Venous thromboembolism in Cushing syndrome: results from an EuRRECa and Endo-ERN survey

M Cherenko¹, N M Appelman-Dijkstra¹, A L Priego Zurita¹, N R Biermasz¹, O M Dekkers¹, F A Klok², N Reisch³, A Aulinas⁴, B Biagetti⁵, S Cannavo⁶, L Canu⁷, M Detomas⁸, F Devuyst⁹, H Falhammar¹⁰, R A Feelders¹¹, F Ferrau⁶, F Gatto¹², C Grasselli¹³, P van Houten¹⁴, C Hoybye¹⁰, A M Isidori¹⁵, A Kyrilli⁹, P Loli¹⁶, D Maiter¹⁷, E Nowak³, R Pivonello¹⁸, O Ragnarsson¹⁹, R V Steenaard²⁰, N Unger²¹, A van de Ven¹⁴, S M Webb⁴, D Yeste²², S F Ahmed^{1

23

24}, A M Pereira²⁵

Affiliations

¹ Department of Medicine, Division of Endocrinology, Leiden University Medical Centre, Leiden, Netherlands.
² Department of Medicine, Division of Thrombosis and Haemostasis, Leiden University Medical Centre, Leiden, Netherlands.
³ Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany.
⁴ Department of Endocrinology, Fundacio de Gestio Sanitaria Hospital de la Santa Creu i Sant Pau, IR-SantPau and CIBERER Unit 747 (ISCIII), Barcelona, Spain.
⁵ Department of Endocrinology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
⁶ Endocrine Unit, University Hospital AOU Policlinico G. Martino, Messina, Italy.
⁷ University Hospital Florence Careggi, Florence, Italy.
⁸ Department of Internal Medicine, University Hospital Würzburg, Wuerzburg, Germany.
⁹ Department of Endocrinology, Hôpital Universitaire de Bruxelles, Hôpital Erasme, Brussels, Belgium.
¹⁰ Department of Endocrinology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
¹¹ Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Netherlands.
¹² IRCCS Ospedale Policlinico San Martino, Genova, Genoa, Italy.
¹³ Cardiovascular Medicine Unit, AUSL-IRCCS, Reggio Emilia, Italy.
¹⁴ Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, Netherlands.
¹⁵ Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
¹⁶ Division of Endocrinology, San Raffaele Vita-Salute University, IRCCS San Raffaele Hospital Milan, Italy.
¹⁷ Department of Endocrinology, Cliniques universitaires Saint-Luc - UCLouvain, Brussels, Belgium.
¹⁸ Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Diabetologia, Andrologia e Nutrizione, Università "Federico II" di Napoli, Naples, Italy.
¹⁹ Sahlgrenska Academy, Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine (O.R.), University of Gothenburg, Sweden.
²⁰ Department of Internal Medicine, Máxima MC, Veldhoven, Netherlands.
²¹ University Hospital Essen, Department of Endocrinology, Diabetes and Metabolism, Essen, Germany.
²² Pediatric Endocrinology Service, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. CIBER Enfermedades Raras, Instituto Carlos III, Madrid, Spain.
²³ University of Glasgow, Office for Rare Conditions, Glasgow, UK.
²⁴ University of Glasgow, Developmental Endocrinology Research Group, Royal Hospital for Children, Glasgow, UK.
²⁵ Department of Endocrinology & Metabolism, Amsterdam University Medical Centre, Amsterdam, Noord-Holland, Netherlands.

PMID: 38614126
PMCID: PMC11103746
DOI: 10.1530/EC-24-0046

Venous thromboembolism in Cushing syndrome: results from an EuRRECa and Endo-ERN survey

M Cherenko et al. Endocr Connect. 2024.

. 2024 May 7;13(6):e240046.

doi: 10.1530/EC-24-0046. Print 2024 Jun 1.

