Pereira, A.M.

Increased myocardial fibrosis and left ventricular dysfunction in Cushing's syndrome (Article)

2012-01-01T00:00:00Z

Objective: Active Cushing's syndrome (CS) is associated with cardiomyopathy, characterized by myocardial structural, and ultrastructural abnormalities. The extent of myocardial fibrosis in patients with CS has not been previously evaluated. Therefore, the objective of this study was to assess myocardial fibrosis in CS patients, its relationship with left ventricular (LV) hypertrophy and function, and its reversibility after surgical treatment. Design and methods: Fifteen consecutive CS patients (41 ± 12 years) were studied together with 30 hypertensive (HT) patients (matched for LV hypertrophy) and 30 healthy subjects. Echocardiography was performed in all patients including i) LV systolic function assessment by conventional measures and by speckle tracking-derived global longitudinal strain, ii) LV diastolic function assessment using E/E′, and iii) myocardial fibrosis assessment using calibrated integrated backscatter (IBS). Echocardiography was repeated after normalization of cortisol secretion (14±3 months). Results: CS patients showed the highest value of calibrated IBS (-15.1±2.5 dB) compared with HT patients (-20.0±2.6 dB, P<0.01) and controls (-23.8±2.4 dB, P<0.01), indicating increased myocardial fibrosis independent of LV hypertrophy. Moreover, calibrated IBS in CS patients was significantly related to both diastolic function (E/E′, r=0.79, P<0.01) and systolic function (global longitudinal strain, r=0.60, P=0.02). After successful surgical treatment, calibrated IBS normalized (-21.0±3.8 vs - 15.1±2.5 dB, P<0.01), suggestive of regression of myocardial fibrosis. Conclusions: Patients with CS have increased myocardial fibrosis, which is related to LV systolic and diastolic dysfunction. Successful treatment of CS normalizes the extent of myocardial fibrosis. Therefore, myocardial fibrosis appears to be an important factor in the development and potential regression of CS cardiomyopathy.

Incidence of venous thromboembolism in patients with Cushing's syndrome: A multicenter cohort study (Article)

2011-11-01T00:00:00Z

Context: Venous thrombosis has frequently been reported in patients with endogenous Cushing's syndrome (CS). Objective: The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients with CS prior to treatment and after surgery. Design and Setting: We conducted a multicenter cohort study at all university medical centers in The Netherlands. Patients: Consecutive patients diagnosed withendogenousCS of benign originbetweenJanuary 1990 and June 2010 were eligible for inclusion. Patients surgically treated for nonfunctioning pituitary adenoma served as controls for the incidence of postoperative VTE in ACTH-dependent CS. Main Outcome Measures: We documented all objectively confirmed VTE during 3 yr prior to, and 3 yr after treatment onset. The incidences of VTE were expressed as incidence rates. Results: A total of 473 patients (mean age 42 yr, 363 women) were included (360 ACTH-dependent pituitary CS). The total number of person-years was 2526. Thirty-seven patients experienced VTE during the study period, resulting in an incidence rate of 14.6 [95% confidence interval (CI) 10.3-20.1] per 1000 person-years. The incidence rate for first-ever VTE prior to treatment was 12.9 (95% CI 7.5-12.6) per 1000 person-years (17 events). The risk of postoperative VTE, defined as risk within 3 months after surgery, was 0% for ACTH-independent and 3.4% (95% CI 2.0 -5.9) for ACTHdependent CS (12 events in 350 patients); most events occurred between 1 wk and 2 months after surgery. Compared with the controls, the risk of postoperative VTE in patients undergoing transsphenoidal surgery was significantly greater (P = 0.01). Conclusions: Patients with CS are at high risk of VTE, especially during active disease and after pituitary surgery. Guidelines on thromboprophylaxis are urgently needed. Copyright

High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly (Article)

2011-04-01T00:00:00Z

Objective: To establish the prevalence of osteoporosis, vertebral fractures (VFs), and non-VFs in acromegaly patients with long-term controlled disease and factors potentially influencing fracture risk. Design: Case-control study. Patients and measurements: Eighty-nine patients (46% male, mean age: 58 years) were included. We studied VFs and non-VFs, bone mineral density (BMD), and markers of bone turnover. In 48 patients, BMD assessment was also obtained 7 years prior to the current study. To compare VF prevalence, data from a sample of the Dutch population (n=3469) were used. Results: VF prevalence was 59% (men 64% and women 54%), significantly increased when compared with controls (odds ratio up to 6.5), and independent of the duration of disease control, BMD, markers of bone turnover, and acromegalic disease characteristics. Mean number of VFs per patient was 3.4G0.3 (range 1-8). There was no relationship between the number and severity of fractures, parameters of bone turnover, and follow-up BMD measurements. BMD did not change during prolongation of follow-up by 7 years of controlled acromegaly. Conclusion: There is a very high prevalence of VFs in acromegaly patients with long-term controlled disease, independently of BMD. In view of the significant morbidity and mortality associated with VFs in general and the inability of BMD to predict fracture risk in acromegalic patients, we propose to include VF assessment, for example by lateral conventional radiographs of the spine in the screening of patients with acromegaly, both at diagnosis and during follow-up after establishment of disease control.