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CME Evaluation

Oral Communication Session

Venous Thromboembolism

Session: Thrombophilia

OC 16.3 - Distinct proteomic profiles after remission of Cushing syndrome, but coagulation-related proteins remained abnormal

Sunday, June 23, 2024
10:00 – 10:15 ICT
Room: 111 A-C

    Co-Author(s)

  • BV

    Britte F. Van Der Vliet

    MSc student
    Department of Thrombosis & Hemostasis, Leiden University Medical Center
    Leiden, Zuid-Holland, Netherlands

    • Presenting Author(s)

  • Eleonora Camilleri, MD

    MD PhD candidate
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
    Leiden, Zuid-Holland, Netherlands

    • Co-Author(s)

  • NB

    Nienke R. Biermasz

    MD, PhD, prof
    Department of Medicine, Division of Endocrinology, and Center for Endocrine Tumors Leiden, Leiden University Medical Center, Leiden, The Netherlands
    Leiden, Zuid-Holland, Netherlands

  • Suzanne C. Cannegieter

    MD, PhD, prof
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
    Leiden, Zuid-Holland, Netherlands

  • RC

    Robert A Cordfunke

    Research technician
    Department of Immunology, Leiden University Medical Center
    Leiden, Zuid-Holland, Netherlands

  • OD

    Olaf M Dekkers

    Professor at Leiden University Medical Center, Chair of the scientific board internal medicine, LUMC
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
    Leiden, Zuid-Holland, Netherlands

  • JD

    Jan Wouter Drijfhout

    PhD, Associate professor
    Department of Immunology, Leiden University Medical Center
    Leiden, Zuid-Holland, Netherlands

  • ND

    Natasja Dolezal

    Research technician
    Department of Immunology, Leiden University Medical Center
    Leiden, Zuid-Holland, Netherlands

  • LH

    Leo J. Hofland

    PhD, prof
    Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands.
    Rotterdam, Zuid-Holland, Netherlands

  • Erik Klok, MD, PhD, FESC

    Leiden University Medical Center

  • OM

    Onno C. Meijer

    PhD, prof
    Department of Medicine, Division of Endocrinology, and Center for Endocrine Tumors Leiden, Leiden University Medical Center, Leiden, The Netherlands.
    Leiden, Zuid-Holland, Netherlands

  • AP

    Alberto M. Pereira

    MD, PhD, prof
    Department of Endocrinology and Metabolism, Amsterdam University Medical Center, Amsterdam, The Netherlands
    Amsterdam, Noord-Holland, Netherlands

  • LR

    L. Renee Ruhaak

    PhD, Associate professor
    Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden
    Leiden, Zuid-Holland, Netherlands

  • MT

    Maxim Treep

    MsC
    Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands,
    Leiden, Zuid-Holland, Netherlands

  • Bv

    Bart JM van Vlijmen

    PhD, associate professor
    Department of Thrombosis & Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
    Leiden, Zuid-Holland, Netherlands

  • TP

    Ticiana Paes

    MD
    Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands.
    Rotterdam, Zuid-Holland, Netherlands

  • RF

    Richard A. Feelders

    MD PhD
    Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center (MC), University Medical Center Rotterdam, Rotterdam, Netherlands.
    Rotte, Zuid-Holland, Netherlands

Background: Cortisol excess in Cushing syndrome (CS) leads to a spectrum of abnormalities including hypercoagulability (due to enhanced coagulation and impaired fibrinolysis). This results in a major increase in the risk of venous thromboembolism (VTE) compared to the general population. Whether these abnormalities fully reverse after CS treatment is unknown.

Aims: To compare plasma proteomic profiles within CS patients before and after remission, focusing on coagulation-related proteins.

Methods: Patients diagnosed with CS at the Erasmus Medical Center, Rotterdam, between 2012-2022 were included. Blood samples were taken during active CS and after long-term remission (≥1 year cortisol normalization). We quantified 159 proteins, among which 23 coagulation-related proteins, through quantitative targeted proteomics. Protein levels were compared before and after remission (paired t-tests adjusted for false discovery rate) and mean differences estimated through a linear mixed model (adjusted for body mass index and CS severity). Plasma of 40 healthy volunteers was used to define the normal range of protein levels (reference) and thus normalization.

Results: We included 27 CS patients, with a median age of 47 years (IQR 31-52), of which 21 (78%) were female. We observed different proteomic profiles after remission compared to active CS, with 71 differentially expressed proteins (Figure 1). Among these were 14 coagulation-related proteins, such as factor IX (adjusted mean difference -0.2% [95%CI -0.3 to -0.1]), protein C (-0.2%, 95%CI -0.3 to -0.1) and Z (-0.2%, 95%CI -0.3 to -0.1), and thrombin-activatable fibrinolysis inhibitor (-0.1%, 95%CI -0.2 to -0.03) (Figure 2). In total, 9 coagulation-related proteins tended towards normalization but still remained abnormal after remission.

Conclusion(s): Proteomic profiles of CS were different during long-term remission compared to active CS, although several proteins including those related to coagulation and fibrinolysis remained abnormal. This might explain the observed long term increased VTE risk despite CS remission.