ACTA ENDOCRINOLOGICA (BUC)

Context. Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. Objective. The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. Subjects and methods. The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. Results. Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. Conclusions. Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%

Context. Nonalcoholic fatty liver disease is common in type 2 diabetes mellitus patients, being difficult to diagnose. Objective. To find a correlation between elastographic parameters and lab results, for facilitating the diagnosis of nonalcoholic fatty liver disease. Design. This is a cross sectional study, conducted at the Departments of Diabetes, Nutrition and Metabolic Diseases, and Gastroenterology and Hepatology, of the Clinical Emergency Hospital “Pius Brinzeu” Timisoara. Subjects and Methods. We included 190 type 2 diabetes mellitus patients, collected data regarding medical history, clinical and biological features and applied the Alcohol Use Disorders Identification Test. We excluded patients with other causes of liver disease. Liver steatosis and fibrosis were evaluated through transient elastography, yielding two parameters: liver stiffness as an indicator of liver fibrosis stage, expressed in kPa, and liver steatosis stage, assessed by controlled attenuation parameter, expressed in dB/m. Data were analyzed using SPSS 15. Results. The analyzed group comprised 113 patients. Elastographic measurements showed that 93.8% of the patients had steatosis (controlled attenuation parameter ≥232.5 dB/m) and 70.8% severe steatosis (controlled attenuation parameter ≥290 dB/m). Severe steatosis was more common in women (75.7%) than in men (68.1%) (p<0.0001). From the patients with steatosis, 47.2% had liver stiffness values suggestive for fibrosis and 19.8% for cirrhosis. Most patients with steatosis and severe fibrosis were obese (66.7%). Triglycerides/HDLc ratio >4 correlated with hepatic steatosis (p=0.04), being more common in patients with severe fibrosis/cirrhosis (58.3%) than in those with absent or mild fibrosis (36.2%). Conclusions. Our study found a clear correlation between type 2 diabetes mellitus and the presence of liver steatosis. It correlates with body mass index, waist circumference (in men) and triglycerides/HDLc ratio. Controlled attenuation parameter is a useful noninvasive method for detection and quantification of liver steatosis.

Introduction. Ties between the endocrine system and mental health are undeniably a consistent point of interest in modern day medicine. Furthermore, mental disturbances due to hormonal changes following childbirth have been mentioned in medical literature since Hippocrates. Considering the dramatic endocrine, paracrine and autocrine changes that occur during gestation, labour and postnatal phase, hormonal theories are not to be ignored in the treatment of postpartum disorders. Results. Reproductive hormones are known to modulate behavioural, emotional and cognitive response, therefore rapid changes in estradiol and progesterone plasma concentrations during pregnancy and labour create a vulnerable terrain leading towards postpartum disorders. New research shows that women suffering from postpartum disorders have abnormal neural responses, suggesting a neuroendocrine explanation for postpartum syndromes. Conclusion. To facilitate further research in this area, we present new information on several hormonal interactions and the psychiatric response involved in pregnancy and labour, offering an interdisciplinary outlook on pregnancy and postpartum disorders. There is enough evidence to suggest that estradiol, progesterone, oxytocin, cortisol and thyroid hormones are some of many hormones involved in postpartum syndromes and tackling their perinatal imbalance with pharmacological substituents or antagonists could be useful as an adjuvant form of treatment in future patients.

Introduction. Autoimmunity derives from a complex interplay of genetic and environmental factors. Major histocompatibility complex (MHC) alleles and non-MHC loci have been identified as susceptibility markers. Few studies evidenced an association between autoimmune thyroid disease (ATD) and CT60 or 49 A/G polymorphisms in the CTLA-4 gene. Objectives. The aim of our research was to investigate in a pilot case-control study whether other two CTLA-4 gene polymorphisms, i.e. the CTLA-4 1661 A/G and the CTLA-4 658 C/T single nucleotide polymorphisms (SNP), are involved in genetic predisposition to ATD. Material and methods. Between January and April 2009, 42 subjects entered the study. Of these, ATD (i.e. chronic autoimmune thyroiditis, Graves’ disease) was diagnosed in 21 patients, whereas in 21 subjects no signs of autoimmunity were identified. CTLA-4 gene polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. No association was observed between the CTLA-4 1661A/G gene polymorphism in patients with ATD and controls (p = 0.094, by chi-square test). Likewise, no statistically significant difference was noticed between groups with regard to the CTLA-4 658 C/T gene polymorphism (p = 0.649). Conclusions. At the time being, this is the first case-control study that examined and demonstrated lack of association between CTLA-4 -1661 A\G and -658 C\T SNP and ATD; however, larger numbers of subjects are needed to clarify the role of CTLA-4 gene polymorphisms in endocrine autoimmunity.

