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1. Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study

Author

Glöckner, Stephan, Sinnott, Richard O., Stell, Anthony, Fragoso, Maria C., Kastelan, Darko, Pupovac, Ivana D., Simunov, Bojana, Cazenave, Sarah, Haissaguerre, Magalie, Tabarin, Antoine, Bertherat, Jérôme, Libé, Rossella, Kienitz, Tina, Quinkler, Marcus, Langton, Katharina, Eisenhofer, Graeme, Beuschlein, Felix, Brugger, Christina, Reincke, Martin, Riester, Anna, Spyroglou, Ariadni, Burger-Stritt, Stephanie, Deutschbein, Timo, Fassnacht, Martin, Hahner, Stefanie, Kroiss, Matthias, Ronchi, Cristina L., Palimeri, Sotiria, Tsagarakis, Stylianos, Tsirou, Ioanna, Vassiliadi, Dimitra A., Basile, Vittoria, Ingargiola, Elisa, Reimondo, Giuseppe, Terzolo, Massimo, Canu, Letizia, Mannelli, Massimo, Ettaieb, Hester, Haak, Harm R., Kerkhofs, Thomas M., Biehl, Michael, Feelders, Richard A., Hofland, Johannes, Hofland, Leo J., Grytaas, Marianne A., Husebye, Eystein S., Ueland, Grethe A., Ambroziak, Urszula, Bednarczuk, Tomasz, Kondracka, Agnieszka, Macech, Magdalena, Zawierucha, Malgorzata, Paiva, Isabel, Dennedy, M. Conall, Sajwani, Ahmed, Sherlock, Mark, Crowley, Rachel K., Ivovic, Miomira, Marina, Ljiljana, Deeks, Jonathan J., Sitch, Alice J., Arlt, Wiebke, Bancos, Irina, Chortis, Vasileios, Giligan, Lorna C., Hughes, Beverly A., Lang, Katharina, Ivison, Hannah E., Jenkinson, Carl, Manolopoulos, Konstantinos, O'Neil, Donna M., O'Reilly, Michael W., Papathomas, Thomas G., Prete, Alessandro, Shackleton, Cedric H.L., Taylor, Angela E., Asia, Miriam, Sutcliffe, Robert P., Guest, Peter, Skordilis, Kassiani, Bancos, Cristian, Chang, Alice, Davidge-Pitts, Caroline J., Delivanis, Danae A., Erickson, Dana, Natt, Neena, Nippoldt, Todd B., Thomas, Melinda, Young Jr., William F., Taylor, Angela E, Sitch, Alice J, Davidge-Pitts, Caroline J, Pupovac, Ivana D, Papathomas, Thomas G, Gilligan, Lorna C, Grytaas, Marianne A, Ivison, Hannah E, Shackleton, Cedric H L, Ronchi, Cristina L, Delivanis, Danae A, Sutcliffe, Robert P, Feelders, Richard A, Haak, Harm R, Dennedy, M Conall, Ueland, Grethe A, Vassiliadi, Dimitra A, O'Reilly, Michael W, Young, William F, Jr, and Deeks, Jonathan J

Published
2020
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2. AKR1D1 is a novel regulator of metabolic phenotype in human hepatocytes and is dysregulated in non-alcoholic fatty liver disease

Author

Nikolaou, Nikolaos, Gathercole, Laura L., Marchand, Lea, Althari, Sara, Dempster, Niall J., Green, Charlotte J., van de Bunt, Martijn, McNeil, Catriona, Arvaniti, Anastasia, Hughes, Beverly A., Sgromo, Bruno, Gillies, Richard S., Marschall, Hanns-Ulrich, Penning, Trevor M., Ryan, John, Arlt, Wiebke, Hodson, Leanne, and Tomlinson, Jeremy W.

Published
2019
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4. Urinary steroid metabolomics for adrenocortical cancer diagnosis. Comparison of gas chromatography mass spectrometry to liquid chromatography mass spectrometry

Author

Taylor, Angela, primary, Bancos, Irina, additional, Gilligan, Lorna, additional, van, Veen Rick, additional, Chortis, Vasileios, additional, Shaheen, Fozia, additional, Jenkinson, Carl, additional, O'Neil, Donna M, additional, Hughes, Beverly, additional, Hawley, James M, additional, Keevil, Brian, additional, Shackelton, Cedric H L, additional, Deeks, Jonathan, additional, Sitch, Alice J, additional, Biehl, Michael, additional, and Arlt, Wiebke, additional

Published
2022
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7. Dual-5α-Reductase Inhibition Promotes Hepatic Lipid Accumulation in Man

Author

Hazlehurst, Jonathan M., Oprescu, Andrei I., Nikolaou, Nikolaos, Di Guida, Riccardo, Grinbergs, Annabel E. K., Davies, Nigel P., Flintham, Robert B., Armstrong, Matthew J., Taylor, Angela E., Hughes, Beverly A., Yu, Jinglei, Hodson, Leanne, Dunn, Warwick B., and Tomlinson, Jeremy W.

Published
2016

8. The Agenda for Post-Adoption Services.

Author

Logan, Janette and Hughes, Beverly

Abstract

Points out that, contrary to the British Government's argument in the White Paper that services can be changed with no additional funding, the commitment of substantial financial and human resources are needed to provide adequate postadoption services. (SW)

Published
1995

17. Mitotane Therapy in Adrenocortical Cancer Induces CYP3A4 and Inhibits 5α-Reductase, Explaining the Need for Personalized Glucocorticoid and Androgen Replacement

Author

Chortis, Vasileios, Taylor, Angela E., Schneider, Petra, Tomlinson, Jeremy W., Hughes, Beverly A., OʼNeil, Donna M., Libé, Rossella, Allolio, Bruno, Bertagna, Xavier, Bertherat, Jérôme, Beuschlein, Felix, Fassnacht, Martin, Karavitaki, Niki, Mannelli, Massimo, Mantero, Franco, Opocher, Giuseppe, Porfiri, Emilio, Quinkler, Marcus, Sherlock, Mark, Terzolo, Massimo, Nightingale, Peter, Shackleton, Cedric H. L., Stewart, Paul M., Hahner, Stefanie, and Arlt, Wiebke

Published
2013

18. Steroid Profiling in Adrenocortical Carcinoma Reveals Mitotane as a Strong Inducer of CYP3A4 and Inhibitor of 5α-Reductase with Major Implications for Cortisol and Androgen Metabolism

Author

Chortis, Vasilis, primary, Schneider, Petra, additional, Taylor, Angela E, additional, Tomlinson, Jeremy W, additional, Hughes, Beverly A, additional, Smith, David J, additional, Libe, Rossella, additional, Allolio, Bruno, additional, Bertagna, Xavier, additional, Bertherat, Jerome, additional, Beuschlein, Felix, additional, Fassnacht, Martin, additional, Mannelli, Massimo, additional, Mantero, Franco, additional, Opocher, Giuseppe, additional, Porfiri, Emilio, additional, Quinkler, Marcus, additional, Terzolo, Massimo, additional, Shackleton, Cedric HL, additional, Stewart, Paul M, additional, Hahner, Stefanie, additional, and Arlt, Wiebke, additional

Published
2011
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20. Genotype-Phenotype Analysis in Congenital Adrenal Hyperplasia due to P450 Oxidoreductase Deficiency

Author

Krone, Nils, Reisch, Nicole, Idkowiak, Jan, Dhir, Vivek, Ivison, Hannah E., Hughes, Beverly A., Rose, Ian T., OʼNeil, Donna M., Vijzelaar, Raymon, Smith, Matthew J., MacDonald, Fiona, Cole, Trevor R., Adolphs, Nicolai, Barton, John S., Blair, Edward M., Braddock, Stephen R., Collins, Felicity, Cragun, Deborah L., Dattani, Mehul T., Day, Ruth, Dougan, Shelley, Feist, Miriam, Gottschalk, Michael E., Gregory, John W., Haim, Michaela, Harrison, Rachel, Haskins Olney, Ann, Hauffa, Berthold P., Hindmarsh, Peter C., Hopkin, Robert J., Jira, Petr E., Kempers, Marlies, Kerstens, Michiel N., Khalifa, Mohamed M., Köhler, Birgit, Maiter, Dominique, Nielsen, Shelly, OʼRiordan, Stephen M., Roth, Christian L., Shane, Kate P., Silink, Martin, Stikkelbroeck, Nike M. M. L., Sweeney, Elizabeth, Szarras-Czapnik, Maria, Waterson, John R., Williamson, Lori, Hartmann, Michaela F., Taylor, Norman F., Wudy, Stefan A., Malunowicz, Ewa M., Shackleton, Cedric H. L., and Arlt, Wiebke

Published
2012

22. Urine Steroid Metabolomics as a Biomarker Tool for Detecting Malignancy in Adrenal Tumors

Author

Arlt, Wiebke, Biehl, Michael, Taylor, Angela E., Hahner, Stefanie, Libé, Rossella, Hughes, Beverly A., Schneider, Petra, Smith, David J., Stiekema, Han, Krone, Nils, Porfiri, Emilio, Opocher, Giuseppe, Bertherat, Jerôme, Mantero, Franco, Allolio, Bruno, Terzolo, Massimo, Nightingale, Peter, Shackleton, Cedric H. L., Bertagna, Xavier, Fassnacht, Martin, and Stewart, Paul M.

Published
2011

23. Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study

Author

Bancos, Irina, primary, Taylor, Angela E, additional, Chortis, Vasileios, additional, Sitch, Alice J, additional, Jenkinson, Carl, additional, Davidge-Pitts, Caroline J, additional, Lang, Katharina, additional, Tsagarakis, Stylianos, additional, Macech, Magdalena, additional, Riester, Anna, additional, Deutschbein, Timo, additional, Pupovac, Ivana D, additional, Kienitz, Tina, additional, Prete, Alessandro, additional, Papathomas, Thomas G, additional, Gilligan, Lorna C, additional, Bancos, Cristian, additional, Reimondo, Giuseppe, additional, Haissaguerre, Magalie, additional, Marina, Ljiljana, additional, Grytaas, Marianne A, additional, Sajwani, Ahmed, additional, Langton, Katharina, additional, Ivison, Hannah E, additional, Shackleton, Cedric H L, additional, Erickson, Dana, additional, Asia, Miriam, additional, Palimeri, Sotiria, additional, Kondracka, Agnieszka, additional, Spyroglou, Ariadni, additional, Ronchi, Cristina L, additional, Simunov, Bojana, additional, Delivanis, Danae A, additional, Sutcliffe, Robert P, additional, Tsirou, Ioanna, additional, Bednarczuk, Tomasz, additional, Reincke, Martin, additional, Burger-Stritt, Stephanie, additional, Feelders, Richard A, additional, Canu, Letizia, additional, Haak, Harm R, additional, Eisenhofer, Graeme, additional, Dennedy, M Conall, additional, Ueland, Grethe A, additional, Ivovic, Miomira, additional, Tabarin, Antoine, additional, Terzolo, Massimo, additional, Quinkler, Marcus, additional, Kastelan, Darko, additional, Fassnacht, Martin, additional, Beuschlein, Felix, additional, Ambroziak, Urszula, additional, Vassiliadi, Dimitra A, additional, O'Reilly, Michael W, additional, Young, William F, additional, Biehl, Michael, additional, Deeks, Jonathan J, additional, Arlt, Wiebke, additional, Glöckner, Stephan, additional, Sinnott, Richard O., additional, Stell, Anthony, additional, Fragoso, Maria C., additional, Pupovac, Ivana D., additional, Cazenave, Sarah, additional, Bertherat, Jérôme, additional, Libé, Rossella, additional, Brugger, Christina, additional, Hahner, Stefanie, additional, Kroiss, Matthias, additional, Ronchi, Cristina L., additional, Vassiliadi, Dimitra A., additional, Basile, Vittoria, additional, Ingargiola, Elisa, additional, Mannelli, Massimo, additional, Ettaieb, Hester, additional, Haak, Harm R., additional, Kerkhofs, Thomas M., additional, Feelders, Richard A., additional, Hofland, Johannes, additional, Hofland, Leo J., additional, Grytaas, Marianne A., additional, Husebye, Eystein S., additional, Ueland, Grethe A., additional, Zawierucha, Malgorzata, additional, Paiva, Isabel, additional, Dennedy, M. Conall, additional, Sherlock, Mark, additional, Crowley, Rachel K., additional, Deeks, Jonathan J., additional, Sitch, Alice J., additional, Bancos, Irina, additional, Giligan, Lorna C., additional, Hughes, Beverly A., additional, Ivison, Hannah E., additional, Manolopoulos, Konstantinos, additional, O'Neil, Donna M., additional, O'Reilly, Michael W., additional, Papathomas, Thomas G., additional, Shackleton, Cedric H.L., additional, Taylor, Angela E., additional, Sutcliffe, Robert P., additional, Guest, Peter, additional, Skordilis, Kassiani, additional, Chang, Alice, additional, Davidge-Pitts, Caroline J., additional, Delivanis, Danae A., additional, Natt, Neena, additional, Nippoldt, Todd B., additional, Thomas, Melinda, additional, and Young Jr., William F., additional

