Endocrine Abstracts

The human adrenal cortex consists of three layers in which specific steroid hormones are produced. Human adrenal NCI-H295A (A) and NCI-H295R (R) cells, originate from the same adrenocortical tumor and express all genes essential for steroidogenesis. Therefore they often serve as a suitable model to study human steroidogenesis. No data are available comparing steroidogenesis of A vs. R cells. Assuming no difference, research data from these two cell lines are directly compared....

We showed previously that a single dose of ethanol acts as a stressor in female rats (Milovanovic et al., 2003). In order to extend this observation, we investigated whether the effect of ethanol on ACTH is dose-related and possible interactions between nitric oxide (NO) and alcohol on the level of ACTH. To this end, adult female Wistar rats showing diestrus day 1 were treated with: (a) ethanol (2 or 4 g/kg, i.p.), (b) Nω-nitro-L-arginine-methyl ester (L-NAME), whi...

Objective: The Antiphospholipid Syndrome (APS) is a thrombophilic disorder characterised by recurrent venous and/or arterial thromboses and increased pregnancy morbidity. There is growing evidence supporting a functional interplay between the neuroendocrine and immune system; the hypothalamic-pituitary-adreal (HPA) axis plays a pivotal role in this network. Previous studies have described normal cortisol levels in APS patients while occurrence of acute adrenal failure was repo...

The prevalence of hypothyroidism in women of childbearing age is relatively high. The incidence of hypothyroidism during pregnancy has been calculated as between 0.3% and 0.7%. Overt abnormalities in thyroid function are common endocrine disorders affecting more than 19.2% of pregnant women in certain geographic areas of Hungary. 80% of Hungarian inhabitants are living in an iodine deficient area. The aim of this study was to investigate the prevalence of thyroid dysfunction i...

Acute pancreatitis is a real medical problem with high patients mortality. Pathogenic interdependence between pancreas follicles function and islet endocrine secretion is under research. PP cells are pancreatic polypeptide (PP) producing cells, they determine about 1% islets, but their function is not completely known yet. Vagus nerve and peptidergic stimulation regulates PP secretion.The aim of study was to estimate cerulein induced pancreatitis effects...

Acute and chronic alcohol intake and alcohol withdrawal induce dysfunction of neuroendocrine and other regulatory systems. The aims of this study were to assess a possible hypothalamo-pituitary-adrenal (HPA) axis dysfunction in population of alcoholics, using dexamethasone suppression test (DST). The study was approved by local Ethical Committee. The serum and urinary cortisol were compared between the groups of 89 male patients (64.5% depressive and 35.5% nondepressive alcoho...

Adriamycin (ADR) is a potent chemotherapeutic agent, effective in treatment of leukemias, lymphomas and of many solid tumours. However, its clinical usage is often limited by cardiotoxicity, induced by oxygen radical damage of membrane lipids.Melatonin (MEL), is a well-known antioxidant. It has been shown that melatonin can scavenge free radicals, both directly or indirectly, stimulating the activity of antioxidative enzyme, e.g., glutathione peroxidase ...

Background: CHF manifestations can be explained by the biologic effects of tumor necrosis factor-alpha (TNF-alpha). Interleukin-10 (IL-10) has potent deactivating properties and is considered a potent anti-inflammatory cytokine that inhibits TNF-alpha production. This study was designed to examine the role of IL-10 in patients with CHF and to test its correlation with pro-inflammatory markers.Methodology: Fifty patients with CHF were studied. Patients we...

Prostate homeostasis and function are regulated by complex interactions between the fibromuscular stroma and secretory epithelium via locally-derived and systemic paracrine- and autocrine-acting growth factors and sex steroid hormones. Stromal tissue remodelling due to alterations in transforming growth factor beta (TGF-β) and sex steroid hormone signalling are associated with benign prostatic hyperplasia (BPH) and prostate cancer (PCa), two of the most common proliferati...

Although the existence of the interaction between sex steroids and immune system is well known, the mechanisms of this interaction are still unclear. Recently a second form of GnRH (GnRH-II) has been described in human, which is significantly expressed in immune tissues suggesting a potential function. In a recent in-vitro study it has been demonstrated that GnRH-II decreases local expression of IL-2R in peripheral lymphocytes (1). However in-vivo interactions of...

Recent reports have revealed that leptin’s effects are not restricted to central control of body weight, demonstrating instead that leptin is a pleiotropic hormone with a wide variety of different biological actions. Leptin exhibits undesirable effects in autoimmune diseases, in atherosclerosis, and possibly in several types of cancer, and increases the risk of cardiovascular disease in obese people. Therefore, preparation of reagents capable of abolishing leptin’s a...

The numerous growth factors and cytokines take part in mechanisms of tumor growth and metastasing.The aim of this study was determination of sFas, IL-6 and VEGF serum levels in 19 patients with adrenal cortical carcinoma (11 women and 8 men aged 21–72 years). The control group comprised 40 practically healthy donors (22 women and 18 men aged 19–70 years). sFas, IL-6 and VEGF before adrenalectomy and in the control were measured by ELISA. Mean I...

Microvascular endothelium is one of the main character and target involved in the inflammatory response. Upon specific activation, endothelial cells massively recruit Th1 IFNgamma secreting lymphocytes at the inflammatory site. In the present study, we investigate the intracellular signalling mediating TNFalpha (T) and IFNgamma (I) inflammatory response in a human endothelial cell line (HMEC-1) in vitro and the interfering effects of rosiglitazone (RGZ), a peroxisome pr...

The intensive physical activity is often associated with cardiac changes, particularly involving the right ventricular (RV) chamber. However, the molecular mechanisms involved in the RV physiologic adaptation to long-term training are not completely understood. In the present study we investigated the role of the growth hormone/insulin like growth factor 1 (GH/IGF-1) axis in the RV remodeling of athletes.Nineteen male top levels rowers and 19 age-matched...

Among well-known circulating melanoma markers 5-S-cysteinyldopa (5-SCD), a precursor of pheomelanin biosynthesis and S-100 beta (S-100B) are extensively investigated. Our earlier observations confirmed that serum concentration of 5-SCD and S-100B correlates well with the stages and progression of the disease. Interleukin-6 (IL-6) is a multifunctional inflammatory cytokine implicated in advanced stage of various diseases and tumour recurrence. Malignant melanoma cells are known...

Introduction: Interferon alpha (IFN alpha) is a cytokine with pleiotropic effects and via different pathways influences secretion of certain cytokines and hormones. Growth Hormone (GH) secreted from the pituitary has its physiological effects on various target tissues. The question is how IFN alpha administered in various type of diseases influences GH secretion. This study investigated acute effect of IFN-alpha on GH mRNA expression in rat anterior pituitary<p class="abst...

Background: There is growing evidence that adhesion molecules, proinflammatory cells and cytokines play an important role in a variety of cardiac pathophysiological conditions; Cytokines are responsible for the modulation of immune and inflammatory processes. It has been suggested that cytokines such as IL-1, IL-2, IL-6, IL-10 and TNF alpha are important modulators of atherosclerotic effects with IL-2 and Interferon γ having a proinflammatory atherogenic effect and IL-8 a...

Background: The patomechanism of developing ischemic heart disease (i.h.d.) is stenosis of coronary blood vessels with plaque placed on vascular endothelium built with monocytes/macrophages, foam cells, oxidized LDL, leukocytes, platelets and collagen. Atherosclerotic lesions are heavily infiltrated by cellular components associated with inflammation and influenced by other inflammatory factors. Trimetazidine, a clinically effective antianginal agent acts by optimizing cardiac...

Objectives: Insulin resistance (IR) is a very common metabolic abnormality in obesity, which is often associated with reduced growth hormone (GH) secretion. GH deficiency is associated with increased in intra-abdominal fat and several parameters of the metabolic syndrome. IGF-I improves IR but the IGF-binding proteins are supposed to regulate its bioactivity although only little information exists. We postulated that the elevated insulin levels due to IR do not only suppress G...

Anorexia nervosa (AN) is an eating disorder, resulting in sustained low weight. In AN, similarly to syndromes of lipodystrophy, one observes the significant loss of the adipose tissue. In lipodystrophies, despite the lack of subcutaneous adipose tissue, insulin resistance is observed. Adipose tissue is known as a source of a variety of bioactive peptides, known as adipocytokines. The aim of the present study was to examine the plasma concentration of adipocytokines in relation...

Betacellulin, one of several peptides activating the EGFR (ErbB1) and related receptors, is a multipotent growth factor known to posses the unique ability to promote growth and differentiation of pancreatic β-cells.We investigated the effects of betacellulin overexpression in a recently established transgenic mouse model (Schneider et al., Endocrinology 146, 5237–5246, 2005). In transgenic animals, overall glucose metabolism was improved...

The role of adipokines and inflammatory cytokines of adipose tissue for development of the growth hormone deficiency (GHD)-related metabolic derangements has not yet been completely understood. Therefore, we screened the protein level of 120 adipokines in subcutaneous adipose tissue (ScAT) of patients with GHD in adulthood.Subjects and methods: Sixteen GHD (10M/6F) with BMI 27±1.0 kg/m2, age 30±2 yrs and sixteen controls matched for ...

Aim: to establish a human in vitro system for the study of pituitary cells in culture and subsequently to study the influence of the pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α on the function of the somatotrophic cells inclusive the ability of the cells to produce IL-6 and IL-8.Methods: Pituitary adenomas were obtained from hypophysectomies of patients with acromegaly. The tissue was enzymatically d...

Background: Some recent studies have revealed the relationship among excess ferritin, coronary heart disease, and insulin resistance. To assess the association between serum ferritin concentration and Impaired Fasting Glucose, a prediabetes situation with insulin resistance, this study was designed in Zanjan, Iran.Materials & Methods: 187 people including 91 impaired fasting glucose (IFG) subjects and 96 normal glucose subjects who had been recognize...

Background: Resistin is a recently discovered adipocyte-secreted hormone that links obesity with insulin resistance and/or metabolic and cardiovascular risk. This study was designed to investigate whether serum resistin concentrations constitute a significant coronary risk factor, with a particular focus on diabetes and one of its microvascular complications; nephropathy.Methodology: Serum resistin was measured in 86 overweight patients with acute corona...

Tribulus terrestris (TT) is used in the Arabic folk medicine to Q1 treat various diseases. The aim of this study was to investigate the protective effects of TT in diabetes mellitus (DM). Diabetes is known to increase reactive oxygen species (ROS) level that subsequently contributes to the pathogenesis of diabetes. Rats were divided into six groups and treated with either saline, glibenclamide (Glib), or TT for 30 days. Rats in group 1 were given sa...

Objective: In last decades prevalence of type 2 diabetes mellitus (DM) in children and young people worldwide has been reported increase. It is necessary to know according to biochemical and genetic characteristics the frequency of DM no corresponding to type 1 in our population. The objective of this study was to determine the prevalence of mutations on hepatic nuclear factor 1 [alpha], and 4 [alpha] in diabetic patients younger than 35 years old with features of clinical aut...

A sustained, high circulating level of free fatty acids (FFAs) is an important risk factor for the development of insulin resistance, islet beta-cell dysfunction, and pathogenesis of type 2 diabetes. Here, we report a novel mechanism of chronic exposure of oleic acid (OA)-induced rat insulin release impairment. Following a 4-day exposure to 0.1 mM OA, there was no significant difference in basal insulin release when comparing OA-treated and untreated islets in the presence of ...

Background and aims: Type 2 Diabetes Mellitus affects a growing number of people allover the world. It is associated with serious complications. Several studies have shown that it is possible to prevent and minimize type 2 diabetes complications if it is treated appropriately over time. In our Hospital there is, since 1998, an outpatient clinics of diabetes. This study aimed to determine the quality of care provided to diabetic patients in our institution.<p class="abstext...

MA is a marker of greatly increased cardiovascular morbidity and mortality in T2DM patients.Objective: To perform a prospective study of normoalbuminuric T2DM patients, analysing the association between CVRF at baseline and the development of MA at follow-up.Materials and methods: The prospective observational study was performed at Montes de Barbanza public health center, a specialized secondary referral center, which provides ser...

Background and Aims: The identification of metabolic syndrome (MS) is important so that components of this syndrome can be managed appropriately to prevent or delay progression of associated cardiovascular risk factors. The aim of our study was to determine the prevalence of the Metabolic Syndrome as the NCEP/ATP III criteria in a selected population of type 2 diabetes from the Tirana Register of Diabetes.Materials and Methods: In Tirana district we rand...

Background: Glitazones (GZ) influence androgen biosynthesis in PCO syndrome. At present it is unknown whether a) steroid hormone metabolism is influenced by GZ in patients with type 2 diabetes b) there is a differential effect of RGZ and PGZ on steroid hormone metabolism c) this effect is sex-specific and d) this effect is mediated by changes in insulin sensitivity. Therefore, urinary steroid profiles and serum total testosterone and DHEA levels were analysed before and after ...

Objective: The status of carbohydrate metabolism of pregnant women with positive glucose challenge test (GCT), but normal oral glucose tolerance test (OGTT); and their neonates have not defined clearly.Methods: Pregnant women with normal GCT (n: 120), with abnormal glucose challenge test (AGCT) but normal OGTT (n: 67) and those with gestational diabetes (GDM) (n: 67) were included into the study. Local ethical committee approval was ...

Objective: The thiazolidinediones are new and potentially useful developments in the treatment of type 2 diabetes and impaired glucose tolerance. We tested the effects of the thiazolidinedione, rosiglitazone on blood pressure in normotensive type 2 diabetes.Methods: After receiving approval from the local ethics committee, 25 normotensive diabetic patients were were enrolled to the study. Before the rosiglitazone treatment we measured plasma glucose, HbA...

Objective: Thiazolidinediones (TZDs) have become a powerful tool for lowering insulin resistance. The problem of cardiovascular adverse events including fluid retention and risk of heart failure, although of a low incidence, should be well known and recognized. We aimed to evaluate the effects of rosiglitazone treatment on cardiac function and show whether these effects are reversible when we continued this treatment.Methods: Fourty-six type 2 diabetic p...

Objective: To assess the sensitivity of exercise induced heart rate (HR) and baroreceptor reflex (BR) chronotrope reaction and HR variability for an early detection of autonomic nervous system impairment in non-insulin dependent diabetes mellitus (NIDDM) patients with arterial hypertension.Design and Methods: On 25 NIDDM pts (group A, 63±1.8 yrs. aged men, HbA1C 10.2±0.9%), 17 essential hypertension (EH) pts without glucose metabolis...

Objective: To compare 2 modalities of bolus-basal insulin therapy with aspart-detemir, according to the moment of administration of detemir (DET), before the lunch or bed-time, in type 1 diabetic patients with poor metabolic control.Methods: We conducted a prospective study of 40 type 1 diabetic patients, with poor metabolic control (HbAc 7–12%), randomized to receive treatment with 1 injection of DET before the lunch or bed-time and followed-up dur...

An experimental study was designed to test a drug candidate for the treatment of diabetes mellitus in rats with streptozotocin (STZ) diabetes.Diabetes was induced in outbred male rats (280–300 g) by single iv injection of streptozotocin 50 mg/kg. The animals showing hyperglycemia (12–15 mM) 72 hours after injection were randomized to receive daily intragastric doses of distilled water, glibenclamid 8 mg/kg, or polyclonal antibodies to C-termina...

This trial was undertaken in order to evaluate the effects of endurance training on health cost in type 2 diabetes. 35 diabetic patients were randomly assigned to 2 groups: After 10 drop-outs, 15 followed a training program (8 sessions followed by training at home at the level of the ventilatory threshold VT) while 10 had only routine treatment. Both groups were followed over 1 year with evaluation at 30, 120, 240 and 365 days for health costs, blood pressure, and a...

Background: Phosphoprotein enriched in diabetes (PED) is a scaffold protein widely produced in different tissues; it is involved in multiple cellular functions, including insulin-regulated glucose transport. Previous findings showed that in individuals with type 2 diabetes (T2D) the PED gene is overexpressed in skeletal muscle (SM) and adipose tissue (AT), both target tissues for insulin activity. Our group has recently evidenced that PED protein is also expressed in periphera...

Background: The aim of our study was to assess the effectiveness of α-lipoic acid for the reducing the risk of developing peripheral diabetic neuropathy.Subjects and methods: We have studied 38 patients with type I and II diabetes, from age 28 to 35. The mean duration of disease was 9 years. Patients were divided in two groups. In group I were included 15 patients which got α-lipoic acid in order to prevent peripheral diabetic neuropathy in dos...

Objective: Familial combined hyperlipidemia (FCH) is the most common familial hyperlipidemia with a high risk of the early atherosclerosis. The aim of this study was to compare levels of s-ICAM-1 and s-VCAM-1 in asymptomatic members of FCH families with healthy controls and to find out relation between s-ICAM-1, respective s-VCAM-1, and risk factors accompanying FCH. We also investigate association between adhesion molecules and intima-media thickness of common carotid artery ...

Introduction: The increased insulin resistance seen in Type 2 diabetic patients has been shown to be associated with abdominal fat accumulation, hypertension, and dyslipidaemia. The dyslipidaemia is characterized by raised serum triglycerides and decreased high density lipoprotein cholesterol (HDL) levels. The aim of the present study was to investigate the relationship between abdominal fat, lipid and adipokine secretion in South African type 2 diabetic patients of Indian and...

Although, high doses of cyclosporine (cyclo)has been demonstrated to inhibit the development of type 1diabetes mellitus (T1D), its usefulness was limited by its toxicity. Since methotrexate (Mtx) and cyclo have been shown to synergistically act in other disease processes, we determined if low dose cyclo and Mtx therapy could inhibit the development of diabetes and reduce or eliminate the need for insulin therapy in a pilot study.Methods: Insulin dose and...

Background: Pregnancy may adversely affect the progression of diabetic retinopathy and can have serious implications for the pregnant women.Aim: To asses the impact of pregnancy on the progression of diabetic retinopathy in women with type 1 and type 2 diabetes mellitus and to identify risk factors for the progression of retinopathy during pregnancy.Methods: 306 diabetic women, 229 (75.4%) with type 1 and 77 (23.9%) with type 2 di...

The aim of this study was to compare the efficacy of treatment with insulin alone, insulin plus acarbose, insulin plus metformin or insulin plus rosiglitazone in type 2 diabetic subjects who were previously on insulin monotherapy, and to evaluate the effects of these treatments on cardiovascular risk factors including lipid profile, C-reactive protein (CRP) and fibrinogen. Sixty-six poorly controlled type 2 diabetic patients on insulin monotherapy were involved. They were rand...

Glucose is slowly linked to haemoglobin in a non-enzymatic reaction and the determination of a glycated protein (HbA1c) is used for long term monitoring blood glucose concentrations. Radiometabolism studies in sheep showed that a haemoglobin-adduct formation also takes place with epinephrine or norepinephrine.The aim of our study was to elucidate if there is a competition between catecholamines and glucose for binding sites on proteins of the erythrocyte...

Diabetes mellitus type 2 (DM2) is affecting physical and psychological health.Objective: Compare anthropometric data, body composition, lipids levels, emotional state, quality of life (QoL) of DM2 patients and that of healthy persons of the same age.39 persons (58.1±9.6 years) with DM2 (18 male, 21 female) and 41 healthy persons (54.3±9.9 years) (22 male, 19 female). Profile of Mood State (POMS) used for emotional state e...

Beta-blockers (BB) may be less effective than other antihypertensive drugs for stroke prevention in patients with primary hypertension (ASCOT and LIFE studies). Our study compares arterial stiffness and central PP between users (BB+) and non users of BB (BB-), among menopausal women with hypercholesterolemia and no history of CV disease.Methods and Results: We used the baseline data of 664 menopausal women, screened for the Cashmere study, a12-month doub...

Little is known about the prevalence and significance of islet cell immunity in elderly patients with type 2 diabetes. The low antibody titers against islet-cell antigens in LADA elderly patients may be a sign of a less aggressive autoimmune diabetes.The objective: To establish the changing frequency and titers of GADA and IAA in elderly diabetics.Material: 83(56F;27M)diabetic patients (60–91 y) divided in age related groups. ...

Introduction: The patients with ACS and scheduled for an elective coronary angiography have high frequency of both newly and previously diagnosed diabetes. The diabetic patients with acute myocardial infarction have an increased risk of death. Elevated blood HYC is strongly related to an increased risk for atherosclerosis and cardiovascular disease. This association is particularly evident in patients with diabetes.Aim of the study: An attempt to evaluat...

Carotid artery intima-media thickness (CCA-IMT) highly correlates with cardiovascular events in type 2 diabetes (T2DM). We aimed to determine the cardiovascular mortality and morbidity incidence regarding CCA-IMT and Framingham Score compared with preceding results of T2DM individuals. Our aim was to determine whether ultrasonographic evaluation of carotid arteries may predict cardiovascular mortality, morbidity and diabetic complications in T2DM patients.<p class="abstext...

Introduction: It has been shown with many studies that sulphonylureas may have a negative effect on parameters of insulin resistance while improving glucose regulation. However not all of the sulphonylureas have the same effect. This analysis assessed the different effects of sulphonylureas on some metabolic parameters of insulin resistance.Method: Newly diagnosed 25 T2DM individuals who were naive of oral antidiabetic therapy were recruited and randomiz...

Study objective: To study blood pressure (BP) levels and aortic dimensions in women with Turner syndrome (TS).Materials and methods: 102 women with TS (mean age 37.7 years; 18–62 years). 24 hour ambulatory BP measurement and echocardiography was performed on participants.Results: Mean BP systolic (sys) and diastolic (dia) values were (±SD): sysBPday 128.0±15.3; diaBPday 81.6±11.8; sysBPnight 110.4...

Objective: Abnormal lipid profile is an important risk factor in the development of macrovascular atherosclerotic complications in patients with type 2 diabetes mellitus (T2D). The aim of this study was to investigate the relationship between lipid profile and lipid peroxidation in type 2 diabetics with and without coronary artery disease (CAD).Materials and methods: We studied 80 patients with T2D, 40 with CAD and 40 without CAD. We also studied 50 non-...

Serum testosterone level is known to inversely correlate with insulin sensitivity and obesity in men. Furthermore, there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in Type 2 diabetic men. Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance. We report a double-blind placebo controlled crossover study in 20 hypogonadal Type 2 diabetic men examining the effect of testostero...

Serum testosterone level is known to inversely correlate with insulin sensitivity and obesity in men. Furthermore, there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in Type 2 diabetic men. Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance. We report a double-blind placebo controlled crossover study in 20 hypogonadal Type 2 diabetic men examining the effect of testostero...

Different interdependences with symptoms of insulin resistance give us the possibility to consider steatosis as a disorder of the liver with metabolic syndrome (MS).The aim of study is to assess the role cholesterol-HDL in rise of diabetic steatohepatosis.40 patients with Diabetes Mellitus type 2 (DM) and signs of MS were examined to determine spreading of steatohepatosis as one of the factors of insulin resistance. Only 8 of them ...

The aim of the research is to study the functional state of liver parenchyma in patients with type 2 diabetes and to analyze hepatobiliary system disorders depending on marker of metabolic syndrome (MS).The study involved 22 patients with type 2 diabetes and MS and 8 healthy persons. Dynamic hepatoholecystoscintigraphy was performed using RKC 301T gamma camera after Tc-99m mesida administration and bile-expelling meal.We establishe...

Background and aims: The aim of this study was to assess the effects of docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) on the heart rate variability (HRV), some biochemical parameters in patients (pts) with Type 2 diabetes mellitus and cardiovascular aunonomic neuropathy (CAN).Materials and methods: 39 pts with CAN (54±5 yrs) were allocated in two groups: A (n=26) were receiving capsules of fish oil every day (2.0 g EPA, 2.0 g DHA and ...

Background and aims: The present study has examined the effect of α-lipoic acid (ALA) and nicotinamide (NA) on the heart rate variability (HRV), superoxide dismutase (SOD), gluthation peroxidase (GPO), catalase activities, reduced gluthatione (GSH), malondialdegide (MDA) contents in the RBCs’ in Type 2 diabetic patients (T2DM) with cardiovascular autonomic neuropathy (CAN).Materials and methods: 59 patients with T2DM and CAN (59.3±7.9 year...

Objective: The aim of this study was to test the hypothesis that type 2 diabetes mellitus is associated with increased oxidative stress in Iranian subjects.Materials and methods: The study population consisted of Fifty-nine patients with type 2 diabetes (mean age 62.5±8.7 years). Type 2 diabetes was diagnosed according to the American Diabetes Association criteria. 36 patients had diabetes complications and 23 patients had no complications. For the ...

Background: The prevalence of primary hyperaldosteronism (PA) has recently been reported as high as 7.5% in patients with hypertension from unselected populations (USP) and up to 22% in selected populations (SP). Whether increased screening and diagnosis of PA will lead to more findings of curable PA (aldosterone producing adenoma, APA) is unclear.Methods: Three-hundred fifty-three consecutive patients with hypertension, age 20 to 88 years were included ...

Background: Liquorice in moderate doses increases blood pressure (BP) in healthy individuals (NT) as well as patients with hypertension (HT) due to increased cortisol effect. Glycyrrhetinic acid, the active substance in liquorice, inhibits 11beta-hydroxysteroid-dehydrogenase type 2 (11betaHSD2) which converts the active hormone cortisol to the inactive hormone cortisone. Recently it has been reported that treatment with glucocorticoids decreases serum levels of cobalamin (B12)...

Objective: Increased abdominal visceral adipose tissue (VAT) deposition is associated with insulin resistance in obese and/or hypertensive patients. We investigated the association of insulin sensitivity with the amount of VAT in young, lean, non-treated males with recently established high normal blood pressure or hypertension grade 1 (HT).Subjects and methods: Twenty-one subjects with HT (age 20.3±0.6 years, BMI 22.4±0.5 kg/m2, sys...

Aim: We had the aim to determine the insulin treatment strategy that could prevent or decrease the occurrence of hypoglycaemia while providing better regulation of blood glucose in Tip 2 diabetic patients with cardiac failure.Method: The patients demonstrating similar characteristics with respect to the age, body mass index, the duration of diabetes and heart failure were randomized into two groups as insulin glargine (n: 19) and NPH (n: 11...

Objective: The short-term cardiovascular effects of continuous ghrelin infusion in healthy humans remain to be studied.Methods: Fifteen healthy, young and normal-weight men volunteered to participate in a randomized double-blind, placebo-controlled cross-over study. The local ethics committee approved the study. We used a constant infusion of human ghrelin at a rate of 5 pmol/kg body weight per minute for 180 minutes and measured peak left ventricular my...

Recent data suggest that circulating retinol binding protein-4 (RBP4) is involved in the pathogenesis of insulin resistance in rodents and humans. Moreover, protein C inhibitor (PCI) which specifically binds retinoic acid was found to be increased in myocardial infarction survivors who are also insulin-resistant.Therefore, we investigated the association of insulin resistance with plasma retinol binding factors (RBP4 and PCI active antigen) in nondiabeti...

Congenital hypoglycemic hyperinsulinemia (CHI) is a clinical and genetic heterogeneous entity. Clinical manifestations can vary from serious life threatening to milder difficultly identifiable cases. Children who don’t react adequate to medical treatment are subject to pancreatic recession. The molecular ethiology are from recessive mutations of the ABCC8 (SUR1) and KCNJ11 (Kir6.2) to dominant mutations of the GCK or GDH genes. Focal dysplasia ...

Background: It has been thought that L-carnitine is effective in improving insulin-mediated glucose disposal either in healthy subjects or in type 2 diabetic patients,and carnitine plays an important role in diabetes mellitus omplications (cardiovascular disease).Objective: We designed this study to investigate the effects of oral L-carnitin administration on fasting plasma glucose (FPG) and glycosylated hemoglob (HbA1c), in patients with diabetes mellit...

Context: Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and obesity, both predisposing factors to type 2 diabetes. A very recently described adipokine, retinol-binding protein 4 (RBP-4), has been shown to modulate insulin signalling and possibly lead to IR. At present, there is no data that depict the relative expression of RBP-4 in either serum or adipose tissue of PCOS women.Objectives: In women with PCOS compared to matche...

Cushing’s syndrome (CS) is associated with hypercoagulable state, mainly dependent on corticosteroid-induced increase of von Willebrand factor (VWF) levels, even though this does not affects all patients. In normals plasma VWF levels are genetically determined by ABO blood groups and polymorphisms G/C −1793, C/T −1234, A/G −1185, G/A −1050 of VWF promoter. These SNPs segregate as haplotype 1 (G/C/A/G) and haplotype 2 (C/T/G/A) with genotype 1/1 (GG...

Gestational diabetes mellitus (GDM) identifies a population of women at high risk of subsequent type 2 diabetes mellitus, representing an early stage in the natural history of the disease. Systemic inflammation is associated with the development of type 2 diabetes but the data concerning pro- and anti-inflammatory cytokines in patients with GDM are limited. The aim of our study was to investigate serum concentrations of interleukin-8 (IL-8), IL-18 and IL-10 in pregnant women w...

Objective: To study if the use of continuous glucose monitoritation systems in real time (GUARDIAN REAL TIME®) in the diabetic patients could improve the metabolic control.Material and method: 15 type 1diabetic patients studied (age: 33.8±13.40, years of evolution: 17.06±11.32) in intensive treatment (5 multidoses, 10 insulin pump) which were made one first blind 4 days long monitoritation to them, PERIOD 1 (P. BLIND) with senso...

Introduction: Approximately 90% of the hypertensive population is characterized as having essential hypertension. Apart from renin and K+, ACTH plays an important role in aldosterone secretion, being a potent stimulant under situations of stress. Up to date, the association between stress and aldosterone-related hypertension has not been studied and that is the aim of our study.Methods: 36 hypertensive patients and 14 matched for age and sex c...

Aim: To study prevalence of foot complications in patients on dialysis therapy and evaluate the role the haemodynamic changes during dialysis procedure in development of foot problems.Methods: 109 dialysis patients, mean age 49 years. 60 of them had diabetes mellitus (DM): 29 on haemodialysis (HD), 31 on peritoneal dialysis (PD). Non-diabetic patients (NDM): 24 HD, 25 PD.Vascular status: doppler, photoplethysmography. Polyneuropath...

Introduction: In recent years, interferon (IFN) is used in treatment of chronic hepatitis and the studies about the side effects of IFN therapy are increasing.Objective: We aimed to investigate the effects of IFN therapy on glucose metabolism.Materials and methods: Study group was consisted with 30 patients who were diagnosed as chronic hepatitis. Sixteen of 30 were chronic hepatitis B and 14 were chronic hepatitis C. Diagnose was ...

Ghrelin circulates in two different forms. Acylated ghrelin (AG), a natural ligand of the GH Secretagogue receptor (GHS-R) type 1a, exerts several biologic central and peripheral actions including stimulation of GH secretion, but also modulation of insulin secretion, glucose and lipid metabolism. Unacylated ghrelin (UAG), despite unable to bind the GHS-R1a, is biologically active showing some influence in vitro and in vivo on glucose and lipid metabolism likely m...

Aim: To define concentrations (conc) of steroid hormones in patients (pts) with preserved gonadal function, suffering from coronary artery disease (CAD), and to assess their relations to patients’ weight.Material: Pts with coronarographically proved CAD: C-W group (gr)-52 women (W) in the age 43±3 years, with stable menstrual rhythm, C-M gr-46 men (M) in the age 52±6 years. Healthy volunteers: H-W gr-15 W (H-W) in the age 41±4 years, ...

Objective: To evaluate the monitoritation systems acceptance: capillary glucose measurements and continuous glucose sensors (CGSM and GUARDIAN).Research design and methods: 15 diabetics patients were monitoritatied in two diferents periods of time. (Period 1: Guardian, 86 hours long. Period 2: CGSM 72 hours long). Later, they had to fill a satisfaction questionnaire concerning several aspects which were valued from 0–6.<table boarder="1" cellpad...

Objectives: The aim of this study was to analyze the influence of DHEA therapy on fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) plasma concentrations in men with decreased serum DHEAS levels and angiographically verified coronary heart disease (CHD).Material and methods: The study included thirty men aged 41–60 years (mean age 52±0.90 yr) with serum DHEAS concentration <2000 μg/l, who were...

Aim: To set up, in acromegaly without diabetes mellitus, a correlation between the disease activity in GH-secreting adenoma (AA) - assessed by minimum GH serum level during an oral glucose tolerance test (OGTT) - and severity of insulin resistance (IR), assessed by HOMA-IR index.Methods: 75 out of 88 consecutive patients with acromegaly hospitalized in our department were included in this study. 13 patients proved to have diabetes mellitus and were exclu...

FPLD is a rare monogenic cause of insulin resistance. We document responses to treatment with metformin in 2 adolescent sisters with FPLD due to heterozygosity for R482W LMNA gene mutation.The probands, aged 14 and 16 years, presented with secondary amenorrhoea, hirsutism and progressive acanthosis nigricans. Phenotypically they showed central obesity, nuchal enlargement, and thin muscular arms. These changes occurred post-pubertally. Anthrpometri...

Patients with primary hyperparathyroidism (PHPT) are insulin resistant. The effect of PHPT on lipid levels and low-grade inflammation leves is unknown. The aim of our study was to estimate the cardiovascular risk profile in patients with PHPT. Methods: In patients with PHPT (N=19; age: 58.15±8.38 years; PTH 180.83±104.15 ng/l, calcium 2.97±0.19 mmol/l) insulin sensitivity (measured using euglycemic hyperinsulinemic clamp - M value), lipids (total choleste...

It was reported that patients with primary hyperparathyroidism (PHPT) are insulin resistant, and that surgical treatment may improve insulin sensitivity in this group of patients. The aim of our study was to evaluate the effect of surgical treatment on insulin sensitivity in patients with PHPT. Methods: In patients with PHPT (N=19; age: 58.15±8.38 years) insulin sensitivity was estimated using euglycemic hyperinsulinemic clamp (M value) before and 3 months after su...

Aims: Studies on statins and insulin-sensitivity in T2DM are highly controversial. We aimed to evaluate the effect of RSV in type-2 diabetic people and whether its action may be phenotype-dependent, i.e. triglyceride (TG)-related (study approved by the local Ethical Committee).Methods: 48 type-2 diabetic pts (22 M:26 F), in a poor glycaemic control with oral agents, insulin or a combination therapy (unchanged over the study), were given RSV 10 mg for 12 ...

