibitor-1 levels and von Willebrand factor activity. Mean follow-up period was 28,2±15,5 months. Cumulative endpoint included major adverse cardiac event, stent thrombosis, angina recurrence or angiographically confirmed restenosis.

Results. According to univariate regression analysis we revealed that diabetes mellitus [exp (B) 0,344 95% CI 0,118-1,004, p=0,049], PRU [exp (B) 1,009; 95% CI 1,002-1,017, p=0.01], number of stented arteries [exp (B) 4,00; 95% CI 1,475-10,848, p=0.01], number of implanted stents [exp (B) 3,672; 95% CI 1,366-9,872, p=0.01], baseline levels of PAI-1 [exp (B) 1,000, 95% CI 0,999-1,000, p=0.03] and von Willebrand activity [exp (B) 1,000, 95 1,000-1,000% CI, p=0.01]. The presence of CYP2C19*2 carriers revealed no significant impact on outcome after PCI. Using ROC-curve analysis to determine cutoff values for PRU was 202 (AUC 0,664; 95%CI 0,531-0,796, р=0,02), PAI-1 level - 75,95 ng/ml, (AUC 0,726, 95%CI 0,576-0,876, р=0,01), von Willebrand factor activity – 155,5% (AUC 0,724, 95%CI 0,561-0,887, р=0,01). Multivariate analysis revealed that concomitant diabetes mellitus, PRU ≥202, PAI-1 level ≥75.95 ng/ml, von Willebrand factor activity ≥155.15% are independent predictors of adverse cardiac events. Based on our findings we developed predictive models for risk stratifying of patients with CAD before PCI.

Introduction. Critical limb ischemia (CLI) occurs approximately 20 times more frequently among diabetic patients. Frequency of amputations is higher too. Main treatment goal in these situations is in reconstruction of arterial blood flow with bypass surgery or endovascular interventions. Nevertheless, long-term prognosis of survival, limb preservation and life quality among Russian patients that underwent this therapy remains unclear, as well as influencing risk factors.

The aim of the study was to evaluate the long-term prognosis in diabetic patients with critical limb ischemia (CLI) after peripheral angioplasty with active and nonactive follow-up period.

Methods. 81 diabetic patients with CLI underwent PTA in 88 limbs. Patients were divided into 2 groups: group A (n = 51) – with active follow up (FU) period (visits every 3-6 months during 5 years) and group B (n = 30) - without active FU period (the second visit in our center was performed in 5 years after PTA). Diagnosis and treatment of CLI were based on recommendation of TASC II. The primary outcome was cumulative survival, secondary outcome were cases of repeat PTA and major amputations (MA) after 5 years after surgery.

Results. Only 44 (86%) patients from group A finished FU period. There were 37 (46%) men, with mean age 64,1[54-68] years, mean HbA1c 7,9±1,4%, mean duration of diabetes 16,5[0,8-43] years, diabetes type 1/2 - 8/73 (90% of type 2). 82% had arterial hypertension, 5% - strokes, 18,5% - myocardial infarction. Chronical kidney disease of stage 1-2 was detected in 55,5%, stage 3-5 – in 30,8%. Anemia was diagnosed in 67,5%, arrhythmias – in 7,4%. 49,3% of patients suffered from diabetic retinopathy. Patients from both groups were comparable in comorbidities, severity of lower limb artery obstruction’s and degree of tissue damage (p<0,05): peripheral arterial disease (PAD) 4-6 classes according Graziani classification in both groups was in 75(93%) cases; Rutherford classification in both groups: 4 category-12(15%), 5category in 43(53%), and 6 category in 29(31%) patients. Repeat PTA was performed in group A in 15 (35%), in group B in 5(16%) cases. There were major amputations in groups: A-4(9%) vs group B – 4(12%) (log-rank, p<0,05). Cumulative survival in groups: A-80%, in group B-67%. (log-rank, p<0,05).

Conclusion. CLI in diabetic patients is accompanied by different complications and is characterized by severe morphological lesions of the lower limbs arteries and soft tissue lesions. Active FU period have advantages in diabetic patients with CLI after PTA: timely done reinterventions with decrease the risk of major amputations and cumulative survival. 

Introduction. The glucose intolerance later gestational diabetes is a very important indicator that helps establish the prognosis of diabetes in pregnant women who have had gestational diabetes (1). In this study we followed for one year to all gestational diabetes who were treated at the Hospital of Fuerteventura in endocrinology consultation,Canary Island, Spain. The aim was to study what factors might be related to glucose intolerance in the immediate postpartum.

Materials and methods. All pregnant women served with the diagnosis of gestational diabetes during April 2012 to May 2013, diagnosed according to the criteria of the ADA (2), were subjected to routine procedure of specialized gynecology and endocrinology unit, first: test loading test with 50 grams of glucose, and if blood glucose was greater whom 140 mgdl,SOG was performed with 100 grams glucose three hours. All these patients were followed up with a minimum of a monthly review by both gynecology and endocrinology as was given a standard diet and as controls if necessary insulin treatment. In addition glycemia in the first quarter, glycated hemoglobin in the second and third quarter was measured, if there was family history of diabetes, as well as history of previous gestational diabetes, presence of other diseases, hypertension in pregnancy, if they had done treatment with diet or insulin. Finally, it determines if the birth was eutocic or dystocia. All the analyzes were performed in the Hospital Fuerteventura laboratory by standard autoanalyzer. SPSS v.24 program for frequency valuations and statistical analyzes. Was measured frequencies, all dependent and independent variables and logistic regression analysis, ANOVA and linear correlation with statistical significance of ≤0.05 was performed.

Results. Of the 60 diabetic gestational included in the study, 49 completed the assessment of oral glucose tolerance test at 0 and 120 minutes, 81'7%, of these 57.1% were normal, 41.8% had glucose intolerance which were 26.5% impaired fasting glucose and 14’3 were intolerant, 2.5 were diabetic. In these patients: 57.6 percent had a normal vaginal delivery and 39.0% were dystocia. When we analyze all the variables according to the diagnosis of glucose intolerance, just correlated test 50 grams of glucose, ANOVA (p <0.033) with degrees of impaired glucose tolerance and there was a correlation positive linear between higher blood glucose value post 50 grams of glucose and glucose intolerance in the immediate postpartum. When we analyze dystocia, there was no correlation with any of the studied variables.

Discussion. Interestingly in this study it is among correlation values loading test with 50g glucose and the presence of glucose intolerance and diabetes immediately after birth of gestational diabetes. It is known that after 50 grams of glucose greater than 200 glucose has an almost certain chance of having gestational diabetes (2) and according to some centers especially in the United States is not necessary to make a confirmatory SOG (2), however, their relationship to the immediate postpartum, it has not been seen in another study that we know until now and therefore part of their predictive value for gestational diabetes, could already give us an indication of glycemic alteration itself will happen in the immediate postpartum (3). Compared with other studies, the prevalence of glucose intolerance is similar to other high-risk populations, such as the Indian population (4), which gives the Canarian population at high risk of developing diabetes in the future. This study shows that the overload test with 50 grams of glucose is not only indicative of a very high suspicion of gestational diabetes, but can also help establish the prognosis of a future change in glucose metabolism in gestational diabetes.

Background and aims. Placental hormones and proteins are important regulators of insulin resistance during pregnancy. However, the data concerning the assosiation between placental lactogen (PL) and placental growth factor (PLGF) level in early pregnancy and further development of gestational diabetes mellitus (GDM) are limited and incostintent. The aim of this study was to compare the level of these two placental proteins and homeostasis model assessment of insulin resistance (HOMA-IR) in early pregnancy among women diagnosed with and without GDM months later.

Materials and methods. A nested case-control study was conducted in a prospective cohort of pregnant women. Among them, 78 incident GDM cases were identified and 95 women who were not diagnosed with GDM were randomly selected as a control group. Blood was sampled for measurements of PL, PLGF, fasting plasma glucose and insulin at 8-14 weeks of pregnancy. All the women underwent oral glucose tolerance test (OGTT) at 24-32 weeks. GDM was diagnosed according to the International Association of Diabetes In Pregnancy Study Groups (IADPSG) recommendations (fasting glucose ≥5.1 mmol / l and / or 1 hour ≥10.0 mmol / l and / or 2 hours ≥8.5 mmol / L). The maternal and neonatal anthropometric parameters were also measured. Statistical analysis included Student's t-test, logistic regression and Pearson's correlation.

Results. There was no difference between GDM and control groups in the mean levels of PL (0,70 +/- 0,53 vs 0,81 +/- 0,58 mg/L, р =0,215 ) and PLGF (60,7 +/- 169.6 vs 46,6+105,6 pg/ml, р=0,503). Women with GDM were older (30.2 +/- 3.9 vs 28.4 +/- 4.7 years, p = 0.008), had higher first trimester body mass index (BMI) (25.2 +/- 5.2 vs 23.1 +/- 4.6 kg/m2, р = 0.006), higher levels of insulin (10.3 +/- 5.5 vs 7.9 +/- 3.9 mU/L, p = 0,007) and HOMA-IR ( 2.17 +/- 1.1 vs 1.7 +/- 0.9, p = 0,007) compared to the control group. Women with GDM also had a higher level of fasting plasma glucose (4.8 + 0.6 and 4.6 + 0,5 mmol/L, p = 0.063), although the difference did not reach statistical significance. HOMA-IR was positively associated with the development of GDM (OR: 1.62, 95% CI: 1.12 - 2.34, P = 0.01) and the association retained under a multivariable analysis controlling for age and BMI (OR: 1.59, 95% CI: 1.04 - 2.45, P = 0.033). Maternal PL and PLGF were not related to the results of OGTT, HOMA-IR or neonatal anthropometry. A positive correlation between PL level and gestational age at the time of blood sampling was observed (r = 0.657, p <0.001).

Conclusion. Serum concentrations of PL and PLGF in pregnant women at 8-14 weeks’ gestation were not associated with HOMA-IR and later development of GDM. Higher HOMA-IR score in early pregnancy is significantly associated with an elevated risk for GDM.

Introduction. The key element of successful treatment of gestational diabetes mellitus (GDM) is a well-organized diet and physical activity plan for the patient. In order to better monitor everyday life activity of patients and get more well-formed information on the process of treatment, a mobile application with electronic diary was given to patients at Almazov Federal North-West Medical Research Centre.

The aim of the study is to assess the beneficial action of mHealth app diary usage in clinical practice of gestational diabetes treatment.

Materials and methods. Android application diaCompanion was developed and given to a group of patients with detected GDM, who used it to keep records of food intake, blood glucose measurements, insulin injections, physical activity, sleep and ketones. These records were formed into unified electronic diaries and sent remotely to attending physicians. The developed diary app contained necessary functionality for disease management, including embedded food database with micronutrient and macronutrient parameters for more than 2000 local food items, record analysis and editing, database management, automated data retrieval and forwarding to attending physician.

Results. By the end of May 2016, 85 patients were included in the study with 39 of them already ended the course. A total of 11020 measurements of blood glucose, and 11747 meals recorded by patients into the application were analyzed. The average number of recorded days per patient was 49 (a minimum of 2 and a maximum of 128 days). The average glucose levels were 4.9 + 0.7 mmol/L at fasting state, 6.3 ± 1.1 mmol/L-1 hours after breakfast, 6.2 ± 0.8 mmol/L after lunch, and 6.2 ± 0.9 mmol/L after dinner. In the analysis of food diaries the average daily energy intake was 1125 ± 405 kcal and the daily consumptions of carbs, proteins and fats were 104±42 g, 66±25 g and 60±22 g respectively. These figures are well below the recommended dietary allowance for pregnant women, may be due to underreporting by patients.

Conclusion. Although the study is being in progress, the general impact of app usage revealed a high convenience of this practice from the physician’s perspective. Current approach made it possible to preserve and organize the data, which might otherwise be lost or not collected. This data may be used in medical studies, carried out on patients with GDM.

Background and aims. Due to changes in criteria of diagnosis of GDM in Russia from 2013, it is relevant to study clinical course of GDM and pregnancy outcomes depending on terms and methods of diagnosis of GDM.

Material and methods. 192 pregnant women aged 29,4±5,5ys, with a body weight 68,8±14,8 kg, BMI 25,3±5,3. 1st group: 86 pregnant women with high fasting glucose level before 20th week of pregnancy, 2nd group: 43 pregnant women with hyperglycemia in OGTT after 20th week of pregnancy, 3rd group: 63 pregnant women without GDM - control group.

Results. Pregnant women with GDM were older than non-GDM women (29,5±5,4ys., 30,8±5,3ys., 28,4±5,7ys, р=0,05) and had higher body weight (72,3±16,9 kg, 68,0±12,4 kg, 64,4±11,5 kg, р=0,016). There weren't difference in age, BMI between groups 1st and 2nd. The proportion of compliant women was the same in groups 1st and 2nd (38,4% and 34,9%, p=0,85). Pregnant women who needed insulin were older and had higher BMI (32,4 ± 5,3 ys. vs. 28,9 ± 5,4 ys, р=0,04; 29,7 ± 7,1vs.25,6 ± 5,7, р=0,03 respectively). The number of women treated by insulin was higher in 2nd group (46,6%vs.15,5%, p=0,03). Women, who treated by insulin, were younger and had higher BMI in 1st group compared with 2nd group (29, 0±4,7ys vs 35,0±4,3ys, р=0,03; 34,4±5,7 vs 26,1±5,9 respectively, р=0,02). There was a significant difference in delivery term and summary severe adverse outcomes (macrosomia, preterm delivery, stillbirth) between non-compliant women with GDM and 3rd group (38,6±2,7ws 1st group, 38,0±1,9ws 2nd group, 39,5±1,09ws 3rd group, р=0,008; 34,3% 1st group, 66,7% 2nd group, 19,4% 3rd group, р=0,027). The frequency of macrosomia and summary adverse pragnancy outcomes (hypoglicemia, neonatal jaundice, clavicle fracture, asphyxia) was higher in non-compliant women with GDM compared with compliant women ((29,5% vs. 12,2%, р=0,03; 70,5% vs. 46,3%, р=0,02 respectively).

