Blood pressure variability within a single visit and all-cause mortality.

BACKGROUND: Within-visit variability of repeated sequential readings of blood pressure (BP) is an important phenomenon that may affect precision of BP measurement and thus decision making concerning BP-related risk and hypertension management. However, limited data exist concerning predictive ability of within-visit BP variability for clinical outcomes. Therefore, we aimed to investigate the association between the variability of three repeated office BP measurements and the risk of all-cause mortality, independent of BP levels. METHODS: Data collected through the National Health and Nutrition Examination Survey (NHANES) were analysed. NHANES is a program of studies designed to assess health and nutritional status of adults and children in the United States. A complete set of three sequential BP measurements, together with survival status, were available for 24969 individuals (age 46.8±;19.3 years, 49% males). Multivariable logistic regression models were used to determine the prognostic ability of the examined demographic, clinical, and haemodynamic indices. RESULTS: Among various examined indices of variability of systolic (SBP) and diastolic (DBP) blood pressure measurements, the standard deviation of DBP (DBPSD) was the stronger independent predictor of mortality (odds ratio 1.064, 95% Confidence Interval: 1.011-1.12) after adjustment for age, sex, body mass index, smoking, SBP, heart rate, history of hypertension, diabetes mellitus, hypercholesterolaemia, and cardiovascular events. CONCLUSION: Within-visit variability of three sequential office DBP readings may allow for the identification of high-risk patients better than mean SBP and DBP levels. The predictive value of within-visit BP variability and methods to improve its clinical application are worthy of further research.

Incidence of pituitary incidentalomas in patients with adrenal adenomas.

With the advent of modern imaging modalities, endocrine incidentalomas are increasingly being discovered. We aimed to investigate the presence of pituitary incidentalomas (PI) in patients with adrenal incidentalomas (AI), and identify potential metabolic correlates in this cohort. 26 patients (18 females) with AI discovered on abdominal computerized tomography were studied. All patients underwent pituitary magnetic resonance imaging (MRI) and endocrine investigations to evaluate functional adrenal pathology, anterior pituitary hormonal status, insulin-resistance indices and presence of metabolic syndrome. Pituitary MRI revealed a microadenoma and a 4×5 mm cyst in 1 patient respectively, and an empty sella in 4 (2 partial) patients. Overall, 6/26 (23%) patients with an AI had evidence of pituitary imaging pathology but only 8% had a PI; none had any evidence of abnormalities in pituitary function. Subclinical hypercortisolism was the only hyperfunctional status detected in 4 patients with AI but was unrelated to the pituitary findings. No abnormality of insulin secretion and action was found between patients with or without pituitary pathology. In the present study 23% of patients with AI had some alteration in pituitary morphology, and 2 a PI without accompanying pituitary hormonal deficit or metabolic derangement. Further studies are required to address this issue and identify a potential pathogenetic mechanism.

Effects of low-dose metformin and rosiglitazone on biochemical, clinical, metabolic and biophysical outcomes in polycystic ovary syndrome.

The aim of this study was to compare the effect of low-dose metformin and rosiglitazone on clinical, biochemical, ultrasound features and endothelial function in patients with polycystic ovary syndrome (PCOS). After randomisation, a group of 17 women received metformin 500 mg b.d. (MG) and a group of 18 received rosiglitazone 4 mg o.d. (RG) for 3 months. Serum FSH, LH, testosterone, fasting glucose, insulin, IGF-1, IGFBP-3, CRP were measured at baseline and follow-up. Ovarian scan and microcirculation studies were also performed. It was found that there was a reduction in hyperandrogenaemia, insulin resistance, lipidaemia, CRP levels, ovarian volume and number of follicles in both groups. No improvement in endothelial- dependent function was noted but a significant improvement in endothelial-independent function in rosiglitazone group. It was concluded that low-dose therapeutic regimen with rosiglitazone and metformin, has comparable beneficial impacts on metabolic, hormonal and morphological features of PCOS but no obvious effect on vascular parameters in a population of predominantly mild PCOS.

Current size criteria for the management of neuroendocrine tumors of the appendix: are they valid? Clinical experience and review of the literature.

