Endocrine Abstracts

Patients with Cushing's disease are well known to develop easy bruising due to cortisol excess but are also predisposed to thrombembolism.

We present four patients who developed thromboembolism during active Cushing's disease.

Case 1- Four year history of hypertension, osteoporosis and central obesity. A DVT developed prior to referral. Initial urinary free cortisol(UFC)was 524nmol/24hrs. Inferior petrosal sinus sampling indicated a left pituitary adenoma.

Case 2- Five year history of central obesity, moon face, bruising, proximal myopathy, hirsutism, hypertension and diabetes. Initial UFC was 663nmol/24hr. ACTH was 71ng/l. Pituitary fossa enlarged. An extensive left middle cerebral thrombosis developed after pituitary surgery followed by a DVT one month later.

Case 3 -Three year history of obesity, hirsutism, irregular periods and abdominal striae. Initial UFC was 1289mmol/24hours. Cortisol failed to suppress on low dose dexamethasone test(LDDT) and partially suppressed on high dose dexamethasone test(HDDT). ACTH was 139ng/l. Pituitary microadenoma demonstrated on MRI. A DVT developed requiring an inferior vena cava filter prior to pituitary surgery. Thrombophilia screen was negative.

Case 4-Two years of Cushingoid features. Investigations showed raised UFC, failure to suppress cortisol on LDDT and partial suppression on HDDT. Required ITU admission after PE induced acute hypoxic breathlessness.

Discussion In Cushing's disease thromboembolic risk factors include obesity, age, hypertension, raised haematocrit, immobility and major surgery. Cortisol excess has been shown to increase coagulability and reduce fibrinolysis.

Canine studies in Cushing syndrome have shown increased levels of thrombin-antithrombin complexes, procoagulaion factors II,V,VII,IX,X,XII and reduced antithrombin. Limited human studies show increases in Factors VIII,XII,XI,IX and V,prothrombin, fibrinogen,plasminogen and alpha2 antiplasmin. Plasminogen activator inhibitor, tissue plasminogen activator and von Willebrand factor were normal in one series of Cushing's syndrome but increased in another of Cushing's disease.

A high degree of suspicion for thromboembolism must prevail when managing patients with Cushing's disease.