Conclusions: Pregnant women with GDM diagnosed on base of high fasting glucose level, need insulin less frequently. Pregnancy outcomes in women with GDM depend on compliance rather than on terms or methods of diagnosis. 

Background. A facial expression of emotions recognition is one of the basic psychological abilities. Sex steroids are able to strongly modulate the process of interpretation of facial expressions, as it has been shown in Turner syndrome patients.

Objective. The aim of this study was the assessment of ability to interpret the facial emotions in women with polycystic ovary syndrome (PCOS).

Methods. Participants completed a visual emotional task in which they were asked to recognize the emotion expressed of 80 randomly chosen facial expressions from NimStim set (Tottenham et al., 2009). With dedicated software we were able to assess the accuracy of patients facial emotion recognition (in comparison to NimStim validation set) and time required to provide the answer. Patients with psychotic personality have been excluded using Eysenck Personality Questionnaire (EPQ). All the patients underwent also hormonal tests including gonadotropins, estradiol and androgen concentrations.

Patients. 80 women diagnosed with PCOS and hyperandrogenemia were included to the study. The control group consisted of 60 healthy, euovulatory women matched by age.

Intervention. Each patient underwent visual emotional and EPQ tasks using specifically designed software.

Main outcome measures. The accuracy rate (AR) and time required to recognize emotion (TE) of following emotions: anger, disgust, fear, happiness, sadness, surprise, calm and neutral has been measured.

Results. Patients with PCOS showed significantly reduced AR for calm (0.76¬+/-0.09) and surprise (0.67+/-0.18) emotions in comparison to controls (0.81+/-0.09, 0.79+/-0.08 respectively). The TE for the anger was higher in PCOS group. Estradiol concentrations showed a statistic tendency (p=0.07) for correlation with TE for the happiness in controls.

Conclusions. In this study we showed for the first time that patients affected by hyperandrogenism shows signs of disturbed recognition of facial expression of emotions. 

Methods. The data was collected from individual patients referred to our department and from the personal contact with patients whose data was available through the Russian database. All subjects had medical records sufficient to confirm CD.

Results. The following complications during pregnancy were suggested to be more common: arterial hypertension (45%), uterus hypertonus (41%), miscarriage risk (36%), late preeclampsia (18%), gestational diabetes (14%), fetal hypoxia (14%), placental detachment (10%). The common complications during delivery were entanglement umbilical cord of the fetus (n=9 ), fetal hypoxia (n= 8), bleeding (n=6 ), arterial hypertension (n= 4),CNS depression syndrome (n= 4).

Women whose CD was manifested during or after the pregnancy had less complications as compared to women who had CD before pregnancy. The newly diagnosed during pregnancy or just after pregnancy patients with CD were more likely to achieve remission after the postpartum neurosurgery (100% of remission), as compared to women who suffered from CD before pregnancy (69% of remission). Moreover, the exacerbation of CD was registred after delivery (in 18 out of 22 subjects) and 50% (in 4 out of 8 subjects) recurrence rate in patients who were in remission before pregnancy.

The age of children (n=22 ) varied from 1 to 10 years, and 70% were practically healthy at the moment of examination. However, some children suffered from headache ( 27% or n = 6), dizziness (27% or n = 6) or expansion pyelocaliceal system (14% or n=3). The identified data seems to be not differed from the population. According to Russian database, 33% of children were born with health problems in 2014.

Conclusions. The complication rate in pregnancy rises with the activity of CD, but up to 70% of newborns are healthy and the existing health problems seems to be not specific. Up to 50% of patients with the history of CD might had the recurrences of the disease after the delivery. Consequently, pregnancy in CD should be prolonged, but careful examination must be recommended to all women with the history of CD after delivery. 

Background. Intense physical exercise influences the secretion of hormones involved in several metabolic processes. In particular, an acute cortisol (C) and growth hormone (GH) increase after an acute physical activity is widely demonstrated in literature. Moreover, the testosterone (T)/C ratio was recently proposed as a performance index in male athletes. On the contrary, little is known about hormonal changes in women under physical activity and only few studies evaluated the hormonal trend in an extended period of time.

Aim. To evaluate the hormonal changes during an annual volleyball female regular season.

Methodology. A longitudinal, retrospective, observational clinical trial was carried out. 28 female professional volleyball players belonging to the same team were enrolled. For each subject, blood samples were collected after 36 hours of rest in four visits. Visit 1 was performed at the beginning of the training phase, visit 2 and 3 were performed during and Visit 4 were performed at the end of the regular season. GH, insulin-like growth factor (IGF)-1, T and C were assessed by immunoenzimatic assays.

Results. Both GH and IGF-1 were above the normal range at visit 1 (5.08 ± 5.22 ng/ml; 265.88 ± 105.85 ng/ml). In particular, five athletes had GH above the normal range (17.8%). No alterations of other hormones were found at Visit 1. C significantly changed during the regular season (p=0.009), with higher levels at Visit 2 (p=0.049), compared to visit 1 and the following visits. Similarly, T significantly changed during the season (p=0.013), even if a clear trend was not demonstrated. The post-hoc test showed two peaks of T at Visit 2 and Visit 4 (p=0.029 and p=0.024, respectively). Accordingly, the T/C ratio significantly changed during visits (p=0.009), decreasing of about 30% in the first phase of the regular season, suggesting an overreaching of subjects enrolled.

Conclusion. Here we found that chronic intense physical activity influences hormonal levels in female volleyball players. In particular, C secretion is increased at the beginning of the regular season, whereas T serum levels shows a significant fluctuation during the regular season. Moreover, we suggest that T/C ratio could be useful in the evaluation of the training overload in female athletes.

Aims. Sexuality of 26-36-year-old type 1 diabetes mellitus patients (T1D) was compared with published results of sexuality of healthy men from general population (HM) and sexuality of European Male Ageing Study (EMAS) different age more than 40-year-old men, assessed using EMAS- Sexual Functioning Questionnaire (SFQ).

Materials and metods. EMAS-SFQ was answered by 122 T1D patients with different duration of disease. Results were presented as scores of sexuality domains and ratio of percent of specific sexual parameter of Lithuanian HM or T1D divided to percent of different age of EMAS or different cities investigated in EMAS. Results of HM of 26-36-year-old were comparable with these of EMAS 40-49-year-old men, and results of T1D of 26-36-year-old were similar with these of EMAS 50-59 -year- old men.

Results. Masturbation (M) score of HM was statistically higher than in T1D males (p < 0, 05). This increase was independent of duration of T1D, but was due to lower number of men who never masturbate (lower number of 0 points in calculating the M score). Comparison of M score between HM and T1D who ever masturbated did not reveal statistically significant result.M did not differ significantly between the groups of males with regular, non-regular sexual partner and without partner at all (p=0.811). The same result appears when T1D and HM groups are analysed separately. When the M of T1D males are compared with HM statistically significant difference of M (p<0.01) was observed from the first 0-5 years of the disease.When males having regular or non-regular sex partner were compared with the ones without partner at all in the groups of HM, T1D males and the group of all participants, statistically significant differences of M was observed only in T1D male group (p=0.048) but not in the groups of healthy males (p=0.773) or all participants (p=0.160)

Sexual functioning distress was higher in T1D in all the groups of the duration of disease, including 0-9 -year-duration of diabetes, in comparison with HM and EMAS 40-70 +.

Negative changes of sexual functioning were statistically significant only than comparing the whole group of T1D and HM, but differed significantly comparative with EMAS 50-70+ men. Used as single item of erectile dysfunction is also useful and is highly discriminative in most cases. Low incidence of erectile dysfunction is evident in comparison of HM with all the other groups of investigated men.

Conclusions. Use of multidomain sexual function questionnaire EMAS-SFQ proved to be useful for sexuality investigation of the males of different ages. Multiple domains have its own prerogatives, but use of single items (masturbation and erection) may be equally important.
Since healthy men sexuality of 26-36-years is comparable with EMAS 40-49-year-old men, and 26-36-year-old T1D is similar to EMAS 50-59-year-old men, „plateau“ of HM during 20-60 years is expected and decreased sexuality early in 40-ties may be a sign of aging in males.

Background. Steroidogenesis is a complex enzymatic process in which cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) play an important role. Phosphodiesterase-5 inhibitors(PDE5i) increase cGMP, improving NO availability.

Objective. to investigate whether long-term, chronic treatment with the PDE5i Vardenafil affects adrenal and testicular steroidogenesis in diabetic men, using liquid chromatography-mass spectrometry (LC-MS/MS).

Design. A longitudinal, prospective, investigator-started, randomized, placebo-controlled, double-blind, clinical-trial was carried out.

Setting and Participants. 54 male patients affected by T2DM diagnosed within the last 5 years were enrolled. 26 and 28 patients were assigned to the verum and placebo-group, respectively.

Interventions. The study consisted of an enrolment phase, a treatment phase (24weeks) (Vardenafil/placebo 10mg twice-daily), and a follow-up phase (24weeks).

Outcome measurements: progesterone (P), 17-hydroxyprogesterone (17OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), corticosterone, 11-deoxycortisol and cortisol (C), were evaluated using LC-MS/MS.

Results. No differences were seen in sex testicular steroids between study and control group. For the adrenal gland, steroids were considered according to the zona in which they are produced. Considering steroids produced in the zona fasciculata, no significant differences were seen in 11-deoxycortisol and C among visits, both in the study and in the control group. For the zona reticularis, DHEA significantly decreased during treatment only in the study group (p=0.007). At post-hoc test DHEA showed higher levels at visit 2 and 8 than in other visits. The DHEAS/DHEAS ratio significantly increased during treatment only in the verum group. Considering the adrenal zona glomerulosa, corticosterone significantly changed among visits both in the study and in the control group (p<0.001). At post-hoc test, in both groups, corticosterone was significantly higher at visit 2 (p=0.028), 8 (p=0.003), and 10 (p=0.044), i.e. in coincidence with the complete clinical and instrumental examination performed only at these visits according to the study protocol.

Conclusions. This is the first double-blind, placebo-controlled clinical-trial in which steroidogenesis is extensively investigated by LC-MS/MS in T2DM men chronically treated with Vardenafil for 6 months, and followed-up for 6 months after therapy-withdrawal. Chronically administered Vardenafil reduces DHEA levels and increases DHEAS/DHEA ratio as possible consequences of modulation of steroidogenic enzymes by tissue changes in cGMP and/or cAMP availability. A possibly stress-related increase in corticosterone is suggested for the first time.

Background. Hypogonadotropic hypogonadism (HH) is a disorder characterized by delayed or absent pubertal development due to pathology of the hypothalamic-pituitary-gonadal axis. HH may be both congenital (Kallmann’s syndrome) and sporadic. Congenital or isolated HH is divided into with anosmia/hyposmia (KS) and with normal olfaction (nIHH). Nowadays several tens of genes involved in the functioning of the reproductive axis are known. However DNA lesions can be found just in 5-15% of such cases of HH.

Aim. So we decided to measure mRNA expression of several genes which can be found in leukocytes of peripheral blood - namely GNRHR and GNRH1 (are necessary for adequate biological effect of GnRH); PROK2 and CHD7 (are responsible for the migration of GnRH neurons), WDR11 and DUSP6 (are involved in normal sexual development).

Methods. A quantitative determination of mRNA expression of these genes were comlpeted in the fresh peripheral blood sample by PCR in real time.

Results. Examined patients: 9 women with hypogonadotropic hypogonadism (age from 18 to 28 y.o.); duration of the disease from 2 to 15 years; 3 of them – amenorrhea I and 6 – amenorrhea II. Reasons of amenorrhea II were: stress, excessive exercises, rapid body weight loss, past use of oral contraceptives. The control group: 19 healthy women; age from 19 to 37 y.o.; with regular ovalutory menstrual cycle, some of them have children. mRNA expression of examined genes differed from normal patterns in each case of hypogonadotropic hypogonadism. Changes in GNRHR, GNRH1 and DUSP6 mRNA expression were found in most of cases. However variations of mRNA expression were multidirectional in each case and there was no similarity among expression profiles of patients according to amenorrhea type or anamnestic factors.

Conclusions. According to our preliminary results, in women with hypogonadotropic hypogonadism the functional activity damage of “reproductive-responsible” genes could be found in each case. Probably mRNA expression measuring could be a perspective method for proving hypothalamo-pituitary level of reproductive disorders and may help to determine which genes should be tested for DNA impairment.

Background. The cyclical effects of hormones during the menstrual cycle (MC) are responsible for driving ovulation. The information about roles of adipokines within the scope of MC are not definite. Leptin plays a role in sexual function and regulating the onset of puberty. Thin girls often fail to ovulate or release an egg from an ovary during menstruation cycles. Leptin also acts on specific receptors in the hypothalamus to inhibit appetite. Levels of leptin are increased in women suffering from premenstrual syndrome.

Aim. The aim of our study was to describe physiological changes of selected steroids and adipokines at healthy women during the MC.

Methods. Twenty-seven women with regular menstrual cycles were included in the study. Each sample was collected in cooled EDTA tubes, centrifuged at 2000 rpm in a refrigerated centrifuge, and stored at –80 °C. For all samples we measured luteinizing hormone (LH), follicularstimulating hormone (FSH), sex hormone-binding globulin (SHBG), testosterone, dehydroepiandrosterone (DHEA), estradiol, 7α-DHEA, 7β-DHEA, 7-oxoDHEA, 17-hydroxyprogesterone (17-OH P), progesterone, cortisol, adrenocorticotropic hormone (ACTH) by RIA and IRMA. Levels in plasma of hormones associated with food intake (c-peptide, ghreline, GIP, GLP, GLP-1, glucagon, insulin, leptin, PAI-1, resistin and visfatin) were measured using magnetic bead-based multiple assays (x-MAP technology, Luminex Corporation). Two kits were used: the 10-plex Bio-Plex Pro Human Diabetes assay and the 2-plex Bio-Plex Pro Human Adiponectin and Adipsin assay (both Bio-Rad Laboratories).

Patient. Twenty-seven women with regular menstrual cycles (cycle length 28±2 days) were included in the study. The average age of the women was 31.8±3.56, and average BMI 22.9±2.8. The women used no hormonal contraceptives or other medicines influencing the production of steroid hormones, and were non-smokers. Before enrollment in the study, all signed informed consent that was approved by the local ethical committee of the Institute of Endocrinology.

Intervention. Fasting blood samples were taken in the morning between 7 and 8 am. The first sampling was done at the start of the menstrual cycle (1st or 2nd day). Subsequent samples were taken at regular intervals every three days, for a total of 10 samples taken during the study.

Main outcome measures. During the MC we found increased levels of testosterone, estradiol, progesterone, and 17-hydroxyprogesterone during ovulation. SHBG gradually increased after ovulation. There was a significant decrease in resistin levels during ovulation, followed by an increase in the latter part of the cycle. Adipsin showed a notable increase during ovulation, but this increase was not statistically significant.

Results. Classical changes in gonadotropins, estrogens and progesterone during the menstrual cycle are accompanied by less striking but significant changes in 17-hydroxyprogesterone and testosterone. No significant changes show dehydroepiandrosterone and its 7-oxygenated metabolites. Adipokines show a tendency to increase during ovulation, while ghrelin and resistin decrease. There is also a remarkable association of sex hormone binging globuline (SHBG) on the day of the cycle.

Conclusions. Our results demonstrate that changes to adipokines during the menstrual cycle are not substantial. Differing leptin levels are characteristic for premenstrual syndrome. Precise descriptions of physiological changes in healthy women are important in helping us understand the significance of the changes accompanying various pathological states.

Introduction. Obesity is a chronic disease with a great impact on the cardiovascular system through its association with type II diabetes, hypertension, dyslipidemia, metabolic syndrome (MetS) and also through direct alterations in cardiac performance and morphology. Recent long term studies prove that substantial weight loss obtained via bariatric surgery is capable of improving cardiac risk factors associated with severe obesity, decreasing the mortality rates.

Aim: to assess the long-term changes in cardiovascular risk and cardiac structure in obese patients who had lost weight after laparoscopic sleeve gastrectomy (LSG).

Methods. Fifty-two severe obese patients (44±9 years, 57.7% women, BMI=45±8 kg/m2) underwent clinical and biochemical examination and Doppler echocardiograms before and 5 years after LSG.

Results. Pre-operatively, 78.4% of patients were hypertensive, 46.2% had diabetes, 73.1% MetS and 44.2% presented left ventricle hypertrophy (LVH), reflecting high cardio-metabolic risk. The patients reassessment was made 61.7±10.5 months after LSG, when a decrease in BMI of 21.9±10% was achieved (p<0.001). The prevalence of hypertension (64.7%), diabetes (32.7%) and MetS (28.8%) decreased compared to the pre-operative examination (p=0.019, p<0.001, p=0.036). An increase in left ventricle mass and left ventricle mass index (LVMI) (p<0.001) and in the prevalence of LVH (57.7%-p=0.001) was recorded. Patients were divided into two groups based on the decrease in LVMI (positive response-38.5%) or increase in LVMI post-surgery (negative response-61.5%), compared with pre-operative values. The group of patients with negative response had lost less weight (p=0.006), had a poor glycemic control (p=0.022), and higher systolic (p=0.004) and diastolic (p=0.030) pressure values compared to the first evaluation.

Conclusion. The increase of LVMI after LSG indicates that this study should continue, including a larger number of patients. It is important to identify the factors that can predict an inappropriate response to surgery, in order to prevent and treat them.

Background. The abdominal obesity is associated with a low-grade chronic inflammatory status, to which the complement system is an important contributor. Recent studies documented the close association between modified low-density lipoproteins (mLDL) and the increase of C3 production in human macrophages. In several reports, C3 and the degree of C3 activation (C3a and C3a-desArg) have been linked to diabetes and cardiovascular disease (CVD). However the studies of C3-convertase functional activity haven’t been taken yet.

Aim: to evaluate a potential association between mLDL level and C3-convertase stabilization of the classical pathway of complement system activation in middle-aged individuals with abdominal obesity at low cardiovascular risk.

Patients and methods. A pilot study, including 45 patients without evidence of atherosclerosis at low CVD risk in the next 10 years according to SCORE, was designed. Abdominal obesity was detected according to the IDF criteria (2009). All patients underwent a comprehensive clinical evaluation with lipid profile and glucose analyzes. The level of mLDL (U) and the C3-convertase functional activity (%) - a key enzyme complex of the classical pathway complement activation, were assessed by using original techniques. Receiving data have been analyzed and compared in the total sample and separately among patients with abdominal obesity.

Results. Analysis included 45 participants (mean age: 41(9) years; body mass index: 27(5) kg/m²; and 47% male). Mean lipid values were as follows: total cholesterol: 5.4 (1) mmol/l; LDL-C: 3.8 (1) mmol/l; HDL-C: 0.98 (0.3) mmol/l; triglycerides 2.5 (1.5–2.1) mmol/l. 27 (60%) participants of the sample had signs of abdominal obesity. Among them 41 % (11) with overweight, 44 % (12) with obesity. There were found significant differences in the mLDL level of patients with abdominal obesity and without it (p< 0,01). The median of mLDL level of patients with abdominal obesity was 15.25 U (12.3 – 24.6), while the median of mLDL level of patients without abdominal obesity was 9 U (5.7 – 12.4). Plasma mLDL levels were associated with smoking and triglycerides (Spearman up to 0.6, p<0.05), independently of low-density lipoprotein-cholesterol and other variables. The activity of stabilized C3-convertase was high (mean 18.5 (7.6)%) in the majority of patients (82%), independently of BMI, waist circumference, blood pressure, levels of TG, LDL-C, HDL-C and mLDL-C. No significant correlation between C3-convertase activity and lipoprotein fractions was found.

Conclusion. Our findings underscore the role of mLDL in early atherosclerosis among the asymptomatic middle-age sample with abdominal obesity at low risk of CVD. The observed fact of stabilization of C3 convertase, apparently, can serve as a predictor of the autoimmune nature of abdominal obesity. One product of the enhanced C3 cleavage is C3a-desArg, which is a hormone that stimulates the acylation and triglyceride synthesis. The association between lipid homeostasis, obesity and innate immune system need to be studied in larger samples.

Adipocytes exposed to high glucose concentrations exhibit impaired insulin signaling. Binding of insulin to its membrane receptor activates insulin metabolic pathway leading to IRS-1 and AKT phosphorylations. The accumulation of visceral adipose tissue (VAT) correlates with insulin resistance and metabolic syndrome. Anthocyanins (ACN) are bioactive food compounds of great nutritional interest. We have shown that protocatechuic acid (PCA), a major metabolite of ACN, might exert insulin-sensitizer activities in human visceral adipose tissue. The aim of this work was to define the protective role of PCA against insulin-resistance induced by high glucose in VAT.

Methodology: VAT obtained from control subject (BMI≤25) were separated in four experimental groups: i) PCA: samples treated for 24 h with 100 μM PCA, ii) GLU: VAT treated with 30 mM glucose for 24 h, iii) PCA+GLU: 1 hour incubation with 100 μM PCA before adding glucose (30 mM, 24 h), iv) CTR: vehicle. After treatment, VAT groups were (or not) acutely stimulated with insulin (20 nM, 20 min). Tyr-IRS-1 and Ser-Akt phosphorylations were assessed by Western blotting (WB) in basal or insulin stimulated tissues in all experimental groups. Samples were assessed for IRS-1, IR, Akt and GLUT4 protein content by WB.

Results: No differences in protein contents between experimental groups were found. GLU tissues showed a lower increment in insulin-stimulated phosphorylation of IRS-1 and Akt compared to CTR and PCA samples. This impaired activation was completely reversed by the pretreatment with PCA.

Conclusion: An in-vitro insulin-resistance condition induced by high glucose was established in biopsies of VAT. PCA restores the ability of GLU-tissues to fully respond to insulin by increasing IRS-1 and Akt phosphorylations. These results confirm the insulin-sensitizer effect of PCA on VAT previously reported by our group. An anthocyanin rich diet might help to protect against insulin-resistance in VAT.

Introduction. The diagnosis of non-HIV lipodystrophies is challenging, especially since borderline forms with type 2 diabetes have been described (Strickland Diabetes Care 2013).

Aim: to identify the most specific anthropometric and biological parameters enabling to differentiate lipodystrophic from obese and control subjects.

Methods. This prospective study (clin.gov 2009-AO-1169-48) included 94 patients divided in 3 groups adjusted for age and gender: 52 lipodystrophic patients (among whom 16LMNA–mutated lipodystrophies (LDM),16non-LMNAmutated partial lipodystrophies (LDNM), and 20 other types of lipodystrophies), 28 obese (O; 12 diabetic (OD) and 16 non-diabetic (OND)) and 14 normal-weighed healthy subjects (C). The anthropometric (DEXA, MRI) characteristics and leptin levels of the patients were recorded. Three ratios were calculated to assess the respective part of fat and lean mass (FM/LM), intra- and whole abdominal fat (IAF/WAF) and adipose tissue function (leptin/WAF).

Results. The three groups differed by the FM, LM, IAF, WAF, leptinemia, trunk FM/LM (P<0.0001), IAF/WAF (P<0.001) and leptin/WAF (P<0.01). The main distinctive feature of LDM compared to C was IAF (188±38vs 82±23 cc;P<0.01) whereas BMI, FM, LM, WAF and leptinemia were similar. The ratios ranges of the five subgroups were as follows: IAF/WAF: 0.5 in LDMvs0.3 in all other subgroups; trunk FM/LM: 0.2 in LDM and C, increased from 0.5 to 0.7 and 0.8 respectively in LDNM, OD, OND); leptin/WAF: decreased to 2.3 and 1.6 in respectively LDM and LDNM compared to C (2.7), and increased in OD (3.7) and OND (5.6).

Conclusion. Increased intra/whole abdominal fat ratio, hypoleptinemia and preserved fat/lean mass ratio characterized lipodystrophic laminopathies, in contrast with obese people who showed an increased fat/muscle mass, hyperleptinemia and preserved intra/whole abdominal fat ratio. Non-mutated lipodystrophic patients were intermediate, with decreased leptin/WAF ratio, close to LDM, and increased IAF/WAF and FM/LM ratios close to the obese population.

During the menopausal transition, women experience a number of symptoms due to declining estrogen levels, including vasomotor symptoms and vulvar and vaginal atrophy (VVA). Unlike vasomotor symptoms, vaginal dryness and dyspareunia, the main symptoms of VVA, typically worsen without treatment and can significantly impact the quality of life. Up to 60% of postmenopausal women may be affected by VVA, but many women unfortunately do not seek treatment due to embarrassment, cardiovascular and oncologic risk factor, or other factors. Therefore, local estrogen treatment is still controversial due to the systemic absorption of estradiol and its potential effects on the breast and endometrium.

The fact that up to 26% of women using systemic hormonal therapy continue to experience symptoms of urogenital atrophy is sufficient reason to justify not recommending systemic hormonal therapy in women with vaginal symptoms only; many women initially require a combination of systemic and local estrogen therapy, especially when it is used at low doses.

Intravaginal application of DHEA as an alternative treatment compared to local estrogen therapy. Intravaginal DHEA does not increase serum E2 levels and may be a better option for long term treatment of VVA as there is no increase in serum E2 levels with DHEA. Previous data have shown that intravaginal dehydroepiandrosterone (DHEA, prasterone) improved all the domains of sexual function, an effect most likely related to the local formation of androgens from DHEA.

As the first non-hormonal alternative to estrogen-based products for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a non-steroidal estrogen receptor agonist/antagonist, also known as a selective estrogen receptor modulator (SERM), which seems to be effective in genitourinary symptoms.