We evaluated the latest pathological criteria for completion right hemicolectomy (RHC) in patients with appendiceal neuroendocrine tumors (ANETs) with emphasis on the size of the primary tumor. Data of 28 consecutive patients who underwent RHC for ANETs in three tertiary hospitals were reviewed retrospectively to assess the indications for completion RHC. 10/28 patients were found to have residual disease (36%). In 8/28 patients (29%), the tumor diameter was <1 cm (mean 0.7 ± 0.2 cm, range 0.5-0.9 cm); the indications for RHC included: tumor presence in surgical margins (1 patient), extensive mesoappendiceal invasion (EMI) (1 patient), vascular invasion (VI) (3 patients), Ki-67 ≥2% (3 patients); residual disease was present in 1 patient (3.5%). In 13/28 patients (46%), the tumor diameter was ≥1 and <2 cm (mean 1.30 ± 0.2 cm, range 1.0-1.8 cm); the indications for RHC were: EMI (2 patients), VI (2 patients), Ki-67 ≥2% (2 patients); residual disease was present in 5 patients (18%). In 7/28 patients (25%), the tumor diameter was ≥2 cm (mean 2.5 ± 0.7 cm, range 2.0-4.0 cm). In this final subgroup, RHC was an accepted practice irrespective of other pathologic findings: the tumor was present in surgical margins in 2 patients, in 5 patients VI was demonstrated, and Ki-67 ≥2% was found in 5 patients; residual disease was present in 4 patients (14%). Using the latest European Neuroendocrine Tumor Society criteria for RHC, residual disease may be missed in 18% of ANET patients.

Comparisons in the epidemiology, diagnostic features and cure rate by transsphenoidal surgery between paediatric and adult-onset Cushing's disease.

OBJECTIVE: There are few published comparisons between paediatric and adult-onset Cushing's disease (CD). We compare the epidemiology, diagnostic features and cure rate by transsphenoidal surgery (TSS) in these groups. DESIGN: Retrospective review of patient databases in a single university hospital centre. PATIENTS: Totally, 41 paediatric (mean age 12.3 ± 3.5 years; range 5.7-17.8) and 183 adult (mean age 40 ± 13 years; range 18.0-95.0) patients with CD were investigated. RESULTS: Paediatric CD was characterised by male (63%) and adult CD by a female predominance (79%, P<0.0001). There were small but significant differences in clinical presentation. Biochemical features of CD were comparable except the serum cortisol increase during a CRH test: mean change (105%, n=39) in paediatric and (54%, n=123) in adult subjects (P<0.0001). Macroadenomas were more common in adult (15%, 28/183) than in paediatric (2%, 1/41, P=0.04) CD. Corticotroph microadenomas were more easily visualised by pituitary magnetic resonance imaging (MRI) in adult (76%, 50/66) compared with paediatric (55%, 21/38, P=0.045) CD with poorer concordance of imaging with surgical findings in children (P=0.058). The incidence of ACTH lateralisation by bilateral simultaneous inferior petrosal sinus sampling was comparable in paediatric (76%, 25/33) and adult (79%, 46/58; P=0.95) patients with good surgical concordance in both (82% paediatric and 79% adult). Cure rates by TSS were comparable, with a paediatric cure rate of 69%. CONCLUSION: Several features of paediatric CD are distinct: increased frequency of prepubertal CD in males, the different clinical presentation, the decreased presence of macroadenomas and the frequent absence of radiological evidence of an adenoma on MRI.

Clinical value of right hemicolectomy for appendiceal carcinoids using pathologic criteria.

