Analysis of the proportion and clinical characteristics of obstructive sleep apnea in women with polycystic ovary syndrome.

PURPOSE: To investigate the proportion and clinical characteristics of obstructive sleep apnea (OSA) in Chinese patients with polycystic ovarian syndrome (PCOS) through home sleep apnea test (HSAT) and to evaluate the reproductive endocrine and metabolic characteristics in these patients. METHODS: The study was a cross-sectional analysis of infertile PCOS patients who underwent sleep respiratory monitoring between January and December 2019 at Peking University Third Hospital Reproductive Medical Center and respiratory and critical care medicine department. The prevalence of OSA, body mass index (BMI), menstruation, reproductive endocrine, and metabolic characteristics were collected in patients with PCOS. Logistic regression was performed to identify significant relationships among these factors and OSA. RESULTS: Amont 328 patients with PCOS, the prevalence of OSA was 40% (131/328), and six cases (5%) were severe. Univariate analysis showed that BMI and blood pressure were significantly higher in patients with OSA than in those without OSA (P < 0.05), whereas the anti-Mullerian hormone was lower than that in patients without OSA. In terms of glucose and lipid metabolism, the glycosylated hemoglobin (HbA1c), fasting plasma glucose, and fasting insulin levels were significantly higher in patients with PCOS and comorbid OSA than in those without OSA (all P < 0.05). Patients with OSA also had higher triglyceride, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels and lower high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis revealed that higher BMI, elevated serum testosterone, and decreased high-density lipoprotein cholesterol (HDL-C) are correlated with occurrence of OSA (P < 0.05). CONCLUSION: OSA in patients with PCOS was associated with multiple alterations in indexes of reproductive endocrine and metabolic disorders.

Manifestaciones endocrinas de los tumores germinales del sistema nervioso central en niños / Endocrine manifestations of central nervous system germ cell tumors in children

INTRODUCCIÓN: Los tumores germinales del sistema nervioso central deben ser correctamente diagnosticados, pues su tratamiento suele ser eficaz y no siempre requieren cirugía. Los objetivos del estudio son describir las manifestaciones endocrinas de estas neoplasias y comparar su momento de aparición con el de las alteraciones neurológicas y visuales. PACIENTES Y MÉTODOS: Revisión de historias de pacientes menores de 14 años atendidos en una unidad de endocrinología pediátrica desde 2000 hasta 2018. Pruebas estadísticas: Wilcoxon y Fisher. RESULTADOS: Se estudió a 12 pacientes (10 mujeres) con una edad al diagnóstico de 9,4±1,7 años y un tiempo de seguimiento de 5,5±3,0 años; 10 presentaban tumores de la región selar, uno pineal y uno bifocal. Las alteraciones clínicas que llevaron al diagnóstico eran neurológicas o visuales en 9casos y hormonales en 3. De los que consultaron por síntomas neurológicos o visuales, 7 refirieron previamente alteraciones hormonales, luego, estas estaban presentes en 10 de los niños al diagnóstico; la más frecuente fue la diabetes insípida central (8 casos). El periodo medio de presencia de síntomas endocrinológicos previos al diagnóstico fue de 25,0±26,2 meses, mucho más largo que el de los neurooftalmológicos, de 2,0±2,1 meses (p = 0,012). CONCLUSIONES: Casi todos los tumores germinales intracraneales presentaron al diagnóstico manifestaciones endocrinas, la más frecuente de las cuales fue la diabetes insípida central. Los síntomas hormonales suelen presentarse bastante antes que los neurooftalmológicos. La correcta valoración clínica y endocrinológica puede adelantar el diagnóstico de estos tumores

INTRODUCTION: Central nervous system germ cell tumors need to be adequately diagnosed because their treatment is usually effective and they do not always require surgery. The study objectives are to describe the endocrine manifestations of these tumors and to compare the time of their onset to that of the occurrence of neurological and visual changes. PATIENTS AND METHODS: The medical histories of patients under 14 years of age seen at a pediatric endocrinology unit between 2000 and 2018 were reviewed. Wilcoxon and Fisher statistical tests were performed. RESULTS: We found 12patients (10 females) with an age at diagnosis of 9.4±1.7 years and a follow-up time of 5.5±3.0 years, 10with tumors in the sellar region, and each one with a pineal gland and a bifocal tumor. Clinical changes leading to diagnosis were neurological and/or visual in 9patients and hormonal in three. Seven patients diagnosed on the basis of neurological or visual symptoms had previously reported hormonal changes, giving us a total of 10 children at diagnosis (the most common diagnosis was central diabetes insipidus, found in 8). Endocrine symptoms had been present before diagnosis for 25.0±26.2 months, considerably longer than neuro-ophthalmological complaints (2.0±2.1 months, p = 0.012). CONCLUSIONS: Almost all intracranial germ cell tumors have associated endocrine manifestations at diagnosis, with central diabetes insipidus the most common. Hormonal symptoms usually appear long before neuro-ophthalmological manifestations. Adequate clinical and endocrinological assessment may allow for an earlier diagnosis of these tumors

