Showing papers in "Endocrine in 2014"

Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial.

Abstract: The aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases, insulin resistance, oxidative stress, and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease (NAFLD). Fifty-three patients with NAFLD were enrolled in a parallel, double-blind, placebo-controlled study. The patients were randomly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 (n = 27) or a placebo (n = 26), every 14 days for 4 months. Serum aminotransferases, high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor α, malondialdehyde (MDA), total antioxidant capacity, transforming growth factor β1, as well as grade of hepatic steatosis and homeostasis model assessment of insulin resistance were assessed pre- and post-intervention. In patients who received vitamin D supplement compared to the controls, the median of serum 25(OH)D3 significantly increased (16.2 vs. 1.6 ng/ml, P < 0.001). This increase accompanied by significant decrease in serum MDA (-2.09 vs. -1.23 ng/ml, P = 0.03) and near significant changes in serum hs-CRP (-0.25 vs. 0.22 mg/l, P = 0.06). These between-group differences remained significant even after controlling for baseline covariates. Other variables showed no significant changes. Improved vitamin D status led to amelioration in serum hs-CRP and MDA in patients with NAFLD. This might be considered as an adjunctive therapy to attenuate systemic inflammation and lipid peroxidation alongside other treatments for NAFLD patients.

Zinc and insulin in pancreatic beta-cells

Abstract: Zinc (Zn2+) is an essential element crucial for growth and development, and also plays a role in cell signaling for cellular processes like cell division and apoptosis. In the mammalian pancreas, Zn2+ is essential for the correct processing, storage, secretion, and action of insulin in beta (β)-cells. Insulin is stored inside secretory vesicles or granules, where two Zn2+ ions coordinate six insulin monomers to form the hexameric-structure on which maturated insulin crystals are based. The total Zn2+ content of the mammalian pancreas is among the highest in the body, and Zn2+ concentration reach millimolar levels in the interior of the dense-core granule. Changes in Zn2+ levels in the pancreas have been found to be associated with diabetes. Hence, the relationship between co-stored Zn2+ and insulin undoubtedly is critical to normal β-cell function. The advances in the field of Zn2+ biology over the last decade have facilitated our understanding of Zn2+ trafficking, its intracellular distribution and its storage. When exocytosis of insulin occurs, insulin granules fuse with the β-cell plasma membrane and release their contents, i.e., insulin as well as substantial amount of free Zn2+, into the extracellular space and the local circulation. Studies increasingly indicate that secreted Zn2+ has autocrine or paracrine signaling in β-cells or the neighboring cells. This review discusses the Zn2+ homeostasis in β-cells with emphasis on the potential signaling role of Zn2+ to islet biology.

Impact of social determinants of health on outcomes for type 2 diabetes: a systematic review

Abstract: Social determinants of health include the social and economic conditions that influence health status. Research into the impact of social determinants on individuals with type 2 diabetes has largely focused on the prevention of or risk of developing diabetes. No review exists summarizing the impact of social determinants of health outcomes in patients with type 2 diabetes. This systematic review examined whether social determinants of health have an impact on health outcomes in type 2 diabetes. Medline was searched for articles that (a) were published in English (b) targeted adults, ages 18 + years, (c) had a study population which was diagnosed with type 2 diabetes, (d) the study was done in the United States, and (e) the study measured at least one of the outcome measures—glycemic control, cholesterol (LDL), blood pressure, quality of life or cost. Using a reproducible strategy, 2,110 articles were identified, and 61 were reviewed based on inclusion criteria. Twelve were categorized as Economic Stability and Education, 17 were categorized as Social and Community Context, 28 were categorized as Health and Health Care, and three were categorized as Neighborhood and Built Environment. Based on the studies reviewed, social determinants have an impact on glycemic control, LDL, and blood pressure to varying degrees. The impact on cost and quality of life was not often measured, but when quality of life was investigated, it did show significance. More research is needed to better characterize the direct impact of social determinants of health on health outcomes in diabetes.

Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity

Abstract: The global prevalence of obesity has significantly increased in most industrialized countries. Anti-obesity drugs are scarce, and indications to change their life style are impractical. Therefore, to identify diets able to produce significantly and maintained weight loss is mandatory. The present work evaluated the efficacy of a very low-calorie-ketogenic (VLCK) diet in obesity. A group of obese patients were randomized into two groups: the VLCK diet group and a standard low-calorie diet (LC group). The follow-up period was 12 months. Both groups received external support, counseling, to perform physical activity and adhered to the diet. The VLCK diet induced a 30–45 days of mild ketosis and significant effects on body weight within 15 days. At 2 months, the weight reductions in the VLCK diet and LC diet groups were 13.6 ± 3.9 and 4.8 ± 2.7 kg, respectively (p < 0.0001). At the end of the study, at 12 months, the weight reductions were 19.9 ± 12.3 and 7.0 ± 5.6 kg, respectively (p < 0.0001), and more than 88 % of patients in the VLCK diet group lost more of 10 % of their initial weight. Lean mass was practically unaffected. The VLCK diet was well tolerated and the side effects were moderate and transitory. In a group of obese patients, the VLCK diet was significantly more effective than a standard LC diet. At one year follow-up in the group with VLCK diet, most of the patients loss more than 10 % of their initial weight and lean mass was well preserved.

