Incidence of high chromogranin A serum levels in patients with non metastatic prostate adenocarcinoma.

BACKGROUND: ChromograninA in prostate carcinoma (PC) indicate NE differentiation. This tumour is more aggressive and resistant to hormone therapy. PATIENTS AND METHODS: We analyzed the incidence of pre-operative ChromograninA serum levels in non metastatic PC patients. Serum PSA and ChromograninA were analyzed before treatment. Clinicopathological parameters were evaluated in relation to serum ChromograninA. 486 patients were enrolled. RESULTS: We found 352 pT2 and 134 pT3. 21 patients were N+. 278 patients had Gleason score levels <7; 173 patients had levels = 7 (122 were 3+4 and 51 4+3); and 35 patients with levels >7. Median PSA pre-operative level was 7.61 ng/ml. PSA was significantly associated with pT stage (pT2 with PSA abnormal 23.6% vs pT3 48.5%, p < 0.0001) and with a Gleason score (PSA abnormal 60% in the Gleason score was >7 vs 29.5% in the Gleason score = 7 vs 27.3% in the Gleason score <7, p < 0.0001). In 114 patients pre-operative ChromograninA levels were elevated (23.5%). Serum ChromograninA levels had no significant association with PSA (p = 0.44) and pT stage (p = 0.89). abnormal ChromograninA levels increased from a Gleason score of <7 (25.5%) to >7 (31.4%) (p = 0.12). The serum ChromograninA levels in the two groups of patients were subdivided before and after 2005 on the basis of different used assays, showing no correlation with serum ChromograninA and other parameters. CONCLUSIONS: This study showed that ChromograninA levels correlated to NE differentiation and possible aggressiveness of PC. Pre-operative circulating ChromograninA could complement PSA in selecting more aggressive PC cases, particularly in the presence of a higher Gleason score. Complementary information is provided by the absence of a correlation between serum ChromograninA and PSA levels.

Microalbuminuria in insulin sensitivity in patients with growth hormone-secreting pituitary tumor.

CONTEXT: Impaired glucose tolerance and diabetes mellitus are frequently present in acromegalic patients in whom the degree of impaired glucose metabolism seems directly correlated with GH levels. Microalbuminuria is reported to be directly correlated with insulin resistance, and both conditions predict cardiovascular disease mortality. OBJECTIVE: Our objective was to investigate the microalbuminuria levels as a marker of endothelial dysfunction in acromegalic patients. DESIGN: We conducted an observational, multicenter, open prospective study. SUBJECTS: Subjects included 74 patients with active acromegaly (52 with normal glucose tolerance, 16 with impaired glucose tolerance, and six with diabetes), and 50 healthy subjects matched for age, gender, and body mass index were studied as controls. RESULTS: In the whole group, mean GH and IGF-I levels were 24.2+/-3.9 ng/ml and 700.1+/-23.0 microg/liter, respectively. The insulin sensitivity index (ISI) in the patients was lower than in the controls (P<0.0005). In impaired glucose tolerance and diabetic patients, microalbuminuria was higher than in normal glucose tolerance patients (P<0.05 and P<0.0005 respectively). Hypertensive patients had higher levels of microalbuminuria than normotensive ones (P<0.005). The levels of microalbuminuria related to creatinine were directly correlated with fasting glucose levels (r=0.27; P=0.0019), fasting insulin levels (r=0.28; P=0.017), and insulin after 90 (r=0.26; P=0.027) and 120 min after glucose load (r=0.26; P=0.023) and indirectly correlated with ISI composite (P<0.0001; r=-0.48). By a multivariate analysis, the log-ISI composite was the strongest predictor of microalbuminuria (t=-3.19; P=0.0021). CONCLUSIONS: Impairment of glucose tolerance in acromegaly is associated with high levels of microalbuminuria. For this reason, microalbuminuria should be part of cardiovascular risk assessment in these patients.

Non-invasive evaluation of endothelial dysfunction in uncomplicated obesity: relationship with insulin resistance.

Obesity is associated with increased cardiovascular morbidity and amortality. Endothelial dysfunction, involved in the pathogenesis of cardiovascular events, has been demonstrated in obese patients with invasive techniques requiring artery catheterization. The aim of our investigation was to evaluate, with a non-invasive method readily employable on clinical grounds, impaired vasodilatation and its relationship with insulin resistance in uncomplicated obesity. 15 uncomplicated obese subjects (BMI = 36.6 +/- 3.2) and 10 lean controls (BMI = 22.9 +/- 1.25) were enrolled in this study. All subjects underwent measurement of endothelium-dependent (FBFr) vasodilatation by forearm venous occlusion pletysmography after increasing times of ischemia, and measurement of insulin sensitivity by the euglycemic hyperinsulinemic clamp technique (M index), by fasting glucose and insulin (HOMA-IR) and by oral glucose tolerance test (ISI index). Endothelium-independent (N-FBFr) vasodilatation was assessed as well. The FBFr was markedly blunted in obese patients versus lean controls (30 s: 2.12 +/- 0.34 vs. 3.63 +/- 0.22, P < 0.01; 60 s: 2.34 +/- 0.42 vs. 3.82 +/- 0.53, P < 0.01; 180 s: 3.20 +/- 0.45 vs. 7.15 +/- 0.35, P < 0.01; 300 s: 4.08 +/- 0.94 vs. 14.1 +/- 0.82, P < 0.001). The N-FBFr was not different in the two groups. High correlation was found between M index and FBFr at all ischemia times. HOMA-IR and ISI were not related with FBFr. The non-invasive evaluation of endothelial dysfunction by a simple and reliable method based on venous occlusive plethysmography shows high correlation between impaired endothelium-dependent vasodilatation and insulin resistance in uncomplicated obesity. This non-invasive test of endothelial function may be routinely performed in the assessment of cardiovascular risk in uncomplicated obesity.