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      Serum soluble urokinase plasminogen activator receptor (suPAR) in adults with growth hormone deficiency

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          Abstract

          Growth hormone deficiency (GHD) syndrome is associated with adverse levels of several risk factors for cardiovascular diseases (CVD), including metabolic inflammation. However, the impact of GHD and GH treatment on low-grade inflammation is unknown. The aim of the study was to establish the level of the low-grade inflammation biomarker soluble urokinase plasminogen activator receptor (suPAR) in adults with GHD and the response to long-term GH treatment. Measurements of suPAR and CRP were performed in bio-bank serum samples from 72 adults, 34 males and 38 females, with GHD before and during at least 5 years of GH treatment. Mean age was 52.5 ± 15.5 years, BMI 27.3 ± 5 kg/m 2. Clinical evaluations and blood sampling were performed at routine visits. Data on demography, anthropometry, lab results and clinical events were retrieved from post-marketing surveillance study databases and medical records. suPAR and high-sensitive (hs) CRP were analysed using ELISA and immunochemistry, respectively. At baseline blood pressure, lipid profile and fasting glucose were within the normal reference range. Baseline geometric mean and 95% CI of suPAR was 2.9 (2.7–3.3) ng/mL and of CRP 2.3 (0.6–4.0) mg/L. Mean follow-up was 8 ± 2 years. The suPAR levels remained stable during follow-up, although individual increases were seen on occurrence or presence of co-morbidities. In contrast, levels of CRP decreased. In conclusion, the decrease in CRP and indirectly the absence of an expected increase in suPAR over time indicates a favourable effect of GH on low-grade inflammation.

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          Most cited references 31

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          Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee.

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            Premature mortality due to cardiovascular disease in hypopituitarism

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              Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection.

              Human immunodeficiency virus-1 (HIV-1) infection has been shown to result in up-regulation of the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this up-regulation is paralleled by higher serum levels of soluble uPAR (suPAR) in patients with advanced HIV-1 disease and whether the serum level of suPAR is predictive of clinical outcome. Using an enzyme-linked immunosorbent assay, the level of suPAR was measured retrospectively in serum samples from 314 patients with HIV-1 infection. By Kaplan-Meier and Cox regression analyses, the serum suPAR levels were correlated to survival with AIDS-related death as the end point. High levels of serum suPAR (greater than median) were associated with poor overall survival, and Kaplan-Meier analysis on patients stratified by suPAR level demonstrated a continuous increase in mortality rates with higher suPAR levels. After adjustment for accepted prognostic markers-including Centers for Disease Control and Prevention-defined clinical stages, CD4 counts, viral load, beta2-microglobulin, and age-the prognostic strength of suPAR remained highly significant, indicating that the serum suPAR level is a novel, strong, and independent predictor of survival in HIV-1 infection. This report is the first to demonstrate an important association between the plasminogen activator system and disease progression in HIV-1 infection.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                June 2019
                10 May 2019
                : 8
                : 6
                : 772-779
                Affiliations
                [1 ]Patient Area Endocrinology and Nephrology , Infection and Inflammation Theme, Karolinska University Hospital, Stockholm, Sweden
                [2 ]Department of Molecular Medicine and Surgery , Karolinska Institute, Stockholm, Sweden
                [3 ]Department of Medicine , Karlstad Hospital, Karlstad, Sweden
                [4 ]NUTOPI Sp. z o. o. , Poznan, Poland
                [5 ]Clinical Research Centre , Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
                Author notes
                Correspondence should be addressed to C Höybye: charlotte.hoybye@ 123456sll.se
                Article
                EC-19-0159
                10.1530/EC-19-0159
                6547304
                31151091
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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