Published
2020
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25. Glucocorticoids regulate AKR1D1 activity in human liver in vitro and in vivo

Author

Nikolaou, Nikolaos, primary, Arvaniti, Anastasia, additional, Appanna, Nathan, additional, Sharp, Anna, additional, Hughes, Beverly A, additional, Digweed, Dena, additional, Whitaker, Martin J, additional, Ross, Richard, additional, Arlt, Wiebke, additional, Penning, Trevor M, additional, Morris, Karen, additional, George, Sherly, additional, Keevil, Brian G, additional, Hodson, Leanne, additional, Gathercole, Laura L, additional, and Tomlinson, Jeremy W, additional

Published
2020
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26. Accurate non-invasive diagnosis and staging of non-alcoholic fatty liver disease using the urinary steroid metabolome

Author

Moolla, Ahmad, primary, de Boer, Jasper, additional, Pavlov, David, additional, Amin, Amin, additional, Taylor, Angela, additional, Gilligan, Lorna, additional, Hughes, Beverly, additional, Ryan, John, additional, Barnes, Eleanor, additional, Hassan-Smith, Zaki, additional, Grove, Jane, additional, Aithal, Guruprasad P., additional, Verrijken, An, additional, Francque, Sven, additional, Van Gaal, Luc, additional, Armstrong, Matthew J., additional, Newsome, Phillip N., additional, Cobbold, Jeremy F., additional, Arlt, Wiebke, additional, Biehl, Michael, additional, and Tomlinson, Jeremy W., additional

Published
2020
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35. AKR1D1 is a novel regulator of metabolic phenotype in humanhepatocytes and is dysregulated in non-alcoholic fatty liver disease

Author

Nikolaou, Nikolaos, Gathercole, Laura L., Marchand, Lea, Althari, Sara, Dempster, Niall J., Green, Charlotte J., van de Bunt, Martijn, McNeil, Catriona, Arvaniti, Anastasia, Hughes, Beverly A., Sgromo, Bruno, Gillies, Richard S., Marschall, Hanns-Ulrich, Penning, Trevor M., Ryan, John, Arlt, Wiebke, Hodson, Leanne, and Tomlinson, Jeremy W.

Abstract

Objective:Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. Steroidhormones and bile acids are potent regulators of hepatic carbohydrate and lipid metabolism. Steroid 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyzes afundamental step in bile acid synthesis.Methods:Human liver biopsies were obtained from 34 obese patients and AKR1D1 mRNA expression levels weremeasured using qPCR. Genetic manipulation of AKR1D1 was performed in human HepG2 and Huh7 liver celllines. Metabolic assessments were made using transcriptome analysis, western blotting, mass spectrometry, clin-ical biochemistry, and enzyme immunoassays.Results:In human liver biopsies,AKR1D1expression decreased with advancing steatosis,fibrosis and inflamma-tion.Expression was decreasedin patients with type 2 diabetes. In human liver cell lines,AKR1D1knockdown de-creased primary bile acid biosynthesis and steroid hormone clearance. RNA-sequencing identified disruption ofkey metabolic pathways, including insulin action and fatty acid metabolism.AKR1D1knockdown increased he-patocyte triglyceride accumulation, insulin sensitivity, and glycogen synthesis, through increasedde novolipo-genesis and decreasedβ-oxidation, fueling hepatocyte inflammation. Pharmacological manipulation of bileacid receptor activation prevented the induction of lipogenic and carbohydrate genes, suggesting that the ob-served metabolic phenotype is driven through bile acid rather than steroid hormone availability.Conclusions:Genetic manipulation of AKR1D1 regulates the metabolic phenotype of human hepatoma cell lines,driving steatosis and inflammation. Taken together, the observation thatAKR1D1mRNA is down-regulated withadvancing NAFLD suggests that it may have a crucial role in the pathogenesis and progression of the disease.

Published
2019

36. Increased central adiposity and decreased subcutaneous adipose tissue 11β-hydroxysteroid dehydrogenase type 1 are associated with deterioration in glucose tolerance-A longitudinal cohort study

Author

Crowley, Rachel K., Woods, Conor P., Hughes, Beverly A., Gray, Joanna, McCarthy,Theresa, Taylor, Angela E., Gathercole, Laura L., Shackleton, Cedric H.L., Crabtree, Nicola, Arlt, Wiebke, Stewart, Paul M., and Tomlinson, Jeremy W.

Abstract

Objective and Context. Increasing adiposity, ageing and tissue‐specific regeneration of cortisol through the activity of 11β‐hydroxysteroid dehydrogenase type 1 have been associated with deterioration in glucose tolerance. We undertook a longitudinal, prospective clinical study to determine if alterations in local glucocorticoid metabolism track with changes in glucose tolerance. Design, Patients, and Measurements. Sixty‐five overweight/obese individuals (mean age 50.3 ± 7.3 years) underwent oral glucose tolerance testing, body composition assessment, subcutaneous adipose tissue biopsy and urinary steroid metabolite analysis annually for up to 5 years. Participants were categorized into those in whom glucose tolerance deteriorated (“deteriorators”) or improved (“improvers”). Results. Deteriorating glucose tolerance was associated with increasing total and trunk fat mass and increased subcutaneous adipose tissue expression of lipogenic genes. Subcutaneous adipose tissue 11β‐HSD1 gene expression decreased in deteriorators, and at study completion, it was highest in the improvers. There was a significant negative correlation between change in area under the curve glucose and 11β‐HSD1 expression. Global 11β‐HSD1 activity did not change and was not different between deteriorators and improvers at baseline or follow‐up. Conclusion. Longitudinal deterioration in metabolic phenotype is not associated with increased 11β‐HSD1 activity, but decreased subcutaneous adipose tissue gene expression. These changes may represent a compensatory mechanism to decrease local glucocorticoid exposure in the face of an adverse metabolic phenotype.

Published
2019

38. Steroid Metabolomics: A Powerful Technique for Differentiating Inborn Disorders of Steroidogenesis

Author

Baranowski, Elizabeth S., Ghosh, Sreejita, Shackleton, Cedric HL, Taylor, Angela E., Hughes, Beverly A, Biehl, Michael, Guran, Tulay, Bunte, Kerstin, Tino, Peter, Arlt, Wiebke, and Intelligent Systems

Abstract

Background: The urinary steroid metabolome is considered the fingerprint of adrenal gland function. Novel methods using mass spectrometry profiling have seen the advent of a new era for metabolomics with powerful implications for both diagnostics and discovery. Its interpretation is difficult and performed by few specialists with the expertise to do so. This makes it a relatively inaccessible tool for the majority of Clinical Endocrinologists. Objective: To create an automatous method for accurate diagnosis and differentiation of inborn steroidogenic disorders using 34 distinct measured urinary steroid metabolites, that is accurate, reproducible and suitable for high-throughput use. Methods: Using GC/MS, 829 healthy control urines were analysed (302 neonates and infant, 149 children, 18 adolescents, 326 adults, 34 unknown age) and baseline urine from 118 newly diagnosed with inborn steroidogenic disorders (P450 oxidoreductase deficiency, 21 hydroxylase deficiency, 5a reductase deficiency, 17bHSD3 deficiency, 17 hydroxylase deficiency, 3bHSD2 deficiency, 11b hydroxylase type 1 and type 2 deficiency and cyt B5 deficiency). We custom-designed an interpretable machine learning technique, Angle Learning Vector Quantisation, designed to distinguish these conditions using the urinary steroid metabolome. We looked at all possible steroid ratios and by means of ANOVA reduced this to 165 most informative steroid ratios. Using these, the method is able to computationally determine a reduced list of the most relevant ratios to differentiate specific disorders. The method runs independent of sex and age information, method of urine collection (spot, nappy, 24 h collection), and compensates for missing measurements. Results: Our machine learning method was able to predict an affected urine vs a healthy urine with a sensitivity of 100% and specificity of 97%. For our three most prevalent conditions (PORD, SRD5A2 and CYP21A2), the method correctly identified the specific condition in 96% of cases. Where it incorrectly identified the condition, it was mistaken for a biologically very similar one. Conclusion: We have developed a novel machine learning which is highly sensitive and specific. With further validation, it has potential for application in routine clinical practice.

Published
2018

39. AKR1D1 is a novel regulator of metabolic phenotype in human hepatocytes and is dysregulated in non-alcoholic fatty liver disease

Author

Nikolaou, Nikolaos, primary, Gathercole, Laura L, additional, Marchand, Lea, additional, Althari, Sara, additional, Dempster, Niall J, additional, Green, Charlotte J, additional, van, de Bunt Martijn, additional, McNeil, Catriona, additional, Arvaniti, Anastasia, additional, Hughes, Beverly A, additional, Sgromo, Bruno, additional, Gillies, Richard S, additional, Ryan, John, additional, Arlt, Wiebke, additional, Hodson, Leanne, additional, and Tomlinson, Jeremy W, additional

Published
2019
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40. Steroid metabolomics: a rapid computational approach for accurate differentiation of inborn disorders of steroidogenesis

Author

Baranowski, Elizabeth S, primary, Ghosh, Sreejita, additional, Shackleton, Cedric HL, additional, Taylor, Angela E, additional, Hughes, Beverly A, additional, Gilligan, Lorna C, additional, Utari, Agustini, additional, Faradz, Sultana MH, additional, van, Herwaarden Antonius E, additional, Claahsen-van, der Grinten Hedi L, additional, Biehl, Michael, additional, Guran, Tulay, additional, Bunte, Kerstin, additional, Tino, Peter, additional, and Arlt, Wiebke, additional

Published
2019
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42. Differential regulation of 5[beta]-reductase (AKR1D1) expression and activity by glucocorticoids in human and rodent liver

Author

Nikolaou, Nikolaos, primary, Morgan, Stuart, additional, Larner, Dean, additional, Sharp, Anna, additional, Raouf, Zachariah, additional, Hughes, Beverly, additional, Digweed, Dena, additional, Whitaker, Martin, additional, Ross, Richard, additional, Lavery, Gareth, additional, Arlt, Wiebke, additional, Gathercole, Laura, additional, and Tomlinson, Jeremy, additional

Published
2019
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43. Increased central adiposity and decreased subcutaneous adipose tissue 11β‐hydroxysteroid dehydrogenase type 1 are associated with deterioration in glucose tolerance—A longitudinal cohort study

Author

Crowley, Rachel K., primary, Woods, Conor P., additional, Hughes, Beverly A., additional, Gray, Joanna, additional, McCarthy, Theresa, additional, Taylor, Angela E., additional, Gathercole, Laura L., additional, Shackleton, Cedric H. L., additional, Crabtree, Nicola, additional, Arlt, Wiebke, additional, Stewart, Paul M., additional, and Tomlinson, Jeremy W., additional

Published
2019
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45. Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism

Author

Arlt, Wiebke, Lang, Katharina, Sitch, Alice J., Dietz, Anna S., Rhayem, Yara, Bancos, Irina, Feuchtinger, Annette, Chortis, Vasileios, Gilligan, Lorna C., Ludwig, Philippe, Riester, Anna, Asbach, Evelyn, Hughes, Beverly A., O’Neil, Donna M., Bidlingmaier, Martin, Tomlinson, Jeremy W., Hassan-Smith, Zaki K., Rees, D. Aled, Adolf, Christian, Hahner, Stefanie, Quinkler, Marcus, Dekkers, Tanja, Deinum, Jaap, Biehl, Michael, Keevil, Brian G., Shackleton, Cedric H.L., Deeks, Jonathan J., Walch, Axel K., Beuschlein, Felix, Reincke, Martin, and Intelligent Systems

Subjects
Clinical Medicine, R1
Abstract

BACKGROUND. Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess. METHODS. We performed mass spectrometry–based analysis of a 24-hour urine steroid metabolome in 174 newly diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71 bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56 patients with endocrine inactive adrenal adenoma, 104 patients with mild subclinical, and 47 with clinically overt adrenal cortisol excess. We also analyzed the expression of cortisol-producing CYP11B1 and aldosterone-producing CYP11B2 enzymes in adenoma tissue from 57 patients with aldosterone-producing adenoma, employing immunohistochemistry with digital image analysis. RESULTS. Primary aldosteronism patients had significantly increased cortisol and total glucocorticoid metabolite excretion (all P < 0.001), only exceeded by glucocorticoid output in patients with clinically overt adrenal Cushing syndrome. Several surrogate parameters of metabolic risk correlated significantly with glucocorticoid but not mineralocorticoid output. Intratumoral CYP11B1 expression was significantly associated with the corresponding in vivo glucocorticoid excretion. Unilateral adrenalectomy resolved both mineralocorticoid and glucocorticoid excess. Postoperative evidence of adrenal insufficiency was found in 13 (29%) of 45 consecutively tested patients. CONCLUSION. Our data indicate that glucocorticoid cosecretion is frequently found in primary aldosteronism and contributes to associated metabolic risk. Mineralocorticoid receptor antagonist therapy alone may not be sufficient to counteract adverse metabolic risk in medically treated patients with primary aldosteronism. FUNDING. Medical Research Council UK, Wellcome Trust, European Commission., Glucocorticoid excretion in primary aldosteronism patients is increased and correlates with both clinical metabolic risk parameters and intra-tumoral expression of the cortisol-producing enzyme CYP11B1.

Published
2017

47. Staging of non-alcoholic fatty liver disease through LC-MS/MS analysis of the urinary steroid metabolome

Author

Moolla, Ahmad, primary, Taylor, Angela, additional, Gilligan, Lorna, additional, Boer, Jasper De, additional, Amin, Amin, additional, Pavlov, David, additional, Hughes, Beverly, additional, Hassan-Smith, Zaki, additional, Armstrong, Matt, additional, Newsome, Philip, additional, Shah, Tahir, additional, Van, Gaal Luc, additional, Verrijken, An, additional, Francque, Sven, additional, Grove, Jane, additional, Guha, Neil, additional, Aithal, Guruprasad, additional, Barnes, Ellie, additional, Arlt, Wiebke, additional, Biehl, Michael, additional, and Tomlinson, Jeremy, additional

Published
2018
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50. Accurate staging of non-alcoholic fatty liver disease through analysis of the urinary steroid metabolome

Author

Moolla, Ahmad, primary, Amin, Amin, additional, Hughes, Beverly, additional, Arlt, Wiebke, additional, Hassan-Smith, Zaki, additional, Gilligan, Lorna, additional, Armstrong, Matt, additional, Newsome, Philip, additional, Shah, Tahir, additional, Van, Gaal Luc, additional, Verrijken, An, additional, Francque, Sven, additional, Grove, Jane, additional, Guha, Neil, additional, Aithal, Guruprasad, additional, Barnes, Ellie, additional, Biehl, Michael, additional, and Tomlinson, Jeremy, additional

Published
2017
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