ACTA ENDOCRINOLOGICA (BUC)

Context. Intermedin (IMD) is the member of calcitonin gene-related peptide family, and tightly associated with type 2 diabetes mellitus (T2DM). The change of plasma IMD levels in T2DM is still unknown. Objective. We aimed to investigate the plasma levels of IMD in patients with T2DM. Design. Fortyone patients with T2DM who were hospitalized in the endocrinology department of Civil Aviation General Hospital from January 2012 to June 2015 were enrolled, and 44 volunteers were selected as the control group. Subjects and Methods. Plasma level of IMD was detected by ELISA. Diagnostic value of IMD was analyzed by area under the receiver operating characteristic (ROC) curve (AUC). Results. The plasma level of IMD in T2DM group was higher than that in the healthy control group, whereas smoking or cardiovascular complications did no influence the IMD levels. IMD levels were correlated with BMI, DBP, triglyceride, uric acid, urea nitrogen, fasting and 2 hours postprandial blood glucose, and HbA1C. The greatest value of AUC for IMD was only 58.73%. Conclusions. Although plasma levels of IMD were increased in patients with T2DM, the very low diagnostic value of IMD for T2DM might not be used for the disease diagnosis.

Introduction: Leptin, which is known to regulate appetite and energy expenditures, may also contribute to mediate the effects of fat mass on the bone.\r\nObjective: The aim of this study was to analyse to what extent leptin and total body composition influence the maintenance of bone mass.\r\nSubjects and methods: We evaluated 34 women divided into two BMI-matched groups based on the ovarian function: 12 premenopausal women, aged 34.08?7.18 years and 22 postmenopausal women aged 61.31?4.51 years, respectively. Total body composition (total fat mass, trunk fat mass and lean mass) and bone mineral density were measured by means of dual-energy X-ray absorptiometry (DXA). Serum leptin concentrations were assessed by ELISA.\r\nResults: The bone mineral content was influenced by both the fat mass (women with normal menstrual cycles r=0.62, p=0.03; postmenopausal women r=0.625, p=0.002) and the trunk fat mass (r=0.597, p=0.004 premenopausal women; r=0.675, p=0.001 postmenopausal women), independently of the ovarian function. Only for the postmenopausal group we could identify a significant correlation between leptin levels and the total body bone mineral density (r=0.479, p=0.024) and the total body bone mineral content (r=0.605, p=0.003), respectively. The serum leptin levels were highly significantly correlated with the total fat mass and the trunk fat mass for both groups. No difference was obtained with regard to the serum leptin levels between pre- and postmenopausal women.\r\nConclusions: Our results suggest the role played by leptin and the fat mass in the maintenance of bone mass.

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Background. There are scarce data about prevalence of mineral metabolism (MM) disorders in Romanian predialysis patients, so we assessed their occurrence and relationships in mild to severe chronic kidney disease (CKD). Methods. One hundred fifteen non-dialysis CKD (eGFR 31, 95% CI 29-35mL/min) and 33 matched non-CKD subjects entered this multicentric, cross-sectional study. Serum 25-hydroxyvitamin D (25OHD), intact parathyroid hormone (iPTH), phosphate (PO4), total calcium (tCa) and alkaline phosphatase (AP) were measured, along with demographic and past medical history data. Results. Hypovitaminosis D was equally prevalent in Controls and CKD (91% vs. 96% had 25OHD<30ng/mL). Increasing proportions of hyperparathyroidism (33% - stage 2 to 100% - stage 5; p<0.001) and hyperphosphatemia (2% - stage 3 to 38% - stage 5; p<0.001) were found. Hypocalcemia was more prevalent in stage 5 (25% vs. 6% in stage 4, none in stage 3 and Controls, p<0.001). Mineral metabolism parameters correlated with eGFR. In addition, iPTH was directly associated with PO4, AP, and urinary albumin-tocreatinine ratio (ACR), but inversely with tCa and 25OHD, while negative correlation of 25OHD with age, AP, ACR, and C-reactive protein emerged. In multiple regression, eGFR was the only predictor of iPTH (Beta -0.68, 95%CI -1.35 to -0.90, R2 0.46, p<0.001), whereas age and ACR were the determinants of 25OHD (a model which explained 14% of its variation). Conclusions. Hypovitaminosis D was very common irrespective of CKD presence and severity, and it seems worsened by older age and higher albuminuria. Hyperparathyroidism preceded hyperphosphatemia and hypocalcemia, and it seems mostly dependent on kidney function decline