Sarcopenic obesity in aging population: current status and future directions for research

Abstract: The combination of sarcopenia and obesity, an age-related change in body composition, is a concern in the aged society. Sarcopenic obesity is not the combination of two conditions, but is more related to cardio-metabolic and functional abnormalities. Sarcopenic obesity is associated with more physical functional decline than simple obesity. Sarcopenic obesity may be more insulin resistant, and have a higher risk for metabolic syndrome and atherosclerosis than simple obesity. However, the prevalence of sarcopenic obesity differs substantially among studies because of the lack of a standard definition. For further understanding of the pathophysiological role of sarcopenic obesity, a standardized definition for both sarcopenia and obesity is necessary.

Hypocalcemia following thyroid surgery: incidence and risk factors. A longitudinal multicenter study comprising 2,631 patients

Abstract: Postoperative hypocalcemia is the most frequent complication of total thyroidectomy. It may have a delayed onset, and therefore delays the discharge from the hospital, requiring calcium replacement therapy to alleviate clinical symptoms. During a 7-month period, 2,631 consecutive patients undergoing primary or completion thyroidectomy were prospectively followed up and underwent analysis regarding postoperative hypoparathyroidism. Data were prospectively collected by questionnaires from 39 Italian endocrine surgery units affiliated to the Italian Endocrine Surgery Units Association (Club delle Unita di EndocrinoChirurgia-UEC), where thyroid surgery is routinely performed. The incidence of hypoparathyroidism was 28.8 % (757 patients), including transient hypocalcemia (27.9 %-734 patients) and permanent hypocalcemia (0.9 %-23 patients). The rate of asymptomatic hypocalcemia was 70.80 %. The incidence of permanent hypocalcemia was higher in the symptomatic hypocalcemia group (7.5 %) than in asymptomatic one (1.5 %). Female patients experienced a transient postoperative hypocalcemia more frequently than male patients (29.7 and 21.2 %, respectively; p < 0.0001). The percentage developing hypocalcemia in patients in which parathyroid glands were intraoperatively identified and preserved was higher than in the patients in which the identification of parathyroid glands was not achieved (29.2 vs. 18.7 %, p < 0.01). This prospective study confirmed the main risk factors for postoperative hypocalcemia: thyroid cancer, nodal dissection, and female gender. It farther showed that identifying parathyroids has an important role to prevent permanent hypocalcemia though with a higher risk of transient hypocalcemia. A suitable informed consent should especially emphasize the importance of some primary factors in increasing the risk of hypocalcemia after thyroid surgery.

Muscle-bone interactions: basic and clinical aspects.

Abstract: Muscle and bone are anatomically and functionally closely connected. The traditional concept that skeletal muscles serve to load bone and transform skeletal segments into a system of levers has been further refined into the mechanostat theory, according to which striated muscle is essential for bone development and maintenance, modelling and remodelling. Besides biomechanical function, skeletal muscle and bone are endocrine organs able to secrete factors capable of modulating biological function within their microenvironment, in nearby tissues or in distant organs. The endocrine properties of muscle and bone may serve to sense and transduce biomechanical signals such as loading, unloading or exercise, or systemic hormonal stimuli into biochemical signals. Nonetheless, given the close anatomical relationship between skeletal muscle and bone, paracrine interactions particularly at the periosteal interface can be hypothesized. These mechanisms can assume particular importance during bone and muscle healing after musculoskeletal injury. Basic studies in vitro and in rodents have helped to dissect the multiple influences of skeletal muscle on bone and/or expression of inside-organ metabolism and have served to explain clinical observations linking muscle-to-bone quality. Recent evidences pinpoint that also bone tissue is able to modulate directly or indirectly skeletal muscle metabolism, thus empowering the crosstalk hypothesis to be further tested in humans in vivo.

