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Sirazum Choudhury Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Commonwealth Building, London, UK
Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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Tricia Tan Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Commonwealth Building, London, UK
Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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Katharine Lazarus Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Commonwealth Building, London, UK
Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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Karim Meeran Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Commonwealth Building, London, UK
Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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Introduction Between 1928 and 1938, patients with Addison’s disease had a 100% 5-year mortality ( 1 ). With the availability of glucocorticoid replacement therapy, initially with animal adrenocortical extract and later synthetic 11

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David J F Smith Department of Endocrinology, 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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Sirazum Choudhury Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK
Department of Clinical Biochemistry, Imperial College Healthcare NHS Trust, London, UK
Department of Investigative Medicine, 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
Department of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK

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mineralocorticoid production in primary adrenal failure. The mainstay of treatment is glucocorticoid replacement, with either hydrocortisone or prednisolone ( 2 ). Both work by binding to the glucocorticoid receptor (GR) for which prednisolone has the greater

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Salem A Beshyah Department of Medicine, Dubai Medical College, Dubai, United Arab Emirates
Diabetes and Endocrine Clinic, Mediclinic Airport Road Hospital, Abu Dhabi, United Arab Emirates

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Khawla F Ali Department of Medicine, Royal College of Surgeons in Ireland Medical University of Bahrain, Adliya, Bahrain

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Hussein F Saadi Department of Endocrinology, Medical Subspecialties Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

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therapy? (Once daily (full dose), Twice daily, Three times daily, Four times daily).  5. How do you perceive the impact of Ramadan fasting (RF) on adrenal insufficiency and its management (There is no concern on glucocorticoid replacement therapy

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Marcus Quinkler Endocrinology in Charlottenburg, Berlin, Germany

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Bertil Ekman Departments of Endocrinology and Medical and Health Sciences, Linköping University, Linköping, Sweden

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Claudio Marelli Shire International GmbH, Zug, Switzerland

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Sharif Uddin Shire, Lexington, Massachusetts, USA

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Pierre Zelissen Department of Internal Medicine and Endocrinology, University Medical Center Utrecht, Utrecht, the Netherlands

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Robert D Murray Department of Endocrinology, Leeds Teaching Hospitals NHS Trust, St James’s University Hospital, Leeds, UK

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on behalf of the EU-AIR Investigators
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glucocorticoid replacement therapies ( 21 ). The primary objective of the EU-AIR is to monitor the safety of long-term treatment with once-daily modified-release hydrocortisone and other glucocorticoid replacement therapies in patients with AI. All enrolled

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Ditte Sofie Dahl Sørensen Department of Endocrinology and Metabolism, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Jesper Krogh Department of Endocrinology and Metabolism, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Åse Krogh Rasmussen Department of Endocrinology and Metabolism, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Mikkel Andreassen Department of Endocrinology and Metabolism, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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profiles in adult patients with 21-hydroxylase deficiency have shown a substantial circadian rhythm highly influenced by glucocorticoid replacement ( 6 ). Most recent clinical guideline from the US Endocrine Society suggests levels of androstenedione and 17

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Sophie Howarth Clinical and Translational Research Institute, Newcastle University, Newcastle upon Tyne, UK
Department of Endocrinology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Luca Giovanelli Department of Endocrinology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Catherine Napier Department of Endocrinology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Simon H Pearce Clinical and Translational Research Institute, Newcastle University, Newcastle upon Tyne, UK
Department of Endocrinology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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within 4 weeks of diagnosis, one study demonstrated a >50% reduction in endogenous steroid production in the 4 weeks after starting glucocorticoid replacement ( 25 ). The nature of Addison’s disease means that endogenous steroid replacement is likely to

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Stephanie Burger-Stritt Endocrinology and Diabetes Unit, Department of Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany

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Linda Bachmann Endocrinology and Diabetes Unit, Department of Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany

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Max Kurlbaum Endocrinology and Diabetes Unit, Department of Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany

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Stefanie Hahner Endocrinology and Diabetes Unit, Department of Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany

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outcomes with current glucocorticoid replacement therapy . Clinical Endocrinology 2015 82 2 – 11 . ( https://doi.org/10.1111/cen.12603 ) 10.1111/cen.12603 25187037 25 Jenkins JS Sampson PA . Conversion of cortisone to cortisol and prednisone to

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Johan G Beun AdrenalNET, The Netherlands

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Pia Burman Department of Endocrinology, Skåne University Hospital, Lund University, Sweden

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Olle Kämpe Department of Medicine (Solna), Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
Department of Endocrinology, Diabetes and Metabolism, Karolinska University Hospital, Stockholm, Sweden

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Eystein S Husebye Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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Stephanie Hahner Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Germany

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Jette Kristensen Addison Foreningen i Danmark, Denmark

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Alida Noordzij AdrenalNET, The Netherlands

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Per Dahlqvist Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Adrenal insufficiency is a life-threatening condition requiring chronic glucocorticoid replacement therapy, as well as stress adaptation to prevent adrenal crises. To increase patients’ self-sustainability, education on how to tackle an adrenal crisis is crucial. All patients should carry the European Emergency Card.

