The hypercoagulable state in Cushing's disease is associated with increased levels of procoagulant factors and impaired fibrinolysis, but is not reversible after short-term biochemical remission induced by medical therapy.
J Clin Endocrinol Metab
; 97(4): 1303-10, 2012 Apr.
Article
in En
| MEDLINE
| ID: mdl-22278425
ABSTRACT
CONTEXT Cushing's disease (CD) is accompanied by an increased risk of venous thromboembolism. Surgery is the primary treatment of CD. OBJECTIVE:
The aim of the study was to compare hemostatic parameters between patients with CD and controls and to evaluate the effect of medical treatment of CD on hemostasis. DESIGN ANDSETTING:
During 80 d, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline, and ketoconazole, which suppresses adrenocortical steroidogenesis, at four university medical centers in The Netherlands. PATIENTS Seventeen patients with de novo, residual, or recurrent CD were included. MAIN OUTCOMEMEASURES:
We measured urinary free cortisol and parameters of coagulation and fibrinolysis.RESULTS:
Patients with CD had significantly higher body mass index (P < 0.001), shortened activated partial thromboplastin time (P < 0.01), and higher levels of fibrinogen, Factor VIII, and protein S activity (P < 0.05) compared to healthy control subjects. In addition, fibrinolytic capacity was impaired in patients with CD as reflected by prolonged clot lysis time (P < 0.001) and higher levels of plasminogen activator inhibitor type 1, thrombin-activatable fibrinolysis inhibitor, and α2-antiplasmin (P < 0.01). There were no statistically significant differences in von Willebrand factorantigen, antithrombin, and protein C activity. After 80 d, 15 of 17 patients had normalized urinary free cortisol excretion. Despite biochemical remission, only slight decreases in antithrombin (P < 0.01) and thrombin-activatable fibrinolysis inhibitor (P < 0.05) levels were observed. Other parameters of coagulation and fibrinolysis did not change significantly.CONCLUSIONS:
The hypercoagulable state in patients with CD, which is explained by both increased production of procoagulant factors and impaired fibrinolysis, is not reversible upon short-term biochemical remission after successful medical therapy. This may have implications for the duration of anticoagulant prophylaxis in patients with (cured) CD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pituitary Hormones, Anterior
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Blood Coagulation
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Blood Coagulation Factors
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Thrombophilia
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Pituitary ACTH Hypersecretion
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Fibrinolysis
Type of study:
Clinical_trials
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Risk_factors_studies
Limits:
Adult
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Aged
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Humans
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Male
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Middle aged
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2012
Document type:
Article
Affiliation country: