High prevalence of venous thrombotic events in Cushing's syndrome: data from ERCUSYN and details in relation to surgery

Author:

Isand Kristina1ORCID,Feelders Richard2,Brue Thierry3ORCID,Toth Miklos4,Deutschbein Timo5,Reincke Martin6ORCID,Kršek Michal7,Santos Alicia89,Demtröder Frank10,Chabre Olivier11,Strasburger Christian J12,Aulinas Maso Anna89,Volke Vallo1,Pereira Alberto M13,Lohmann Rüdiger14,Gich Saladich Ignasi15,Amaral C,Ambrogio A,Aranda G,Arosio M,Balomenaki M,Beck-Peccoz P,Berr-Kirmair C,Bertherat J,Bolanowski M,Bollerslev J,Thierry Brue,Cardoso H,Carvalho D,Cavagnini F,Ceccato P,Chabre O,Chanson P,Christ E,Demtröder Zentrum fur Endokrinologie F,Denes J,Deutschbein T,Dimopoulou C,Dreval A,Droste M,Duarte J S,Dusek T,Ertürk E,Evang J A,Fajardo C,Fazel J,Feelders R A,Fica S,García-Centeno R,Ghigo E,Goth M,Greenman Y,Halperin I,Hanzu F A,Hermus A,Johannsson G,Hubina E,Kamenicky P,Kasperlik-Zaluska A,Kirchner J,Kastelan D,Komerdus I,Kraljevic I,Krsek M,Kruszynska A,Lamas C,Lambrescu I,Lang S,Luger A,Maiter D,Marpole N,Martin S,Martinie M,Martins Oliveira M J,Moros O,Netea-Maier R,Newell-Price J,Orbetzova M,Paiva I,Pecori Giraldi F,Percovich J C,Pereira A M,Pfeiffer M,Pickel J,Pirags V,Ragnarsson O,Reghina A D,Reincke M,Riesgo P,Roberts M,Roerink S,Rowan C,Rudenko P,Sahnoun M A,Salvador J,Santos A,Scaroni C,Sigurjonsdottir H A,Skoric Polovina T,Smith R,Stachowska B,Stalla G,Strasburger C,Tabarin A,Terzolo M,Tőke J,Tóth M,Touraine P,Trainer P J,Tsagarakis S,Valassi E,Vila G,Vinay S,Wagenmakers M,Webb S,Werner S,Young J,Zdunowski P,Zacharieva S,Zopf K,Zopp S,Zosin I,Webb Susan M89,Wass John16,Valassi Elena917ORCID,

Affiliation:

1. Institute of Biomedicine and Translational Medicine, University of Tartu , Ülikooli 18 , 50090, Tartu, Estonia

2. Department of Internal Medicine, Section of Endocrinology, ENETS Center of Excellence, Erasmus MC and Erasmus Cancer Institute , 3015 Rotterdam , The Netherlands

3. Aix Marseille Univ, APHM, INSERM, MMG, Department of Endocrinology Hospital La Conception , MarMaRa Institute, 13305 Marseille , France

4. Department of Internal Medicine and Oncology, Semmelweis University , 1083 Budapest , Hungary

5. Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg , 97080 Würzburg , Germany

6. Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Ludwig-Maximilians-Universität München , 80336 Munich , Germany

7. Third Department of Internal Medicine, First Faculty of Medicine, Charles University, General University Hospital , 12808 Prague , Czech Republic

8. IIB-Sant Pau and Department of Endocrinology, Hospital Sant Pau, Dept Medicine, UAB, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII , 08025 Barcelona , Spain

9. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747) , Barcelona , Spain

10. Zentrum für Endokrinologie, Diabetologie, Rheumatologie Dr. Demtröder & Kollegen , 44137 Dortmund , Germany

11. University Grenoble Alpes, UMR 1292 INSERM-CEA-UGA, Endocrinologie CHU Grenoble Alpes , F-38000 Grenoble , France

12. Clinical Endocrinology, Charite-Universitätsmedizin , Campus Mitte, 10117 Berlin , Germany

13. Department of Endocrinology & Metabolism, Amsterdam University Medical Center, and University of Amsterdam , 1081 Amsterdam , Netherlands

14. Health Care Consulting GmbH, Lohmann & Birkner Health Care Consulting GmbH , 13407 Berlin , Germany

15. Department of Clinical Epidemiology and Public Health, Hospital de la Santa Creu i Sant Pau (IIB Sant Pau) , 08025 Barcelona , Spain

16. Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals , OX37LE Oxford , United Kingdom

17. Endocrinology and Nutrition Department, Germans Trias i Pujol Hospital and Research Institute , Badalona 08916 , Spain

Abstract

Abstract Objective The aim of this study was to evaluate the prevalence of venous thromboembolism (VTE) in patients included in the European Registry on Cushing's syndrome (ERCUSYN), compare their clinical characteristics with those who did not develop VTE and identify risk factors for VTE. Design A retrospective observational cohort study. Methods Data extraction from the registry was taken on February, 7, 2022. At the time there were 2174 patients diagnosed with Cushing's syndrome (CS) and 95 VTEs were reported in the database. Results Of 95 VTE events 70 (74%) were in pituitary-dependent CS patients, 12 (12.5%) in adrenal-dependant CS, 10 (10.5%) in ectopic CS, and 3 (3%) in CS due to other causes. Sex, 24-hour urinary free cortisol (UFC) value at diagnosis, as well as the number of operations remained statistically significant predictors of VTE. Of patients who were treated with at least one surgery, 12 (13%) VTE occurred before and 80 (87%) after the surgery. Nearly half of these VTEs occurred within six months since the operation (36; 45%). Over half of the centers that reported VTE did not routinely anticoagulate CS patients. Anticoagulation schemes varied widely. Conclusion Patients with CS have an elevated risk of developing VTE for an extended period of time. From ERCUSYN cohort patients have higher risk for VTE if they need multiple surgeries to treat CS, are males and have high UFC values at the diagnosis of CS. Since there is no agreement on thromboprohpylaxis, a protocol for VTE prevention that is widely adopted appears to be necessary for patients with CS.

Funder

Novartis, Ipsen, HRA, and the European Society of Endocrinology

Publisher

Oxford University Press (OUP)

Subject

Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism

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