ECE2018 Oral Communications Novel aspects of puberty development and Cushing's disease (5 abstracts)
Diabetes mellitus and muscle weakness are independently associated with mortality in patients with Cushing’s syndrome. Data from ERCUSYN
Elena Valassi 1 , Antoine Tabarin 2 , Thierry Brue 3 , Richard A Feelders 4 , Martin Reincke 5 , Romana Neteia-Maier 6 , Miklós Tóth 7 , Maria Yaneva 8 , Susan M Webb 1 , Stylianos Tsagarakis 9 , Philippe Chanson 10 , Marija Pfeifer 11 , Michael Droste 12 , Irina Komerdus 13 , Darko Kastelan 14 , Dominique Maiter 15 , Olivier Chabre 16 , Holger Franz 17 , Alicia Santos 1 , Christian J Strasburger 18 , Peter J Trainer 19 , John Newell-Price 20 & Oskar Ragnarsson 21
1IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, UAB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, Barcelona, Spain; 2Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; 3Association pour le Devéloppement des Recherches Biologiques et Médicales, Marseilles, France; 4Erasmus University Medical Centre, Rotterdam, Netherlands; 5Medizinische Klinik und Poliklinik IV, Campus Innestadt, Klinikum der Universitat Munchen, Munchen, Germany; 6Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 72nd Department of Medicine, Semmelweis University, Budapest, Hungary; 8Medical University of Sofia, Sofia, Bulgaria; 9Athens Polyclinic General Hospital & Evangelismos Hospital, Athens, Greece; 10Univ Paris Sud, Université Paris-Saclay UMR-S1185, Le Kremlin Bicetre, Paris F-94276, Assistance Publique-Hopitaux de Paris, Hopital de Bicetre, Service de Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicetre, Insitut National de la Santé et de la Recherche Médicale U1185, Le Kremlin Bicetre, Paris, France; 11Medical Faculty, University Medical Centre Ljubljana, University of Ljubljana, Ljubljana, Slovenia; 12Praxis fur Endokrinologie Droste, Oldenburg, Germany; 13Moscow Regional Research Clinical Institute n.a. Vladimirsky, Russian Federation, Moscow, Russia; 14Department of Endocrinology, University Hospital Zagreb, Zagreb, Croatia; 15UCL Cliniques Universitaires St Luc, Brussels, Belgium; 16Hospitalier Universitaire, Grenoble, France; 17Lohmann & Birkner Health Care Consulting GmbH, Berlin, Germany; 18Division of Clinical Endocrinology, Department of Medicine CCM, Charité-Universitatsmedizin, Berlin, Germany; 19Department of Endocrinology, Christie Hospital, Manchester, UK; 20Academic Unit of Diabetes, Endocrinology and Reproduction, Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK; 21Institute of Medicine at Sahlgrenska University Hospital, Gothenburg, Sweden.
Background: Patients with active Cushing’s syndrome (CS) have increased mortality.
Aims: Evaluate cause of death in a large cohort of CS patients, and establish factors associated with increased mortality.
Methods: We analysed 1514 patients included in the European Registry on Cushing’s syndrome (ERCUSYN): 1022 (68%) had pituitary-dependent CS (PIT-CS), 379 (25%) adrenal-dependent CS (ADR-CS), 71 (5%) had an ectopic source (ECT-CS) and 42 (3%) other causes (OTH-CS). Median duration of follow-up was 139 weeks.
Results: Fifty-one patients died (3.3%): 23 (2.2%) PIT-CS, 7 (1.8%) ADR-CS, 18 (20%) ECT-CS and three (6.7%) OTH-CS. The commonest cause of death in patients with PIT-CS and ADR-CS were infectious (n=8), cardiovascular (n=3), and cerebrovascular diseases (n=3). The commonest cause of death in patients with ECT-CS was progression of the underlying tumor (n=10), infections (n=3) and cardiovascular disease (n=2). The median (interquartile range) time from diagnosis to death was 67 (11–203) weeks in patients with PIT-CS and ADR-CS and 9 (3.6–48) weeks in patients with ECT-CS (P=0.007). Patients who died had a higher prevalence of diabetes mellitus (59 vs 35%; P=0.001) and muscle weakness (86 vs 69%; P=0.012) at diagnosis. The prevalence of hypertension, skin manifestations and depression at diagnosis did not differ between groups. By regression analysis, age (Odds ratio (OR) 1.05 (95% CI 1.02–1.07); P<0.001), diabetes (OR 2.14 (95% CI 1.07–4.27); P=0.030), and muscle weakness (OR 2.5 (95% CI 1.01–6.15); P=0.045) were significantly associated with mortality. Of 51 deceased patients, 23 (45%) died within 90 days from start of treatment and 3 (6%) before any treatment initiation. Of these, 7 (33%) had PIT-CS, 5 (24%) had ADR-CS, 12 (57%) had ECT-CS, and 2 (10%) OTH-CS. The commonest cause of death in these patients was infection (n=9). Two-thirds of patients who died within 90 days from start of treatment had diabetes, vs.35% in the whole ERCUSYN cohort (P=0.001). By regression analysis, age (OR 1.06 (95% CI 1.03–1.10); P<0.001) and diabetes mellitus (OR 2.9 (95% CI 1.1–7.2); P=0.025) were independently associated with death within 90 days from start of treatment.
Conclusion: Mortality was highest in patients with ectopic CS. Irrespective of etiology, older age, muscle weakness and diabetes at diagnosis were independently associated with increased mortality. Infectious diseases were the commonest cause of death soon after diagnosis and initiation of treatment, and patients with diabetes mellitus seem to be especially vulnerable, emphasizing the need for careful clinical vigilance at that time.
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Endocrine Abstracts
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