PNA Medical Corner: Analysis of High Mortality In Cushing’s

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Philippe ChansonThis month the PNA Medical Corner features an article co-written by longtime PNA member Dr. Philippe Chanson of the Hospital Bicetre and University Paris XI. It found that patients with ectopic Cushing’s Syndrome were most likely to die, and infectious disease was most often the culprit when patients died soon after diagnosis. Patients who are older and male had a higher mortality.


Eur J Endocrinol. 2019 Sep 1. pii: EJE-19-0464.R1. doi: 10.1530/EJE-19-0464. [Epub ahead of print]

High mortality within 90 days of diagnosis in patients with Cushing's syndrome - Results from the ERCUSYN registry.
Valassi E1, Tabarin A2, Brue T3, Feelders RA4, Reincke M5, Netea-Maier R6, Toth M7, Zacharieva S8, Webb SM9, Tsagarakis S10, Chanson P11, Pfeifer M12, Droste M13, Komerdus I14, Kastelan D15, Maiter D16, Chabre O17, Franz H18, Santos A19, Strasburger CJ20, Trainer PJ21, Newell-Price J22, Ragnarsson O23.

Objective Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate causes and time of death in a large cohort of patients with CS, and to establish factors associated with increased mortality. Methods In this cohort-study, we analysed 1564 patients included in the European Registry of CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. Results Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary- dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and two due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n=8), and progression of the underlying tumour (n=10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of these deaths were infections (n=10; 37%). Age, ectopic CS and active disease were associated with overall death before and within 90 days from start of treatment. Conclusion Mortality rate was highest in patients with ectopic CS. Infectious diseases were the commonest cause of death soon after diagnosis, emphasizing the need for clinical vigilance at that time, especially in patients with diabetes mellitus.

Author Information

1 E Valassi, Endocrinology, Universitat Autonoma de Barcelona, Barcelona, Spain.
2 A Tabarin, Endocrinology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
3 T Brue, Endocrinology, Hôpitaux de la Timone, Marseille, France.
4 R Feelders, Endocrinology, Erasmus Universiteit Rotterdam, Rotterdam, Netherlands.
5 M Reincke, Endocrinology, Ludwig-Maximilians-Universitat Munchen, Munchen, Germany.
6 R Netea-Maier, Endocrinology, Radboud Universiteit, Nijmegen, Netherlands.
7 M Toth, Endocrinology, Semmelweis Egyetem, Budapest, Hungary.
8 S Zacharieva, Endocrinology, Sofiski universitet Sveti Kliment Ohridski, Sofija, Bulgaria.
9 S Webb, Medicine/Endocrinology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
10 S Tsagarakis, Endocrinology, Evaggelismos General Hospital, Athens, Greece.
11 P Chanson, Endocrinology, Assistance Publique - Hôpitaux de Paris, Paris, France.
12 M Pfeifer, Endocrinology, Ljubljanski Univerzitetni klinicni center, Ljubljana, Slovenia.
13 M Droste, Endocrinology, Oldenburg Hospital, Oldenburg, Germany.
14 I Komerdus, Endocrinology, Moscow Region State University, Moskva, Russian Federation.
15 D Kastelan, Endocrinology, Zagreb Department of Health and Veterans, Zagreb, Croatia.
16 D Maiter, Endocrinology, Académie universitaire Louvain, Bruxelles, Belgium.
17 O Chabre, Endocrinology, Grenoble Universites, Saint-Martin-d'Heres, France.
18 H Franz, Consulting, Lohmann-Birkner, Berlin, Germany.
19 A Santos, Endocrinology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
20 C Strasburger, Endocrinology, Charite Universitatsmedizin Berlin, Berlin, Germany.
21 P Trainer, Endocrinology, Manchester Metropolitan University, Manchester, United Kingdom of Great Britain and Northern Ireland.
22 J Newell-Price, Endocrinology, Sheffield Health and Social Care NHS Foundation Trust, Sheffield, United Kingdom of Great Britain and Northern Ireland.
23 O Ragnarsson, Endocrinology, Sahlgrenska Academy, Goteborg, Sweden.