BACKGROUND: Appendiceal carcinoids (AC) are usually adequately treated by appendectomy. The European Neuroendocrine Tumours Society (ENETS) has recently reconsidered the previous pathologic criteria to identify patients at high risk of extra-appendiceal disease, who are thought to require right hemicolectomy (RHC). AIM: The aim of this retrospective, observational study was to evaluate previous and currently introduced criteria, in identifying patients with AC in whom RHC is justified. SUBJECTS AND METHODS: Twelve patients who underwent RHC for AC were retrospectively identified. Demographic and follow-up data were collected and appendectomy specimens were reviewed for the presence of indications leading to RHC defined as: tumor diameter ≥2 cm, tumor location at the base, mesoappendiceal extension, mitotic index Ki-67≥2%. RHC specimens were examined to identify evidence of extra-appendiceal disease, remaining and/or metastatic disease. RESULTS: Four patients fulfilled two criteria and 8 one criterion for RHC. Two patients had tumors ≥2.0 cm, 5 located at the base, 8 invading the mesoappendix and periappendiceal fat; Ki-67 PI was 1% in all cases measured except one, in which it was 3%. Post-RHC, 3 patients (25%) had extra-appendiceal disease (no residual disease was identified in surgical margins); 1 had tumor at the colon specimen and 2 had lymph node metastasis. All 3 patients fulfilled only one pathologic criterion; 1 had tumor mesoappendiceal extension and 2 tumor location at the base of the appendix. CONCLUSIONS: Applying previous and currently introduced pathologic criteria, 25% of high-risk patients with AC had identifiable extra-appendiceal disease following RHC that might be not detected following the recently introduced ENETS criteria.

The value of 11C-5-hydroxy-tryptophan positron emission tomography in neuroendocrine tumor diagnosis and management: experience from one center.

Many neuroendocrine tumors (NET) are small and may escape localization by conventional imaging techniques. In such cases, 11C-5-hydroxy-tryptophan (11C-5-HTP) positron emission tomography (PET) has been tested as an additional diagnostic tool. Nine patients with clinically, biochemically and/or histologically confirmed NET and negative computerized tomography (CT) or magnetic resonance imaging (MRI), and 111In-pentetreotide (Octreoscan) scintigraphy underwent imaging with 11C-5-HTP-PET/CT in order to: 1) detect the primary tumor lesion in three patients; 2) detect residual disease in two patients with appendiceal carcinoid, one with rectal carcinoid, one with midgut carcinoid, and one with ectopic ACTH secretion (EAS) due to residual pulmonary carcinoid; and 3) restage a patient with medullary thyroid carcinoma (MTC) and hepatic metastases. 11C-5-HTP-PET/CT detected lesions in the mediastinum in a patient with EAS due to a pulmonary carcinoid, further hepatic metastases in a patient with carcinoid syndrome (CS) from a NET of unknown primary, further hepatic metastases in the patient with MTC, and hepatic metastases in the patient with midgut carcinoid. The 11C-5-HTP-PET/CT findings contributed to radical cure of the patient with recurrent EAS, and pointed towards bilateral adrenalectomy in the patient with EAS without evident primary tumor. In addition, 11C-5- HTP-PET/CT directed towards combined surgical and medical treatment in the patient with CS and multiple rather than single hepatic metastases and in the patient with midgut carcinoid, and towards continuation of medical treatment in the patient with MTC. 11C-5-HTP-PET/CT is a useful imaging technique, providing additional information for the diagnosis, staging and decision-making regarding management of patients with NET.

Light sensitivity and pain sensation during cataract surgery. A comparative study of two modes of anaesthesia.

The objective of this study was to compare the light sensitivity and pain experienced by patients undergoing cataract surgery under subtenon and topical with intracameral anaesthesia. Fifty-four patients were randomly assigned to receive either two drops of proxymethacaine 0.5% as topical anaesthesia with 0.5 ml preservative-free 1% intracameral lidocaine or 4 ml 2% lignocaine as subtenon anaesthesia. Light sensitivity and overall pain perception were recorded at the end of surgery. The mean pain score in the subtenon group (0.11; range 0-1) was lower than in the topical group (1.07; range: 0-3, P < 0.001). The mean light-sensitivity score was lower in the subtenon group (0.26; range: 0-4) than in the topical group (1.29; range: 0-4, P = 0.001). Subtenon anaesthesia was more effective in suppressing light sensitivity and pain during cataract surgery than topical with intracameral anaesthesia. This suggests that use of subtenon anaesthesia may lead to a more comfortable operative experience.

The acute effect of Orlistat on dietary glycotoxins in diabetics and healthy women.

