Changes in coagulation indexes and occurrence of venous thromboembolism in patients with Cushing's syndrome: results from a prospective study before and after surgery

OBJECTIVES: 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). DESIGN: Prospective study conducted on patients with CS evaluated at diagnosis and 12 months after surgery. PATIENTS AND 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

Diagnosis and treatment of autoimmune hypophysitis: A short review

Abstract Medical therapy of autoimmune hypophysitis with immunosuppressive drugs can be effective to induce remission of the disease by treating both pituitary dysfunction and compression symptoms. We describe the case of a 41-yr-old man with autoimmune hypophysitis in whom prednisone therapy induced remission of the disease but was followed by a sudden relapse after withdrawal. A second trial of corticosteroid was started and succeeded in inducing remission of the disease. Eight months after the second withdrawal pituitary function was restored, pituitary mass had disappeared, only partial diabetes insipidus remained unchanged. Review of the literature identified 30 articles, among case reports and case series, reporting a total of 44 cases of autoimmune hypophysitis treated with glucocorticoids and/or azathioprine. Combining all the cases, medical therapy resulted to be effective in reducing the pituitary mass in 84%, in improving anterior pituitary function in 45%, and in restoring posterior pituitary function in 41%. Clinical aspects of autoimmune hypophysitis are discussed and a possible algorithm for the diagnosis and treatment of the disease is propose

Serum pituitary antibodies in normal pregnancy and in patients with postpartum thyroiditis: a nested case-control study

OBJECTIVES: The aim of this study was to evaluate antipituitary antibody (APA) prevalence in a series of patients with postpartum thyroiditis (PPT) during pregnancy and in the postpartum. DESIGN: We conducted a nested case-control study on consecutive PPT and normal pregnant women at the Centre for Endocrine and Diabetes Sciences in Cardiff and at the Department of Endocrinology in Pisa. METHODS: We enrolled 30 women with PPT: 17 were hypothyroid (Hypo), 7 with hyperthyroidism (Hyper) and 6 with a transient hyperthyroidism followed by hypothyroidism (Biphasic). Twenty-one healthy pregnant women served as controls. APA (measured using indirect immunofluorescence), free thyroxine, free triiodothyronine, TSH, antithyroid autoantibodies, and thyroid ultrasound were performed during pregnancy and postpartum. The stored sera have been sent to Pisa, where serum APA, IGF1, and cortisol were measured. RESULTS: APA were found in 8 out of the 30 PPT patients (26.7%) and in one normal pregnancy (4.7%, P=0.063). Three out of the seventeen Hypo with PPT (17.6%), three out of the seven Hyper PPT (42.8%), and two out of the six Biphasic PPT (33.3%) were positive for APA. APA prevalence was not significantly different in the PPT subgroups (P=0.453). With one exception, APA all increased in the postpartum period (87.5%, P<0.016). Basal serum IGF1 and cortisol were in the normal range with the exception of two patients with positive APA who presented low serum IGF1 levels (36 and 45 ng/ml). CONCLUSIONS: APA are frequently present in the postpartum period in patients affected by PPT. Further studies are necessary to evaluate whether APA in PPT patients are associated with pituitary function impairment