There is now a new alternative to systemic hormone therapy with estrogen/gestagens. The tissue-selective estrogen complex (TSEC) which combines a SERM (bazedoxifene, BZA) with conjugated equine estrogens (CEE) is designed not only to improve menopausal symptoms but to prevent osteoporosis, while maintaining the benefits of estrogen therapy on vasomotor symptoms and vulvovaginal atrophy, but antagonizing stimulatory effects on the endometrium and mammary gland. The two studied doses of BZA/CEE (20 mg BZA + 0.425 mg CEE and 20 mg BZA + 0.625 mg CEE) have been shown to improve the percentage of superficial cells, reducing the percentage of basal cells. Thus, 20 mg BZA + 0.625 mg CEE reduces the severity of symptoms caused by atrophic vulvovaginitis by 56% and normalizes vaginal histology and pH. This efficacy persists for 2 years.

Here we aim to evaluate current experimental and actual clinical strategies to achieve the main therapeutic goal for genitourinary syndrome and VVA in menopause which is the relief of symptoms, a better quality of life and women’ s health in menopausal women not eligible for Hormonal Replacement Therapy (HRT).

Background. Prostacyclin (PGI2) of luteal origin is involved in the control of corpus luteum (CL) development and function in cattle. PGI2 may regulate the process of angiogenesis and may stimulate progesterone (P4) secretion by luteal cells via its specific receptors, PTGIR. In contrast to cattle, the role of PGI2 in the pig CL has not yet been described.

Aim. The present study aimed to investigate the effect of PGI2 on 1) P4 secretion by luteal cells, and 2) the expression of angiogenesis-related genes in endothelial cells of the porcine CL.

Methods. CL collected from gilts on day 5-7 of the estrous cycle were used for enzymatic isolation of luteal (Experiment 1) and endothelial (Experiment 2) cells. In Exp. 1, cultured luteal cells were incubated with increasing (0, 0.01, 0.1, 1, 5 µM) doses of PGI2 analogues: iloprost (ILO) and carbaprostacyclin (cPGI2) for 8 h. To determine the effective doses of PGI2 analogues, P4 concentration in culture medium was examined by RIA. Thereafter, luteal cells were treated with ILO and cPGI2 at the concentration of 1 and 5 µM in the presence or absence of PTGIR antagonist (CAY10441). After 8 h of incubation the medium was collected for P4 determination. In Exp. 2, isolated endothelial cells were treated for 24 h with ILO and cPGI2 at doses of 1 and 5 µM. Then, cells were collected for analysis of Ang-1 and -2 mRNA expression using qPCR.

Results. Both, ILO and cPGI2 affected P4 secretion by luteal cells. Elevated levels of P4 were observed in medium after treatment of luteal cells with 1 µM of ILO and 0.1, 1 and 5 µM of cPGI2 compared with control values (p<0.05). The addition of CAY10441 inhibited the stimulatory effect of ILO on P4 secretion, while did not change P4 production by luteal cells incubated with cPGI2. Moreover, PGI2 analogues differentially affected (p<0.05) the expression of proangiogenic factors. ILO stimulated Ang-2, whereas cPGI2 positively affected Ang-1 mRNA expression in endothelial cells at concentrations of 1 µM and 5 µM, respectively.

Conclusion. PGI2 affects P4 secretion during luteal phase of the estrous cycle and may regulate the process of angiogenesis in the porcine CL.

Obestatin, an anorexigenic peptide acting at the central nervous system and on the periperial level, can co-create neuroendocrine network, which modulate the gonadotrophic axis activity. The aim of this study was to investigate the role of intracerebroventricular obestatin infusion on the activity of the gonadoliberine (GnRH) neurons activity.

The experiment was performed on peripubertal Polish Merino sheep (n=24). Animals were divided into 2 groups: control (Ringer-Lock solution infusions; n=12) and experimental (obestatin infusion, 25μl/120μl/h; n=12). Infusions were performed over three consecutive days; blood samples were collected on day 0 and day 3. After the experiment, the animals were slaughtered, and the chosen brain tissue was preserved for IHC and Real Time RT-qPCR analysis.

It was also shown that exogenous obestatin changes the selected gene expression of GnRH pulse generator, decreases the secretory activity of GnRH neurons, resulting from the inhibition of GnRH release from median eminence terminal nerves, and also decreases the GnRH receptor gene expression in pituitary. On the basis of the obtained results it can be concluded that obestatin may be involved in the modulation of reproduction processes in animals at the level of the central nervous system. However, the mechanism of its action requires further research, especially identifying the obestatin receptor itself.

Background. Our recent results showed that tumor supressor miR-30a is firmly downregulated in Thyroid carcinomas. On the other hand, recent studies showed RNA- and DNA- binding proteins LIN28B and HMGA2 induce EMT, thus playing an important role in dedifferentiation and cancer malignification. Finally, latterly several authors agreed on the importance of a robust activation of PI3K for thyroid cancer emergency and progression.

Aim: to study the link between the emergency of LIN28B and HMGA2, miR-30a silencing and PI3K hyperactivation, and to determine their effect on thyroid cancer progression.

Methors. MiRNA targets computational predictions were performed with MiRanda algorythm. LIN28B and miR-30a expression vectors were transfected in ATC derived and normal thyroid cell lines; mRNA and protein levels were determined by qPCR, Luciferase and Western Blot. Invasion, proliferation and cell cycle assays were performed in Transwell, cell counter, and FACScan respectively.

Results. MiRanda algorythm identified multiple miR30a recognition elements in all LIN28B, HMGA2 and PI3K effectors. LIN28B expression correlated with PI3K activating mutations in ATC derived cell lines. Overexpression of miR30a resulted in LIN28B, HMGA2, and several PI3K effectors silencing, and in an increase in p27(Kip) protein levels. Inversely, LIN28B overexpressing cells showed a decrease in miR30a levels and an increased expression of HMGA2 and PI3K effectors. The general outcome was a significant decrease in invasion and proliferation in miR-30a overexpressing cells and, conversely, an increase in these parameters by LIN28B.

Conclusions. These data suggest the existence of a PI3K regulated feedback with a double-negative loop between miR-30a and LIN28B. Here, PI3K activation acts to switch the steady states. Initially, high miR-30a levels repress LIN28B expression. After PI3K is activated, LIN28B is produced and miR-30a is repressed. This state reinforces PI3K hyperactivation. Thus, the feedback implements a tumoral gene expression shift, contributing to thyroid cancer progression.

Background. TAZ/WWTR1 (transcriptional coactivator with a PDZ-binding domain) is a transcriptional cofactor involved in the Hippo Signalling pathway, which is described to have a key role in the control of cell proliferation, apoptosis, the inhibition of cell-cell contact, stem cell self-renewal and tissue regeneration. TAZ has been reported to regulate these processes through the transactivation of transcription factors in the nucleus, where it has also been shown to interact with Smad2/3-Smad4 complexes favouring nuclear accumulation under TGFβ stimulation. TAZ co-activates Pax8, a master gene of thyroid differentiation, within the thyroglobulin promoter. Furthermore, Pax8 is the main positive regulator of sodium iodide symporter (NIS) expression and it has been reported to interact with Smad3 causing NIS transcriptional repression mediated by TGFβ.

Aim. Therefore, the aim of this work was to study the involvement of TAZ in the expression of NIS, since it is an important protein not only for the correct function of the thyroid gland, but also for radioiodide treatment in thyroid cancer.

Methods and Results. Strikingly, we observed that TAZ negatively regulates the transcriptional activity of Pax8 within the NIS promoter. Furthermore, we provided evidence that TAZ could play an important role in the downregulation of NIS expression by TGFβ; we detected that TAZ protein is mainly located in the nucleus under treatment with this cytokine and its silencing induces a partial recovery of NIS protein and mRNA levels. Our results also demonstrated an increased expression of TAZ in thyroid carcinoma cell lines, in which NIS levels are typically decreased. Specifically, TAZ nuclear translocation is increased in those thyroid carcinoma cells with mutated BRAFV600E or when this oncogene is conditionally activated. Since we have described that this mutation increases the secretion of TGFβ, this could be connected with the decreased levels of NIS in these cells.

Conclusion. This study has shed light on the important role of the Hippo pathway in the regulation of NIS expression in thyroid cells, repressing Pax8 activity and impaired thyroid differentiation. Given that this protein has been identified to be overexpressed in thyroid carcinoma, future research of the role of TAZ in thyroid tumorogenesis will enable development of new strategies to treat thyroid cancer.

Thyroid carcinoma is the most common endocrine malignancy, and its incidence is rapidly rising in the world. Its initiation and progression involves multiple genetic and epigenetic alterations whereby BRAF and RAS mutations lead to the activation of the ERK signaling pathway. Recently, significant advances have been accomplished by developing pharmacological agents directed against the kinases of the RAS-ERK pathway. However, most of the molecules tested have undesired side effects and promote drug resistance. Consequently, it is imperative to find alternative RAS-ERK pathway inhibitors. It has been shown that by inhibiting ERKs dimerization it is possible to suppress tumor progression. DEL22379, a small molecule inhibitor for ERK dimerization, has been identified to impede the growth of melanoma tumor cells driven by RAS-ERK pathway oncogenes, without affecting ERK phosphorylation (Cancer Cell 28:17082 2015). The aim of this work is to study the role played by ERK dimerization and its inhibition using DEL22379 in thyroid cancer progression. We have used an in vitro model of thyroid tumor cells harboring oncogenic drivers (RAS or BRAF) to complete viability, migration and invasion assays as well as an orthotopic mouse model with anaplastic cells as an in vivo model. We observed that in BRAF mutated cells, ERK dimer formation is sustained for longer compared to the RAS mutated or control cells, resulting in the altered activation of the effected signaling pathway. RAS mutated cells are resistant to DEL22379 in vitro, while BRAF mutated cells are not able to form ERK dimers upon inhibitor addition. Consequently, these cells lose their invasive and migratory potential as well as displaying low viability. Preliminary results suggest DEL22379 treatment inhibits tumor growth in orthotopic mice. These results describe a new molecule that could be effectively used as a therapy in thyroid cancers harboring BRAF or RAS mutated genes. We have observed it is able to partially revert the tumorigenic phenotype, which may result in an improved prognosis in thyroid cancer patients.

Background. From 2005 to 2015 routine calcitonin (CT) screening was performed in our department in all patients with multinodular goiter (MNG) using the same assay.

Aim. We investigated possible associations between unstimulated serum CT levels and the presence of either thyroid autoimmunity (AITD) or thyroid neoplasia.

Methods. This is a retrospective study of 648 patients (559 female [F] 86.3%, 89 male [M] 13.7%, age range 18-89, median 58 years,). CT≤4.6 pg/ml [F] and ≤11.5 pg/ml [M] was defined as normal. Patients were stratified into 4 groups according to CT. Group1: CT<0.05 (undetectable), Group2: CT [F&M] within normal range, Group3: CT:4.7-10 [F] & 11.6-20 [M], Group4: CT>10 [F] & >20 [M]. Furthermore patients were subcategorized in those with Autoimmune Thyroid Disease (AITD) and those without (non-AITD).

Results. The distribution of patients was: Group1: n=186 (28.7%), Group2: n=422 (65.1%), Group3: n=29 (4.5%), Group4: n=11 (1.7%). Of the patients with AITD history 23.4% belonged to Group1, 68.6% to Group2, 6.4% to Group3 and 1.6% to Group4 (x2, p=0.037). Forty seven patients (7.3%) underwent total thyroidectomy. Histopathological examination revealed: Medullary Thyroid Carcinoma (MTC) n=3 (3/3 Group4), C-Cell Hyperplasia (CCH) n=5 (3/5 Group3, 2/5 Group4), Papillary Thyroid Carcinoma (PTC) n=17 (7/17 Group1, 10/17 Group2), MNG n=22 (8/22 Group1, 10/22 Group2, 2/22 Group3, 2/22 Group4). 2/5 patients with CCH had PTC. 1/17 PTC patient had mixed PTC-MTC. Patients with MTC had remarkably higher CT levels (253-1222 pg/ml) compared to those with CCH (5.8-16.1 pg/ml).

Conclusions. This study reaffirms the positive correlation between CT levels and the presence of MTC or CCH, clearly and conspicuously distinguished by the range of CT levels, albeit in a small number of patients with these diagnoses. Patients with AITD have more frequently detectable or slightly increased CT levels.

Background. Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder affecting the retroorbital tissues. Although the role of TRAb in GO is now accepted by many researchers and clinicians, their use in the disease management of GO is less well studied than the role of TRAb for the diagnosis and therapy monitoring of Graves’ disease.

Aim: to evaluate the relation between TRAb level and the activity of GO, the course of GO and the effectiveness of the treatment.

Materials and methods. We have studied 26 patients with GO and Grave’s Disease. Activity of GO was measured with the clinical activity score (CAS), we defined active GO as a CAS≥3. TSH, FT4 and TRAb were evaluated. All patients had received intravenous methylprednisolone (ivMP) pulse therapy in cumulative dose 6000 mg. We observed patients for 1 year after pulse therapy. TRAb level was evaluated before, 3, 6 and 12 months after pulse therapy.

