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Thrombin generation in Cushing’s Syndrome: do the conventional clotting indices tell the whole truth?

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Abstract

Cushing’s Syndrome (CS) is associated with an increased mortality, where hypercoagulability seems to have a crucial role in both arterial and venous thrombosis. Parameters of in vitro thrombin generation (TG) such as lag time, peak thrombin and endogenous thrombin potential (ETP), that describe the time until thrombin burst, the peak amount of TG and the total amount of thrombin generated, respectively as well as classical clotting markers were evaluated in 33 CS patients compared to both a group of 28 patients matched for the features of Metabolic Syndrome (MetS) and 31 healthy individuals. CS and MetS patients had shorter lag time (p < 0.0001), higher peak and ETP (p < 0.0001) than healthy controls, though lag time was less shortened in CS (p < 0.0001) respect to MetS group. Prothrombin time (PT) was increased (p < 0.0001) in both CS and MetS patients, while partial thromboplastin time (PTT) was shorter (p < 0.0001) in CS compared to both MetS and healthy group (p < 0.0001). Factor VIII (FVIII), Antithrombin (AT), protein C and S were increased only in CS patients (p < 0.0001). lag time, AT and FVIII correlated to night salivary cortisol (r = + 0.59; p = 0.0005, r = + 0.40; p = 0.003, r = + 0.40; p = 0.04, respectively); PTT correlated inversely to urinary free cortisol (r = −0.45; p = 0.009). BMI correlated negatively to lag time (r = −0.40; p = 0.0001) and positively to peak and ETP (r = + 0.34; p = 0.001, r = + 0.28; p = 0.008, respectively). Obese and diabetic patients had shorter lag time (p = 0.0005; p = 0.0002, respectively), higher ETP (p = 0.0006; p = 0.007, respectively) and peak (p = 0.0003; p = 0.0005, respectively) as well as a more prolonged PT (p = 0.04; p = 0.009, respectively). Hypertensive individuals had higher ETP (p = 0.004), peak (p = 0.0008) and FVIII (p = 0.001). Our findings confirm a prothrombotic state in both CS and MetS patients, though lag time was less shortened in CS. The high levels of endogenous physiological anticoagulants, could possibly represent a protective mechanism against hypercoagulability seen in CS patients.

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Acknowledgments

We thank Professor Franco Mantero (University of Padova) for his continuous encouragement and advice as well as Doctor Barry Woodhams for his critical reading of the manuscript.

Conflict of interest

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Endocrinology Unit, Department of Medicine-DIMED, University of Padua, Via Ospedale, 105, 35128, Padua, Italy

    S. Koutroumpi, N. Albiger, M. Barbot, F. Mantero & C. Scaroni

  2. 2nd Chair of Internal Medicine, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy

    L. Spiezia, M. Bon, S. Maggiolo, S. Gavasso & P. Simioni

  3. Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy

    A. Frigo

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  1. S. Koutroumpi
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Correspondence to C. Scaroni.

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S. Koutroumpi and L. Spiezia equally contributed to this work.

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Koutroumpi, S., Spiezia, L., Albiger, N. et al. Thrombin generation in Cushing’s Syndrome: do the conventional clotting indices tell the whole truth?. Pituitary 17, 68–75 (2014). https://doi.org/10.1007/s11102-013-0467-3

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