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Filippo Ceccato Department of Medicine DIMED, University of Padova, Padova, Italy
Endocrine Disease Unit, University-Hospital of Padova, Padova, Italy
Department of Neuroscience DNS, University of Padova, Padova, Italy

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Elisa Selmin Department of Medicine DIMED, University of Padova, Padova, Italy

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Giorgia Antonelli Department of Medicine DIMED, University of Padova, Padova, Italy
Laboratory Medicine, University-Hospital of Padova, Padova, Italy

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Mattia Barbot Department of Medicine DIMED, University of Padova, Padova, Italy
Endocrine Disease Unit, University-Hospital of Padova, Padova, Italy
Department of Neuroscience DNS, University of Padova, Padova, Italy

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Andrea Daniele Department of Medicine DIMED, University of Padova, Padova, Italy

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Marco Boscaro Department of Medicine DIMED, University of Padova, Padova, Italy

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Mario Plebani Department of Medicine DIMED, University of Padova, Padova, Italy
Laboratory Medicine, University-Hospital of Padova, Padova, Italy

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Carla Scaroni Department of Medicine DIMED, University of Padova, Padova, Italy
Endocrine Disease Unit, University-Hospital of Padova, Padova, Italy

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Context

The low-dose short synacthen test (LDSST) is recommended for patients with suspected central adrenal insufficiency (AI) if their basal serum cortisol (F) levels are not indicative of an intact hypothalamic–pituitary–adrenal (HPA) axis.

Objective

To evaluate diagnostic threshold for salivary F before and 30 min after administering 1 μg of synacthen, performed before 09:30 h.

Design

A cross-sectional study from 2014 to 2020.

Setting

A tertiary referral university hospital.

Patients

In this study, 174 patients with suspected AI, 37 with central AI and 137 adrenal sufficient (AS), were included.

Main outcome measure

The diagnostic accuracy (sensitivity (SE), specificity (SP)) of serum and salivary F levels measured, respectively, by chemiluminescence immunoassay and liquid chromatography-tandem mass spectrometry.

Results

Low basal serum or salivary F levels could predict AI. For the LDSST, the best ROC-calculated threshold for serum F to differentiate AI from AS was 427 nmol/L (SE 79%, SP 89%), serum F > 500 nmol/L reached SP 100%. A salivary F peak > 12.1 nmol/L after administering synacthen reached SE 95% and SP 84% for diagnosing central AI, indicating a conclusive reduction in the likelihood of AI. This ROC-calculated threshold for salivary F was similar to the 2.5th percentile of patients with a normal HPA axis, so it was considered sufficient to exclude AI. Considering AS those patients with salivary F > 12.1 nmol/L after LDSST, we could avoid unnecessary glucocorticoid treatment: 99/150 subjects (66%) had an inadequate serum F peak after synacthen, but salivary F was >12.1 nmol/L in 79 cases, who could, therefore, be considered AS.

Conclusions

Salivary F levels > 12.1 nmol/L after synacthen administration can indicate an intact HPA axis in patients with an incomplete serum F response, avoiding the need to start glucocorticoid replacement treatment.

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Natacha Driessens Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Madhu Prasai Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Orsalia Alexopoulou Department of Endocrinology, Cliniques Universitaires Saint Luc, Brussels, Belgium

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Christophe De Block Department of Endocrinology-Diabetology-Metabolism, Universitair Ziekenhuis Antwerpen & University of Antwerp, Drie Eikenstraat, Edegem, Belgium

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Eva Van Caenegem Department of Endocrinology, Academisch Ziekenhuis Sint-Jan Brugge – Oostende AV, Ruddershove, Brugge, Belgium

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Guy T’Sjoen Department of Endocrinology, Ghent Universitary Hospital, C. Heymanslaan, Gent, Belgium

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Frank Nobels Department of Endocrinology, Onze-Lieve Vrouw Ziekenhuis, Moorselbaan, Aalst, Belgium

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Christophe Ghys Department of Endocrinology, Universitair Ziekenhuis Brussel, Laarbeeklaan, Brussels, Belgium

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Laurent Vroonen Department of Endocrinology, Cliniques Universitaires de Liège, Avenue de l’hôpital, Liège, Belgium

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Corinne Jonas Department of Endocrinology, CHU UCL Namur - Godinne, Avenue Docteur Gaston Thérasse, Yvoir, Belgium

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Bernard Corvilain Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Dominique Maiter Department of Endocrinology, Cliniques Universitaires Saint Luc, Brussels, Belgium

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countries ( 1 ) and the lowest in Japan. Despite the advent of glucocorticoid replacement therapy in the early 1950s, life expectancy remains lower than in the general population ( 2 ), with increased morbidity and impaired quality of life ( 3 , 4

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