Aim: Hypoadiponectinemia is known to be associated with insulin resistance, diabetes and obesity. Since gestational diabetes is together with increased body mass index (BMI) and decreased insulin sensitivity, the evaluation of adiponectin levels in these patients is interesting. We investigated the relationship between adiponectin and glucose tolerance during pregnancy and after delivery.Materials and methods: We evaluated plasma adiponectin levels, insu...

Systemic lupus erythematosus (SLE) is a multisystem multifactorial autoimmune disorder. The survival of SLE patients has been improved by the administration of immunomodulatory therapy. Patients, however, are affected by late onset complications of the disease such as atherosclerosis. Lipoprotein Lp(a) is a known risk factor for the development of atherosclerosis.The aim was to study Lp(a) levels and their relationship with disease activity in SLE patien...

Epidemiological studies indicate that rheumatoid arthritis (RA) patients have increased mortality. Cardiovascular disease seems to be one of the major causes of death in patients with RA. Lipoprotein disorders are observed in patients with systemic autoimmune disorders as well as in patients with RA. Lipoprotein Lp(a) is an independent risk factor for the development of cardiovascular disease.The aim of the study was estimate lipoprotein Lp(a) levels and...

Beta-cell function of HIV-infected patients on highly active antiretroviral therapy (HAART), who display lipodystrophy, may be impaired. An early defect in beta-cell function may be characterized by an increased secretion of 32–33 split proinsulin (SP) and intact proinsulin (IP).To address this issue the secretion pattern of SP and IP of 16 HIV-infected men with lipodystrophy (LIPO) and 15 HIV-infected men without lipodystrophy (NONLIPO) were studie...

Aim: To assess concentration (conc) of arginine vasopressin (AVP) and conc of N- terminated naturetic propeptyde type B (NTpBNP) in patients (pts) after cardiac arrest (CA) and their role for clinical state of pts after CA.Material: 52 pts after CA, 36 men and 16 women, in the age 62±13 years. CA was caused by ventricular fibrillation in 31 cases, by asystolia in 15 and by pulseless electrical activity in 6. 28 pts died after CA (P-CA-D), 24 survive...

Background: Low plasma adiponectin concentrations are associated with diabetes mellitus. Resuts from animal studies suggest that adiponectin plays an important role in regulating insulin action. Leptin levels found to be low in patients with diabetic ketoacidosis (DKA). The recent studies showed that insulin replacement during DKA increased leptin concentrations. In our study, we aimed to determine the effect of insulin replacement on serum leptin and adiponectin concentration...

Standard Autonomic Function tests AFT may not detect subclinical CAN. Modalities exist (Frequency Domain) using PSA of HRV, which may detect subclinical CAN.We performed standard AFTs (HR response to deep breathing, Valsalva, Tilt at 1 min and 6 min) and PSA of HRV on these tests in 46 subjects (29 DM and 17 Controls) matched for age and sex. We sought to establish if those DM subjects considered normal by AFT would exhibit abnormalities in PSA of HRV. W...

Aims: The aim of study was to evaluate glucose control in obese diabetics during six months of treatment with glargin insulin in combination with metformin and glimepirid.Methods: In beginning of study excluded patients who had coronary heart and kidneys disease before. In study included 43 obese diabetics with type 2 diabetes [23 male and 20 female, BMI=29.82±1.91 kg/m2, aged 42–65 yr], who had previously been treated with different...

Cardiac complications account for three quarter of deaths among diabetic patients. Many studies have shown that high-sensitivity C-reactive protein (hs-CRP) correlated with the inflammatory process of atherosclerosis in the coronary artery. This study is designed to determine the levels of plasma hs-CRP in Type II diabetic patients with microalbuminuria and its association with other biochemical markers used for diabetic monitoring. All biochemical parameters were analyzed usi...

Ectopic adrenocorticotropin secretion (EAS) accounts for 10–15% of cases of Cushing’s syndrome and comprises a spectrum of lesions from highly malignant tumours to a variety of less aggressive neuroendocrine tumours. Selective removal of the primary lesion is the optimal management. It is therefore mandatory to localize the source of ectopic ACTH.As no single test is accurate enough to distinguish the ectopic from the pituitary sources of ACTH,...

Adrenocortical sarcoma is an extremly rare tumour associated with a quite pejorative evolution.We report the case of a fifty-eight years old woman presenting a chronic asthenia and acute flank pain. She had no hypertension, no clinical sign of virilization or hypercorticism. Abdominal ultrasonography revealed an 8 centimeters mass above the right kidney. CT scan aspect evoked an adrenal carcinoma embolizing vena cava. Hormonal assays did not reveale any inappropriate secretion...

Medullary Thyroid Carcinoma (MTC) can be associated with Hirschsprung’s disease (HSCR). Mutations in exon 10 of the RET proto-oncogene were found in patients with co-occurrence of HSCR and MTC. The aim of the study was to screen the MTC risk exons in patients with HSCR. The genetic analysis comprised 73 HSCR patients (53 males, 20 females) who were operated on and followed-up during 2001-2006. The cohort consisted of 48 patients with classical HSCR, 11 with long colonic a...

17α-Hydroxylase-C17,20-lyase (P45017α) is a key regulator enzyme of the steroid hormone biosynthesis in both the adrenals and the testes. Inhibition of this enzyme can block androgen synthesis in an early step, and may thereby be useful in the treatment of prostatic carcinoma, which is androgen-dependent in the majority of cases. Abiraterone and its analogues have been found strong inhibitors of P45017α suggesting that steroid de...

Increased basal or pentagastrin-stimulated calcitonin level is the cornerstone for the biological diagnosis of medullary thyroid carcinoma, but is also observed in patients with C-cell hyperplasia (CCH) of the thyroid. In a prospective multicenter study we re-evaluated the reference ranges of basal calcitonin (bCT) in 287 euthyroid controls without thyroid disease (142 men-45 smokers, 3 deprived, 145 women-27 smokers). The CT levels were measured using 2 different assays (Cis-...

An increased cardiovascular risk has been described in patients (pts) with adrenal incidentaloma (AI), similarly to pts with overt Cushing’s syndrome (CS). Some echocardiographic abnormalities and alterations in adipokine secretion involved in insulin resistance, inflammation and atherosclerosis have been reported in pts with CS. In this study the possible correlation between echocardiographic parameters and adipokine levels in pts with AI was evaluated.<p class="abst...

A high incidence of serum anti thyro-peroxidase antibodies (TPOAb) has been found in breast cancer (BC). Aim of this study was to evaluate the predictive value of TPOAb in BC. The study group included 47 women submitted to mastectomy for high malignancy degree BC (tumor size >5 cm and/or n° lymph-nodes >3), followed for 5 years. No patient had distant metastases. All were evaluated for thyroid disorders after breast surgery and before any anti-tumoral adjuvant the...

Background: Surgically treated patients with NFA often present with secondary hypogonadism. Hypogonadism is a well known risk factor for osteopenia or osteoporosis. The aim of this study was to assess (a) the frequency of osteopenia/osteoporosis in a single centre Swiss cohort of patients with operated NFA and (b) whether gender or hypogonadism impacts on bone density at follow up.Methods: Data of patients with NFAs diagnosed between 1967 and 2005 were a...

Background: Adrenocortical carcinoma (ACC) is a rare and heterogeneous malignancy with incompletely understood pathogenesis and poor prognosis. Computerized tomography (CT) and magnetic resonance imaging (MRI) are routinely performed for imaging of the adrenal mass and for standard staging of chest and abdomen as lung and liver are the primary organs for metastatic spread in ACC. Contrast ultrasound is a non-invasive procedure which has been shown to have a high sensitivity an...

Several studies show that characteristics of metabolic syndrome are often seen in patients with adrenal incidentaloma. The aim of our study was to evaluate metabolic factors in these patients. 208 patients (148 female and 60 male, age 55.08±11.02 y’s and BMI 27.91±4.6 kg/m2) were admitted and biochemical, endocrine testing were performed. Lipid status: cholesterol 5.77±1.26 mmol/L, triglyceride 1.92±0.98 mmol/L. 113(55%) patients were hypert...

Despite a wide spectrum of imaging diagnostics, GEP-NETs often stay undetectable until the time of dissemination. Removing of a primary tumour together with disseminated lymph nodes even with the presence of liver metastases is the most appropriate treatment to delay progression of the disease. SRS followed by RGS gives a possibility to detect occult GEP-NET intra-opratively. 99mTc-HYNIC/EDDA-octreotate, a somatostatin analogue with high affinity to sst2 was applied...

Background: Apart from inactivation of the MEN1 gene, molecular events essential for tumorigenesis of the endocrine pancreas are poorly characterized. A potentially useful approach for understanding tumor progression is to study transcription factors operating in fetal pancreatic development. The Notch signaling cascade with expression of the transcription factors Hes1, Hey1, and Ascl1 plays a vital role in sustaining the balance between cell prolif...

The cut-off values able to differentiate between reactive or neoplastic C cell hyperplasia (CCH) or to predict sporadic medullary thyroid cancer (MTC) are still debated both for basal and stimulated calcitonin (bCT and sCT). Aim of the present study was to define the prevalence and the histological patterns of CCH in 15 patients with multinodular goiter (MNG), bCT>10 pg/ml and sCT levels >50 pg/ml. These data were compared with those from 16 patients with MNG and bCT l...

Thyroid cancer represents the second more frequent tumor among those diagnosed during pregnancy. Indeed, during pregnancy thyroid volume increases by 20–30% and new nodules can appear, due to the effect of choriogonadotropin which stimulates thyroid growth. Hence, it has been proposed that thyroid cancer diagnosed during pregnancy could harbour a poorer prognosis. Aim of the present study was to compare the clinical outcome in the following 3 groups of patients affected w...

Many single nucleotide polymorphisms (SNPs) of the RET gene have been described both in the general population and in patients with sporadic medullary thyroid cancer (sMTC), MEN2 or Hirschsprung disease. Some association studies reported a higher prevalence of these variants in the affected patients, suggesting a possible role in modifying the risk of occurrence of the disease. However, data from different cohorts of sMTC are discrepant and the aim of the present study ...

Radioactive and transgenic tracing experiments indicate that in the adult adrenal stem cells persist in the periphery of the cortex, which migrate centripetally and populate the inner cortical zones upon differentiation. However, investigation of these cells has been hampered by the lack of known marker genes. Vital Hoechst dye exclusion has been described as a method for isolating a side population (SP) from mouse bone marrow, which was enriched with stem cells. Utilizing thi...

A retrospective analysis of the results of all intra-arterial calcium stimulations performed at St. Vincent’s Hospital, Dublin, in the years 2001-2006. All patients with symptoms suggestive of hypoglycemia had 72 hour fasting test with evidence of inappropriately elevated insulin and c-peptide at the time of hypoglycemia. These patients were investigated further with pancreatic imaging and selective intra-arterial calcium stimulation with hepatic venous sampling (ASVS). A...

The increasing use of somatostatin (SRIF) analogues prompted extensive investigations on SRIF receptor (SSR) in human tumours. Human prostate cancer (PCa) may differentially express SSRs from the normal tissue. Moreover, SSR and dopamine (D) receptors (DR) may interact to form homo- and heterodimers with enhanced functional activity. In the present study, using the human androgen-dependent PCa cell line LNCaP, we investigated: 1) SSR and DR subtype expression in different cult...

Somatostatin (SRIF) has been demonstrated to inhibit in vitro proliferation of normal and transformed cells via SRIF receptors (SSRs). Moreover, like other neuroendocrine molecules, SRIF and SSRs may play a significant role in the progression and neuroendocrine differentiation of human prostate cancer (PCa). However, conflicting results have been reported in the literature on SSR heterogeneity and specific cell localization in PCa. In the present study, using the human ...