Metabolic syndrome and endometrial cancer: a meta-analysis

Abstract: We performed a systematic review and meta-analysis on the association of metabolic syndrome with endometrial cancer. A systematic literature search of electronic databases (Medline, ISI Web of Knowledge and Scopus) was conducted and complemented by cross-referencing to identify studies published before 31 January 2013. Core items of identified studies were independently extracted by two reviewers, and results were summarized by random effects meta-analysis. We identified six studies, which reported on 3,132 cancer cases. Metabolic syndrome was associated with an increased risk of endometrial cancer (RR: 1.89, 95 % CI 1.34-2.67, P < 0.001), with significant heterogeneity among studies (I (2) = 92 %, P < 0.001), but no indication for publication bias in the Egger's test (P = 0.240). A sensitivity analysis omitting two studies produced no heterogeneity (I (2) = 0 %) and attenuated the association (RR: 1.39, 1.31-1.48, P < 0.001). The risk estimates for any single factor of the syndrome were 2.21 (P < 0.001) for higher values of body mass index and/or waist, 1.81 (P = 0.044) for hyperglycemia, 1.81 (P = 0.024) for higher blood pressure values, and 1.17 (P < 0.001) for high triglyceride levels; there was no significant association with low HDL-cholesterol. Metabolic syndrome is associated with an increased risk of endometrial cancer; among the components of the syndrome, obesity/high waist is that more strongly associated with endometrial cancer.

Association between leisure time physical activity and metabolic syndrome: a meta-analysis of prospective cohort studies.

Abstract: A great number of prospective studies have investigated the relationship between leisure time physical activity (LTPA) and metabolic syndrome (MetS) risk However, the results have been inconsistent The aim of this study was to clarify the relationship between LTPA and MetS risk Literature databases were searched including PubMed and Embase up to June 2013 A total of 17 studies, including 64,353 participants and 11,271 incident cases, were included in the meta-analysis A high level of LTPA was statistically associated with decreased risk of MetS [high vs low: relative risk (RR) = 080, 95 % confidence interval (CI) 075-085], whereas a moderate level of LTPA was weakly associated with decreased risk of MetS (moderate vs low: RR = 095, 95 % CI 091-100) Subgroup analyses indicated that the association between a moderate level of LTPA and decreased risk of MetS was only significant in men (moderate vs low: RR = 088, 95 % CI 081-097) and in studies with more than a 10-year follow-up period (moderate vs low: RR = 090, 95 % CI 084-097) A high level of LTPA was statistically associated with decreased risk of MetS in each subgroup A higher level of LTPA is associated with a lower risk of MetS These findings could have public health implications with regard to prevention of MetS through lifestyle interventions

Utility of the trabecular bone score (TBS) in secondary osteoporosis

Abstract: Altered bone micro-architecture is an important factor in accounting for fragility fractures. Until recently, it has not been possible to gain information about skeletal microstructure in a way that is clinically feasible. Bone biopsy is essentially a research tool. High-resolution peripheral Quantitative Computed Tomography, while non-invasive, is available only sparsely throughout the world. The trabecular bone score (TBS) is an imaging technology adapted directly from the Dual Energy X-Ray Absorptiometry (DXA) image of the lumbar spine. Thus, it is potentially readily and widely available. In recent years, a large number of studies have demonstrated that TBS is significantly associated with direct measurements of bone micro-architecture, predicts current and future fragility fractures in primary osteoporosis, and may be a useful adjunct to BMD for fracture detection and prediction. In this review, we summarize its potential utility in secondary causes of osteoporosis. In some situations, like glucocorticoid-induced osteoporosis and in diabetes mellitus, the TBS appears to out-perform DXA. It also has apparent value in numerous other disorders associated with diminished bone health, including primary hyperparathyroidism, androgen-deficiency, hormone-receptor positive breast cancer treatment, chronic kidney disease, hemochromatosis, and autoimmune disorders like rheumatoid arthritis. Further research is both needed and warranted to more clearly establish the role of TBS in these and other disorders that adversely affect bone.

Transarterial embolization (TAE) is equally effective and slightly safer than transarterial chemoembolization (TACE) to manage liver metastases in neuroendocrine tumors.

Abstract: Liver metastases from neuroendocrine tumor (NET) can be treated by transarterial embolization (TAE) or transarterial chemoembolization (TACE). The goal of TAE and TACE is to reduce blood flow to the tumor resulting in tumor ischemia and necrosis. In this retrospective study, the effectiveness and safety of TAE-TACE in the treatment of liver metastases in patients with NET was compared. Thirty patients with a histologically confirmed gastro-entero-pancreatic NET with liver metastases were retrospectively investigated. Seventeen patients underwent TAE, while 13 patients underwent TACE. Tumor response, degree of devascularization in treated lesions, and progression free survival (PFS) were evaluated in the whole population and then separately in TAE and TACE subgroups. In all patients treated with TAE and TACE, there was a significant size reduction of lesions as compared to baseline. Per lesion reduction was 2.2 ± 1.4 versus 3.3 ± 1.5 cm for TAE (p < 0.001) and 2.2 ± 1.5 versus 3.4 ± 1.7 cm for TACE (p < 0.001). In the whole population, the median PFS for all patients was 36 months (16.2-55.7 CI), without significant difference between TAE and TACE. In no patient did adverse events grade 3 and 4 as well as TAE/TACE-related death occurred, while the post-embolization syndrome occurred in 41 % of patients treated with TAE and 61 % of those treated with TACE. TAE and TACE are both effective in NET patients with liver metastases. TAE should be preferred to TACE in light of its similar anti-tumor effects and slightly better toxicity profile.

Which diet for prevention of type 2 diabetes? A meta-analysis of prospective studies

Abstract: No specific diet is recommended to prevent type 2 diabetes. We did a meta-analysis of prospective cohort studies to assess the association between different diets and prevention of type 2 diabetes. We did a comprehensive search of multiple electronic databases (Medline, Scopus, EMBASE, and ISI web of knowledge) until August 2013 using predefined criteria. We included prospective cohort studies that evaluated the role of different diets in type 2 diabetes prevention. Studies were selected by 2 independent reviewers. We did random-effects meta-analyses to determine the relative risk (RR) of incident diabetes associated with healthful dietary patterns. A total of 21,372 cases of incident diabetes, from 18 prospective studies, with 20 cohorts, in 4 world regions were identified. In the random-effect meta-analysis of the 20 cohorts, RR was 0.80 (95 % confidence interval (CI) = 0.74-0.86, P 10 years), and type of diets (Mediterranean and DASH, Dietary Approaches to Stop Hypertension, diets). There was a difference between at risk and general population (P = 0.0487), but the evidence was limited to two studies only. The results of our study demonstrate that several healthy diets are equally and consistently associated with a 20 % reduced risk of future type 2 diabetes.

Antihypertensive medications, bone mineral density, and fractures: a review of old cardiac drugs that provides new insights into osteoporosis.

Abstract: Osteoporosis is increasing in prevalence and importance as society's age, with the clinical consequence of fractures of the hip, spine, and upper extremity, leading to impaired quality of life, loss of function and independence, and increased morbidity and mortality. A major risk factor for osteoporosis is older age, and cardiovascular diseases also share this risk factor; therefore, osteoporosis and cardiovascular disease often coexist and share risk factors. Medications used for the treatment of cardiovascular diseases, in particular antihypertensive drugs, have been shown in a variety of studies of varying designs to modulate bone health in both a positive or negative manner. In this article, we reviewed the pharmacology, potential mechanisms, and possible effects on bone mineral density and fracture risk of commonly prescribed antihypertensive medications, including thiazide and non-thiazide diuretics, beta-blockers, calcium channel blockers, renin-angiotensin-aldosterone system agents, and nitrates.

Anti-hypertensive treatment in pheochromocytoma and paraganglioma: current management and therapeutic features

Abstract: Pheochromocytoma (PH) and paraganglioma (PG) are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and the sympathetic ganglia, respectively. Although are unusual cause of hypertension (HT) accounting for at most 0.1–0.2 % of cases, they may lead to severe and potentially lethal hypertensive crisis due to the effects of the released catecholamines. However, both PH and PG may be asymptomatic as ~30 % of subjects are normotensive or have orthostatic hypotension and in these cases the 24 h ambulatory blood pressure (BP) monitoring is an important toll to diagnose and treat HT. HT treatment may be difficult when PH or PG occurs in pregnancy or in the elderly subjects and in these cases a multidisciplinary team is required. When surgical excision is mandatory the perioperative management requires the administration of selective α1-adrenergic blocking agents (i.e., doxazosin, prazosin or terazosin) followed by a β-adrenergic blockade (i.e., propranolol, atenolol). This latter should never be started first because blockade of vasodilatory peripheral β-adrenergic receptors with unopposed α-adrenergic receptor stimulation can lead to a further elevation of BP. Although labetalol is traditionally considered the ideal agent due to its α- and β-adrenergic antagonism, experimental studies do not support its use in this clinical setting. As second regimen, the administration of vasodilators as calcium channel blockers (i.e., nicardipine, nifedipine) may be required to control BP. Oral and sublingual short-acting nifedipine are potentially dangerous in patients with hypertensive emergencies and are not recommend. The latest evidences into the diagnosis and treatment of hypertensive crisis due to PH and PG are reviewed here.

Endurance training enhances skeletal muscle interleukin-15 in human male subjects

Abstract: Regular endurance exercise promotes metabolic and oxidative changes in skeletal muscle. Overexpression of interleukin-15 (IL-15) in mice exerts similar metabolic changes in muscle as seen with endurance exercise. Muscular IL-15 production has been shown to increase in mice after weeks of regular endurance running. With the present study we aimed to determine if muscular IL-15 production would increase in human male subjects following 12 weeks of endurance training. In two different studies we obtained plasma and muscle biopsies from young healthy subjects performing: (1) 12 weeks of ergometer cycling exercise five times per week with plasma and biopsies before and after the intervention, and (2) 3 h of ergometer cycling exercise with plasma and biopsies before and after the exercise bout and well into recovery. We measured changes in plasma IL-15, muscle IL-15 mRNA and IL-15 protein. Twelve weeks of regular endurance training induced a 40% increase in basal skeletal muscle IL-15 protein content (p < 0.01), but with no changes in either muscle IL-15 mRNA or plasma IL-15 levels. However, an acute bout of 3-h exercise did not show significant changes in muscle IL-15 or plasma IL-15 levels. The induction of muscle IL-15 protein in humans following a regular training period supports previous findings in mice and emphasizes the hypothesis of IL-15 taking part in skeletal muscle adaptation during training.

Creatine supplementation and aging musculoskeletal health.

Abstract: Sarcopenia refers to the progressive loss of muscle mass and muscle function and is a contributing factor for cachexia, bone loss, and frailty. Resistance training produces several physiological adaptations which improve aging musculoskeletal health, such as increased muscle and bone mass and strength. The combination of creatine supplementation and resistance training may further lead to greater physiological benefits. We performed meta-analyses which indicate creatine supplementation combined with resistance training has a positive effect on aging muscle mass and upper body strength compared to resistance training alone. Creatine also shows promise for improving bone mineral density and indices of bone biology. The combination of creatine supplementation and resistance training could be an effective intervention to improve aging musculoskeletal health.

Pharmacokinetics, safety, and efficacy of DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and renal or hepatic impairment. A systematic review of the literature.

Abstract: Renal or hepatic impairment, often encountered in patients with type 2 diabetes, influences the pharmacokinetics and bioavailability of antihyperglycemic agents. An emerging concern is whether pharmacotherapy with incretin-based agents, the most recent drug classes to be introduced for type 2 diabetes, can be safely used in patients with renal insufficiency or hepatic damage. This literature review examines the results of studies on these novel drug classes, with a view to provide the practitioner with a balanced, evidence-based position when considering incretin-based therapies in patients with type 2 diabetes and impaired kidney or liver function. All currently available dipeptidyl peptidase-4 (DPP-4) inhibitors appear to be appropriate pharmacotherapeutic choices in patients with declining renal function, with linagliptin affording the added advantage of not requiring dose adjustment or periodic monitoring of drug-related kidney function. In contrast, caution is warranted with the use of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with moderate or severe renal impairment. The slightly wider evidence base for liraglutide than for exenatide or lixisenatide is not sufficient to support its use in severe renal impairment. What little evidence there is for incretin-based therapies in hepatic impairment has come from a few past hoc analysis of clinical trials, with most precautions and warnings reflecting the paucity of knowledge about incretin efficacy or safety in this condition.

Circulating irisin levels are not correlated with BMI, age, and other biological parameters in obese and diabetic patients.

Abstract: Increasing evidence demonstrates that skeletal muscle produces and releases substances such as cytokines capable of modulating different metabolic processes [1]. Accordingly, these cytokines are classified as ‘‘myokines’’ [2]. A novel peptidic myokine named ‘irisin’ has been recently identified [3]. Irisin may prove beneficial not only in monitoring and/or the treatment of obesity and diabetes, but also for a wide range of pathological conditions that are characterized by a variable imbalance of energy demand and expenditure [4, 5]. Consequently, great expectations have been rapidly made based on these findings. In this regard, a new concept, ‘‘irisinemia,’’ has been recently suggested to monitor metabolic disorders such as type 2 diabetes (T2D) or obesity, and therefore metabolic syndrome (MetS) [2]. However, several studies assessed circulating irisin concentrations in obese and/or T2D patients, throwing controversial results and conclusions [6]. Therefore, the aim of this study was to evaluate the circulating irisin levels in obese and T2D patients as well as to determine whether irisin levels correlate with other commonly used biochemical parameters in clinical medicine.

Endocrine evaluation of erectile dysfunction.

Abstract: Erectile dysfunction is highly prevalent, affecting up to half of men in their 50-70s, and has been variably associated to a variety of causes including unhealthy lifestyles, such as smoking or overweight, or comorbidities such as hypertension, diabetes mellitus, and neurological disorders. General interest toward ED has exploded since the introduction of phosphodiesterase type 5 inhibitors-oral drugs that are widely accepted as the first line treatment in patients suffering from this conditions. In the last decade, the time lapse between first symptoms of sexual disorders and seeking of medical advice has greatly reduced. Unfortunately, none of the PDE5i has been proven curative, but rather acts as a symptomatic treatment. The availability of very active and safe drugs, however, diminished the space for diagnosis and search of etiological treatments. This is particularly true for the several endocrinopathies associated with ED. A number of epidemiological data support an inverse relationship between sexual health and testosterone levels, and it is well accepted that testosterone deficiency is a good marker of sexual and physical frailty. However, several other hormones, including LH, prolactin, TSH, and FT4 are involved in sexual functioning and should be investigated in a proper work-out of ED. Existing guidelines provide information almost entirely focusing on late-onset hypogonadism and therapeutic strategies; this mini-review aims to provide a wider spectrum of the diagnostic endocrine work-out of ED patients unrevealing the complexity of conditions, overt or subclinical, which can affect ED.

