Cardiovascular accidents represent the most important cause of death in patients with Cushing's syndrome. This prospective study aims at evaluating carotid arteries by echo-Doppler ultrasonography and clinical and metabolic markers of atherosclerosis in 25 patients with Cushing's disease (CD) before and after 1 yr of remission. Thirty-two sex- and age-matched subjects (control-1) and 32 body mass index-matched subjects (control-2) served as controls. At diagnosis, CD patients had higher body mass index, waist to hip ratio (WHR), total, low-density lipoprotein-cholesterol and total/high-density lipoprotein (HDL) ratio, glucose and insulin, as well as lower HDL-cholesterol than control-1; they had higher WHR and total/HDL ratio and lower HDL-cholesterol than control-2. They also had higher intima-media thickness (IMT), and lower systolic lumen diameter and distensibility coefficient (DC) than either control group. Atherosclerotic plaques were detected in 31.2% of patients, 0 control-1, and 6.2% of control-2 subjects. One year after remission, WHR, LDL-cholesterol, and IMT significantly decreased, whereas systolic lumen diameter and DC significantly increased. However, all of the above parameters were still abnormal compared with control-1, but not control-2. A significant correlation was found between WHR, glucose and insulin levels, and right and left carotid IMT. WHR was the best predictor of left IMT and left DC in active, but not in cured, patients. The duration of hypercortisolism was the best predictor of right DC in active but not in cured patients. In conclusion, patients with CD have severe atherosclerotic damage. The persistence of a metabolic syndrome, vascular damage, and atherosclerotic plaques after cortisol level normalization makes these subjects still at high cardiovascular risk despite disease remission.
Patients with Cushing's disease (CD) mainly die because of cardiovascular accidents. The aim of this study was to evaluate whether patients with CD still have increased cardiovascular risk and suffer from premature atherosclerosis once cured. Fifteen patients cured from CD for a long term period (5 yr), 30 sex-and age-matched controls, and 30 body mass index (BMI)-matched controls were included in this study. BMI; waist to hip ratio (WHR); systolic (SBP) and diastolic (DBP) blood pressures; serum total, low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol; serum triglycerides, fibrinogen, and lipoprotein(a) levels; prothrombin time; activated partial thromboplastine time; and basal and glucose load-stimulated insulin and glucose levels were measured in patients and controls. By echo-Doppler ultrasonography, the intima media thickness (IMT), systolic and diastolic media-media distances, blood systolic (SPV) and diastolic (DPV) peak velocity, systolic (SLD) and diastolic (DLD) lumen diameter, and distensibility coefficient (DC) were measured at both common carotid arteries where the presence, size, and location of atherosclerotic plaques were also evaluated. Compared with a sex- and age-matched control population, CD patients had BMI (P < 0.001), WHR (P < 0.001), SBP (P < 0.005), DBP (P < 0.05), fasting glucose (P < 0.001) and insulin (P < 0.05), glucose load-stimulated glucose and insulin levels (P < 0.05), total cholesterol (P < 0.05), LDL cholesterol (P < 0.01), fibrinogen (P < 0.01), and lipoprotein(a) (P < 0.05) levels higher and HDL cholesterol levels (P < 0.05) lower than controls. At ultrasonography, in the patients, IMT (P < 0.05), SPV (P < 0.05) and DPV (P < 0.001) were significantly increased whereas SLD (P < 0.001), DLD (P < 0.001), and DC (P < 0.05) were significantly decreased compared to controls. In addition, CD patients had higher WHR (P < 0.05), DBP (P < 0.05), glucose load-stimulated glucose and insulin levels (P < 0.05), and fibrinogen levels (P < 0.01) and lower HDL cholesterol (P < 0.05) levels than BMI-matched controls. At ultrasonography, increased common carotid arteries IMT (P < 0.05) and DPV (P < 0.05) and decreased DLD (P < 0.05) and DC (P < 0.05) were measured in patients compared to those in BMI-matched controls. Atherosclerotic plaques were found in 26.7% of patients, in none of the sex- and age-matched controls, and in 3.3% of the BMI-matched controls. In CD patients, a significant correlation was found between both WHR and fasting serum insulin levels and DBP (r = 0.52 and r = 0.55; P < 0.05), triglycerides levels (r = 0.56 and r = 0.77; P < 0.05), and IMT (r = 0.64 and r = 0.56; P < 0.05). Right (r = -0.70; P < 0.005) and left (r = -0.65; P < 0.01) DC were inversely correlated to the duration of CD in the patient group. At the multiple regression analysis, WHR was the best predictor of fasting insulin levels (beta = 0.77; P < 0.05), and vice versa, fasting insulin level was the best predictor of WHR (beta = 1.20; P < 0.05). In conclusion, patients cured fro...
PTTG is expressed in approximately 90% of pituitary tumours of different histotypes but with a high variability from one case to another. As expected, PTTG expression parallels that of Ki-67 and both are correlated to a more aggressive behaviour. However, a 2.9% Ki-67 cut-off proved to be the most reliable biological marker for predicting the recurrence potential of these tumours, when an adequate postsurgical follow-up is considered.
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