Human breast cancer tissue is able to concentrate estrogens. 17-beta-estradiol (E2) and estrone (E1) are produced locally through several mechanisms, e.g. from conjugated and unconjugated steroid hormones uptaken from the circulation. This study was aimed to investigate the correlation between endogenous serum sex steroid concentrations and tumour receptor status in postmenopausal breast cancer patients undergoing surgical intervention. The study involved 740 postmenopausal pa...

Germline mutations in the RET gene cause MEN2, an inherited cancer syndrome associated with medullary thyroid carcinoma (MTC). We performed genetic analysis on DNA from whole blood of a 58 yr old female affected by a multifocal MTC. Exons 10, 11, 13, 15 and 16 of RET gene were amplified by PCR using specific primers and characterised by direct automatic sequencing. Here, we report a new RET point mutation: a heterozigous missense mutation Y606C, a G to A nucleotide substitutio...

The von Hippel-Lindau (VHL) syndrome is an inherited multi-tumor disorder characterized by clinical heterogeneity and high penetrance. Pheochromocytoma (Pheo) is present in 10-15% of cases. It can be isolated or associated with other lesions such as hemangioblastomas, kidney cysts or cancer, and pancreatic lesions. Pheos secrete norepinephrine and are generally located in the adrenals. While performing genetic testing in patients affected by apparently sporadic pheos or PGLs, ...

Type 1 deiodinase (D1) catalyses deiodination of tyroxine (T4), which leads either to synthesis of triiodothyronine or reverse triiodothyronine (rT3). T3 can influence the process of neoplasia through its receptors which act as transcription factors and regulate the expression of many tumor suppressor genes and oncogenes. The aim of the study was to analyze the changes in expression of alternatively spliced variants of D1 mRNA in clear cell Renal Cell Carcinoma (ccRCC), which ...

RET is a tyrosine kinase receptor activated by GDNF, NTN, ART and PSPN through GFRa1,2, 3 and 4 respectively. Activation of the receptor elicits intracellular pathways such us Ras/MAPK and PI3K/AKT leading to differentiation and proliferation. Our group has previously shown that RET is expressed specifically in the somatotroph cell population within the pituitary gland, both in rats and in humans. We have also shown that, in absence of its ligand GDNF, RET induces activation o...

BRAF point mutations are found in 29-69% of papillary thyroid carcinoma (PTC). BRAF is a serine-threonine kinase involved in the phoshorylation of MAPK signaling pathway. The mutation is located in the exon 15 of BRAF, resulting in the substitution of valine to glutamate at codon 600 (V600E). Mutation generates unregulated B-Raf activity that leads to increased cellular proliferation. The aim of this study was to determine the frequency of BRAF mutation in the Czech population...

In vitro and in vivo studies suggest that catecholamines, in addition to their hemodynamic effect, exert a direct influence on the vascular wall, leading to eutrophic and hypertrophic remodeling. This finding is in agreement with that recently reported by our group on patients with pheochromocytoma (PHEO) who show carotid intima media thickness (IMT) and vascular fibrosis higher than essential hypertensives matched for classic cardiovascular risk factors, includi...

PURPOSE: To report a case of Cushing’s syndome caused by ectopic ACTH secretion related to a thymic carcinoid presented with trombositopenia.CASE: years old male presented with fatigue, skin rash. At presentation, physical findings showed Cushingoid appearance, with moon face, hyperpigmentation, easy bruising and buffalo hump. His laboratory findings showed platelet: 90.000 (150.000–450.000), ACTH: 609 pg/ml (0–46 pg/ml), baseline cortisol...

There are limited data inquiring the relationship between somatostatin analogues and insulin sensitivity among acromegalic cases. This study was conducted to evaluate short-term effects of lanreotide autogel (LA), administered every 28 days by deep subcutaneous injection, on insulin sensitivity among acromegalic patients with pituitary tumors. Before and following six months of LA treatment, insulin resistance and beta-cell function were calculated by using homeostasis model a...

Multiple endocrine neoplasia type2A (MEN 2A) is a syndrome of familial cancers characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia of the parathyroid glands. RET protooncogene is the responsible gene for MEN 2A; in more than 96% of MEN 2A families mutations in RET exon 10 or exon 11 are identified. Herein we report a MEN 2A case affected by a mutation (Gly533Cys) in exon 8. A 66-yr-old male patient was referred to our Department due ...

Objective: Seventeen patients (9 women, 8 men aged 36 years, 22–58) radically resected for ACC were treated with adjuvant mitotane and prospectically followed from 2000 to 2006.Methods: Stage of ACC: was: 1 stage I,; 12 stage II, 4 stage III; Weiss score 6, 3–9; Ki67% 20, 4–67. Eleven patients had functional tumors. Median duration of treatment was 15 months (range:4–84) and 14 patients are currently on mitotane, 2 died, 1 discontinue...

Retinoic acid (RA) treatment has been used in the last decade for redifferentiation of metastatic thyroid cancer that have lost radioiodine uptake (RIup) with heterogeneous results.Aim: To evaluate the improvement of RIup after a course of RA treatment.Method: Retrospective analysis of 29 patients with radioiodine negative metastatic disease (17 men /12 women; 22 papillary, 4 follicular and 3 oncocytic tumours). RA was given at a d...

Introduction: Cortistatin (CST) is a 17 amino-acid neuropeptide involved in sleep regulation. Due to its structural resemblance to somatostatin (SS), CST binds with high affinity to the 5 known SS receptors. CST also binds to the putative MrgX2 receptor. Previously we demonstrated that various types of human immune cells and tissues as well as lymphoid cell lines express CST mRNA. We suggested that CST plays a regulatory role in immune cell function both in physiological and p...

Extracellular nucleotides, via specific plasma membrane receptors (P2Rs) of the X and Y subtype, modulate several cell functions, including cell-to-cell cross talk. We have previously demonstrated the expression of several functional P2XRs subtypes, including P2X7, in primary human thyrocytes. P2X7 is the main player in inflammation and immunomodulation; a strong expression of this receptor has been shown in several human solid tumors. Polymorphisms of the gene enco...

Extracellular ATP modulates several biological processes via activation of plasma membrane receptors (P2Rs) in normal human thyrocytes (NT). We characterized P2Rs expression and function in two thyroid cancer cell lines: FB1 (anaplastic cancer) and FB2 [papillary cancer (PTC)]. P2Rs expression was evaluated by RT-PCR and WB, intracellular Ca2+changes by fluorimetric technique (Fura2-AM), IL-6 release by ELISA, intracellular [i(ATP)] and extracellular ATP [...

In the 1980 s the discovery of expression of somatostatin receptors on NET cells made the use of somatostatin analogues in diagnosis and therapy possible.The aim: Of the study was to assess response of targeted radio-nuclide therapy with radio-labelled somatostatin analogue 90Y-[DOTA0,D-Phe1,Tyr3]-octreotate (DOTATATE) in treatment of disseminated NETs.Material and methods: 12 patients (a...

In ESC for the period since October 2004 till October 2006 were operated 69 patients with acromegaly. Men were 22 (32%), women – 47 (68%). Age of patients changed from 24 till 68 (middle – 47).All patients were separated into 2 groups: surgery (group 1) and combination treatment (group 2), which consist of surgery and somatostatin analogues therapy before and after surgery.In most cases were macroadenomas, only 5 patients...

Objective: Incidentally found adrenal tumour (adrenal incidentaloma = AI) is the most frequent adrenal disorder. Every patient with AI has to be evaluated carefully to choose the best method of management. We present our experience with a group of 1300 patients with AI, registered at our department.Material and methods: Material consisted of 1300 patients (female/male ratio 2.6, age 10–87 years) with AI ranging in size from 0.8 to 23.0 cm. Methods: ...

In recent years, adrenal tumors (AT) are no rare disease. They may arise from all zones of adrenal cortex and medulla, benign or malignant, sometimes as metastases of distant malignances. Patient’s present hormone excess or mass effect, but part of them is clinically silent. The aim of this study was to investigate the frequency, hormonal secretion and pathohistology of AT in our patients lasting years. All patients with AT which are hospitalized in the period from Januar...

Papillary thyroid cancer (PTC) cells and immune cells can kill each other by death ligands. Death ligands induce apoptosis only in sensitive cells. The sensitivity to apoptosis is regulated in a complex and poorly understood manner. The aim of this study was to investigate the Fas ligand (FasL) and Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) expression in PTC cells and tumor infiltrating immune cells. Twenty-six PTCs without and fifteen PTCs with cervical l...

Introduction: Leptin and adiponectin have opposing properties and are implicated as molecular mediators between obesity and (aggressive) prostate cancer. Adiponectin, circulates inversely proportional to visceral fat accumulation, and has demonstrated anti-proliferative effects in prostate cancer cells; circulating leptin levels increase with visceral fat accumulation and has shown mitogenic effects. We propose that adiponectin and leptin interact in prostate cancer cell growt...

Introduction: Visfatin/PBEF is a novel adipokine circulating inversely proportional to visceral fat mass and exerts insulin-mimetic effects; it is expressed in normal, inflamed and tumour tissues. Visfatin/PBEF has also been identified as NMPRTase, a key intracellular enzyme involved in NAD+ metabolism, replenishing NAD+ during cellular respiration. Inhibition of NMPRTase by the anti-cancer agent FK866 has been shown to induce apoptosis in tumours. Prosta...

Due to its rarity, initial endocrine abnormalities in acromegaly are difficult to investigate in a large cohort, especially with respect to cofounding variables. We searched the German Acromegaly Register for data on the first presentation of patients with acromegaly.Up to November 2005, 1485 patients with acromegaly had been entered into the database. Male patients demonstrated significantly higher random GH (21.0 (0.2–620.0) ng/ml, median (range))...

Objectives: Adrenocortical carcinoma (ACC) is a rare tumor with poor prognosis and limited therapeutic options. Survivin is an anti-apoptotic molecule expressed by neoplastic and tumor-specific endothelial cells of various carcinomas, but rarely or only weakly in normal differentiated tissue. In melanoma and pancreatic cancer, preliminary results of a survivin vaccination trial (www.clinicaltrials.gov) indicated that an immunological response in patients is often paralleled by...

The incidence of differentiated thyroid cancer gradually increased in the last few decades. Primery thyroid cancer is usually located in the thyroid gland and can be classified into well differentiated and poorly differentiated forms. Sooner or later, these cancers metastatize into local lymphnodes or distant organs.We present the histories of two patients with anusual forms of thyroid cancer.A woman of 64 was admitted in our depar...

Issue: The use of thyroglobulin (Tg) as tumor marker in differentiated thyroid cancer (DTC) is limited in the presence of thyroglobulin-antibodies (TgAb) but it is generally believed that this is true only for TgAb concentrations over the normal ‘cut off’ point.The aim: Of this study was to investigate if TgAb-s in the normal range, considered to be physiological, may also influence the accuracy and clinical relevance of Tg measurement.<p c...

Dopamine receptors was suggested to be expressed in medullary thyroid cancer (MTC). The aim of the current study was to evaluate the expression of D2 dopamine receptor in MTC and the effectiveness of the dopamine agonist cabergoline in patients with MTC. Five paraffin-embedded cases of MTC obtained after thyroidectomy were used to evaluate D2 receptor expression by immunohistochemistry. Fifteen patients (7 males, 8 females, 36–78 years) with post-sur...