Background. Hashimoto thyroiditis (HT) is an autoimmune disease and the most common cause of hypothyroidism. The widespread lymphocyte infiltration in the thyroid gland and intolerance of the body against its thyroid antigens leads to the destruction of thyroid cells and impaired thyroid function. Granulysin (GNLY) is a cytolytic antimicrobial peptide that has been associated with a wide range of diseases such as various infections, cancer, transplantation, and skin problems. However, there are a few studies investigating the relationship between HT and granulysin. Aim. Our study aims to investigate whether granulysin levels and GNLY gene polymorphism contribute to the damaged immune response leading to HT. Material and Methods. 100 unrelated patients diagnosed with HT and 140 healthy individuals were included in our study. Frequencies of GNLY rs10180391 and rs7908 gene polymorphisms were determined using PCR- RFLP method and serum granulysin levels were determined using ELISA. Results. There is no statistical significance between patient and control groups in terms of genotype and allele frequencies of GNLY gene polymorphisms and serum levels of granulysin. Conclusion. In conclusion, granulysin and GNLY gene polymorphisms do not appear to relate to HT disease.

Background: Published data sustain the participation of vascular renin angiotensin system (RAS) on alteration of pulmonary vessels reactivity during the allergic airway inflammation. Ghrelin is a growth hormone-releasing peptide involved in modulation of immune function.\r\nObjective: This study aims to investigate the interaction between ghrelin and local RAS from rat pulmonary vessels during ovalbumin ? induced allergic airway disease. Methods: The angiotensinogen (AGT) ? induced contractions were assessed on isolated pulmonary artery and veins from ovalbumin sensitized rats receiving either saline (OSR) or ghrelin (OSG) by endotracheal instillation. Experiments were performed in the absence or the presence of losartan, D-ALA7, chymostatin and N&#969;-nitro-L-arginine methyl ester (L-NAME).\r\nResults: The AGT contractile effects mediated by AT1 receptors were lower with at least 25% on vessels from OSG than from OSR. The D-ALA7 and L-NAME significantly increases the AGT ? induced contraction on OSG. The amount of nitric oxide released after stimulation with AGT is higher on OSG and it is blocked by D-ALA7.\r\nConclusion: Our results suggested that pulmonary delivery of ghrelin could modulate the local RAS from pulmonary vessels by promoted the angiotensin 1-7 mediated effects. These data sustained the existence of another possible way for ghrelin?s beneficial effects on the lung.

Despite several attempts to establish the role of QUS in clinical practice, issues such as definition of osteoporosis based on QUS, screening strategy and therapy efficacy for patients identified by QUS as having high risk of fracture remain a matter of debate. The present study aimed to evaluate the diagnostic agreement between two QUS techniques (heel QUS and proximal phalanges QUS) and DXA in an unselected population of Romanian women aged 24- 80 years, as well as to offer cut-off levels for QUS to distinct between women with or without osteoporosis identified by DXA. In women measured by both DXA and calcaneus QUS (c- QUS), bone mineral density (BMD) moderately correlated with stiffness index (SI) (L1-L4: r=+0.51, p<0.001; femoral neck: r=+0.53, p<0.001; hip: r=+0.57, p<0.001), while in women examined by both DXA and phalanx QUS (ph-QUS), BMD was positively related to amplitude-dependent speed of sound (Ad-SoS) (L1-L4: r=+0.47, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001) and ultrasound bone profile index (UBPI) (L1-L4: r=+0.44, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001). At a T-score cutoff level of -2.5SD, the high specificity but low sensitivity suggests a low false positive rate of c-QUS as a diagnostic test; still, several patients with the disease may not be correctly diagnosed. At the same cut-off level, ph-QUS showed higher sensitivity and lower specificity. Diagnostic agreement between DXA and QUS was poor, with k-scores ranging from 0.33 to 0.39 for c-QUS and from 0.14 to 0.29 for ph-QUS, respectively. Lowering c-QUS T-score cutoff for lumbar spine osteoporosis screening to -1.5SD and ph-QUS T-score cut-off to -1.9SD, respectively, improved sensitivity and had a minor effect on diagnostic agreement. Regardless of the evaluated site, neither c-QUS nor ph-QUS does represent an adequate predictor of BMD in Romanian women. Changing the diagnostic T-score threshold from -2.5 SD to -1.5 SD and -1.9 SD in subjects examined by c-QUS or ph-QUS, respectively, is followed by improved sensitivity and diagnostic agreement in the identification of patients with vertebral osteoporosis. Cut-off values may allow QUS to be used as a screening tool for spine and femur osteoporosis.

Background. Skull metastasis has not been reported from mixed medullary follicular thyroid carcinoma (MMFTC). Objective. To present a patient with expansile lytic skull metastasis. Case report. A 61 year lady is presented with goiter for 7 years and 8 cm diameter painful swelling over frontal bone for 18 months, aspiration from which revealed sheets and clusters of polygonal cells, similar to aspiration from hypoechoic nodule in right thyroid lobe. Serum calcitonin (569pg/mL) and carcinoembryonic antigen (11.2ng/mL) were elevated. Histopathology of 3.8×3.1cm nodule in thyroidectomy specimen revealed irregular islands of small polygonal tumor cells with extracellular amyloid deposits (suggesting medullary thyroid carcinoma (MTC)), intermingled with thyroid follicular cells showing capsular and vascular invasion (follicular thyroid carcinoma (FTC)). Immunohistochemistry of the thyroid tumor was negative for calcitonin and for thyroglobulin. Post-operative serum calcitonin and stimulated thyroglobulin were respectively 97 pg/mL and 11.5 ng/mL. I131 whole body scan revealed intense uptake in region of the skull metastasis with small uptake in thyroid bed. She received 150 mCi of I131with resolution of pain, heaviness, throbbing, reduction in swelling size, and lack of disease progression. Conclusions. Skull metastasis was the presenting feature of MMFTC which improved with I131 therapy. Patients with lytic skull metastasis should be evaluated for occult thyroid malignancy.

Context. Ghrelin, in both its acylated and desacylated forms, and leptin can modulate fetal energy balance and development. Objective. The aim of our study is to assess desacylated ghrelin (DAG) and leptin values and influence on intrauterine and postnatal growth in infants with intrauterine growth restriction. Design, subjects and methods. We performed a prospective study on 39 infants recruited over five months, 20 appropriate - for - gestational - age (AGA) infants and 19 small-for-gestational-age (SGA) infants, in which we measured DAG and leptin in the umbilical cord blood and we compared their respective values between the two groups, along with auxological parameters at birth and at 10 months of postnatal age. Results. Our results show that both DAG and leptin have lower values in SGA infants and correlate with most of the anthropometrical parameters at birth. Both hormones correlate with weight at 10 months in SGA infants, but this correlation lacks in AGA infants. Whereas DAG in the cord blood can be considered a predictor for weight at 10 months (β=0.207, p=0.001), the same cannot be stated about leptin (β=0.078, p=0.195). Conclusion. DAG and leptin are involved in both intrauterine and postnatal development, but the extent of their role is still to be determined.