Results: At the time of initial treatment all patients had active GO, 60% with CAS 3-4 and 40% with CAS 5-7. On year after the pulse therapy of GO, all patients were classified into responders (69,2%) and non-responders (30,8%) according to their clinical manifestations. Pulse therapy considered as effective if GO activity decreased with CAS ≤ 2. Serum TRAb level was significantly higher in patients who non-responded to therapy – 34,8 U/L vs 17,5 U/L (p≤0,01). This level was significantly decreased in patients responded to treatment – 1,6 U/L vs 12,4 U/L (p≤0,01). TRAb level above 28,8 U/L before treatment (p≤0,01), 10,1 U/L after 3 months of treatment (p≤0,01), 5,1 U/L after 6 months of treatment (p≤0,01) and 8,2 U/L after 3 months of treatment (p≤0.01) was associated with higher risk of non-responding.

Conclusion: We conclude, that TRAb level may serve not only as predictor of GO activity and severity, but changes in the level of antibodies could be of additional help for the disease management with ivMP.

Introduction. While thyroid nodules are extremely pervasive, the chances that a nodule is malignant are small. The annual incidence of thyroid carcinoma is 0,5-10 per 100000. A hefty 75-80% of all thyroid carcinoma cases are papillary thyroid carcinoma, which is referred to as differentiated thyroid carcinoma.

Relevancy. Papillary thyroid carcinoma is the most common thyroid carcinoma. Peak onset ages are from 40 to 60 years old. Furthermore the increasing incidence has been observed among younger people. With the discovery of a thyroid nodule, a complete history and physical examination focusing on the thyroid gland should be performed.

Aim: to determine papillary carcinoma’s background pathology, proceed the ubiquitous approach of thyroid nodule’s diagnosis, dynamic control and treatment.

Material and Methods. This study covered the period of 2010-2014. 183 patients attending Erebuni medical center’s General and Endocrine Surgery Department were included in this analysis. Postoperative pathohistological examination has authenticated the diagnosis: papillary thyroid carcinoma. The study has not included the patients who underwent only preoperative cytological examination without postoperative pathohistological diagnosis and the patients who underwent surgical treatment for the relapse.

Results. In a massive 53,6%(98) of 183 observed patients' papillary thyroid carcinoma has occurred de novo. However 46,4%(85) has had background pathology such as Hashimoto's thyroiditis(18,6%(34)) and Adenomatoid hyperplasia (27,8%(51)). A major 59,6%(109) has been above 40 years old, the other 40,4% has been under 40.

Conclusion. To sum up there might be a possible connection between papillary carcinoma, Hashimoto's thyroiditis and Adenomatoid hyperplasia. We suggest ultrasound follow-up and double cytological examination(if the previous one is mistrustful) among patients who have Hashimoto's thyroiditis(ultrasound examination confirmation, high level of antibodies) and Adenomatoid hyperplasia( cytological examination confirmation).

Aim: to examine prognostic significance of patient-related, tumor-related and treatment-related factors for intrathyroidal papillary thyroid carcinomas (PTC), via multivariate analysis.

Material and methods. This study included 153 patients with intrathyroidal PTCs (pT1/pT2/pT3) surgically treated in our Institution during two-decade period. Patients with locally invasive tumors (pT4) and initial distant metastases (M1) were excluded. Parameters of interest were: gender (male; female), age (<=45; >45 years), tumor size (pTNM classification WHO 1984), multifocality (no; yes), histological type of PTC (pure; microcarcinoma; follicular; poorly differentiated), presence of lymphonodal metastases (pN1a; ipsilateral-pN1b; contralateral-pN1b; total), surgery extent (total thyroidectomy; total thyroidectomy with lymphonodal dissections). Univariate and multivariate analysis of all parameters was performed in order to distinguish factors of significance for disease-free survival (DFS) and cancer-specific overall survival (cs-OS).

Results. In the follow-up, 10% of patients had locoregional or distant relapse, while 5.2% died due to PTC. Univariate analysis distinguished older age, male gender, tumors over 4cm in diameter, multifocality and poorly differentiated PTC-types as unfavorable prognostic factors for cs-OS. DFS was significantly shorter in males vs. females, as well as in patients with multifocal vs. solitary PTC. Tumor multifocality was unfavorable prognostic factor for both DFS and cs-OS. Independent prognostic factors for intrathyroidal PTCs, based on Cox multivariate analysis, were multifocality and gender for DFS, and multifocality and age at diagnosis for cs-OS.

Conclusions. Prognostic factors define risk groups within population of differentiated PTCs providing timely, adequate treatment and opportunity for longer quality life of patients with PTCs.

Introduction. Graves' ophthalmopathy (GO) also known as thyroid-associated orbitopathy (TAO), is an autoimmune disorder of the retrobulbar tissue, closely linked to autoimmune thyroid disease. Less than 5-10% patients with Graves' disease will develop clinically relevant, active and progressive orbital complications. Treatment of this disease is difficult and often unsatisfactory. Glucocorticoids have been used for treatment of GO because of their anti-inflammatory and immunosuppressive actions during the active phase of GO.

Case Report. In June 2013, 57 years old female patient referred to our clinic with complains of: heat intolerance, weight loss, fatigue, tachycardia, high blood pressure - classical picture of thyrotoxicosis. In 2006 subtotal resection of thyroid gland for Grave`s disease was performed. Laboratory studies revealed: TSH-0.01 (N=0.4-4.0µIU/ml); FT4-2.68 (N=0.89-1.76ng/dl); Hematology-leukocytes 4.7 (N=5.2-12.4µL); ESR-14(N=2-15); Thyroid ultrasound showed two nodules in the left lobe: 7X8X11mm, 8X8X8mm. Thyroid scintigraphy with TC-99m excluded hot and cold nodules. Anti-THS-Rec.-2.45 (N=<2.0 LU/L). The patient was given Thiamazole 30mg/day, Propranolol 10mg/day, Prednisolone 15mg/day. After six weeks of treatment the patient’s general condition was significantly improved: FT4-0.96; The dose of Thiamazole was decreased till 10mg/day, Propranolol 5mg/day, Prednisolone withheld. After 4 months the patient attended our clinic with complains of: lacrimation and duality, pain and exophthalmos of left eye. Thyroid function was within normal range. In order to exclude tumor, MRI of the head was performed- the tumor was excluded. Graves' ophthalmopathy was diagnosed. Pulse therapy was begun with Intravenous Methylprednisolone infusion according the following scheme: 1st week 1000mg once a day during 3 days, then 500 mg weekly for 3 weeks and 250 mg weekly for 3 weeks. After that the same infusion once in ten days – (total 4 infusion). Methylprednisolone 4mg 4tab. 3 times a day and Panangin 2tab. two times a day was given per-os. Glucose levels were monitored, it was always normal. After 14 weeks of pulse therapy optimized visual acuity and improvement of soft-tissue inflammatory signs and symptoms were evident.

Conclusion. High-dose of i/v steroid therapy provides efficient and stable improvement in Graves' ophthalmopathy

Background. Acromegaly is a rare serious condition characterized by chronic hypersecretion of growth hormone (GH) from a pituitary adenoma and induces the synthesis of insulin-like growth factor I (IGF-1). The idea of the crucial GH importance not only in the control of cell proliferation and differentiation, but, also, in the regulation of immune cells metabolism allows to think that chronic excess GH/IGF-I in acromegaly is the potent effector distortion of the immune response mechanisms.

Aim. To study the NAD(P)-dependent dehydrogenases level in blood lymphocytes and their interaction with GH/IGF-1 concentration in patients with active acromegaly.

Methods. The level of NAD(P)-dependent dehydrogenases in blood lymphocytes was studied in a group of 88 patients with active acromegaly, mean age 51.0±12.5 years. The NAD(P)-dependent dehydrogenases activity was determined by biochemiluminescence method. The concentrations of GH and IGF-1 were measured by ELISA.

Results. Studying the activity of mitochondrial NAD(P)-dependent dehydrogenases found a decrease in all NAD-dependent oxidoreductase: NADIDH, NADGDH, and MDH (P<0.01), which allows to state the low level flow in the tricarboxylic acid cycle. In active acromegaly were revealed the decreasing activity of all studied oxidoreductases: glucose-6-phosphate dehydrogenase (P<0.01), NAD–lactate dehydrogenase (LDH) (P<0.001), NADH–LDH (P<0.001), NAD–malate dehydrogenase (MDH) (P<0.001), NADH–MDH (P<0.001), NADP–MDH (P<0.001), NAD–glutamate dehydrogenases (GDH) and NADH–GDH (P<0.001), NADP–GDH and NADPH–GDH (P<0.001), NAD–isocitrate dehydrogenases (IDH) and NADP–IDH (P<0.01 and P<0.001 respectively), and, also, glutathione reductase (P<0.001). Our data observed that decreasing activity of NADP–GDH positively correlated with the basal GH level (r=+0.23, P=0.04) and NADP–MDH activity with IGF-1 level (r=+0.30, P=0.008). The low NADH–MDH activity negatively correlated to the basal GH concentration (r=−0.23, P=0.04).

Conclusion. The chronic excess of GH/IGF-1 causes a significant depletion of metabolic lymphocytes reserves and may play an important role in several systems malignancies of acromegaly patients. This pathway continues to attract interest as a potentially useful target for therapeutic design of acromegaly.

Introduction. Previous studies demonstrated a relationship between T1- and T2-weighted signal intensity and tumor growth patterns and potential as well as hormonal activity in somatotropinomas. Further investigation of these findings could serve to define predictive diagnostic and treatment factors based on MRI characteristics.

newly diagnosed patients with acromegaly and to compare them with the corresponding morphological and biochemical characteristics.

Methods. Seventy five patients with newly acromegaly were included in the study. Pre-treatment T1- and T2-weighted MR-images of all patients were analyzed, taking into account the intensity of the signals produced by the tumors, as well as their dimensions and growth direction. Growth hormone and IGF-1 levels were also recorded.

Results. Out of 75 patients, 74.7% were macroadenomas. T1-weighted adenoma signal was hypointense in 45.3% of patients, hyperintense in 18.7% of patients and isointense in all other cases. T2-weighted adenoma signal was hypointense in 32.3% and hyperintense in 40.5% of patients. No statistically significant differences were found between GH and IGF1 levels as well as signal intensity in relation to patient age. Inferior tumor extension was present in 60.0% of patients overall and 33.3% more prevalent in patients with hyperintense T2 signal and 24.5% and 11.7% more prevalent in patients with hypointense and hyperintense T1 signal respectively. Superior extension was observed in 46.7% of patients and did not differ significantly from inferior extension in patients with hypointense T2 signal. The highest levels of IGF1 were associated with superior extension, while the highest levels of GH were associated with inferior extension. Mean adenoma volume was 8.45 times higher and GH levels were 3.8 times higher in patients with hyperintense T2-weighted signal and 2.3 and 1.3 times higher respectively in patients with hyperintense T1-weighted signal.

Conclusion. Hyperintense T1- and T2-weighted MRI signal was associated with larger tumor dimensions, increased GH levels and more frequent inferior extension, all of which indicate higher proliferative potential of the adenomas.

Background. Craniopharyngiomas (CF) - a benign tumor of the embryologic origin. The surgical method of treatment is basic.

Aim: to estimate dynamics of endocrine disorders before and after surgical treatment of CF at different topographical variations.

Results. In group 1: panhypopituitarism -2 (100%), diabetes insipidus (DI) – 0. Both patients had subtotal ablation. After the surgery the nature of disturbance has not changed. In group 2: secondary hypoadrenalism - 9 (60%), hypothyroidism - 11 (73%), hypogonadism - 12 (80%), DI - 7 (46%), hyperprolactinemia - 9 (60%). After the surgery panhypopituitarism - 15 (100%), DI - 14 (93%), hyperprolactinemia - 4 (26 %). In group 3: secondary hypoadrenalism - 3 (30%), hypothyroidism - 6 (60%), hypogonadism - 6 (60%), DI - 2 (20%), hyperprolactinemia - 3 (30%). After the surgery panhypopituitarism - 10 (100%), DI - 10 (100%), hyperprolactinemia - 3 (30 %). In group 4: secondary hypoadrenalism - 6 (40%), hypothyroidism - 9 (60%), hypogonadism - 12 (80%), DI - 5 (33%), hyperprolactinemia - 8 (53%). After the surgery panhypopituitarism - 10 (71%), secondary hypoadrenalism - 12 (85%), hypothyroidism - 13 (92%), hypogonadism - 11 (79%), DI - 11 (78%), hyperprolactinemia - 8 (53%).

Conclusion. The high incidence of endocrine disorders is caused by the localization of the CF with predominance of secondary hypogonadism and hypothyroidism. After the surgery worsening hormone deficiency was mentioned, also while preserving the pituitary stalk. Non-radical ablation of ventricular CF can partially maintain endocrine function.

Background. Endocrine consequences such as growth hormone deficiency (GHD), growth disturbances and metabolic disorders are common in childhood cancer survivors.

Aim: to evaluate and compare the prevalence of growth disturbances and metabolic disorders in childhood posterior cranial fossa tumors (cPCFT) and acute lymphoblastic leukemia (cALL) survivors.

