Oskar Ragnarsson1,2, Daniel S Olsson1,2, Eleni Papakokkinou1,2, Dimitrios Chantzichristos1,2, Per Dahlqvist3, Elin Segerstedt3, Tommy Olsson3, Maria Petersson4,5, Katarina Berinder4,5, Sophie Bensing4,5, Charlotte Höybye4,5, Britt Edén-Engström6, Pia Burman7, Lorenza Bonelli7, Cecilia Follin8, David Petranek8, Eva Marie Erfurth8, Jeanette Wahlberg9, Bertil Ekman9, Anna-Karin Åkerman10, Erik Schwarcz10, Ing-Liss Bryngelsson11, Gudmundur Johannsson1,2. 1. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden. 2. Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden. 3. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. 4. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 5. Department of Endocrinology, Metabolism and Diabetology, Karolinska University Hospital, Stockholm, Sweden. 6. Department of Medical Sciences; Endocrinology, Diabetes and Metabolism, Uppsala University Hospital, Uppsala, Sweden. 7. Department of Endocrinology, Skåne University Hospital, University of Lund, Malmö, Sweden. 8. Department of Endocrinology, Skåne University Hospital, Lund, Sweden. 9. Department of Endocrinology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. 10. Department of Internal Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden. 11. Department of Occupational and Environmental Medicine, Örebro University Hospital, Örebro, Sweden.
Abstract
CONTEXT: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable. OBJECTIVE: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD. DESIGN, PATIENTS, AND METHODS: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality. RESULTS: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome. CONCLUSION: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
CONTEXT: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable. OBJECTIVE: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD. DESIGN, PATIENTS, AND METHODS: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality. RESULTS: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome. CONCLUSION: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
Authors: Maria Fleseriu; Richard Auchus; Irina Bancos; Anat Ben-Shlomo; Jerome Bertherat; Nienke R Biermasz; Cesar L Boguszewski; Marcello D Bronstein; Michael Buchfelder; John D Carmichael; Felipe F Casanueva; Frederic Castinetti; Philippe Chanson; James Findling; Mônica Gadelha; Eliza B Geer; Andrea Giustina; Ashley Grossman; Mark Gurnell; Ken Ho; Adriana G Ioachimescu; Ursula B Kaiser; Niki Karavitaki; Laurence Katznelson; Daniel F Kelly; André Lacroix; Ann McCormack; Shlomo Melmed; Mark Molitch; Pietro Mortini; John Newell-Price; Lynnette Nieman; Alberto M Pereira; Stephan Petersenn; Rosario Pivonello; Hershel Raff; Martin Reincke; Roberto Salvatori; Carla Scaroni; Ilan Shimon; Constantine A Stratakis; Brooke Swearingen; Antoine Tabarin; Yutaka Takahashi; Marily Theodoropoulou; Stylianos Tsagarakis; Elena Valassi; Elena V Varlamov; Greisa Vila; John Wass; Susan M Webb; Maria C Zatelli; Beverly M K Biller Journal: Lancet Diabetes Endocrinol Date: 2021-10-20 Impact factor: 32.069
Authors: Maureen Rakovec; William Zhu; Adham M Khalafallah; Roberto Salvatori; Amir H Hamrahian; Gary L Gallia; Masaru Ishii; Nyall R London; Murugappan Ramanathan; Nicholas R Rowan; Debraj Mukherjee Journal: Endocrine Date: 2022-10-13 Impact factor: 3.925
Authors: Andrew A Crawford; Sean Bankier; Elisabeth Altmaier; Catriona L K Barnes; David W Clark; Raili Ermel; Nele Friedrich; Pim van der Harst; Peter K Joshi; Ville Karhunen; Jari Lahti; Anubha Mahajan; Massimo Mangino; Maria Nethander; Alexander Neumann; Maik Pietzner; Katyayani Sukhavasi; Carol A Wang; Stephan J L Bakker; Johan L M Bjorkegren; Harry Campbell; Johan Eriksson; Christian Gieger; Caroline Hayward; Marjo-Riitta Jarvelin; Stela McLachlan; Andrew P Morris; Claes Ohlsson; Craig E Pennell; Jackie Price; Igor Rudan; Arno Ruusalepp; Tim Spector; Henning Tiemeier; Henry Völzke; James F Wilson; Tom Michoel; Nicolas J Timpson; George Davey Smith; Brian R Walker Journal: J Hum Genet Date: 2021-01-20 Impact factor: 3.172