Background: Somatostatin analogues are very useful in the treatment of symptomatic neuroendocrine tumours, but effects on proliferation remain unclear. Overexpression of the proto-oncogene protein kinase Akt has been demonstrated in certain endocrine tumours, and activates downstream proteins including mTOR and p70S6K, which play a significant role in cell growth and proliferation. We have therefore explored the site of action of somatostatin in causing inhibition of prolifera...

Introduction: In many tissues angiotensin peptides acts as the auto/paracrine growth factors. Their effects are dependent on activation of various intracellular signaling pathways, including mitogen-activated protein kinases (MAPK).Angiotensin II (ang II) is the best known angiotensin peptide. The ang II derivatives, angiotensin III (ang III) and angiotensin IV (ang IV) posses biological activity as well. Both ang II and ang IV are known to promote the p...

Objectives: Adrenocortical carcinoma (ACC) is a rare malignancy with incompletely understood pathogenesis and poor prognosis. Overexpression of epidermal growth factor receptor (EGFR) has been demonstrated in several tumors and is partly associated with a more aggressive phenotype and a worse prognosis. In addition, targeting the EGFR tyrosine kinase represents a successful new therapeutic strategy, e.g. in non-small cell lung cancer. Therefore, we investigated the role of EGF...

Nearly one third of women diagnosed with invasive breast cancer are younger than 50 years with regular menstrual cycles. 60% of these tumors express estrogene and progesterone receptors. Common treatment procedure is surgery followed by chemotherapy, radiotherapy and hormone therapy. Often in younger patients chemotherapy causes permanent amenorrhoea. In case that menses afterwards occurs ovarial suppression is needed, mostly by goserelin, LH-RH agonist. The principle of thera...

Acromegaly secondary to a lung carcinoïd is a very rare entity. Secretion of GHRH (Growth hormone releasing hormone) or GHRH like by neuroendocrine tumor induces pituitary hyperplasia and a production of Growth hormone (GH) with or without others anterior pituitary hormones. Total resection of lung tumor induces normalisation of pituitary function as in our observation.AD, 37 years, male, came to our unit for diabetes mellitus and acromegaly. His ch...

Immature teratoma arising from the brain is very rare. The intra and supra sellar localization is very exceptional. Its clinical symptoms and radiological aspects on TDM are similar to those of craniopharyngiomas but on MRI the fat signal characterize teratomas, but only the histological exam gives the confirmation of this last lesion and makes differential diagnosis with mature tumor whose prognosis is better than the immature one. Our observation illustrates all these proble...

Nowadays neuro-radiological explorations are so frequent that radiologists discover more and more pituitary lesions. In this work we would like to study pituitary microlesions (PML: inferior or equal to 10 mm) in order to analyze age and sex repartition, clinical symptoms leading to the diagnosis, position in the pituitary area and the apparent etiologies.All our patients are examined and hormonal exploration is as complete as possible.<p class="abst...

It is well known that adrenal masses, particularly adenomas are frequently related to metabolic syndrome and insulin resistance. However, there are no reported data about the differences between adenomas and hyperplasia.Authors examined the prevalence of symptoms of the metabolic syndrome and insulin resistance in 25 patients with adrenal incidentalomas (10 men, 15 women) of the mean age 57.9+15 years. 15 patients had adrenal adenoma determined by CT or ...

Background: Primary hyperparathyroidism (HPT) is the most common endocrinopathy in MEN1 and usually its first clinical manifestation. Yet MEN1 is a rare disease, representing only 2–4% of all cases of HTP. We studied the frequency of MEN1 syndrome in HPT patients admitted to our Department.Methods: In a retrospective analysis of 84 suspected HPT patients hospitalized in 1999–2006, case reports of 11 patients with suspected MEN1 were analysed. M...

Background: Somatostatin analogues are used to treat acromegaly patients who, following surgery, have not fulfilled cure criteria (hGH<2,5 ng/ml, IGF-1 below normal range for age and post-OGTT hGH <1,0 ng/ml). We evaluated the efficacy of Sandostatin LAR in managing such patients.Material and method: In our Clinic, 81 acromegaly patients (mean age 51.6±14.4 yrs) were registered over the years 1983-2005. Based on CT i MRI, macroadenoma and mi...

Beta-HLH transcription factors are involved in the ontogenesis of neural/neuroendocrine cells, and may play a role in the pathogenesis of neuroendocrine tumours. Neurogenin 2 (Ngn2) is expressed by the developing mouse pituitary. After preliminary data indicating its expression in the normal human pituitary, we have studied its phenotypic expression in normal and adenomatous pituitary tissues.Methods: Fifty-two pituitary adenomas (PA) – 23 clinicall...

Insulinomas are thought to be the result of reduced ß-cell death and hyperproliferation of this specific and highly differentiated cell type. Specific growth- factors are responsible for inducing ß- cell replication and might therefore be involved in insulinoma formation. Pluripotent islet progenitor cells are thought to be located at pancreatic ducts, which can give rise to novel islets as well as exocrine pancreas formation. TGFß1 signalling disruption has bee...

Adrenocortical carcinoma (AC) is a rare neoplasm with poor prognosis. Medical treatment of AC is actually based on the use of op’DDD (mitotane) with or without traditional chemotherapeutic agents. Only very few information are available about the effectiveness of somatostatin analogs in AC. In human adrenal gland the expression of all five somatostatin receptor (SSTR) subtypes was previously demonstrated. A differential expression was shown in adrenal adenomas and carcino...

A 17-year-old boy was referred to our Department. In his medical history Crohn’s disease had been supposed because of abdominal pain and distention. He had previously undergone minor surgery as having large tongue with neuromas and hypertrophic gums. Due to his marfanoid appearance, arachnodactyly, massive eyebrows and lips together with his medical history, multiple endocrine neoplasia type 2B (MEN2B) was suspected, which is a very uncommon hereditary disease. It consist...

Background: The normal cut-offs of screening and diagnostic tests for autonomous aldosterone (AAS) and cortisol (ACS) secretion are poorly defined, mainly due to the presence of adrenal adenomas among those who have served as controls and the stimulating effect of ACTH on aldosterone secretion.Methods: We investigated cortisol and aldosterone secretion in 151 patients with benign cortical adrenal adenomas (BCAA) and in 119 healthy controls with a normal ...

Immunohistochemical detection of angiotensin receptors AT1 and AT2 in adrenal tumorsAngiotensin II is well known to affect the adrenal cell growth and function. Angiotensin receptors AT1 and AT2 were found to be present in the normal adrenal gland. However, the data on the expression of angiotensin receptors in the adrenal tumors is very scarce.To overcome this gap, the paraffin sections of the adrenal cortical tumors and of pheoch...

Aberrant hormone receptors have been demonstrated in macronodular adrenal hyperplasia or, rarely, unilateral adenomas causing Cushing’s syndrome but their prevalence in adrenal incidentalomas (AI) remains uncertain. Therefore we evaluated patients with bilateral AI for evidence of abnormal response to physiological stimuli. We also compared their biochemical characteristics with those of patients with unilateral AI.Assessment of adrenal function was...

Introduction: The peroxisome proliferator-activated receptors gamma (PPARγ) are nuclear receptors which are detected in normal and pathological tissues. Our earlier study showed the overexpression of PPARγ in human adrenal tumors and pituitary adenomas in comparison to normal glands. The in vitro experiments indicated that ligands of PPARγ inhibit growth of many tumors including pituitary adenomas, thyroid cancers and adrenal carcinomas. However, the data...

Pancreatic NETs often cause difficulties in imaging diagnostics and optimal diagnostic algorithm is searched for. According to the latest reports MDCT sensitivity amounts 60-90%, MR: 80-90%, SRS: 62-100%, EUS: 70-90%.Aim: Assessment of the usefulness of 99 mTc-EDDA/HYNIC-octreotae scintigraphy in detection of primary and metastatic tumours of pancreatic NET in comparison to CT, EUS and IOUS and evaluation of the impact of scintigraphic results...

Background: von Hippel-Lindau syndrome (VHL) is a rare autosomal dominant disease caused by alterations of the vhl tumor-suppressor gene. Patients with VHL are at risk for development of retinal, central nervous system and spine hemangioblastomas, clear-cell renal cell carcinomas, pheochromocytomas, endolymphatic sac tumors and cysts; and pancreatic islet cell tumors. Based on the presence or absence of pheochromocytoma as a phenotypic marker, VHL can be divided into di...

Introduction: Multiple endocrine neoplasia type 1 (MEN 1) may present as a familial or a sporadic disorder with multiple endocrine tumours including parathyroid adenomas or hyperplasias, tumours of endocrine pancreatic and pituitary gland. Familial and sporadic MEN 1-related states which do not fulfill current diagnostic criteria but may be related to MEN 1 syndrome have been also described.Aims: The aim of this study was to examine the prevalence and sp...

There are two types of neoplasms derived from chromaffine tissue: pheochromocytomas (tumors of adrenal core) and paragangliomas (tumors located extraadrenally). Majority of these tumors are sporadic, although according to literature, when DNA analysis is carried out, hereditary disease can be diagnosed in about 25% of patients: Multiple Endocrine Neoplasia type 2 (MEN2A and MEN2B), von Hippel-Lindau Syndrome (VHL), Pheochromocytoma/Paraganglioma Syndrome (PPS) and neurofibroma...

Germinal mutations in protooncogene RET are associated with the inherited medullary thyroid carcinoma (MTC) which occurs as the sole manifestation of disease (FMTC) or, more frequently, as the part of multiple endocrine neoplasia (MEN2). The contribution of RET polymorphism to the occurrence of apparent sporadic MTCs is controversial. In our previous study we have found out that the frequency of RET 769 CTT>CTG polymorphism in patients with MTCs is not significantly higher...

Primary therapy in prolactinomas, the most frequent pituitary adenomas, consists in ergot derivatives dopamine agonists (bromocriptine or cabergoline) which lowers prolactin levels and shrink the tumour. Bromocriptine was the first drug used, but the therapeutic levels are attained after several days/weeks, therefore an acute suppression test is not possible. However, the biological response is variable and 10% of prolactinomas are resistant to medical therapy. In order to eva...

Immunohistochemistry is commonly performed on tumour specimen obtained during transsphenoidal surgery, but its predictive value for clinical outcome is largely unknown. The aim of this study was to compare clinical and biochemical outcome characteristics after surgery with histological tumour properties. This was achieved by matching data from the German Acromegaly Register with those of the Pituitary Tumour Registry of the German pituitary working group. From 285 out of 1543 ...

Background: Typing somatostatin receptor (SSTR) expression in neuroendocrine tumors (NETs) is of relevance to target an octreotide-based diagnostic approach and treatment. The expanding use of immunohistochemistry to detect SSTR is to date not paralleled by an accurate methodological setting and standardized interpretation of the results.Objective: A multicentric study was designed to compare SSTR immunohistochemical expression with in vivo scinti...

Until recently primary aldosteronism /PA/ was thought to be rare, accounting for no more than 0.05–2% of the hypertensive patients. Studies published in the last decade demonstrate that primary hyperaldosteronism is a much more common cause of secondary hypertension than was previously thought, accounting for as many as 5% to 25% of hypertensives in some series. For the present, there are no data concerning the prevalence of PA in Bulgaria which determined the realization...

Epidemiological studies underline that obesity represents a significant risk factor for development of several cancer among them colon cancer. Moreover, multiple recent data indicate that some of adipose tissue-derived hormones may influence the growth of malignant cells. Leptin, the product of the ob gene, is one of them. However, research is still contradictory regarding the role of leptin in colon cancer.The aim of our study was to examine the ...

