Markers of activation of coagulation and fibrinolysis in patients with Cushing's syndrome

Patients with active Gushing's syndrome have an increased thrombotic tenden cy. We chose to reassess the mechanism underlying the thrombophilic state a ssociated with this clinical condition using sensitive markers of coagulati on and fibrinolysis activation in 17 patients with active disease. The resu lts were compared with those obtained in 12 Gushing's patients successfully treated by surgery and in 20 normal individuals. The general pattern of re sults in patients with active disease was the finding of increased levels o f von Willebrand factor (VWF: Ag), a marker of enhanced metabolic function of endothelial cells (VWF:Ag 181 +/- 42 vs 110 +/- 43, p<0.001 in normal su bjects), accompanied by signs of heightened thrombin and plasmin generation , expressed by high levels of thrombin-antithrombin (TAT 5.59 +/- 3.6 vs 3. 06 +/- 0.92 ng/ml in controls, p<0.01) and plasmin-antiplasmin complexes (P AP 407 +/- 176 vs 245 +/- 67 ng/ml in controls, p<0.01). VWF:AS and TAT val ues were significantly higher in hypertensive than in normotensive patients with active disease (205 +/- 40 vs 155 +/- 26 U/dl, p<0.05 and 7.49 +/- 3. 7 vs 3.45 +/- 1.8, p<0.01, respectively). Plasma levels of plasminogen acti vator inhibitor type 1 were higher, though not to a statistically significa nt extent, in patients with active disease compared to controls (12.8 +/- 1 2.3 vs 5.6 +/- 7.4 IU/ml, NS) and positively correlated with body mass inde x (r=0.66, p<0.01). After surgical control of Gushing's syndrome, there was a partial or complete reversal of the abnormalities to values similar to t hose found in normal individuals. Our data suggest that the thrombophilic s tate present in patients with active Gushing's syndrome is related to an en hanced metabolic function of endothelial cells; this in turn may be caused by an heightened production of thrombin with secondary hyperfibrinolysis, P rimary prophylaxis with anticoagulants is recommended in these patients whe n they are exposed to a thrombophilic condition such as surgery. (J. Endocr inol. Invest. 23: 145-150, 2000) (C) 2000, Editrice Kurtis.