AIM: Advanced glycation end products (AGEs) formation is implicated in diabetic complications. Exogenous AGEs, namely glycotoxins, are present in certain foods and are absorbed from the gastrointestinal tract. Experimental data suggest that lifestyle interventions reducing their content in diet have beneficial effect. METHODS: Fourteen healthy (age: 42.14 +/- 12.38 years; body mass index [BMI]: 27.85 +/- 7.06 kg/m2) and ten women with type 2 diabetes (T2DM) (age: 48.70 +/- 9.31 years; BMI: 32.55 +/- 7.14 kg/m2) were enrolled in the study. A meal rich in AGEs was provided in a two-day protocol and on day 2, 240 mg of Orlistat were administered post-meal. RESULTS: On day 1, serum AGEs levels showed a rise at 3 hours post-meal compared to baseline values in both groups (controls: 12.2%; P<0.001), T2DM: 2.6%; P=0.013), but at 5 hours post-meal only in the controls (control: 12.2%; P<0.001); T2DM: 1.9%; P=0.075). On day 2 at 3 hours post-meal control values showed a rise of 3.1% (P=0.003); T2DM of 1.9% (P=0.013); at 5 hours post-meal rise for controls was 4.6% (P=0.012); and for T2DM was 1.8% (P=0.009). The corresponding rise was significantly lower on day 2 only in controls at 3 and 5 hours post-meal (P=0.003; P=0.05, respectively). CONCLUSIONS: Orlistat reduced the absorption of glycotoxins acutely and improved the metabolic profile in the control group, without an apparent beneficial effect in the diabetic group. The clinical significance of this observation should be further investigated in normal population, while in diabetics long-term studies may be required to demonstrate possible clinically significant effects.

Cardiovascular risk factors in adult patients with multisystem Langerhans-cell histiocytosis: evidence of glucose metabolism abnormalities.

BACKGROUND: Langerhans-cell histiocytosis (LCH) is a rare disease with features of chronic inflammation and it may also induce hypopituitarism, conditions associated with an increased risk of cardiovascular diseases. AIM: Cardiovascular and metabolic risk profile investigation in multisystem LCH patients with and without anterior pituitary deficiency. DESIGN: Prospective, observational study. METHODS: Fourteen adult patients with LCH, 7 with and 7 without anterior pituitary deficiency, and 42 controls matched for age, body mass index (BMI) and smoking. Cardiovascular risk factors were estimated in all subjects: glucose and lipid profile, mathematical indices of insulin resistance (IR), blood pressure, structural arterial and functional endothelial properties (intima-media thickness, brachial artery flow-mediated dilatation). Cardiovascular risk factors were estimated in the three groups studied; the effect of disease activity and/or treatment was also determined in patients with LCH. RESULTS: Ten patients had diabetes insipidus, and 7 anterior pituitary hormone deficiencies: 8 patients had active disease and 11 had received systemic treatment. No difference was observed between the study groups in vascular parameters, in lipid profile or in blood pressure. However, the insulin resistance index GIR was decreased in patients with LCH without anterior pituitary deficiency compared to controls (P = 0.033). Three patients had impaired glucose tolerance and one diabetes mellitus type 2. These patients were older and had active disease; there was no association with hypopituitarism and/or previous treatment. CONCLUSION: Adults patients with LCH have abnormalities of glucose metabolism that tend to occur in patients with active disease, and may be a consequence of the pro-inflammatory state.