Acromegaly is amongst other symptoms associated with myopathy, alterations of energy expenditure and insulin action which are mediated by growth hormone (GH) and insulin-like growth factors (IGFs). It is unclear to which extent these abnormalities remain after treatment. Thus, we examined glucose metabolism, intracellular fat deposition and mitochondrial function in patients with prior acromegaly (AM).Six AM (4f/2 m, age: 49±10 years, body mass inde...

Introduction: Neuroendocrine tumors secreting ACTH are a rare cause of Cushing’s syndrome.Diagnostic and therapeutical difficiulties might be caused due to different clinical picture of of neuroendocrine tumors.Patients, diagnostic and therapeutic approach: During 2004–2005 2 female patients 32-years old AL and 67-years old ZS were hospitalized in Endocrinology Department due to severe hypercorticism signs and symptoms. I...

Background: Several susceptibility genes have been found to be associated with development of pheochromocytoma (PHEO): RET, VHL, SDHB and SDHD. We investigate the frequency of germ-line mutations in SDHB and VHL genes in patients with apparently sporadic PHEO.Material and methods: Fifty patients (38 women, mean age 42) with apparently sporadic adrenal and extra-adrenal PHEO were screened. DNA was extracted from whole blood and from paraffin embedded tumo...

Adrenal pheochromocytomas are neoplasms characterized by catecholamine excess. We recently reported on the diagnostic value of plasma metanephrines measured by RIA for the diagnosis of pheochromocytoma. However, RIA may not be used in many laboratories.This study evaluated plasma and urinary metanephrines determined by a newly available ELISA as well as serum chromogranin A (CgA) for the diagnosis of pheochromocytoma. Spontaneous blood samples and 24h-ur...

A 34-year-old woman was initially presented with clinical signs of Cushing’s syndrome (CS). On endocrinological examination, a diagnosis of ACTH dependent CS was established (serum cortisol: 08.00 h: 1245 nmol/l; 24.00 h: 275; plasma ACTH concentration 104 ng/l; inadequate cortisol suppresion on LDDST (787) and suppresion to 318 following HDDST). A magnetic resonance imaging (MRI) confirmed a microadenoma in the left part of the pituitary. Ultrasound examination confirmed...

Background: Mutational screening of the MEN1 gene has been recommended for patients who fulfill clinical criteria for familial or sporadic MEN1 and those suspicious or atypical of MEN1.Patients and methods: Eighteen apparently unrelated individuals (6 males; 12 females, age range 16–71) with clinical manifestations of MEN1 were analised. In addition, we evaluated 7 relatives. Genomic DNA from peripheral blood leucocytes was extracted using st...

Background: Ret protooncogene germ-line mutations are associated with the inherited multiple endocrine neoplasia type 2 syndromes (MEN2a and MEN2b) and also with familial medullary thyroid carcinoma (FMTC). In this study, we report a large scale of mutations in exon 10, 11, 13 and 14 RET protoocogene in patients from Serbia. Our study included patients with MTC.Methods: Our study included 180 patients. Patients were tested for RET protooncogene mutations...

Background: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a new method employed in the management of differentiated thyroid cancer (DTC). The integrated FDG-PET plus computed tomography (PET/CT) fusion imaging system seems able to provide some additional advantages over PET alone, mainly related to a better anatomical localisation of the hypermetabolic metastatic lesions. The influence of serum TSH levels on 18F-FDG uptake by recurrences o...

Growth hormone deficiency leads to profoundly decreased growth velocity and, when untreated, to pituitary dwarfism. We evaluated growth evolution for one to four years under rGH therapy (0.07 IU/kg/day, subcutaneously) at seventeen idiopathic pituitary dwarves with isolated GH deficiency, 13 boys and 4 girls, with a wide span of age at therapy onset (between 4 and 24 years old). Diagnosis was set subsequent to at least two negative GH stimulation tests. All patients were pre-p...

GH deficiency (GHD) can be recognized in a not negligible proportion of thalassemic children, while data on the prevalence of this disorder in adult patients are lacking. Therefore, we elected to study the GH – IGF-I axis in a large group of adult thalassemic subjects.Study design: Ninety-four patients (69 with thalassemia major and 25 with thalassemia intermedia on stable transfusional regimen, 39 men and 55 women, aged 31.5±6.8 years, receivi...

The adrenal gland is composed of the medulla and the cortex, which is further subdivided into three zones: zona glomerulosa (zG), zona fasciculata (zF) and zona reticularis (zR). The zones of the cortex are functionally characterised by their ability to synthesise different steroids and consequently they express different steroidogenic enzymes. These and other markers of the zones have been described but so far no good candidate for a determining factor of zonal establishment ...

Background: Selenoproteins are playing an important role in body homeostasis and development. They control thyroid hormone metabolism and are of prime importance for intracellular redox regulation and cellular defence. The SePP knockout mouse (SePP-KO) is a model of impaired Se metabolism characterized by a disrupted distribution system for organified Se. One of the major phenotypes of the homozygote SePP-KO mice is a reduced increase in size and weight during the growth spurt...

Aim: To assess factors affecting HV during triptorelin suppression treatment for CPP.Materials and methods: Forty-six girls with CPP, with mean age at diagnosis 8.4 yrs who presented with signs and symptoms of puberty before the age of 8 years and were treated with triptorelin for at least 2 years, were studied. All girls were categorized into three groups according to the difference between bone age (BA) and chronological age (ΔBA-CA): group I with...

Growth is an integrated process, resulting from the response of cells to nutrient availability and to hormonal status. Nutrients, in turn, are important regulators of IGF-IGFBP system which are critical regulators of growth. Genetic factors seem to be very important determinant of final stature in countries with high quality of life at variance with underprivileged countries where food intake deficiency is critical. The aim of our study was to evaluate the influence of environ...

Thyroid hormone is absolutely necessary for early brain development.Incidence of thyroid disorders in infancy is 1:4,000.Thyroid hormones can be deficient through hormone synthesis and action or very rarely through defective transport. Some new and exciting transporters for tri-iodothyronine (T3) have recently come to light.MCT 8 gene encodes the protein that transports T3 into neurons. Its mutation result in inability of T3 to enter a developi...

Craniofacial proportions of girls with TS, compared to normal children, show reduced size of the craniofacial complex, retrognathic profile and tendency towards advanced dental age. Growth hormone (GH) treatment in TS positively affects stature, but its effects on craniofacial growth and dental development are largely unknown. The aim of this study was to analyze and to correlate the craniofacial morphology, chronological, dental and bone ages of TS patients receiving GH or no...

Growth is a complex process, influenced to a large extent by GH. Children with GH deficiency (GHD) have typical somatic features, including short stature and a reduction of the craniofacial structures. Dental age (DA) is normally delayed in relation to chronological age (CA). The effect of GH replacement on craniofacial growth is still poorly understood. We studied the craniofacial development and dental maturation in 17 patients (4F, 13M) with GHD of different etiologies. The...

This study was aimed to test our hypothesis that the brain-derived gonadotropin-releasing hormone (GnRH) and dopamine (DA) are delivered to the general circulation in fetal and neonatal rats, i.e. before the establishment of the blood-brain barrier, that is in contrast to adult rats. The GnRH and DA concentrations were measured in plasma and in the brain on the 18th embryonic day (E18), E21, 3rd postnatal day (P3), i.e. before the establishment of the blood-brain barrier, and ...

Diabetes mellitus is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. Diabetes patients usually have accompanying cardiovascular disorders. Sulfonylureas have been the leading oral antihyperglycemic agents for type 2 diabetes treatment, which currently still constitute the most popular anti-diabetic drugs. Nevertheless, concern has arisen over the side effects of sulfonylureas on the cardio...

Objective: Adipocytokines appear to be important in regulating insulin sensitivity. The objective of this study was to compare the levels of adiponectin and leptin in lean, obese and obese diabetic (OD) postmenopausal female (PMF) subjects during 6 months follow-up of Metformin therapy (MT).Methods: We examined plasma levels of adiponectin and leptin in 26 OD PMF with a mean body mass index (BMI) of 36.6±1.8, 10 obese (BMI=35.9±2.2) and 10 lean...

Context: Thiazolidiones (TZD) improves insulin sensitivity in type 2 diabetes via effects on fat metabolism, whereas growth hormone (GH) stimulates lipolysis and induces insulin resistance.Objective: To evaluate the effects of TZD on fat metabolism and insulin sensitivity in GH-treated GH deficient (GHD) patients.Design: Randomized, placebo-controlled, double-blind parallel-group study including 20 GHD patients on continued GH repl...

Objectives: The aim of present study is to determine psychobiological characteristics of sexual dysfunction (SD) associated with metabolic syndrome (MS; as defined by National Cholesterol Education Program’s Adult Treatment Panel III, NCEP-ATP-III criteria) in a consecutive series of 803 male out-patients.Methods: Several hormonal, biochemical and instrumental (penile doppler ultrasound, PDU) parameters were studied, along with psycho...

Objectives: The aim of present study was to verify possible differences in the prevalence of vasculogenic ED and hypogonadism comparing two distinct new definitions of MetS, as National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and International diabetes Federation (IDF) in patients with sexual dysfunction.Methods: Several hormonal, biochemical and instrumental (penile doppler ultrasound) parameters were studied. ANDROTEST S...

Objective: To investigate whether a supervised structured exercise program by 16 weeks improves metabolic, pulmonary and cardiovascular parameters in obese adolescents.Material and methods: We included 38 obese adolescents between 12–15 years old. They participated in a supervised exercise program by 90 minutes, 5 days a week during 16 weeks. At baseline and at the end of the exercise program, we evaluated cardiorespiratory fitness, anthropometric m...

Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity and insulin resistance. Since hyperandrogenism is a PCOS key feature, the aim was to evaluate the effects of androgen receptor activation in terms of continuously administration, beginning pre-pubertal, of either the non-aromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole (L), on...

Introduction: Neonatal events may contribute to the development of disorders such as type 2 diabetes and obesity at adult age. We have previously shown that neonatal testosterone (T) programming of female rats is followed by insulin resistance and changes in adipose tissue distribution with centralization of body fat. Therefore, the aim of this study was to examine the effects of neonatal injection of T, estradiol (E) or dihydrotestosterone (DHT) on insulin sensitivity and siz...

Morbid obesity is associated with a decreased life expectancy and a myriad of serious medical problems. The Roux-en-Y gastric bypass (RYGBP) is the most effective procedure for the treatment of these patients, but it can be responsible of early and late complications. The aim of this prospective study was to evaluate the rate of visceral protein malnutrition (VPM) in morbid obese (MO) patients two years after laparoscopic RYGBP. Albumin (Alb), prealbumin (Prealb), transferrin ...

Aim: To estimate the impact of overconsumption of salty and sweet foods on Body Mass Index (BMI) and Blood Pressure (BP) in children.Patients-Methods: We studied 208 children (105 girls), aged 9.2±3.0 yr, 57 (27.4%) of normal weight, 37 (17.8%) overweight and 114 (54.8%) obese. Overconsumption of NaCl was considered >5 g/day and of free sugar >0.5 g/Kg ideal Body Weight/day. BP was measured as appropriate and BMI was estimated in all childre...

In human adipocytes the cAMP-dependent pathway mediates signals originating from the activation of beta-adrenergic receptors, thus playing a key role in the regulation of important metabolic processes such as lipolysis and thermogenesis. CyclicAMP effects are mainly mediated by cAMP-dependent protein kinase (PKA), a tetrameric enzyme composed by two catalytic subunits associated with two regulatory (R) subunits. There are four different R subunit genes and proteins (R1A, R1B, ...