Additive effect of heavy metals on metabolic syndrome in the Korean population: the Korea National Health and Nutrition Examination Survey (KNHANES) 2009-2010.

Abstract: There have been increasing concerns regarding health problems due to endocrine disrupting chemicals (EDCs). We investigated association of heavy metals, including lead, mercury, and cadmium, with metabolic syndrome (MS) and its individual components in the Korean population. Participants included 1,961 males and 1,989 females 20 years of age or older from the fourth and fifth Korea National Health and Nutritional Examination Surveys of the Korean population (2009 and 2010). We examined the relationship of blood lead, mercury, and cadmium levels with MS and the additive effect of three heavy metals on MS after adjustment for age, sex, body mass index (BMI), region, smoking, alcohol consumption, and regular exercise. Blood concentration of lead showed a significant but modest association with prevalence of MS (P = 0.04). Other heavy metals did not show such a relationship with MS. When the participants were classified according to the sum of category numbers of the three heavy metals, adjusted odds ratios were 1.0, 1.355, 1.638, and 1.556 (P < 0.01). Among components of MS, significant relationship of the sum of heavy metals with hypertension and elevated triglyceride was demonstrated. Blood concentration of lead was positively associated with the prevalence of MS. Of particular interest, cumulative effect of a mixture of lead, mercury, and cadmium on prevalence of MS was stronger than the sum of effect of each heavy metal. Accumulative effect of exposure to heavy metals could be more additive or synergistic than individual exposure in the general population.

Ultrasonographic visceral fat thickness in the first trimester can predict metabolic syndrome and gestational diabetes mellitus

Abstract: The aim of this study is to evaluate whether ultrasonographic visceral fat thickness measurement in the early gestational period is useful for predicting the development of gestational diabetes mellitus (GDM) and metabolic syndrome (MS). The visceral fat thickness and subcutaneous fat thickness were measured via ultrasound at the first prenatal visit. The correlation between visceral and subcutaneous fat thickness and MS parameters, such as dyslipidemia, hypertension, and insulin resistance, was assessed. We also compared the use of visceral fat thickness measurement with body mass index (BMI) and waist circumference (WC) measurements for predicting the development of GDM. The subcutaneous fat thickness was found to be similar in the normal glucose metabolism and GDM groups at the first visit, whereas the visceral fat thickness was found to be considerably higher in the GDM groups (p = 0.04). The visceral fat thickness in the early stage of the gestation was correlated with hyperglycemia, dyslipidemia, high diastolic blood pressure, and insulin resistance. In contrast to subcutaneous fat thickness, BMI, and WC, only the visceral fat thickness was correlated with insulin resistance. The subcutaneous and visceral fat thicknesses at the first visit were significantly higher in the MS group (p = 0.02). There was a good correlation between visceral and subcutaneous fat thicknesses (r = 0.492, p < 0.001); however, there were poor correlations between visceral fat thickness and BMI and WC (r = 0.338, p = 0.01; r = 0.312, p = 0.02). The visceral fat thickness seemed to be a more sensitive predictor of GDM than WC and BMI. The optimal cutoff points for predicting GDM were visceral fat thickness 19.5 mm [area under curve (AUC) = 0.66, p = 0.043], WC 103.5 cm (AUC = 0.64, p = 0.079), and BMI 34.5 (AUC = 0.64, p = 0.069). Ultrasonographic visceral fat thickness measurement in the early period of gestation may be an easy, safe, and cost-effective scan test for predicting the development of metabolic diseases and GDM.

Epicardial adipose tissue in endocrine and metabolic diseases.

Abstract: Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study.

Abstract: Vitamin D deficiency is common among patients with liver diseases. Both cholestatic and non-cholestatic liver diseases can cause vitamin D deficiency. Whether vitamin D status can also affect liver function is poorly understood. To investigate the association between vitamin D status, liver enzymes, and incident liver disease, we included a total of 2,649 individuals from the Monica10 study conducted in 1993-1994. Vitamin D status as assessed by serum 25-hydroxyvitamin, serum alanine transaminase (ALT), aspartate transaminase (AST), and gamma glutamyl transferase (GGT) were measured at baseline. Information on fatal and non-fatal liver disease was obtained from the Danish National Patient Register and The Danish Registry of Causes of Death, respectively. Median follow-up time was 16.5 years, and there were 62 incident cases of fatal and non-fatal liver disease. Multivariable Cox regression analyses with age as underlying time axis and delayed entry showed a statistically significant inverse association between vitamin D status and incident liver disease with a hazard ratio = 0.88 (95 % confidence interval 0.79-0.99) per 10 nmol/l higher vitamin D status at baseline (adjusted for gender, season, alcohol consumption, smoking, physical activity, dietary habits, education, body mass index, and ALT). The risk of having a high level of ALT, AST, or GGT tended to be higher for lower vitamin D levels, although not statistically significant. In this general population study, vitamin D status was inversely associated with incident liver disease. Further studies are needed to determine whether patients in risk of developing impaired liver function should be screened for vitamin D deficiency for preventive purposes.