Inflammatory and endothelial markers in women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) carry a pattern of cardiovascular risk factors. Endothelial dysfunction and chronic inflammation are early findings in the atherosclerotic process. The purpose of the study was to investigate the coexistence of active inflammation markers and endothelial dysfunction in young women with PCOS, and their relationship with metabolic and hormonal abnormalities of the syndrome. MATERIALS AND METHODS: Twenty-five young women with PCOS and 25 controls of similar age and body mass index (BMI) were studied. Endothelial function was assessed by flow-mediated dilatation (FMD) on the brachial artery and smooth muscle cells injury was excluded by nitrate-induced dilatation (NID). Plasma levels of endothelin-1 (ET-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and high sensitivity C-reactive protein (hsCRP) were measured. Hormonal and metabolic profiles were determined in both groups. RESULTS: Flow-mediated dilatation (FMD) was statistically lower in PCOS (P < 0.001), whereas nitrate-induced dilatation (NID) was similar within the two groups. Polycystic ovary syndrome (PCOS) had statistically higher levels of ET-1 (P = 0.03), sICAM-1 (P = 0.01), sVCAM-1 (P = 0.02) and hsCRP (P = 0.01). Furthermore FMD was statistically higher in PCOS population with hsCRP 1 mg L(-1) when compared with PCOS population with hsCRP > 1 mg L(-1) (P = 0.02). Flow-mediated dilatation (FMD) was negatively related to hsCRP (r = -0.512, P = 0.015); ET-1 was positively related to free androgen index (r = 0.27, P = 0.05) and negatively to sex hormone-binding globulin (r = -0.465, P = 0.022); sVCAM-1 was positively related to total testosterone (r = 0.431, P = 0.036); hsCRP was positively related to BMI (r = 0.647, P = 0.001), and negatively related to FMD (r = -0.512, P = 0.015), quantitative insulin sensitivity check index (QUICKI) (r = -0.499, P = 0.018), and MATSUDA index (r = -0.445, P = 0.038). CONCLUSIONS: The present study demonstrates that endothelial dysfunction coexists and is influenced by the presence of increased serum levels of inflammation and endothelial activation markers in young women with PCOS. These parameters appear to be interrelated with hyperandrogenaemia in this insulin-resistant population.

Metformin administration improves endothelial function in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to investigate the endothelial status in young women with polycystic ovary syndrome (PCOS), using a simple and easily reproducible hemodynamic method combined with a biological marker and to evaluate the effect of metformin treatment on these parameters. DESIGN: Descriptive clinical trial. METHODS: Forty young women, 20 with PCOS and 20 normal women of similar age and body mass index were studied. Metformin (1700 mg daily) was administered for 6 months to the PCOS group. The endothelium status and the metabolic and hormonal profile were studied in both groups, as well as after metformin, by flow-mediated dilatation (FMD) on the brachial artery and by measurements of plasma endothelin-1 (ET-1) levels. RESULTS: FMD was impaired in the PCOS group when compared with controls (3.24+/-0.71% vs 8.81+/-1.07% respectively, P<0.0001), but this difference normalized after metformin treatment (PCOS(post-metformin) vs controls: 8.17+/-1.26 vs 8.81+/-1.07%, P = 0.70) since the values significantly improved after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 3.24+/-0.71 vs 8.17+/-1.26%, P=0.003). ET-1 levels were significantly higher in the PCOS women compared with the control group (7.23+/-0.50 vs 4.99+/-0.69 fmol/l, P=0.01), they improved significantly after metformin treatment (PCOS(pre-metformin) vs PCOS(post-metformin): 7.23+/-0.50 vs 3.57+/-0.60 fmol/l, P<0.0001) and their difference compared with the control group was reversed (PCOS(post-metformin) vs controls: 3.57+/-0.60 vs 4.99+/-0.69 fmol/l, P=0.13). Metformin administration improved hyperandrogenemia. However, in this study, mathematical methods used to assess insulin resistance failed to show any detected alteration after treatment with metformin. CONCLUSIONS: PCOS women were found to exhibit endothelial dysfunction compared with controls, which was reversed 6 months after metformin administration.

Presence of metabolic risk factors in non-obese PCOS sisters: evidence of heritability of insulin resistance.

This study was performed to determine whether phenotypically healthy sisters of women with polycystic ovary syndrome (PCOS) have evidence of insulin resistance. We studied 54 women: 17 with PCOS, 17 sisters of these probands and 20 control women with similar age, body mass index (BMI) and waist-to-hip ratio (WHR). The PCOS sisters had neither clinical nor laboratory evidence of hyperandrogenism. However, estimated insulin resistance indices indicated decreased insulin sensitivity in PCOS sisters compared with the controls. No difference of insulin resistance indices was detected between the PCOS and their sisters. This finding provides additional evidence that there is a hereditary trait regarding insulin resistance in the PCOS families.