Materials and methods. 40 subjects (21 men, 19 women) who had undergone treatment for cPCFT (group 1) and 25 subjects (9 men, 16 women) after treatment for cALL (group 2) were assessed. Group 1 underwent surgery, chemotherapy (CT) and craniospinal irradiation in a dose of 34.9 ± 1.6 Gy with a boost to the PCF 51.3 ± 9.2 Gy. Group 2 underwent CT (23 subjects were treated with ALL-BFM-90 protocol; 2 subjects were treated with ALL-MB-2002 protocol). All subjects of the group 2 received cranial irradiation in a dose 12,7±2 Gy. Age at the time of the survey in a group 1 and 2 – 19.8 ± 3.05 and 21.2±3.9 years; age at the time of treatment – 10.9 ± 3.4 and 6.9±3.4 years; follow-up – 7.2 ± 4.2 and 13.8±4.9 years, respectively. 16 age and sex matched healthy controls were included. Patient’s anthropometric and laboratory parameters were measured, GHD was diagnosed in group 1 by 2 tests – insulin tolerance test (ITT) and glucagon stimulation test (GST). In group 2 these tests didn't perform. At the time of the survey no one in both groups received GH replacement therapy. Only 5 subjects (3 boys and 2 girls) in group 1 were treated with recombinant human GH during childhood.

Conclusions. After treatment for cPCFT growth disturbances occurred more often than after cALL therapy. Metabolic disorders were diagnosed with different frequency in both cPCFT and cALL survivors. These patients need endocrinologist’ observation.

Introduction. Pituitary adenomas are the most frequent intracranial tumors. Surgical excision is the primary approach for these tumors, except for prolactinomas, and secondary hypopituitarism is its main complication.

Aim: to assess the prevalence of postoperative hypopituitarism and analyze the risk factors involved in its development.

Materials and methods. Ambispective multicenter observational study. Data were collected from The Molecular Registry of Pituitary Adenomas (REMAH). Univariate and multivariate analysis were performed in 128 patients with histologically confirmed adenomas who underwent transsphenoidal surgery between 2009 and 2015 in hospitals from Madrid, with more than one-month follow-up.

Results. Postoperative hypopituitarism was found in 73.9% of cases (28.4% of new onset). Combined pituitary deficiency was the most frequently observed (46.3%), and hypoadrenalism the most frequent single postsurgical deficit (63.7%). Factors significantly associated with postoperative hypopituitarism in the univariate analysis were: previous hypopituitarism, larger tumor diameter, transsphenoidal endoscopic approach and presence of other postoperative complications (p <0.05). Independent predictors in the multivariate model were: tumor diameter and presurgical hypopituitarism for both single and multiple postsurgical deficits (p <0.05).

Conclusion. Tumor size and previous hypopituitarism were independent predictors of postoperative hypopituitarism. Endoscopic transsphenoidal surgery was associated to a higher rate of hypopituitarism, and can be reconsidered as a modifiable factor in future studies.

Aim: to evaluate the primary complaints of patients with pituitary macroadenomas and “first-referred” specialists for them.

Material and Methods. 351 with pituitary macroadenomas (at least one size >10 mm) were examined: 144 non-functional adenomas (NFA), 65 macroprolactinomas, 142 somatotropinomas. A pituitary adenoma was considered as giant if at least one of the sizes was >40 mm. MRI with an impact study of the pituitary was performed on high field instrument Intera Achieva (PHILIPS company) 3.0 TL, with intravenous extracellular gadolinium contrast agents. Statistical analysis of the results was carried out using the IBM statistical program SPSS Statistics 20 for Windows 7.0 with variation statistics methods for nonparametric data. The data are expressed as Mе [25%, 75%].

Results. The patients’ age ranged from 20 to 80 years and were: NFA 60 [51; 66] y.o., prolactinomas 44 [35; 59] y.o. and somatotropinomas 57 [47; 66] y.o. (р<0.001). Pituitary tumour volumes were: NFA 5,526 [2,460; 11,774] mm3, prolactinomas 5,275 [1,408; 10,566]) mm3 and somatotropinomas 2,814 [1,226; 4,708] mm3 (р<0.001). First patients’ complaints were: NFA – headache (61.7%) and visual disorders (34.8%), prolactinomas – headache (36.8%) and menstrual disorders (27.3%), somatotropinomas – appearance change (31.1%) and headache (32.8%). There was no correlation found between headache and tumour volume however significant correlation was revealed between visual disorders and tumour volume as well as vertical and sagittal sizes of the tumour. The most often “first referred” specialists were: NFA – neurologist (43%) and ophthalmologist (20%), prolactinomas – gynecologist (36.4% of patients of reproductive age) and neurologist (31%); somatotropinomas – endocrinologist (28%) and therapist (25%). Among macroadenomas 32 giant tumors were found: 18 NFA (12.5% of all NFA group), 8 (12.3%) prolactinomas, 6 (4.2%) somatotropinomas. The median age of patients with giant macroadenomas were: NFA 54 [38; 68] y.o., prolactinomas 29 [25; 43] y.o. and somatotropinomas 34 [24; 46] y.o. Tumour volumes of giant adenomas were: NFA 28,190 [21,143; 44,896] mm3; prolactinomas 38,592 [15,994; 78,606] мм3; and somatotropinomas 51,209 [36,703; 102,207] mm3 (p<0.001). Main complaints for patient with giant pituitary tumours were visual impairment (60%, 18 patients – 11 patients with NFA, 4 prolactinomas and 3 somatotropinomas) and headache (44%, 14 patients – 8 patients with NFA, 5 prolactinomas and 1 patient with somatotropinoma). The most often “first referred” specialists were ophthalmologist (50%, 16 patients – 9 patients with NFA, 4 prolactinomas and 3 somatotropinomas) and neurologist (34.4%, 11 cases – 8 patients with NFA, 2 with prolactinomas and 1 with somatotropinoma).

Conclusions. Headache and visual impairment were the most often complaints in our cohort of macroadenoma patients, however there were some discrepancies between groups of tumours with different hormonal activity. Neurologist and ophthalmologist should be aware of patients with pituitary macroadenomas, headache and visual disorders should be strong indications for pituitary MRI especially in patients younger than 50. 

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

Aim: to 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.

Materials 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. Adrenal insufficiency is a common complication of transsphenoidal surgery (TSS) for pituitary adenoma. It is very important to identify patients requiring glucocorticoid replacement, minimising risks of adrenal insufficiency.

Aim: to assess the performance of early ( 3ºday) post-TSS 08:00 a.m. cortisol measurement to detect and exclude secondary adrenal insufficiency.

Methods. We selected patients undergoing TSS in our hospital during 12 months and performed a 3º day postoperative 08:00 a.m. cortisol measurement and cortisol+/-Synachten 6 months post-surgery. All patients received perioperative glucocorticoid replacement (First and second days postsurgery) unless basal cortisol was > 10 microg/dl and cortisol after Synachten > 23 microg/dl previous to surgery. We excluded patients with previous diagnosed and treated adrenal insuficiency. In patients with 3º day cortisol lower than 10 microg/dl we maintained glucocorticoid treatment until reevaluation with cortisol/Synachten 6 months post-surgery.In patients with 3º day cortisol higher than 10 microg/dl glucocorticoids were discontinued.

Results. Data were reviewed from 20 patients (9 males, mean age 52,8 years), 18 with macroadenomas, 8 patients with cushing disease. Patients with adenomas no cushing: all patients with 3º day cortisol > 15 microg/dl had normal cortisol/Synachten 6 months post-surgery. 2 patients with 3º day cortisol between 10 and 15 microg/dl had adrenal insufficiency 6 months postsurgery.1 patient with 3º day cortisol< 10 microg/dl mantained adrenal insuficiency 6 months postsurgery. Cushing disease: all patients with 3º day cortisol > 10 microg/dl had not adrenal insuficiency 6 months postsurgery, all except one with recurrence. All patients with 3º day cortisol <10 microg/dl had not recurrences, all except one with adrenal insufficiency.

Conclusion. A 3º day post-TSS cortisol > 15 microg/dl is a safe cutt off to discarge adrenal insufficiency. In cushing disease, a level < 10 microg/dl predict a low likelihood of recurrences.

Introduction. The relevance of carbohydrate metabolism studying in patients with Cushing disease can be explained by frequent occurrence of glucose metabolism disturbances on the one hand, and difficulties in glucose-lowering therapy in these patients on the other. The effectiveness of hyperglycaemia treatment may be reduced due to difficulties in remission / cure of the underlying disease, as well as to the use of specific drug-therapy, leading to the hyperglycaemia. There is a growing interest in research aimed at studying the role of incretin system in the pathogenesis of secondary hyperglycemia associated with neuroendocrine diseases recently.

Methods. A total of 20 patients with Cushing disease were included, (19 female and 1 male), the mean age was 37.5 years (18-69). All of the patients were diagnosed with Cushing disease for the first time (using urinary free cortisol levels and MRI-data); none of them had a history of previous drug therapy, radiotherapy or pituitary surgery. The mean HbA1c level was 5,8% (5,3-6,2). All patients underwent OGTT, during which glucose, glucagon, GLP1, GLP2, GIP, ghrelin were measured at 0, 30 and 120 min respectively. The control group included 21 patients without previous history of carbohydrate metabolism disturbances. After OGTT 57% were presented without any carbohydrate metabolism disturbances, 28,57% presented with prediabetes and 14,43% were diagnosed with diabetes.

Results. After glucose levels analyzing 40% of patients were diagnosed with early carbohydrate metabolism disturbances ,15% were diagnosed with diabetes. After glucose intake a slight inrease in glucagon levels with a peak by 30’ (p=0,001) compared to gradually decreasing levels in controls was observed . The levels of GIP during OGTT were not significantly different compared to control group. GLP-1 and GLP-2 levels were significantly higher compared to controls (p=0,017 and p<0,001 respectively) with peak levels at 30’. Ghrelin levels were also significantly higher compared to controls (p=0,013)

Conclusion. Incretins levels can be possible markers of specific carbohydrate metabolism disturbances in patients with Cushing disease and presumably will help to differentiate steroid diabetes from T2DM. Further investigations needed to prove these speculations.

Introduction. Pituitary adenomas are the most frequent intracranial tumors of the central nervous system. Except for prolactinomas, surgery is the treatment of choice.

Aim: to assess the percentage of patients with persistent disease after surgery and to identify independent predictors of persistent disease.

Material and methods. Ambispective multicenter observational study. Data were collected from The Molecular Registry of Pituitary Adenomas (REMAH). Univariate and multivariate analysis were performed in 128 patients with histologically confirmed adenomas who underwent transsphenoidal surgery between 2009 and 2015 in hospitals from Madrid, with at least one month of follow-up.

Results. During follow-up, persistent disease was observed in 50.8% of patients (radiological 30.7%, biochemical 2.4%, both 14.2%), especially in nonfunctioning tumors. Factors significantly associated with persistent disease in the univariate analysis were age, male gender, previous hypopituitarism, large tumor diameter and microscopic transsphenoidal surgery (p <0.05). Independent predictors of persistent disease in multivariate analysis were: patients over 76 years old, a greater tumor diameter, multiple hypopituitarism and microscopic transsphenoidal surgery (p <0.05).

Conclusion. Age, tumor size, previous hypopituitarism and the type of surgical technique were independent predictors of persistent disease. These factors could be useful for clinicians in the follow-up of patients to better establish monitoring and treatment algorithms.

Aim: to analyse the outcome of SSA treatment in NFPA and to correlate it with the results of SSTR scintigraphy and immunohistochemistry.

Material and methods. Twenty six NFPA patients after incomplete neurosurgery with positive results of scintigraphy and immunohistochemistry were included in the study. All patients were treated with octreotide LAR 20mg intramuscular every 4 weeks. The tumour size was evaluated in control magnetic resonance imaging after 2 years of SSA therapy.

Results. Tumour size remained stable in the majority of NFPA. Adenoma size reduction was observed in 2 patients with strong expression of SSTR2 in both scintigraphy and immunohistochemistry. Increase of tumour size was noticed in 4 patients whose tumours were characterised not only by the presence of SSTR2 and SSTR5 but also by strong expression of SSTR1 in immunohistochemistry.

Conclusions. Only strong expression of SSTR2 can predict patients response to SSA treatment in NFPA. However, strong expression of SSTR1 observed in some of NFPA gives hope that introduction of new broad spectrum SSA like pasireotide would be more effective, especially in tumour shrinkage.

Background. Bone involvement in patients with β-thalassemia is well known, but only few studies have analyzed bone microarchitecture and the prevalence of intervertebral disc calcifications (IDCs) in these patients.

Aim: to evaluate the bone involvement in a group of patients with β-thalassemia in terms of geometry and bone quality; moreover, we evaluated prevalence and site of IDCs in these patients.

Methods. Our retrospective case-control study was conducted in a population of adults with β-thalassemia, aged between 18 and 50 years. The patients were divided, according with the International Society for Clinical Densitometry, into 2 groups: subjects with Zs ≤ -2.0, below the expected range for age, and subjects with Zs > -2.0, within the expected range for age. Assessment of proximal femur geometry was performed using the Hip Structural Analysis (HSA), that provides the following parameters: Hip Axis Length (HAL), Femoral Strength Index (FSI), Cross-Sectional Moment of Inertia (CSMI) Cross-Sectional Area (CSA), Section Modulus (Z), and buckling ratio (BR). Assessment of bone quality was performed using the Trabecular Bone Score (TBS), stratifying subjects into 3 groups: with abnormal (TBS ≤ 1.200), partially altered (TBS> 1.200 and <1.350), and normal (TBS ≥ 1.350) trabecular microarchitecture. Finally, we evaluated the prevalence of IDCs highlighted by images of Vertebral Fracture Assessment (VFA).