MicroRNA-17-92 cluster regulates osteoblast proliferation and differentiation

Abstract: MicroRNAs (miRNAs) have been identified to play important functions during osteoblast proliferation, differentiation, and apoptosis. The miR-17~92 cluster is highly conserved in all vertebrates. Loss-of-function of the miR-17-92 cluster results in smaller embryos and immediate postnatal death of all animals. Germline hemizygous deletions of MIR17HG are accounted for microcephaly, short stature, and digital abnormalities in a few cases of Feingold syndrome. These reports indicate that miR-17~92 may play important function in skeletal development and mature. To determine the functional roles of miR-17~92 in bone metabolism as well as osteoblast proliferation and differentiation. Murine embryonic stem cells D3 and osteoprogenitor cell line MC3T3-E1 were induced to differentiate into osteoblasts; the expression of miR-17-92 was assayed by quantitative real-time RT-PCR. The skeletal phenotypes were assayed in mice heterozygous for miR-17~92 (miR-17~92 +/Δ ). To determine the possibly direct function of miR-17~92 in bone cells, osteoblasts from miR-17~92 +/Δ mice were investigated by ex vivo cell culture. miR-17, miR-92a, and miR-20a within miR-17-92 cluster were expressed at high level in bone tissue and osteoblasts. The expression of miR-17-92 was down-regulated along with osteoblast differentiation, the lowest level was found in mature osteoblasts. Compared to wildtype controls, miR-17-92 +/Δ mice showed significantly lower trabecular and cortical bone mineral density, bone volume and trabecular number at 10 weeks old. mRNA expression of Runx2 and type I collagen was significantly lower in bone from miR-17-92 +/Δ mice. Osteoblasts from miR-17-92 +/Δ mice showed lower proliferation rate, ALP activity and less calcification. Our research suggests that the miR-17-92 cluster critically regulates bone metabolism, and this regulation is mostly through its function in osteoblasts.

Managing Cushing’s disease: the state of the art

Abstract: Cushing's disease is a rare chronic disease caused by a pituitary adenoma, which leads to excess secretion of adrenocorticotropic hormone (ACTH). The over-production of ACTH leads to hyperstimulation of the adrenal glands and a chronic excess of cortisol, resulting in the signs and symptoms of a severe clinical state (Cushing's syndrome) that leads to significant morbidity, negative impacts on the patient's quality of life, and, if untreated, increased mortality. The management of patients with Cushing's disease is complicated by the heterogeneity of the condition, with signs and symptoms that overlap with those of other diseases, and high subclinical incidence rates. Controversies surrounding the tests used for screening and identifying patients with Cushing's disease add to the challenge of patient management. Surgical intervention to remove the adenoma is the first-line treatment for patients with Cushing's disease, but medical therapies are useful in patients who relapse or are unsuitable for surgery. The recent introduction of pasireotide, the first pituitary-directed medical therapy, expands the number of treatment options available for patients with Cushing's disease. This state-of-the-art review aims to provide an overview of the most recent scientific research and clinical information regarding Cushing's disease. Continuing research into improving the diagnosis and treatment of Cushing's disease will help to optimize patient management.

Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.

Abstract: As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1,250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82 % of adenomas, ErbB2 in 92 %, ErbB3 in 25 %, and ErbB4 in 71 %, with ErbB2 score > EGFR > ErbB4 > ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p = 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas.

Treatment of body composition changes in obese and overweight older adults: insight into the phenotype of sarcopenic obesity

Abstract: In recent years, mounting interest has been directed to sarcopenic obesity (SO), given the parallel increase of life expectancy and prevalence of obesity in Western countries. The phenotype of SO is characterized by the coexistence of excess fat mass and decreased muscle mass, leading to the impairment of physical performance. The aim of the present review was to summarize the impact of different treatment strategies contrasting body composition changes in older obese and overweight subjects, providing insight into the SO phenotype. Revision questions were formulated; relevant articles were identified from Pubmed through a systematic search strategy: definition of the search terms (sarcopenic obesity, diet, nutritional supplements, physical activity, exercise, pharmacological treatment); limits: papers published in the last 10 years; humans; age ≥ 60 years old; body mass index >25 kg/m2; language: English. Studies dealing with sarcopenia associated to cancer cachexia or neurological diseases, any malignant disease, inflammatory or autoimmune diseases, corticosteroids for systemic use, bedridden subjects, and syndromic obesity were excluded. 14 articles were identified for inclusion in the present systematic review, and were grouped basing on the type of the main intervention: data assessing body composition changes after combined lifestyle interventions, exercise/physical activity, dietary interventions, and pharmacological treatment. Most of the studies were randomized, controlled. Sample size ranged from 12 to 439 subjects, and study duration varied from 6 weeks to 12 months. Weight loss based on diet combined with exercise seems to be the best strategy to adopt for treatment of phenotypic aspects of SO, improving metabolic consequences related to excess fat, preserving lean mass, and allowing functional recovery.