Hormone replacement therapy in brain-dead organ donors: a comprehensive review with an emphasis on traumatic brain injury.

BACKGROUND: Organ shortage is an ongoing problem in the United States. Most donor organs are procured following brain death and a significant portion of brain-dead donors result from devastating brain injury. Without a standard practice for hormone replacement therapy (HRT) in the setting of brain death, a comprehensive review of the literature was deemed necessary. METHODS: A search of published literature was conducted with terms "TBI" or "brain injury" or "head injury" AND "hormone" or "management" AND "organ" AND "donor" or "donation." Abstracts and full texts were screened for relevance and inclusion of information on HRT. Additional studies were selected from references cited within these. Excluded studies were non-English, nonhuman based, or had small sample size, (i.e., case reports or series with fewer than five subjects). RESULTS: Fifteen studies were selected for inclusion and contained Level III or Level IV evidence. Combinations of thyroid hormone, insulin, and corticosteroids were the most commonly cited HRT. Ninety-three percent of studies found a significant increase in organ procurement rate among donors who received HRT. Hormone replacement therapy was administered after brain death declaration in eight studies. Only two studies specifically explored the effects of starting HRT earlier and identified even greater procurement rates. Four studies were specific to traumatic brain injury (TBI); the remaining 11 studies involved TBI in 22% to 89% of the sample. CONCLUSION: Organ shortage remains a growing problem in the United States. Donor management including HRT has been proposed to combat the endocrine derangement associated with brain death and, in particular, TBI. While the existing literature reported compelling outcomes using HRT, there remains a need for further Level I and Level II evidence studies to define optimal practice. LEVEL OF EVIDENCE: Review article, level IV.

Metastatic brain carotid body paraganglioma with endocrine activity: a case report and literature review.

A woman with hypertension and hyperglycemia was diagnosed a metastatic brain carotid body paraganglioma. Her blood pressure, glucose, and norepinephrine were normal after craniotomy. Although most carotid body tumors are benign, a few show distant metastasis. This is the first reported case of intracerebral metastases from a carotid body tumor.

Measuring estrogens in women, men, and children: Recent advances 2012-2017.

The measurement of estrogens is important for diagnosing and monitoring the health of women, men, and children. For example, for postmenopausal women or women undergoing treatment for breast cancer with aromatase inhibitors, the measurement of extremely low concentrations of estrogens in serum, especially estradiol, is problematic but essential for proper medical care. Achieving superb analytical sensitivity and specificity has been and continues to be a challenge for the clinical laboratory, but is a challenge that is being taken seriously. Focusing on publications from 2012 to 2017, this review will provide an overview of recent research in the development of methods to accurately and precisely measure estrogens, including a variety of estrogen metabolites. Additionally, the latest in clinical research involving estrogen measurement in women, men, and children will be presented to provide an update on the association of estrogens with diseases or conditions such as breast cancer, precocious puberty, infertility, and pregnancy. This research update will provide context as to why estrogen measurement is important and why laboratories are working hard to support the recommendations made by the Endocrine Society regarding estrogen measurement.

The Stomach as an Endocrine Organ: Expression of Key Modulatory Genes and Their Contribution to Obesity and Non-alcoholic Fatty Liver Disease (NAFLD).

PURPOSE OF REVIEW: Obesity is currently seen in epidemic proportions globally and is one of the largest contributors to the development of NAFLD. The spectrum of NAFLD, particularly the progressive forms of NASH, is likely to become the leading cause of liver disease in the next decade. RECENT FINDINGS: Soluble molecules, encoded by the stomach tissue, have been shown to have pleiotropic effects in both central and peripheral systems involved in energy homeostasis and obesity regulation. As such, the stomach is one of the important players in the complex, multi-system deregulation leading to obesity and NAFLD. The understanding of the stomach tissue as an active endocrine organ that contributes to the signaling milieu leading to the development of obesity and NAFLD is crucial.