Authors

Affiliations

¹ Department of Medicine, Division of Endocrinology, Leiden University Medical Centre, Leiden, Netherlands.
² Department of Medicine, Division of Thrombosis and Haemostasis, Leiden University Medical Centre, Leiden, Netherlands.
³ Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany.
⁴ Department of Endocrinology, Fundacio de Gestio Sanitaria Hospital de la Santa Creu i Sant Pau, IR-SantPau and CIBERER Unit 747 (ISCIII), Barcelona, Spain.
⁵ Department of Endocrinology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
⁶ Endocrine Unit, University Hospital AOU Policlinico G. Martino, Messina, Italy.
⁷ University Hospital Florence Careggi, Florence, Italy.
⁸ Department of Internal Medicine, University Hospital Würzburg, Wuerzburg, Germany.
⁹ Department of Endocrinology, Hôpital Universitaire de Bruxelles, Hôpital Erasme, Brussels, Belgium.
¹⁰ Department of Endocrinology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
¹¹ Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Netherlands.
¹² IRCCS Ospedale Policlinico San Martino, Genova, Genoa, Italy.
¹³ Cardiovascular Medicine Unit, AUSL-IRCCS, Reggio Emilia, Italy.
¹⁴ Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, Netherlands.
¹⁵ Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
¹⁶ Division of Endocrinology, San Raffaele Vita-Salute University, IRCCS San Raffaele Hospital Milan, Italy.
¹⁷ Department of Endocrinology, Cliniques universitaires Saint-Luc - UCLouvain, Brussels, Belgium.
¹⁸ Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Diabetologia, Andrologia e Nutrizione, Università "Federico II" di Napoli, Naples, Italy.
¹⁹ Sahlgrenska Academy, Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine (O.R.), University of Gothenburg, Sweden.
²⁰ Department of Internal Medicine, Máxima MC, Veldhoven, Netherlands.
²¹ University Hospital Essen, Department of Endocrinology, Diabetes and Metabolism, Essen, Germany.
²² Pediatric Endocrinology Service, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. CIBER Enfermedades Raras, Instituto Carlos III, Madrid, Spain.
²³ University of Glasgow, Office for Rare Conditions, Glasgow, UK.
²⁴ University of Glasgow, Developmental Endocrinology Research Group, Royal Hospital for Children, Glasgow, UK.
²⁵ Department of Endocrinology & Metabolism, Amsterdam University Medical Centre, Amsterdam, Noord-Holland, Netherlands.

PMID: 38614126
PMCID: PMC11103746
DOI: 10.1530/EC-24-0046

Abstract

Background: Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE).

Objective: The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis.

Design and methods: A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG's) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022.

Results: Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3-30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years.

Conclusion: Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed.

Significance statement: The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.

Keywords: Cushing disease; Cushing syndrome; endogenous hypercortisolism; thromboprophylaxis; venous thromboembolism.

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Conflict of interest statement

NMA-D the LUMC funding (EuRRECa is funded through ENDO ERN within the European Union within the framework of the EU4H Programme, grant agreement no. 101084921). FAK has received research funding from Bayer, BMS, BSCI, AstraZeneca, MSD, Leo Pharma, Actelion, Farm-X, The Netherlands Organisation for Health Research and Development, the Dutch Thrombosis Foundation, the Dutch Heart Foundation and the Horizon Europe Program, all outside this work and paid to his institution. FG has received funding from research purposes from Pfizer, Ipsen, and Camurus. EN is supported by the Clinician Scientist Program RISE (Rare Important Syndromes in Endocrinology), supported by the Else-Kröner-Fresenius Stiftung and Eva Luise und Horst Köhler Stiftung. RP has received research funding from Recordati AG., Corcept Therapeutics, Strongbridge Biopharma, Neurocrine Biosciences; and served as a consultant for Corcept Therapeutics, Recordati AG., Crinetics Pharmaceuticals, H. Lundbeck A/S. SFA (EuRRECa is funded through ENDO ERN within the European Union within the framework of the EU4H Programme, grant agreement no. 101084921). AMP (Endo-ERN is funded by the European Union within the framework of the EU4H Programme, grant agreement no. 101084921). Other co-authors – none. SFA is Editor-in-Chief of Endocrine Connections. SFA was not involved in the review or editorial process for this paper, on which he is listed as an author.

Figures

**Figure 1**
Overview of countries responding to the survey.

See this image and copyright information in PMC

References

1. Lacroix A Feelders RA Stratakis CA & Nieman LK. Cushing’s syndrome. Lancet 2015386913–927. (10.1016/S0140-6736(1461375-1) - DOI - PubMed
1. Lindholm J, Juul S, Jørgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, Hagen C, Jørgensen J, Kosteljanetz M, Kristensen LO, et al.Incidence and late prognosis of Cushing’s syndrome: a population-based study. Journal of Clinical Endocrinology and Metabolism 200186117–123. (10.1210/jcem.86.1.7093) - DOI - PubMed
1. Gadelha M Gatto F Wildemberg LE & Fleseriu M. Cushing’s syndrome. Lancet 20234022237–2252. (10.1016/S0140-6736(2301961-X) - DOI - PubMed
1. Van der Pas R Leebeek FWG Hofland LJ de Herder WW & Feelders RA. Hypercoagulability in Cushing’s syndrome: prevalence, pathogenesis and treatment. Clinical Endocrinology 201378481–488. (10.1111/cen.12094) - DOI - PubMed
1. Feelders RA & Nieman LK. Hypercoagulability in Cushing’s syndrome: incidence, pathogenesis and need for thromboprophylaxis protocols. Pituitary 202225746–749. (10.1007/s11102-022-01261-9) - DOI - PMC - PubMed

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Venous thromboembolism in Cushing syndrome: results from an EuRRECa and Endo-ERN survey

Affiliations

Venous thromboembolism in Cushing syndrome: results from an EuRRECa and Endo-ERN survey

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources