Salma R Ali1,2, Jillian Bryce2, Houra Haghpanahan3, James D Lewsey3, Li En Tan1, Navoda Atapattu4, Niels H Birkebaek5, Oliver Blankenstein6, Uta Neumann6, Antonio Balsamo7, Rita Ortolano7, Walter Bonfig8,9, Hedi L Claahsen-van der Grinten10, Martine Cools11, Eduardo Correa Costa12, Feyza Darendeliler13, Sukran Poyrazoglu13, Heba Elsedfy14, Martijn J J Finken15, Christa E Fluck16, Evelien Gevers17, Márta Korbonits17, Guilherme Guaragna-Filho18, Tulay Guran19, Ayla Guven20, Sabine E Hannema21,22, Claire Higham23, Ieuan A Hughes24, Rieko Tadokoro-Cuccaro24, Ajay Thankamony24, Violeta Iotova25, Nils P Krone26, Ruth Krone27, Corina Lichiardopol28, Andrea Luczay29, Berenice B Mendonca30, Tania A S S Bachega30, Mirela C Miranda30, Tatjana Milenkovic31, Klaus Mohnike32, Anna Nordenstrom33, Silvia Einaudi34, Hetty van der Kamp35, Ana Vieites36, Liat de Vries37,38, Richard J M Ross26, S Faisal Ahmed1,2. 1. Developmental Endocrinology Research Group, School of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow, UK. 2. Office for Rare Conditions, Royal Hospital for Children & Queen Elizabeth University Hospital, Glasgow, UK. 3. Health Economics and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK. 4. Lady Ridgeway Hospital, Colombo, Sri Lanka. 5. Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark. 6. Centre for Chronic Sick Children, Institute for Experimental Paediatric Endocrinology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 7. Department of Medical and Surgical Sciences, Pediatric Unit, Center for Rare Endocrine Conditions (Endo-ERN), S.Orsola-Malpighi University Hospital, Bologna, Italy. 8. Department of Paediatrics, Technical University München, Munich, Germany. 9. Department of Paediatrics, Klinikum Wels-Grieskirchen, Wels, Austria. 10. Department of Paediatric Endocrinology, Amalia Childrens Hospital, Radboud University Medical Centre, Nijmegen, Netherlands. 11. University Hospital Ghent, Ghent University, Ghent, Belgium. 12. Pediatric Surgery Service, Hospital de Clínicas de Porto Alegre, UFRGS, Porto Alegre, Brazil. 13. Istanbul Faculty of Medicine, Department of Paediatrics, Paediatric Endocrinology Unit, Istanbul University, Istanbul, Turkey. 14. Department of Pediatrics, Ain Shams University, Cairo, Egypt. 15. Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Endocrinology, Amsterdam, The Netherlands. 16. Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics and Department of BioMedical Research, Bern University Hospital Inselspital, University of Bern, Bern, Switzerland. 17. Department of Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK. 18. Department of Pediatrics, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. 19. Marmara University, Department of Pediatric Endocrinology and Diabetes, Pendik, Istanbul, Turkey. 20. Health Science University, Medical Faculty, Zeynep Kamil Women and Children Hospital, Pediatric Endocrinology Clinic, Istanbul, Turkey. 21. Department of Paediatric Endocrinology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands. 22. Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands. 23. Department of Endocrinology, Christie Hospital NHS Foundation Trust, Manchester, University Of Manchester, Manchester Academic Health Science Centre, Manchester, UK. 24. Department of Paediatrics, University of Cambridge, Cambridge, UK. 25. Department of Paediatrics, Medical University-Varna, UMHAT "Sv. Marina," Varna, Bulgaria. 26. Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK. 27. Birmingham Women's & Children's Hospital, Department for Endocrinology & Diabetes, Birmingham, UK. 28. Department of Endocrinology, University of Medicine and Pharmacy Craiova, University Emergency Hospital, Craiova, Romania. 29. Department of Paediatrics, Semmelweis University, Budapest, Hungary. 30. Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular/LIM42, Disciplina de Endocrinologia, Hospital Das Clinicas, Faculdade De Medicina, Universidade de Sao Paulo, São Paulo, Brazil. 31. Department of Endocrinology, Mother and Child Health Care Institute of Serbia "Dr Vukan Čupić," Belgrade, Serbia. 32. University of Magdeburg, Magdeburg, Germany. 33. Karolinska University Hospital, Stockholm, Sweden. 34. Pediatric Endocrinology Regina Margherita Children's Hospital, Città della Salute e della Scienza, University of Turin, Turin, Italy. 35. Wilhelmina Kinderziekenhuis, Division of Pediatric Endocrinology, Utrecht, Netherlands. 36. Centro de Investigaciones Endocrinológicas, División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. 37. The Jesse and Sara Lea Shafer Institute of Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petah Tikvah, Israel. 38. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract
BACKGROUND: Although congenital adrenal hyperplasia (CAH) is known to be associated with adrenal crises (AC), its association with patient- or clinician-reported sick day episodes (SDE) is less clear. METHODS: Data on children with classic 21-hydroxylase deficiency CAH from 34 centers in 18 countries, of which 7 were Low or Middle Income Countries (LMIC) and 11 were High Income (HIC), were collected from the International CAH Registry and analyzed to examine the clinical factors associated with SDE and AC. RESULTS: A total of 518 children-with a median of 11 children (range 1, 53) per center-had 5388 visits evaluated over a total of 2300 patient-years. The median number of AC and SDE per patient-year per center was 0 (0, 3) and 0.4 (0.0, 13.3), respectively. Of the 1544 SDE, an AC was reported in 62 (4%), with no fatalities. Infectious illness was the most frequent precipitating event, reported in 1105 (72%) and 29 (47%) of SDE and AC, respectively. On comparing cases from LMIC and HIC, the median SDE per patient-year was 0.75 (0, 13.3) vs 0.11 (0, 12.0) (P < 0.001), respectively, and the median AC per patient-year was 0 (0, 2.2) vs 0 (0, 3.0) (P = 0.43), respectively. CONCLUSIONS: The real-world data that are collected within the I-CAH Registry show wide variability in the reported occurrence of adrenal insufficiency-related adverse events. As these data become increasingly used as a clinical benchmark in CAH care, there is a need for further research to improve and standardize the definition of SDE.
BACKGROUND: Although congenital adrenal hyperplasia (CAH) is known to be associated with adrenal crises (AC), its association with patient- or clinician-reported sick day episodes (SDE) is less clear. METHODS: Data on children with classic 21-hydroxylase deficiency CAH from 34 centers in 18 countries, of which 7 were Low or Middle Income Countries (LMIC) and 11 were High Income (HIC), were collected from the International CAH Registry and analyzed to examine the clinical factors associated with SDE and AC. RESULTS: A total of 518 children-with a median of 11 children (range 1, 53) per center-had 5388 visits evaluated over a total of 2300 patient-years. The median number of AC and SDE per patient-year per center was 0 (0, 3) and 0.4 (0.0, 13.3), respectively. Of the 1544 SDE, an AC was reported in 62 (4%), with no fatalities. Infectious illness was the most frequent precipitating event, reported in 1105 (72%) and 29 (47%) of SDE and AC, respectively. On comparing cases from LMIC and HIC, the median SDE per patient-year was 0.75 (0, 13.3) vs 0.11 (0, 12.0) (P < 0.001), respectively, and the median AC per patient-year was 0 (0, 2.2) vs 0 (0, 3.0) (P = 0.43), respectively. CONCLUSIONS: The real-world data that are collected within the I-CAH Registry show wide variability in the reported occurrence of adrenal insufficiency-related adverse events. As these data become increasingly used as a clinical benchmark in CAH care, there is a need for further research to improve and standardize the definition of SDE.
