Changes in coagulation indexes and occurrence of venous thromboembolism in patients with Cushing's syndrome: results from a prospective study before and after surgery.
OBJECTIVE
To evaluate whether patients with Cushing's syndrome (CS) had i) changes in coagulative and fibrinolytic parameters associated with CS activity and ii) higher prevalence of venous thromboembolic events (VTE).


METHODS
Prospective study conducted on patients with CS evaluated at diagnosis and 12 months after surgery.


METHODS
Forty patients with active CS (36 with Cushing's disease (CD) and 4 with an adrenal adenoma) were evaluated. Forty normal subjects and 70 patients with non-ACTH-secreting pituitary adenomas served as controls. All patients and controls underwent an assessment of coagulation and fibrinolysis indexes before and after surgery.


RESULTS
CS patients at baseline had a hypercoagulative phenotype when compared with normal subjects (activated partial thromboplastin time (aPTT), fibrinogen, D-Dimer, von Willebrand factor (VWF), plasminogen activator inhibitor 1 (PAI-1 or SERPINE1), antithrombin III (ATIII or SERPINC1), P<0.0001, α(2) antiplasmin, P=0.0004, thrombin-antithrombin complex (TAT), P=0.01, factor IX (F9), P=0.03). Patients with still active disease after surgery had higher coagulative parameters than those in remission (VWF (P<0.0001), PAI-1 (P=0.004), TAT (P=0.0001), ATIII (P=0.0002) and α(2) antiplasmin (or SERPINF2; P=0.006)), whereas aPTT levels (P=0.007) were significantly reduced. VTE occurred in three patients with CD (7.5%): one had a pulmonary embolism and two patients had a deep venous thrombosis; no patients submitted to transsphenoidal surgery for non-Cushing's pituitary adenoma had VTE (P=0.04).


CONCLUSIONS
Patients with CS have a procoagulative phenotype due to cortisol-associated changes in haemostatic and fibrinolytic markers, leading to increased incidence of VTE. Thromboprophylaxis seems to be appropriated in patients with active disease, particularly in the postoperative period.
Manetti
Luca
L
Department of Endocrinology, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124 Pisa, Italy. lmanetti@endoc.med.unipi.it
Bogazzi
Fausto
F
Giovannetti
Clara
C
Raffaelli
Valentina
V
Genovesi
Maura
M
Pellegrini
Giovanni
G
Ruocco
Lucia
L
Iannelli
Aldo
A
Martino
Enio
E
D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000502:physiology*; D001780:Blood Coagulation Tests / Q000639:trends; D003480:Cushing Syndrome / Q000097:blood* / Q000150:complications / Q000601:surgery*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D011300:Preoperative Care / Q000639:trends; D011446:Prospective Studies; D054556:Venous Thromboembolism / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D055815:Young Adult