Von Willebrand factor and fibrinolytic parameters during the desmopressin test in patients with Cushing's disease

Br J Clin Pharmacol. 2011 Jan;71(1):132-6. doi: 10.1111/j.1365-2125.2010.03812.x.

Abstract

What is already known about this subject: Desmopressin is a known haemostatic agent and is also being used, albeit at lower doses, during the diagnostic work-up of Cushing's syndrome, a condition characterized by excess cortisol concentrations and frequent thromboembolic events. No study has yet evaluated whether administration of desmopressin for diagnostic purposes induces significant, adverse changes in endothelial cell markers in these patients.

What this study adds: Administration of desmopressin to patients with Cushing's disease induces changes in endothelial cell markers comparable with those observed in obese and normal weight subjects. It follows, that desmopressin testing does not induce disease-specific untoward changes in coagulatory markers in patients with endogenous hypercortisolism and its use in this context appears safe.

Aims: Desmopressin, a vasopressin analogue, is used for various clinical purposes, including haemostasis and, in recent times, the diagnostic work-up of patients with Cushing's syndrome, a condition associated with a known prothrombotic profile. We decided to evaluate whether and to what extent a diagnostic dose of desmopressin induces significant changes in endothelial parameters in patients with Cushing's disease (CD) and obese and normal weight controls.

Methods: Twelve patients with CD, 10 obese and five normal weight controls were studied. Von Willebrand antigen (VWF:Ag), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured at baseline and up to 4 h after 10 µg desmopressin i.v.

Results: Desmopressin 10 µg transiently increased VWF:Ag and t-PA and decreased PAI-1 in all subjects. The magnitude of the VWF:Ag and t-PA increases after desmopressin was comparable in the three groups (VWF:Ag peak-to-basal ratio 1.9 ± 0.17, 1.5 ± 0.11 and 1.8 ± 0.13 and t-PA peak-to-basal ratio 1.6 ± 0.18, 1.6 ± 0.20 and 1.8 ± 0.24 for CD, obese and controls, respectively, all NS). The PAI-1 decrease observed in patients with CD was comparable with obese (0.7 ± 0.07 and 0.6 ± 0.09, NS) and controls (0.7 ± 0.07 vs. 0.4 ± 0.09, P= 0.08).

Conclusions: Administration of desmopressin to patients with CD for diagnostic purposes induces a transitory increase in VWF:Ag counterbalanced by a decrease in PAI-1 and increase in t-PA. The magnitude of these changes is largely comparable with that observed in obese and normal weight controls. Our data show that testing with desmopressin does not induce disease-specific changes in endothelial markers in patients with CD.

MeSH terms

  • Body Weight
  • Case-Control Studies
  • Deamino Arginine Vasopressin*
  • Fibrinolysis / drug effects*
  • Humans
  • Pituitary ACTH Hypersecretion / blood
  • Pituitary ACTH Hypersecretion / diagnosis*
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Tissue Plasminogen Activator / metabolism*
  • von Willebrand Factor / immunology*
  • von Willebrand Factor / metabolism

Substances

  • Plasminogen Activator Inhibitor 1
  • Von Willebrand antigen
  • von Willebrand Factor
  • Tissue Plasminogen Activator
  • Deamino Arginine Vasopressin