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Magdalena Lech Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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Ruvini Ranasinghe Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Royce P Vincent Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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David R Taylor Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Lea Ghataore Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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James Luxton Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Fannie Lajeunesse-Trempe Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Quebec Heart and Lung Institute, Laval University, Quebec, Canada

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Pia Roser Department of Endocrinology and Diabetes, University Medical Centre Hamburg Eppendorf, Hamburg, Germany

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Eftychia E Drakou Department of Clinical Oncology, Guy's Cancer Centre - Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UK

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Ling Ling Chuah Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Ashley B Grossman Green Templeton College, University of Oxford, Oxford, UK
Barts and the London School of Medicine, Centre for Endocrinology, William Harvey Institute, London, UK
Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK

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Simon J B Aylwin Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Georgios K Dimitriadis Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Obesity, Type 2 Diabetes and Immunometabolism Research Group, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Course Sciences, King’s College London, London, UK
Division of Reproductive Health, Warwick Medical School, University of Warwick, Coventry, UK

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), adrenocorticotrophic hormone (ACTH), cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG), gonadotrophins, DHEAS, testosterone and plasma EDTA ACTH were collected using BD Vacutainer during the same venepuncture. Samples were stored at −80°C until analysis

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Sarah Ying Tse Tan Department of Endocrinology, Singapore General Hospital, Singapore

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Hong Chang Tan Department of Endocrinology, Singapore General Hospital, Singapore

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Ling Zhu Department of Endocrinology, Singapore General Hospital, Singapore

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Lih Ming Loh Department of Endocrinology, Singapore General Hospital, Singapore

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Dawn Shao Ting Lim Department of Endocrinology, Singapore General Hospital, Singapore

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Du Soon Swee Department of Endocrinology, Singapore General Hospital, Singapore

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Yoke Ling Chan Department of Speciality Nursing, Singapore General Hospital, Singapore

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Huee Boon Lim Department of Speciality Nursing, Singapore General Hospital, Singapore

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Shiau Lee Ling Department of Speciality Nursing, Singapore General Hospital, Singapore

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En Jun Ou Department of Speciality Nursing, Singapore General Hospital, Singapore

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Wynn Ee Teo Department of Speciality Nursing, Singapore General Hospital, Singapore

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Xiao Ping Zhang Department of Speciality Nursing, Singapore General Hospital, Singapore

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Hui Fen Goh Department of Speciality Nursing, Singapore General Hospital, Singapore

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Peng Chin Kek Department of Endocrinology, Singapore General Hospital, Singapore

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laboratories measure serum total cortisol concentrations and do not differentiate between the bound and free forms. Cortisol in blood exists in two forms: cortisol that is bound to carrier molecules (cortisol-binding globulin and albumin) and cortisol that is

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Arno Téblick Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

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Ilse Vanhorebeek Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

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Inge Derese Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

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An Jacobs Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

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Renata Haghedooren Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

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Sofie Maebe Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

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Gerdien A Zeilmaker-Roest Department of Neonatal & Pediatric Intensive Care, Division of Pediatric Intensive Care, Erasmus MC – Sophia Children’s Hospital, Rotterdam, the Netherlands

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Enno D Wildschut Department of Neonatal & Pediatric Intensive Care, Division of Pediatric Intensive Care, Erasmus MC – Sophia Children’s Hospital, Rotterdam, the Netherlands

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Lies Langouche Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

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Greet Van den Berghe Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

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-linked immunosorbent assay (MyBioSource Inc., San Diego, CA, USA) and plasma cortisol (Immunotech, Beckman Coulter) and cortisol-binding globulin (CBG) (Riazen, ZenTech s.a., Liège, Belgium) by competitive radioimmunoassay. Plasma albumin was quantified by the

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Lisa Arnetz Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes
Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes

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Neda Rajamand Ekberg Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes
Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes

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Kerstin Brismar Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes
Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes

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Michael Alvarsson Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes
Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes

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differences between groups. Cortisol-binding globulin (CBG) was not measured; however, some studies have shown strong correlations between free (active) and total cortisol, implying no need to correct for CBG (32) . CBG is not affected by age, or the

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Saroj Kumar Sahoo Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
Division of Endocrinology, Mid and South Essex NHS Trust, Broomfield, UK

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Jayakrishnan C Menon Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Nidhi Tripathy Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Monalisa Nayak Department of Liver Intensive Care Unit, King’s College Hospital, London, UK

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Subhash Yadav Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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pre-existing pituitary or adrenal disease were excluded from the study. Those who were using medications affecting cortisol-binding globulin (estrogens) were also excluded from the study. Three hundred and two patients (median age 54 years

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Marloes L P Langelaan Clinical Laboratory, Catharina Hospital Eindhoven, Eindhoven, The Netherlands
Department of Clinical Chemistry and Haematology, Zuyderland Medical Centre, Heerlen, The Netherlands

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Jérôme M H Kisters Department of Internal Medicine, Catharina Hospital Eindhoven, Eindhoven, The Netherlands

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Mirjam M Oosterwerff Department of Internal Medicine, Catharina Hospital Eindhoven, Eindhoven, The Netherlands

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Arjen-Kars Boer Clinical Laboratory, Catharina Hospital Eindhoven, Eindhoven, The Netherlands

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cortisol concentrations ( 8 , 9 ). LC–MS/MS analyses are not influenced by changes in e.g. concentrations of cortisol-binding globulin or cross-reactivity with other corticosteroid substances. In addition, LC–MS/MS analysis enables the analysis of cortisol

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Ramjan Sanas Mohamed Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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Biyaser Abuelgasim Imperial College School of Medicine, Department of Biochemistry, Imperial College Healthcare NHS Trust, London, UK

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Sally Barker Imperial College School of Medicine, Department of Biochemistry, Imperial College Healthcare NHS Trust, London, UK

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Hemanth Prabhudev Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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Niamh M Martin Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK
Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK

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Karim Meeran Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK
Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK

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Emma L Williams Department of Biochemistry, Imperial College Healthcare NHS Trust, London, UK

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Sarah Darch Department of Biochemistry, Imperial College Healthcare NHS Trust, London, UK

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Whitlock Matthew Department of Biochemistry, Imperial College Healthcare NHS Trust, London, UK

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Tricia Tan Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK
Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK

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Florian Wernig Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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there has been any change in the use of diagnostic tests for CS across Europe over the past 5 years. LNSC is not affected by BMI or cortisol binding globulin and therefore accurately reflects serum cortisol concentrations. There is conflicting evidence

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Ferdinand Roelfsema Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Diana van Heemst Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

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Ali Iranmanesh Endocrine Section, Medical Service, Salem Veterans Affairs Medical Center, Salem, Virginia, USA

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Paul Takahashi Primary Care Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA

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Rebecca Yang Endocrine Research Unit, Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota, USA

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Johannes D Veldhuis Endocrine Research Unit, Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota, USA

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5 Purnell JQ Brandon DD Isabelle LM Loriaux DL Samuels MH. Association of 24-hour cortisol production rates, cortisol-binding globulin, and plasma-free cortisol levels with body composition, leptin levels, and aging in adult men

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Amit Kumar Department of Medicine, Christian Medical College and Hospital, Ludhiana, Punjab, India

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Maria Ghosh Department of Biochemistry, Christian Medical College and Hospital, Ludhiana, Punjab, India

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Jubbin Jagan Jacob Department of Endocrinology, Christian Medical College and Hospital, Ludhiana, Punjab, India

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nmol/L) post-APST for patients with co-existing hypoalbuminemia. Since, the laboratory measures total cortisol levels and not free cortisol levels this would mean patients with low albumin and those with changes in cortisol binding globulin levels (e

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L Ghataore Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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I Chakraborti Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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S J Aylwin Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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K-M Schulte Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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D Dworakowska Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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P Coskeran Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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N F Taylor Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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replacement during mitotane treatment is well established in clinical practice. Cortisol monitoring by standard methods is unhelpful due to mitotane-induced cortisol binding globulin increase and ACTH is more useful, with addition of free cortisol assay when

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