Objective. To analyze the association between low bone mineral density (BMD), metabolic syndrome (MS) and sex hormones deficiency in men. Methods. We included in this retrospective study 199 men with osteoporosis or osteopenia and 167 men with normal BMD as controls, aged between 55-85 years old. Patients’ evaluation included: medical history and physical examination, X-ray of thoracic and lumbar spine, measuring BMD at hip and lumbar spine, serum glucose and lipid profile, serum levels of total testosterone (tT), free testosterone (fT) and estradiol (E2). Results. The results revealed a significant association between low BMD and MS (p=0.011). Vertebral fractures were more frequently associated with MS (p=0.041). Patients with MS had lower vertebral BMD (p=0.037) and lower E2 levels (p=0.024) compared with those without MS. In men with MS, E2 deficiency can predict the value of vertebral and hip BMD. fT deficiency can predict only the value of hip BMD. Conclusions. A significant association between MS, low BMD, vertebral fractures and sex steroids deficiency, in particular E2 and fT was found. The presence of MS and sex hormones deficit can predict the reduction of BMD.

Context. Advanced skin cancers have high mortality and morbidity, and early detection is crucial for prognosis. Information regarding the patterns of skin self-examination and tumor early detection in the Central and Eastern Europe is scarce. Objective. Analyze the gender differences in the practices and attitudes related to skin cancer early detection of skin cancer patients in Romania. Methods. Prospective questionnaire- based survey of patients with confirmed diagnosis of skin cancer, registered in a university reference center for dermatooncology between 2011-2012. Results. 122 skin cancer patients completed the survey (response rate 72%). Female skin cancer patients reported lower level of education and likelihood to receive a medical full skin examination. Women were more likely to check their own skin and to detect suspicious lesions on themselves and their partners than men. They delayed longer the presentation to a physician after noticing a suspicious lesion (11.4 months vs. 6.4 months median). 90.76% of all skin cancer patients were not warned by any doctor about their skin cancer risk; 30% of them never check their skin. Conclusions. Women tend to be more concerned about their skin than men, but receive less medical attention and delay longer the diagnosis. Our study also signaled an urgent need of improving the patients and physicians education for skin cancer early detection in Romania.

Our aim was to explore the interactions of intercellular adhesion molecule (sICAM-1), TNF-&#945; (tumor necrosis factor-&#945;), interleukin-1&#945; (IL-1&#945;) and interleukin-6 (IL-6) with\r\ndopamine agonists in a culture of adenomatous cells from an nonfunctional macroadenoma.\r\nMaterials and methods. Tissue specimen from pituitary macroadenoma removed in transsphenoidal surgery was prepared for primary culture. Cells were counted and plated at 105/well into 24-well plates in a final volume of 1ml. Cabergoline in molar doses of 10-6, 10-7, 10-8, 10-9 was added and the cells were incubated for 4 days. sICAM-1, TNF-&#945;, IL-1&#945;, IL-6 were measured from cell-culture supernatants by ELISA kits.\r\nResults. sICAM-1, TNF-&#945;, IL-1&#945; and IL-6 were detected in the untreated control cultures after a 4d period. There was a negative correlation between TNF&#945; and IL-1&#945; (p=0.007).\r\nThe levels of PRL and hGH had measurable values above those found in culture medium without tumor cells. PRL positively correlated with IL-1&#945; ( p=0.05). hGH positively correlated with cell proliferation (p=0.049). Cabergoline treatment showed that IL-6 progressively decreased with the dose, ranging from -27.41% to -76.44%. TNF-&#945; significantly decreased (-65.90%; p<0.03)at the cabergoline 10-7 M dose. IL-1&#945; progressively increased with cabergoline dose, ranging\r\nfrom -2.53% to 345 %. sICAM-1 was significantly reduced by cabergoline at 10-9 (-47.12 %; p=0.045) and 10-6 M (-59.16%; p=0.01) doses. TNF-&#945; positively correlated with PRL (p=0.025); IL-6 positively correlated with hGH (p=0.044); sICAM-1 negatively correlated with hGH\r\n(p=0.009), TNF&#945; (p=0.025) and IL-1&#945; (p=0.044).\r\nConclusions. These data support the existence of an immunoendocrine network in pituitary tumorigenesis; TNF-&#945;, IL-6, IL-1&#945;, sICAM-1 significantly interfered by cabergoline\r\ntreatment in a dose-dependent way. However, future studies on different types of pituitary tumours are needed to confirm these findings.

