Pituitary metastasis: a clinical overview.

The pituitary gland is an unusual site for metastatic spread and has been associated with a poor prognosis. Clinical presentation is variable but can include visual field defects, cranial nerve palsies, anterior pituitary dysfunction and/ or diabetes insipidus. Management options include surgery or radiotherapy, chemotherapy/immunotherapy or a conservative approach. The pituitary should not be overlooked as a site for metastasis in patients with known cancer and can be the first presentation of neoplastic disease in some patients. Given that patients are now living longer with cancer, clinicians should be alert to the varied presentation of pituitary metastasis. We provide a clinical overview of pituitary metastasis with the aid of illustrative clinical cases.

Vitamin D and insulin resistance.

Vitamin D is a steroid hormone, which in active form binds to the vitamin D receptor. Expression of the vitamin D receptor in diverse cell types (pancreatic islet cells, myocytes, hepatocytes and adipocytes) raises the suspicion that vitamin D may be involved in multiple cellular processes, including the response to insulin. Insulin resistance is a characteristic feature of type 2 DM, and its attenuation may reduce the incidence of type 2 DM and cardiovascular disease. In observational studies, low serum 25-hydroxyvitamin D (25-OHD) concentrations are associated with an increased risk of type 2 DM. It has been suggested that increasing serum 25-OHD concentrations may have beneficial effects on glucose and insulin homeostasis. However, cross-sectional and interventional studies of vitamin D supplementation provide conflicting results and demonstrate no clear beneficial effect of vitamin D on insulin resistance. These studies are complicated by inclusion of different patient cohorts, different 25-OHD assays and different doses and preparations of vitamin D. Any possible association may be confounded by alterations in PTH, 1,25-dihydroxyvitamin D or tissue vitamin D concentrations. We identified 39 studies via MEDLINE and PUBMED. We review the evidence from 10 studies (seven observational and three interventional) examining vitamin D and type 2 DM incidence, and 29 studies (one prospective observational, 12 cross-sectional and 16 interventional trials) examining vitamin D and insulin resistance. Based on this data, it is not possible to state that vitamin D supplementation has any effect on type 2 DM incidence or on insulin resistance. Data from the multiple ongoing randomized controlled trials of vitamin D supplementation due to report over the next few years should help to clarify this area.

Increasing Fruit and Vegetable Intake Has No Dose-Response Effect on Conventional Cardiovascular Risk Factors in Overweight Adults at High Risk of Developing Cardiovascular Disease.

BACKGROUND: Improving diet and lifestyle is important for prevention of cardiovascular disease (CVD). Observational evidence suggests that increasing fruit and vegetable (FV) consumption may lower CVD risk, largely through modulation of established risk factors, but intervention data are required to fully elucidate the mechanisms by which FVs exert benefits on vascular health. OBJECTIVE: The aim of this study was to examine the dose-response effect of FV intake on cardiovascular risk factors in adults at high CVD risk. METHODS: This was a randomized controlled parallel group study involving overweight adults (BMI: >27 and ≤35 kg/m(2)) with a habitually low FV intake (≤160 g/d) and a high total risk of developing CVD (estimated ≥20% over 10 y). After a 4-wk run-in period where FV intake was limited to <2 portions/d (<160 g/d), 92 eligible participants were randomly assigned to 1 of 3 groups: to consume either 2, 4, or 7 portions (equivalent to 160 g, 320 g, or 560 g, respectively) of FVs daily for 12 consecutive weeks. Fasting venous blood samples were collected at baseline (week 4) and post-intervention (week 16) for analysis of lipid fractions and high-sensitivity C-reactive protein (hsCRP) concentrations. Compliance with the FV intervention was determined with use of self-reported FV intake and biomarkers of micronutrient status. Ambulatory blood pressure and body composition were also measured pre- and post-intervention. RESULTS: A total of 89 participants completed the study and body composition remained stable throughout the intervention period. Despite good compliance with the intervention, no significant difference was found between the FV groups for change in measures of ambulatory blood pressure, plasma lipids, or hsCRP concentrations. CONCLUSIONS: There was no evidence of a dose-response effect of FV intake on conventional CVD risk factors measured in overweight adults at high CVD risk. This trial was registered at clinicaltrials.gov as NCT00874341.

Dose-response effect of fruit and vegetables on insulin resistance in people at high risk of cardiovascular disease: a randomized controlled trial.

OBJECTIVE: The purpose of this randomized controlled trial was to investigate the dose-response effect of fruit and vegetable (F&V) intake on insulin resistance (IR) in people who are overweight and at high risk of cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: A total of 105 participants (mean age 56 years) followed a 4-week washout diet (one to two portions of F&Vs per day). Ninety-two participants completed the washout and were randomized to receive one to two, four, or seven portions of F&Vs per day for 12 weeks. IR was assessed at the start and end of this 12-week period by the two-step euglycemic-hyperinsulinemic clamp. Compliance was monitored using a combination of 4-day food diaries and plasma biomarkers of F&V intake. RESULTS: A total of 89 participants completed the study. Participants attained self-reported F&V intakes of 1.8, 3.8, and 7.0 portions per day (P < 0.001) per group. There was a significant linear increase in serum lutein status across the groups, indicating good compliance (P < 0.001), and body weight was maintained (P = 0.77). No significant difference was found between groups in terms of a change in measures of whole-body, peripheral, or hepatic IR or adiponectin multimers. CONCLUSIONS: Increased consumption of F&Vs, as advocated in public-health advice, has no effect on IR in overweight individuals who are at high risk of CVD when body weight is maintained. Recent evidence from systematic reviews indicates that particular classes or types of F&Vs may have particular antidiabetic properties; hence, it is possible that benefits may only be observed in response to a more specific fruit or vegetable intervention.

Sex hormone binding globulin and insulin resistance.

Sex hormone binding globulin (SHBG) is a glycoprotein composed of two 373-amino-acid subunits. The SHBG gene and a promotor region have been identified. The SHBG receptor has yet to be cloned but is known to act through a G-protein-linked second-messenger system following plasma membrane binding. The principal function of SHBG has traditionally been considered to be that of a transport protein for sex steroids, regulating circulating concentrations of free (unbound) hormones and their transport to target tissues. Recent research suggests that SHBG has functions in addition to the binding and transport of sex steroids. Observational studies have associated a low SHBG concentration with an increased incidence of type 2 diabetes mellitus (DM) independent of sex hormone levels in men and women. Genetic studies using Mendelian randomization analysis linking three single nucleotide polymorphisms of the SHBG gene to risk of developing type 2 DM suggest SHBG may have a role in the pathogenesis of type 2 DM. The correlation between SHBG and insulin resistance that is evident in a number of cross-sectional studies is in keeping with the suggestion that the association between SHBG and incidence of type 2 DM is explained by insulin resistance. Several potential mechanisms may account for this association, including the identification of dietary factors that influence SHBG gene transcription. Further research to characterize the SHBG-receptor and the SHBG second messenger system is required. An interventional study examining the effects on insulin resistance of altering SHBG concentrations may help in determining whether this association is causal.