Authors: R Louise Rushworth; Georgina L Chrisp; Benjamin Dean; Henrik Falhammar; David J Torpy Journal: Horm Res Paediatr Date: 2017-09-12 Impact factor: 2.852
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Authors: Stefan R Bornstein; Bruno Allolio; Wiebke Arlt; Andreas Barthel; Andrew Don-Wauchope; Gary D Hammer; Eystein S Husebye; Deborah P Merke; M Hassan Murad; Constantine A Stratakis; David J Torpy Journal: J Clin Endocrinol Metab Date: 2016-01-13 Impact factor: 5.958
Authors: Hedi L Claahsen-van der Grinten; Phyllis W Speiser; S Faisal Ahmed; Wiebke Arlt; Richard J Auchus; Henrik Falhammar; Christa E Flück; Leonardo Guasti; Angela Huebner; Barbara B M Kortmann; Nils Krone; Deborah P Merke; Walter L Miller; Anna Nordenström; Nicole Reisch; David E Sandberg; Nike M M L Stikkelbroeck; Philippe Touraine; Agustini Utari; Stefan A Wudy; Perrin C White Journal: Endocr Rev Date: 2022-01-12 Impact factor: 19.871
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Authors: Stefan Pilz; Michael Krebs; Walter Bonfig; Wolfgang Högler; Anna Hochgerner; Greisa Vila; Christian Trummer; Verena Theiler-Schwetz; Barbara Obermayer-Pietsch; Peter Wolf; Thomas Scherer; Florian Kiefer; Elke Fröhlich-Reiterer; Elena Gottardi-Butturini; Klaus Kapelari; Stefan Schatzl; Susanne Kaser; Günter Höfle; Dietmar Schiller; Vinzenz Stepan; Anton Luger; Stefan Riedl Journal: J Klin Endokrinol Stoffwechs Date: 2022-03-02
Authors: Michael Goodman; Rami Yacoub; Darios Getahun; Courtney E McCracken; Suma Vupputuri; Timothy L Lash; Douglas Roblin; Richard Contreras; Lee Cromwell; Melissa D Gardner; Trenton Hoffman; Haihong Hu; Theresa M Im; Radhika Prakash Asrani; Brandi Robinson; Fagen Xie; Rebecca Nash; Qi Zhang; Sadaf A Bhai; Kripa Venkatakrishnan; Bethany Stoller; Yijun Liu; Cricket Gullickson; Maaz Ahmed; David Rink; Ava Voss; Hye-Lee Jung; Jin Kim; Peter A Lee; David E Sandberg Journal: BMJ Open Date: 2022-09-21 Impact factor: 3.006
Authors: Salma R Ali; Jillian Bryce; Houra Haghpanahan; James D Lewsey; Li En Tan; Navoda Atapattu; Niels H Birkebaek; Oliver Blankenstein; Uta Neumann; Antonio Balsamo; Rita Ortolano; Walter Bonfig; Hedi L Claahsen-van der Grinten; Martine Cools; Eduardo Correa Costa; Feyza Darendeliler; Sukran Poyrazoglu; Heba Elsedfy; Martijn J J Finken; Christa E Fluck; Evelien Gevers; Márta Korbonits; Guilherme Guaragna-Filho; Tulay Guran; Ayla Guven; Sabine E Hannema; Claire Higham; Ieuan A Hughes; Rieko Tadokoro-Cuccaro; Ajay Thankamony; Violeta Iotova; Nils P Krone; Ruth Krone; Corina Lichiardopol; Andrea Luczay; Berenice B Mendonca; Tania A S S Bachega; Mirela C Miranda; Tatjana Milenkovic; Klaus Mohnike; Anna Nordenstrom; Silvia Einaudi; Hetty van der Kamp; Ana Vieites; Liat de Vries; Richard J M Ross; S Faisal Ahmed Journal: J Clin Endocrinol Metab Date: 2021-01-01 Impact factor: 5.958
Authors: Hanna Franziska Nowotny; Matthias K Auer; Christian Lottspeich; Heinrich Schmidt; Ilja Dubinski; Martin Bidlingmaier; Jo Adaway; James Hawley; Brian Keevil; Nicole Reisch Journal: J Clin Endocrinol Metab Date: 2021-10-21 Impact factor: 5.958