Background. Genetic variants of the endothelial nitric oxide synthase (eNOS) gene have\r\nbeen reported to be associated with cardiovascular disease. We hypothesized that G894T\r\npolymorphism might trigger many of the endocrine-metabolic changes related to metabolic\r\nsyndrome (MetS).\r\nStudy Design. 148 subjects with MetS and 142 healthy control subjects aged 23-60 years\r\nwere studied. Fasting serum levels of insulin, cortisol, 17-OH Progesterone, DHEA,\r\nandrostendione, IGF1, GH, PRL, CRP, resistin and biochemical profile were evaluated. G894T\r\n(eNOS) polymorphism was assayed by using PCR-RFLP technique.\r\nResults. The frequencies of genotypes and alleles of G894T polymorphism did not deviate\r\nfrom the Hardy-Weinberg equilibrium. In the MetS group the percentages of both GT (51.35 vs.\r\n39.44; OR=2.09; CI=1.27-3.45; p= 0.003) and TT (16.22 vs. 8.45; OR=3.08; CI=1.41-6.74;\r\np=0.003) genotypes and T allele (41.9 vs. 28.2; OR=1.83; CI=1.3- 2.6; p=0.0005) significantly\r\nincreased compared to control group. The G894T polymorphism was more significantly\r\nassociated with the MetS in the presence of cortisol, 17-OH Progesterone, PRL, IGF1 and CRP\r\n(OR= 8.20; 95%CI=2.31-29.08; p=0.001) and significantly stronger in the presence of IGF1,\r\nPRL, 17OHP, resistin and CRP (OR= 10.21; 95%CI=2.42-43.05; p=0.002). The T allele carriers\r\nhad higher values of waist circumference, systolic and diastolic blood pressure, cortisol, 17-OHP,\r\nandrostendione, PRL, resistin and lower values of glucose, HOMA-IR in MetS group; The TT\r\ngenotype carriers had higher values of triglyceride in both control and MetS group.\r\nConclusion. Our results show an interaction between the G894T polymorphism and its\r\nphenotypes in conferring a higher susceptibility to the endocrine changes involved in\r\npathogenesis of MetS suggesting a role of the eNOS gene in the modulation of the molecular\r\nendocrine mechanisms.

Context. In HIV+ patients, several factors related to patient and antiretroviral therapy (ART) could determine early onset of bone mineral density (BMD) disturbances. Objective. Evaluation of bone quality according to gender in patients from the HIV Romanian cohort. Design. A cross-sectional study in “Prof. Dr. Matei Balș” National Institute for Infectious Diseases, Bucharest between 2016-2018. Subject and Methods. We collected data regarding HIV infection, ART history, viral hepatitis co-infections and we calculated patients body mass index (BMI). CD4 cell count, HIV viral load (VL), vitamin-D levels were determined. Dual-energy X-ray absorptiometry (DXA) scans were used to evaluate BMD. Results. We enrolled 97 patients with the median age of 26 years. According to the DXA T-scores, 10 males and 8 females had osteopenia and 4 males and 4 females had osteoporosis. According to Z-scores 2 males and 1 female had osteoporosis. Hip DXA T-scores revealed osteopenia in 6 males and 9 females, whereas T and Z-scores showed osteoporosis in 2 males and 3 females. Lumbar spine (LS) T-score diagnosed osteopenia in 9 males and 6 females, while T and Z-scores revealed osteoporosis in 3 males and females. In males, low T-scores were associated with decreased BMI; low LS DXA Z-scores with low vitamin-D levels; low T and Z-scores and LS-BMD with high VL. Conclusions. Evaluating bone quality in patients with a long history of HIV infection, multiple factors should be taken into account.

Prader Willi syndrome is a complex disease caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11.2-q13. Typical clinical features are hypotonia and feeding difficulties in infancy, followed by hyperphagia and progressive obesity, distinctive dysmorphic features, intellectual disability and behavioural problems. In this paper we present clinical, metabolic and endocrine aspects in five genetically confirmed patients with PWS. Data about thyroid dysfunction, GH deficiency, adrenal insufficiency, and LH/FSH disorder caused by hypothalamic dysfunction in PWS were collected and analyzed. Cardiovascular metabolic profile was also assessed, based on plasma lipids, blood glucose, HbA1c values, and measurements of body weight and blood pressure. Clinical features present in all our patients were marked hypotonia and feeding difficulties in infancy, obesity, dysmorphic face, viscous saliva, small hands and feet, intellectual disability and characteristic behaviour. Adrenal function appeared to be normal in all patients; mild hypothyroidism was identified in one patient; sex development abnormalities were present in three patients and GH levels were within lower normal range in all patients. GH therapy was initiated in two patients, both with unevolutive skeletal anomalies, with good results and no side-effects. Only one patient had a normal lipid profile, underlying the importance of early detection and treatment of cardiovascular risk factors. Our study also illustrates the challenges raised by some features very rarely described in PWS (Blount disease and multiple allergies).