Results. We evaluated 49 patients with β-thalassemia, mean aged 35.16 ± 9.59 years, divided into two groups: 25 patients with Zs ≤ -2.0 and 24 patients with Zs > -2.0. Results demonstrated all statistically significant differences (p<0.001) between the two groups in BMD, Ts and Zs (in all examined districts), and in number of fragility fractures (p=0.0339). HSA showed that there are significant differences between groups only in FSI (p=0.0068) and CSA (p=0.0041). Furthermore, TBS of patients with Zs ≤ -2.0 was significantly lower than individuals Zs > -2.0 (p=0.0006); there was a statistically significant difference between the two groups in categorized TBS (p=0.0061). Finally, we evidenced in 7 patients (14.29%) the presence of at least one IDC.

Introduction. Evaluation of bone quality represents a clinical challenge. Analysis of bone mineral density (BMD) provides useful, but incomplete, information, and new tools are needed. Trabecular Bone Score (TBS) is emerging as a new surrogate marker of bone texture and microarchitecture and, may, therefore, be useful to potentially evaluate the risk of osteoporosis.

Materials and methods. Retrospective study of 18 patients with primary hyperparathyroidism. Clinical, analytical and BMD data were collected form clinical records. TBS was calculated by reevaluating the already existing BMD images. Patients were classified into two different groups according to their treatment: 1) 10 patients who underwent surgery, in whom TBS was evaluated before (B-S) and after surgery (A-S), and 2) 8 patients who received standard medical treatment, in whom TBS was evaluated with a time-lapse of one year.

Results. Basal age, body mass index (BMI), serum calcium, PTH and vitamin 25-OH-D levels, and T-Scores were not significantly different between the two groups. We observed a significant improvement of TBS one year after surgery in the first group (TBS B-S 1.24±0.13 vs TBS A-S 1.29±0.11,p=0.03). A subtle deterioration on TBS was observed one year after standard treatment in the second group (1.25±0.7 vs 1.22±0.7, p=0.29). Overall, surgical patients experienced a TBS increase 4.2%, whilst a decrease of 1.6% was observed in the second group (p=0.026)

Conclusion. Bone microarchitecture, measured by TBS, improves after surgery in patients with primary hyperparathyroidism. This parameter seems promising in the evaluation of bone status in primary hyperparathyroidism. Larger and longer follow-up studies deem necessary to better evaluate the potential utilities of using TBS in the assessment of bone quality.

Introduction. Patients with primary hyperparathyroidism (pHPT) run an increased risk of death, and in some studies cardiovascular diseases were inversely related to glomerular filtration rate (GFR) and urine osmolality.

Aim: to evaluate the renal filtration function and concentration capacity in patients with mild primary hyperparathyroidism.

Materials and methods. The study included 100 patients with pHPT (median age 57 [52;61]), including 33 with mild form (median age 54 [45;60]). Changes in GFR and osmolality index were evaluated in 29 patients after surgery for pHPT. Follow-up period was up to 24 months.

Osmolality index was calculated as urine osmolality to blood osmolality ratio. Renal concentration capacity impairment was diagnosed with osmolality index less than 2. Glomerular filtration rate was calculated by Modification of Diet in Renal Disease Study (MDRD) formula. Chronic kidney disease stage was estimated accordingly to current recommendations.

Results. Osmolality index in patients with mild pHPT was low with median 1.65 [1.4; 2.43]. We found a high prevalence of renal concentration capacity impairment in patients with mild pHPT, that was 70%. Mean GFR was 90.9 [73.3; 95.6] ml/min/1,73 m². Prevalence of chronic kidney disease stages 3-4 was 6% in patients with mild pHPT. Changes in renal concentration capacity in long-term period after surgery for pHPT were characterized by increase of osmolality index, also in patients with mild form (initially 1.75 [1.4; 2.14], after surgery 2.38 [1.84; 2.54]), changing Me was +12.4% in 6-24 months (p=0.012). Changes in renal function in long-term period after surgery for pHPT were characterized by decrease of GFR within the limits of chronic kidney disease stages 1-2, also in patients with mild form.

Conclusions. Renal concentration capacity impairment is common in mild pHPT and is restorated after surgery for pHPT. The findings of this study add cause for measurement of urine osmolality or osmolality index in all patients with pHPT. Our results confirm the requirement of estimating GFR in pHPT patients not only while active disease, but also in remission after surgery for pHPT.

Introduction. The visceral adiposity index (VAI) is a mathematical formula based on simple anthropometric and biochemical parameters and reflects the distribution and function of the adipose tissue.

Aim: to investigate the possible association between the presence of subclinical Cushing’s syndrome (SCS) and VAI in patients with adrenal incidentalomas.

Patients and methods. We studied 258 patients with adrenal incidentalomas. The diagnosis of SCS was based on a post-LDDST cortisol level ≥1.8 mg/dl combined with an abnormal result of at least one other test of the HPA axis, in the absence of clinical signs. The VAI index was calculated as following: Women VAI= [WC/36.58+(1.89×BMI)] ×(TG/0.81)×(1.52/HDL), Men VAI= [WC/39.68+(1.88×BMI)] ×(TG/1.03)×(1.31/HDL).

Results. 122 patients were excluded from the analysis due to overt metabolic problems (8 with BMI>39, 82 with metabolic syndrome and 34 with type 2 diabetes). Among 136 patients who were included in the analysis (42M/94W, 56.9±9.7 y), SCS was diagnosed in 24 (17.6%). Patients with SCS presented with significantly higher levels of insulin (12.4±4.6 vs 9.9±3.2 μIU/ml, p=0.036) and triglycerides (114±36 vs 97±34 mg/dl, p=0.023), larger size of tumors (3.26±0.88 vs 2.28±1.06 cm, p<0.001) and higher calculated VAI (1.77±0.83 vs 1.39±0.69, p=0.045). Regression analysis revealed that the presence of SCS was positively associated with VAI [OR (95% CI) 1.888 (1.051–3.394), p=0.034] but when gender subgroup analysis followed, this was shown only in women [OR (95% CI) 2.284 (1.135–4.595), p=0.021]. Another important prognostic factor for the probability of SCS was the mass size [OR (95% CI) 2.237 (1.441–3.472), p<0.001].

Conclusion. SCS in women with adrenal incidentalomas is associated with adipose tissue dysfunction.

Aim: to evaluate clinical manifestations of hypercortisolism in patients with adrenal Cushing’s (ACush).

Material and Methods. 32 patients (30 (93.7%) female, 2 (6.3%) male, 41.5 [32.2; 54.0] y.o. with ACush.

Results. Adenoma was found in right adrenal in 37.5% of patients, in left – 40.6%, bilateral adenomas in 21.9%. Maximum size of adenoma was 3.3 [3.0;4.2] cm. Level of UFC was 654.1 [383.0;1153.0] nmol/l/h, ACTH – 1.1 [1.1;2.3] pmol/l, serum cortisol after 1-mg overnight dexamethasone suppression test– 644.0 [431.5;710.5] nmol/l. Features that best discriminate Cushing’s syndrome were found not in all patients - proximal muscle weakness - in 81.3%, facial fullness -75.0%, easy bruising - 56.2% and striae - 43.7%. The most frequent (≥80%) complains were weight gain (87.5%), fatigue (84.3%), headache (50-80%). In <50% - poor skin healing, prolonged wound healing, depression, menstrual abnormalities etc. Arterial hypertension diagnosed in 31/32 patients, systolic BP before treatment was 180 [170;220] mm Hg, diastolic BP - 100 [100;110] mm Hg. Antihypertensive therapy: one medication received 5 patients (16.1%), two – 8 (25.8%), three - 12 (38.7%) , four – 1 (3.2%), without therapy - 5 (16.1%). Hypokaliemia were in 26.6%, hypercholesterolemia - 86.6%. In 9 patients diabetes mellitus (DM) diagnosed before diagnosis ACush was made. 75-g OGTT performed in 16 patients without known DM thereafter DM was diagnosed in 2 (12.5%), IGT (impaired glucose tolerance) in 6 (37.5%). Bone densitometry performed in 20 patients: in 5 of them osteoporosis was diagnosed (15.6%), in 5 -osteopenia (15.6%), normal bone density – in 10 (31.2%). Pathological fractures (vertebral, rib fractures etc) were in 3/5 osteoporotic patients.

Conclusions. The most frequent complaints (≥80%) were weight gain, fatigue and proximal muscle weakness. Hypertension and hypercholesterolemia were in 96.9% and 86.6% patients. Diabetes and IGT in 53.1%, hypokaliemia (26.6%), osteoporosis (15.6%).   

Background. The insulin tolerance test (ITT) is the “gold standard” of the secondary adrenal insufficiency (SAI) diagnosis but it is rather difficult to carry out, has some contraindications and requires patient’s hospitalization. The availability of a reliable screening method could reduce the necessity of using ITT.

Aim: to compare different methods of screening with ITT and to work out an optimal diagnostic algorithm of SAI.

Methods. 40 patients (20 women) after craniospinal (CSI) irradiation in a doze 35 Gy were examined. The average age at the time of the observation was 19,5±3 years, at the time of treatment 12,5±3,5 years. Patient’s blood samples were collected for basal cortisol (BC), DHEA-S. ITT was performed for all patients, glucagon stimulation test (GST) was for 27 persons. Patients were divided into groups: SAI and without SAI (W-SAI) after ITT. ROC- analysis was conducted to identify the thresholds for BC, DHEA-S and GST. Cut-off points for BC and DHEA-S levels corresponding to 100% sensitivity (Se) for SAI group and 100% specificity (Sp) for W-SAI patients were estimated to select a group of patients which do not require stimulative tests. Linear regression was used to construct a predictive model (PM) of SAI occurrence after CSI.

Results. 22/40 subjects failed ITT, 13/27 passed GST. 3 patients failed ITT but passed GST. Their level of neutrophils and monocytes was higher than the other patients'. SAI-patients had BC and DHEA-S lower than W-SAI (321±102 vs 516± 183; p=0,003 and 2,6±1,4 vs 5,1±2,1, p=0,003). ROC-analysis showed area under curve (AUC) for GST=0,91 with optimal cut-off for cortisol=489 which corresponds to 100% Sp and 62% Se. AUC was 0,83 for BC and 0,84 for DHEA-S.In 70% patients' BC was in a “grey zone” (32% of them passed ITT), 8% had BC lower than 200 (which corresponds to 100% Se) and 22% more than 499 (100% Sp). 50% of patients were in a “grey zone” for DHEA-S (50% of them had SAI), 18% had DHEA-S level below 2,0 and 32% above 4,7. A combination of BC and DHEA-S in the PM of SAI (0,592+0,001*BC+0,11*DHEA-S) had AUC 94%. This PM didn’t give the prognosis of SAI for 32% (CI: 18-49%) of patients. The addition of maximal cortisol (MC) level during GST (0,53+0,01*BC+0,066*DHEA-S+0,001*MC) increased AUC to 99% and didn’t allow to predict SAI in 8% (3,2% - 24,9%) of patients only.

Conclusions. When the screening methods were used separately, they showed comparable accuracy and it was not high. The PM may be used as optimal screening method for SAI and may allow to use ITT more rarely. But further studies are required to validate the PM proposed in this study.

Background. Primary aldosteronism (PA) is an adrenal disorder which is characterized by the overproduction of the mineralocorticoid hormones by the adrenal glands when not as a result of excessive renin secretion. Different studies report the prevalence of PA in from 7 to 15 % patients with hypertension. Nowadays PA is considered to be the most frequent cause of secondary hypertension taking up to 30% of it. The importance of case detection of PA among hypertensive patients is not a matter of controversy presently. It has been demonstrated recently that patients with PA are more prone to cardiovascular events and target organ damage than essential hypertensive patients.

Aim: to establish renal dysfunction in PA.

Methods. We evaluated 192 low-renin hypertensive patients and 30 normotensive subjects. The mean age of the hypertensives was 47,5±3,4 years. The control group was 51,8±4,2 years old. PA was established in 57 patients, all the others were classified as low-renin essential hypertensives (LREH). Both groups were similar with respect to age (44,7±4,2 in PA, 48,3±3,9 in LREH), sex (female 63% of PA and 67% of LREH) and blood pressure (158±16/96±8 mm Hg in PA, 164±21/99±13 mm Hg in LREH). There were slight differences in BMI (31,4±4,3 in PA and 28,7±3,5 in LREH, p<0,05). PA and LREH patients significantly differed with respect to prevalence of diabetes mellitus (26,3% in PA and 9,6% in LREH, p<0,01) and duration of hypertension (7±5 years in PA and 13±4 in LREH, p<0,05).

Results. We observed an increase in urinary protein excretion in both group. But in group of patients with PA it was higher than in LREH (0,14±0,06 vs. 0,05±0,03 g/24 h, p<0,05). In addition, patients with PA had higher serum creatinine concentrations (101,7±13,2 vs. 83,4±9,1 mkmol/l, p<0,05). Subgroup analyses of normoglycemic subjects showed that PA patients still had a higher creatinine concentration (84,3±11,8 vs. 81,9±10,5 mkmol/l) but the difference was no longer statistically significant. Although, microalbuminuria was significantly higher in non-diabetic PA patients (0,12±0,04 vs. 0,05±0,07 g/24 h, p<0,05). Diabetic subjects in both groups did not differ significantly with respect to microalbuminuria.