Background and aims: The aim of our study is to investigate the possible associations between leptin and fasting insulin and index HOMA-IR in patients with Metabolic Syndrome as Leptin is involved in regulation of body weight.Materials and methods: The study included 100 patients (32 m, 68 f) 25–65 years. They were divided into 2 groups matched by sex, age, weight, body mass index (BMI), waist-to-hip ratio (WHR). Research group included 56 patients ...

Objective: The measurement of epicardial adipose tissue (EAT) sonographically is reported to be related with both obesity and insulin resistance. Hepatic steatosis is one of the best known other coincidence with obesity. We aimed to evaluate the relationships between EAT thickness, hepatic steatosis and insulin resistance in obese patients.Methods: Obese 63 subjects were enrolled into the study. Local ethical committee approval was obtained. Patients wer...

Objective: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing’s syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1), which is predominantly expressed in liver and adipose tissue, regenerates active cortisol from inactive cortisone. Increased 11beta-HSD1 may cause tissue-specific Cushing syndrome with central obesity and impa...

Background: Nonclassic congenital adrenal hyperplasia (NC-CAH) caused by mutations in CYP21B gene is an inherited disorder with various clinical forms in relation to the 21-hydroxylase (21OH) activity. Classic forms are recognized early during neonatal period as salt-wasting crisis or genital ambiguity, while non-classic form presents later with wide hyperandrogenic spectrum. Genetic testing has proved to be the definitive diagnostic method.Aim: To obser...

Abdominal obese (AO) women might have a hyperactivation of the HPA axis. The limitations of previous studies have been often represented by the limited and heterogeneous number of patients enrolled. Our aim was to asses urinary free cortisol (UFC) output during daily and nightly hours in a large cohort of AO women vs. normal weight controls (CT). 107 AO women and 37 CT were enrolled in the study. In basal condition, each subject underwent OGTT, biochemical determinations. Each...

Objectives: Food intake is centrally regulated in hypothalamic nuclei where many G-protein-coupled receptors (GPCRs) are expressed which are known to be involved in weight regulation. Peripheral hormonal signals activate their corresponding receptors in the arcuate nucleus. Orexigenic signals activate POMC expression in one subset of neurons and inhibit AgRP and NPY expression in a second subset. Cleavage products of POMC, α- and β-MSH then stimulate melanocortin-4-r...

Introduction: The vascular protective effects of estrogens are known to be mediated by their binding to specific estrogen receptors (ER). However, the significance of genetic variations of the ER in vascular diseases has not been reported. We have examined the association between stroke and PvuII and XbaI polymorphisms of the estrogen receptor-alpha gene in patients with metabolic syndrome.Methods and subjects: The study population consisted by 84 male a...

Aims: The prevalence of type 2 diabetes due to insulin resistance is increasing in puberty. Authors have investigated whether body weight excess arises only from increased fat content of the body. Different anthropometrical data were also analysed if they are able to predict degree of insulin resistance.Materials and methods: 108 obese children (50 female, 58 male, Tanner st-s1-5, mean age 12.06 years, mean BMI: 30.97 kg/m2) with positive fami...

Metabolic syndrome (MS) represents a prominent risk factor for cardiovascular disease. Parameters of MS were compared between obese women and controls. I: 50 women (31.92±5.83 kg/m2; 54.4±3.64 y’s); Controls: 37 women (23.50±2.13 kg/m2; 53.92±3.95 y’s). Weight, height, waist and hips circumference, sagital abdominal diameter (SAD) and blood pressure (BP) were measured. Blood was taken at 8 am for: fasting glucose, triglycerid...

Background: Physiological elevations of free fatty acids (FFAs) occur in a dynamic bell-shaped fashion lasting some hours, e.g. nocturnally and during exercise. In order to define the metabolic role of physiological elevations in relation to diurnal fluctuations in insulin sensitivity, the present study was designed to identify the metabolic effects of a dynamic 4 hour elevation of FFAs during a glucose clamp.Materials and methods: 8 lean, healthy men we...

Background: Excess glucocorticoids result in Cushing’s syndrome (CS) which is characterised by increased food intake, central obesity, dyslipidaemia and insulin resistance, leading to the metabolic syndrome. AMPK is a regulator of energy homeostasis and plays an important role in the regulation of appetite, glucose uptake, lipogenesis and gluconeogenesis. We hypothesised that the effects of corticosteroids on metabolism would be mediated by changes in AMPK activity in a t...

Recent evidence suggests that endogenous glucocorticoids (GC) may be suppressed by adipocyte-derived leptin and elevated by dietary acidity. Therefore we examined whether these factors might be predictors of potentially bioactive free glucocorticoids independently of adrenocortical activity.Body composition, plasma cortisol, plasma leptin, 24-h urinary excretion rates of net acid (NAE) reflecting daily diet-dependent acid load, total nitrogen, urinary fr...

Objectives: We have examined the relationship between the hepatic enzymes and type 2 diabetes. We have analyzed if the levels of hepatic enzymes are associated with body weight, lipid profile and the treatment with metformin, thiazolidinediones or statins.Methods: 318 patients with type 2 diabetes were included and they were compared with 100 healthy subjects. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamiltranspeptidas...

The endocannabinoid system has recently emerged as an important modulator of several functions of adipose tissue by altering cell proliferation and gene expression. In this work, we investigated the effects of CB1 activation/blockade in mouse 3T3-L1 adypocite cells by using WIN55,212, a CB1/CB2 agonist and rimonabant, a specific CB1 antagonist, in different experimental settings such as acute treatment on pre-adipocytes and on mature adipocytes, and chronic treatment during di...

Some extra-thyroid effects of TSH have been described in vitro and in vivo. TSH has recently been suggested to induce IL-6 secretion from adipocytes. Leptin is the main secretory protein from adipose tissue. Our aim was to evaluate the acute effect of rhTSH-induced TSH surge on serum leptin levels in differentiated thyroid carcinoma (DTC) patients. Ten patients (2 m, 8 f; age range 31–66 years) with stage 1-3 DTC were evaluated during scheduled standard rhTS...

Visfatin is a newly discovered protein secreted by adipose tissue, which is suggested to play a role in pathogenesis of insulin resistance. Polycystic ovary syndrome (PCOS) is heterogeneous disorder, where insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the present study was to asses the relation between serum visfatin and insulin sensitivity and markers of hyperandrogenism in a lean and obese PCOS patients. The stud...

The pathogenesis of insulin resistance is not completely understood, however, there are data that it might be associated with altered tissue carbohydrate and lipid oxidation. Adiponectin may be a key regulator of insulin sensitivity and energy metabolism. The aim of the present study was to determine the association of adiponectin, glucose metabolism (oxidation and storage) and lipid oxidation by applying the euglycemic clamp technique and indirect calorimetry.<p class="ab...

Intramuscular lipids, including ceramide, might be responsible for the development of insulin resistance. Insulin action is also inversely associated with circulating proinflammatory cytokines, like interleukin (IL)-18 and positively related to antiinflammatory factors, like adiponectin and IL-10. The aim of the present study was to estimate the relationships between serum adiponectin, IL-10 and IL-18 concentrations and muscle lipid fractions in healthy humans.<p class="ab...

Aim: To study the prevalence of metabolic syndrome (MS) and its relation with ghrelin in old men.Material and methods: Prospective-population based study (2002–2005) in which 153 independently living men older than 70 y were included. Comorbidities, physical exam, BMI, blood pressure were recorded and blood sample taken for biochemical and hormonal determinations. Metabolic syndrome was defined using IDF criteria.Results: MS w...

Obesity is a major contributor to a range of metabolic disorders responsible for much of the medical morbidity and mortality. Increasing numbers of reports concerning not only obesity, but diabetes, hyperglycaemia and lipid dysregulation in patients treated with antipsychotics have raised concerns about a possible association between these metabolic effects and treatment with these medications. The objective of our study was to investigate the prevalence of obesity and other m...

Adipose tissue secreted hormonal mediators, adipokines play pivotal roles in the regulation of, among others, central nervous and immune systems influencing body weight, insulin action and inflammatory responses. The aim of our present study was to investigate possible associations of thyroid function with plasma levels of three of known adipokines, i.e. leptin, adiponectin and resistin in 74 Caucasian subjects without any endocrine diseases or related therapy. In order to cre...

We have previously shown that the orexigenic hormone NPY is secreted by human adipocytes. The orexigenic hormone NPY(1–36) is truncated by the dipeptidyl-inhibitor IV (DPP-IV) to NPY(3–36) as consequence its affinity changes from receptor Y1 to Y4 and 5. The aim was to investigate whether DPP-IV is expressed in adipose tissue (AT) where it could modulate adipose tissue growth through modulation of NPY activity. This is relevant in light of DPP-IV inhibitors utilised ...

Background: The cardiovascular complication is the main cause of morbidity and mortality in obese patients. Endothelial dysfunction and atherosclerosis have the goal role in development of these diseases. The aim of our study was to reveal the role of nitric oxide during obesity associated arterial hypertension.Subject and method: 200 obese patients (age 35–55) were investigated. Control group comprised 25 healthy subjects. We calculated BMI, determ...

Aims: Central obesity is associated with increased cardiovascular morbidity and mortality. It has been proposed that increased lipid accumulation in vascular tissue and the consequent increase in oxidative stress may be a missing link between obesity and atherosclerosis. The peroxisome proliferators-activated receptor (PPAR)-γ coactivator 1-α (PGC-1α) is a transcriptional coactivator playing an important role in energy metabolism. PGC-1α is present in vascu...

Schizophrenia is a devastating mental illness associated with obesity and diabetes mellitus rates that far exceed those of the general population.The aim was to evaluate changes in positive energy balance (serum insulin, leptin and ghrelin) and hormones involved in neuroendocrine regulations (serum cortisol, growth hormone and prolactin) before treatment with atypical antypsyhotics (SGA) in normal weight patients with schizophrenia.<p class="abstext"...

Introduction: The aim of our study was to determine the frequency of hypogonadism (H) in males with type 2 diabetes (T2D) and its relation with erectile dysfunction (ED) and obesity.Methods: We studied 107 diabetic males who came successively to an Endocrine consultation. The presence of H was determined by total testosterone (T) with an immunofluerescence method and free testosterone (fT) calculated with Vermeulen’s equation, defining H if T<2 ...

There are increasing evidences that leptin, a protein secreted by adipose tissue, may be an important factor contributing to the development of atherosclerosis. In this study, the relationship between plasma leptin levels and markers of inflammation and endothelial activation was investigated in 214 obese nondiabetic children and adolescents. Fasting levels of leptin, C-reactive protein (CRP), fibrinogen (FB), interleukin-6 (IL-6), interleukin-1β (IL-1β), intercellul...

Obesity is an independent risk factor for the development of cardiovascular disease, frequently associated with various metabolic disorders defined as metabolic syndrome. High plasma total homocysteine (Hcy) concentration is now well established as a powerful risk indicator for a wide range of vascular diseases.The aim of this study was to investigate total Hcy levels in obese children and their possible association with both metabolic syndrome and vario...

Introduction: Changes in lifestyle have resulted in an increased number of boese subjects, and obesity is currently an important causative factor of health-related problems in Iran.Aims: To investigate the direct relationship of oxidative stress and antioxidant status with obesity in men.Materials and methods: We measured the plasma levels of malondialdehyde (MDA) as a marker of oxidative stress and vitamin E, glutathione and super...

Ghrelin is known to play an important role in overweight formation and glucose metabolism regulation. The aim was to assess ghrelin basal secretion features in persons with metabolic syndrome (MS).We examined 39 patients (age 35–55years) with MS (IDF criteria) and 28 healthy persons of comparable age. Ghrelin, insulin and C-peptide serum concentrations were measured by immunoenzyme method, lipid spectrum parameters - by spectrophotometry. For IR ass...