Prognostic importance of baseline neutrophil to lymphocyte ratio in patients with advanced papillary thyroid carcinomas

Abstract: Inflammation is associated with several tumor development and progression. However, these associations are not clear in well-differentiated thyroid carcinomas. We assessed whether NLR is a useful prognostic marker in patients with papillary thyroid carcinomas (PTC). The medical records of all patients who underwent thyroid surgery at a single institution between March 2005 and September 2012 were retrospectively evaluated; as a control group, patients who underwent routine health examinations in 2012 were also evaluated. Differences in mean NLR among patient groups were assessed, and clinical characteristics according to NLR quartile were evaluated in patients with PTC. The association between NLR and disease-free survival (DFS) in PTC patients was determined. NLR was significantly higher in the groups with than without thyroid nodules, but did not differ significantly in patients with benign and malignant thyroid nodules. Mean NLR was significantly higher in patients with solid or mixed thyroid than in patients with cystic nodules (1.75 ± 0.92 vs. 1.65 ± 0.74, p = 0.004). Patient follow-up ranged from 6 to 99 months. At 5-year follow-up, 11 patients had disease-specific events. We found that 5-year DFS rate was significantly worse in stages III and IV patients with NLR ≥1.5 than NLR <1.5 (94.1 vs. 99.3 %, p = 0.013). The univariate Cox hazard proportional hazard model for DFS revealed that higher NLR was independently correlated with poorer prognosis (hazard ratio 8.76; 95 % confidence interval 1.09–70.27, p = 0.041). Higher NLR may be a negative prognostic marker for DFS in patients with PTC, especially those with stages III and IV.

Prevalence and impact of hyperandrogenemia in 1,218 women with polycystic ovary syndrome.

Abstract: Hyperandrogenemia modifies phenotypic characteristics of women with polycystic ovary syndrome (PCOS). The aim of the present study is to evaluate (a) the prevalence of hyperandrogenemia in PCOS women (Rotterdam criteria) and (b) the impact of either the degree or the type of hyperandrogenemia on phenotype. Anthropometric, clinical, hormonal, metabolic and ultrasound characteristics of 1,218 women with PCOS were analyzed in this cross-sectional study. The prevalence of hyperandrogenemia was 58.8 %. Women with hyperandrogenemia had higher luteinizing hormone (LH), follicle-stimulating hormone (FSH), free androgen index, lower sex-hormone-binding globulin (SHBG) and fasting glucose levels compared to women with normal androgens (p < 0.001 for all comparisons; p = 0.001 for fasting glucose). Regarding the presence of isolated hyperandrogenemia, the group with only elevated testosterone levels was termed GT and an analogous categorization was made for dehydroepiandrosterone sulfate (GD) and androstenedione (Δ4) (GΔ4), respectively. GT, GD and GΔ4 comprised the 17.2, 7.6 and 4.1 % of total cohort, respectively. These groups differed significantly between them in LH, LH/FSH ratio, and SHBG (p < 0.001). Hyperandrogenemia is found in almost 60 % of women with PCOS (Rotterdam criteria), and it affects hormonal characteristics of these women such as LH and SHBG values. Regarding the impact of isolated hyperandrogenemia on PCOS characteristics, it appears that Δ4 and testosterone elevations are associated with increased LH levels.

Harmful effects of functional hypercortisolism: a working hypothesis.

Abstract: Functional hypercortisolism (FH) is caused by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and usually occurs in cases of major depression, anorexia nervosa, bulimia nervosa, alcoholism, diabetes mellitus, simple obesity, polycystic ovary syndrome, obstructive sleep apnea syndrome, panic disorder, generalized anxiety disorder, shift work, and end-stage renal disease. Most of these states belong to pseudo-Cushing disease, a condition which is difficult to distinguish from Cushing's syndrome and characterized not only by biochemical findings but also by objective ones that can be attributed to hypercortisolism (e.g., striae rubrae, central obesity, skin atrophy, easy bruising, etc.). This hormonal imbalance, although reversible and generally mild, could mediate some systemic complications, mainly but not only of a metabolic/cardiovascular nature, which are present in these states and are largely the same as those present in Cushing's syndrome. In this review we aim to discuss the evidence suggesting the emerging negative role for FH.