Conclusions. Cross-sectional Primary Aldosteronism Prevalence in Italy (PAPY) study showed an increased prevalence of microalbuminuria in PA. The data from German Conn’s Registry showed a significant increase of serum creatinine concentrations in patients with PA but they did not observe any significant differences in protein excretion. In our study the differences in creatinine concentration were diabetes-dependent. Although, we suppose an increase of microalbuminuria in patients with PA to be aldosterone-dependent. However, this hypothesis should be confirmed in wider populations.

Introduction. Recent in vitro and in vivo studies have suggested a role of undercarboxylated osteocalcin (ucOC), not total (TOC) osteocalcin in glucose and energy metabolism.

Aims: to investigate the relationship of ucOC level and blood glucose (BG) control in newly diagnosed type 2 diabetes and its change with BG control improvement.

Subjects and methods. Fifty seven newly diagnosed type 2 diabetic patients with no history of bone metabolism disturbances had two visits3 months apart, with physical examination and blood sampling. The patients had consultation about life style changes, no medication was prescribed on visit 1. Weekly (first month) and biweekly telephone contacts were performed to enhance compliance. Samples for parameters of BG metabolism and bone turnover were collected on visit 1 and 2. Standard automated or semi-automated methods were used for measurements, for ucOC the only available commercial kit.

Results. Forty seven patients completed the study. Thirty two (56%) patients reached the target HbA1c (≤7%). No correlation of ucOC and HbA1c and FBG was observed. Median HbA1c and FBG changed significantly (8.0 to 6.5%; 9.0 to 7.0 mmol/L resp.; Wilcoxon signed rank test p<0.001), ucOC was slightly but not significantly lower (2.0 to 1.4 mcg/L; p=0.465). No correlation between differences in HbA1c and ucOC between Visits 1 and 2 was revealed. There was a significant change in HOMA%B but not HOMA IR, not correlated to ucOC.

Conclusion. This study failed to prove the relationship between blood glucose regulation and ucOC level. However, it does not exclude it, so further research is needed. A lack of robust essay for human ucOC might explain inconclusive results of clinical studies. The fact that as much as 56% patients achieved the target HbA1c with no medication, challenges most BG control guidelines.

Introduction. Cushing's disease (CD) represents 10%–12% of all pituitary adenomas and is seen predominantly in women, with a female-to-male ratio of 8:1. Although most patients with ACTH-secreting adenomas present with benign, small tumors, some have invasive macroadenomas. Rarely, nonfunctional pituitary adenomas (NFPAs) may gain secretory function, but there have been a few case reports of metamorphosis to CD.

Case report. We report the case of a 59-year-old female diagnosed in 2007 with a NFPA and panhypopituitarism. She had two transsphenoidal surgeries and Gamma Knife therapy and started replacement treatment with levothyroxine 75mcg/day and prednisone 5mg/day. The postoperative course was favorable and imagistic follow-up between 2007-2014 showed progressive reduction of the residual tumor and empty sella. From personal history we note noninsulin-dependent diabetes mellitus, postmenopausal osteoporosis treated with bisphosphonates. In January 2015 she suffered visual loss on the right eye. Pituitary MRI showed supra and parasellar tumor recurrence of 27/24/17mm, infiltrating the right side of the cavernous sinus, extending around the right internal carotid artery and optic nerve, compressing the optic chiasm. In March 2015 a third transsphenoidal partial excision of the tumor was performed and in August Gamma Knife therapy was repeated. The histopathological examination was consistent with a pituitary adenoma but immunohistochemical staining for ACTH was positive, with Ki-67=25%. She had no non-specific cushingoid features. Laboratory test: glucose=116mg/dl, HbA1c=7.5%, FSH=3.34mIU/ml, LH=0.585mIU/ml TSH=0.044mcIU/ml, FT4=1.13ng/dl. Prednisone replacement therapy was stopped and CD was confirmed: 8AMcortisol=13.3mcg/dl, 23PMcortisol=11.3mcg/dl, ACTH=70.2pg/ml, 8AMcortisol after 1mg dexamethasone overnight=13.8mcg/dl. Ophthalmic exam: blindness in the right eye, slightly decreased visual field in the left eye. Pituitary MRI 8-month postsurgery revealed a 28/31/28mm invasive tumor. We started treatment with Cabergoline 3mg/week and recommended closely biological and imagistic follow-up, hoping for a good response to radiotherapy.

Conclusions: Our case stresses the importance of regular, lifelong follow-up of patients with NFPAs. Chiloiro et al have reported that pituitary adenomas with Ki-67≥1.5% have a higher risk of recurrence. Although the characteristics of patients with CD have been well known for decades, the diagnosis and management of this disease are often challenging.

Introduction. Thyroid Hormone Resistance (THR) is a rare syndrome with a variable and fluctuating clinical course depending on complex genetic and molecular defects.

Case report. SCPR, a caucasian female patient aged 23, was referred to outpatient endocrine department because of increased T4 levels. There was no evidence of thyroid dysfunction or goiter. Past medical history was negative with normal growth and neurophysiological development and regular menstrual cycles. There was no family history of thyroid disease. Analytical evaluation revealed T4 – 17.9 µg/dL [Reference Value (RV): 4.5-12.5], T3 – 247 ng/mL (RV: 72-170), TSH – 4.9 µU/mL (RV: 0.4-4.0), FT3 – 7.8 pg/mL (RV: 1.8-4.2), FT4 – 2.6 ng/dL (RV: 0.8-1.9), TPOAb 11 U/mL (RV: <35), TgAb < 20 U/mL (RV: <40), TRAb < 1 (RV: <2). The TRH test (200 µg, ev) revealed a normal but high TSH response up to 23 µU/mL (5-25) and a sellar NMR scan showed no abnormalities. No medical treatment was prescribed. Over the follow up period of 10 years thyroid function fluctuated with borderline high FT4 and TSH. Clinical course was marked by the development of obesity, depressive syndrome and the diagnosis of chronic fatigue syndrome with two uneventful pregnancies. Over that period, either Hyperthyroidism or Hypothyroidism were diagnosed and treated at other institutions. Recently genetic testing revealed a new mutation on exon 10 of the β thyroid hormone receptor form c790G>T (p.Val264Phe) with unknown significance.

Discussion. Several important points are illustrated by this case. 1) thyroid function tests may fluctuate over time, only sometimes with clear evidence of THR. 2) clinical manifestations of the syndrome are multiform and the relation to thyroid hormone levels is far from clear with abnormalities of growth and neurophysiological development, infertility, obesity, psychiatric disorders or subtle symptoms suggesting thyroid dysfunction variably reported; 3) interpretation of analytical abnormalities may be difficult with thyroid dysfunction commonly misdiagnosed; 4) medical treatment is controversial; 5) More than 100 mutations have been reported and the particular complexity of thyroid hormone effects – several isoforms of the receptor, homo- or heterodimerization of the receptor with the retinoid X receptor and dominant negative effects making the interpretation of the functional significance of new mutations difficult. 

Background. The elevation of thyroid hormone with a normal or elevated TSH occurs uncommonly. This has different causes and pose a diagnosis challenge namely between TSH-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone. The accurate diagnosis is essential, because delayed diagnosis of TSHoma can lead to tumour growth and poor surgical cure rates, whereas medical, surgical or radioablative treatments in patients with resistance to thyroid hormone are usually unnecessary and potentially harmful.

Case Report. A 23-years-old women with palpitations, fatigue, insomnia and exophthalmia with elevated serum free T4 and TSH, medicated with methimazole 5mg 3id was sent to evaluation in endocrinology department. She did not report headaches or visual problems. Patient’s laboratory tests at admission: TSH 9,6 µUI/mL (0,4–4,0 µUI/mL), Free T4 2,1 pg/dL (0,8–1,9 pg/dL). After stopping anti-thyroid drug presented TSH 2,9 µUI/mL (0,4-4,0 µUI/mL), Free T4 3,7 pg/dL (0,8–1,9 pg/dL), Free T3 11 pg/mL (1,8–4,2 pg/mL); antithyroid peroxidase and antithyroglobulin antibodies and thyroid stimulating immunoglobulin were undetectable; thyroid ultrasound revealed small heterogeneous goiter; thyroid technetium scintigraphy showed diffuse glandular hyperfunctioning; Magnetic resonance imaging revealed a microadenoma with 7,5mm in the left side of pituitary. Remaining anterior pituitary hormones were within normal ranges. The thyrotropin-releasing hormone stimulation test was performed and revealed TSH at 0’ 1,7 µUI/mL, 20’ 14 µUI/mL and 60’ 11 µUI/mL, with free T4 2,3 pg/dL and free T3 5,9 pg/mL, which was consistent with thyroid hormone resistance syndrome. In this clinical setting genetic test was performed and revealed mutation in heterozygosity in THRβ gene: c.1030G>A, p.Gly344Arg. Patient’s mother was also tested and no mutation was found. Her father was not available to do the genetic test. No pituitary surgery or thyroidectomy was performed, nor were prescribed any anti-thyroid drugs.

Conclusions. In this case, an innapropriate TSH secretion was identified and the clinical, biochemical and genetic investigations were consistent with resistance to thyroid hormone. Known that as many as 15% non-ill people may have a small, nonfunctioning pituitary adenoma, patients with thyroid hormone resistance may have incidentally abnormal imaging findings. The high level of clinical suspicion and the proper laboratory, genetic and radiological studies, conduct to a correct diagnosis and prevent unnecessary and potential harmful therapies.

Introduction. The therapeutic management of hypophosphatemic rickets in adulthood aims to reduce bone pain, the extent of osteomalacia and improve fracture healing and surgical recovery, but clinicians need to stay alert as potential risks can sometimes exceed the benefits of treatment.

Case report. We present the case of a 25 year old male patient who was admitted in our department for evaluation presenting severe bone pain. From his medical history we mention that he was diagnosed with rickets at the age of 3 years and received treatment with vitamin D and calcium with no clinical response. A corrective surgery for femur valgus was performed two years later. Because he received high doses of vitamin D without improvement of symptoms the suspicion of vitamin D-resistant rickets was raised at the age of 12 years and treatment with calcitriol 3 tb/day was started with a decline of alkaline phosphatase level from 1144 to 509 UI/l. Two years ago he was diagnosed with renal microlitiasis and left tibial fracture. At present admission he presented with disarmonic short stature, H=149.4 cm (-4.14 SD), W=59 kg, macrocephaly, dental dystrophy and leg bowing. He was under chronic treatment with active vitamin D analog 2 tb/day. Laboratory tests revealed low phosphate (P=2 mg/dl), low 25-OH-vitamin D (19 ng/ml) and 1,25-(OH)2-vitamin D (13.2 pg/ml), normal serum and urinary calcium, normal PTH, high beta crosslaps. In order to diagnose hypophosphatemic rickets, serum FGF23 analysis was performed and it was elevated , but the genetic testing for hypophosphatemic rickets was not available. Because the patient had severe bone pain, a tibial fracture and intented to perform a corrective osteotomy we decided to start medical treatment with elemental phosphorus for 9-12 months, at least 3-6 months before surgery with strict monitoring of serum and urinary calcium and phosphate level, creatinine, alkaline phosphatase and serum PTH.

Conclusion. The key point of the case is the late diagnosis of hypophosphatemic rickets and the challenge in treating our patient in order to minimize the risks of combined treatment with calcitriol and phosphorus giving the fact that he was already diagnosed with nephromicrolitiasis.

Introduction. Since introduction of IFN-β1b for treatment of multiple sclerosis (MS), it was identified that beta interferon-1b can induce multiple alterations in thyroid function; though thyroid dysfunction is generally subclinical and often transient. The frequency of biological thyroid dysfunction has been studied in patients treated with IFN-β1b and was evaluated between 8.3 and 33%. On the other hand, autoimmune thyroid disease, as well as other autoimmune diseases, can occur in MS patients not receiving interferon-β therapy. It is unclear whether the occurrence of these diseases is increased in MS patients.

Case report. A 52-year-old female was diagnosed with a relapsing-remitting multiple sclerosis in 2012 in Lithuania. Beta interferon-1b was initiated. In 2014, after 2 years of treatment, the patient referred for evaluation of hyperthyroidism. Thyroid function tests revealed a TSH of 0.01 μIU/ml (normal range: 0.27-4.2), fT4 of 7.3 pmol/L (normal range: 12.0-22.0) and with positive TPO and TG antibodies. The patient was commenced on carbimazole 60 mg daily. After a month, because of the high level of TSH (45.3 μIU/ml), the dose of carbimazole was roughly decreased to 5 mg daily. Since then the dose of carbimazole varied from 2.5 to 10 mg daily according to the TSH levels. In September 2015 patient attended our clinic. Thyroid function tests demonstrated a TSH of 5.12 μIU/ml (normal range: 0.4-4.0), fT4 of 0.76 (normal range: 0.89-1.76) with positive TPO antibodies. An ultrasonographic study of the thyroid gland revealed multinodular goiter with decreased echogenicity. For the time being, patient was receiving 5 mg of carbimazole daily. The anti-thyroid drug was stopped and after 2 months the thyroid function tests were within normal ranges and, in addition, the patient showed no signs of either hypothyroidism or hyperthyroidism. Certainly, further follow-up of the thyroid function is required.

Conclusion It is now not arguable that among patients treated with IFN-β1b a thyroid dysfunction could be expected. This side effect is sometimes severe. Furthermore, MS itself may be an additional risk factor for developing an autoimmune thyroid disease. So it is crucial to systematically assess thyroid function in MS patients receiving IFN-β1b for treatment.