Assessing the links among environmental contaminants, endocrinology, and parasites to understand amphibian declines in montane regions of Costa Rica.

Amphibians inhabiting montane riparian zones in the Neotropics are particularly vulnerable to decline, but the reasons are poorly understood. Because environmental contaminants, endocrine disruption, and pathogens often figure prominently in amphibian declines it is imperative that we understand how these factors are potentially interrelated to affect montane populations. One possibility is that increased precipitation associated with global warming promotes the deposition of contaminants in montane regions. Increased exposure to contaminants, in turn, potentially elicits chronic elevations in circulating stress hormones that could contribute to montane population declines by compromising resistance to pathogens and/or production of sex steroids regulating reproduction. Here, we test this hypothesis by examining contaminant levels, stress and sex steroid levels, and nematode abundances in male drab treefrogs, Smilisca sordida, from lowland and montane populations in Costa Rica. We found no evidence that montane populations were more likely to possess contaminants (i.e., organochlorine, organophosphate and carbamate pesticides or benzidine and chlorophenoxy herbicides) than lowland populations. We also found no evidence of elevational differences in circulating levels of the stress hormone corticosterone, estradiol or progesterone. However, montane populations possessed lower androgen levels, hosted more nematode species, and had higher nematode abundances than lowland populations. Although these results suggested that nematodes contributed to lower androgens in montane populations, we were unable to detect a significant inverse relationship between nematode abundance and androgen level. Our results suggest that montane populations of this species are not at greater risk of exposure to contaminants or chronic stress, but implicate nematodes and compromised sex steroid levels as potential threats to montane populations.

Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis.

IMPORTANCE: If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune checkpoint inhibitor (ICI) regimens are unknown. OBJECTIVE: To compare the incidence and risk of endocrine AEs following treatment with US Food and Drug Administration-approved ICI regimens. DATA SOURCES: A PubMed search through July 18, 2016, using the following keywords was performed: "ipilimumab," "MDX-010," "nivolumab," "BMS-963558," "pembrolizumab," "MK-3475," "atezolizumab," "MPDL3280A," and "phase." STUDY SELECTION: Thirty-eight randomized clinical trials evaluating the usage of these ICIs for treatment of advanced solid tumors were identified, resulting in a total of 7551 patients who were eligible for a meta-analysis. Regimens were categorized by class into monotherapy with a PD-1 (programmed cell death protein 1) inhibitor, a CTLA-4 (cytotoxic T-lymphocyte-associated protein-4) inhibitor, or a PD-L1 (programmed cell death 1 ligand 1) inhibitor, and combination therapy with PD-1 plus CTLA-4 inhibitors. DATA EXTRACTION AND SYNTHESIS: The data were extracted by 1 primary reviewer (R.B.-S.) and then independently reviewed by 2 secondary reviewers (W.T.B. and A.C.G.-C.) following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inferences on the incidence of AEs were made using log-odds random effects models. MAIN OUTCOMES AND MEASURES: Incidence of all-grade hypothyroidism, hyperthyroidism, hypophysitis, primary adrenal insufficiency, and insulin-deficient diabetes. RESULTS: Overall, 38 randomized clinical trials comprising 7551 patients were included in this systematic review and meta-analysis. The incidence of both hypothyroidism and hyperthyroidism was highest in patients receiving combination therapy. Patients on the combination regimen were significantly more likely to experience hypothyroidism (odds ratio [OR], 3.81; 95% CI, 2.10-6.91, P < .001) and hyperthyroidism (OR, 4.27; 95% CI, 2.05-8.90; P = .001) than patients on ipilimumab. Compared with patients on ipilimumab, those on PD-1 inhibitors had a higher risk of developing hypothyroidism (OR, 1.89; 95% CI, 1.17-3.05; P = .03). The risk of hyperthyroidism, but not hypothyroidism, was significantly greater with PD-1 than with PD-L1 inhibitors (OR, 5.36; 95% CI, 2.04-14.08; P = .002). While patients who received PD-1 inhibitors were significantly less likely to experience hypophysitis than those receiving ipilimumab (OR, 0.29; 95% CI, 0.18-0.49; P < .001), those who received combination therapy were significantly more likely to develop it (OR, 2.2; 95% CI, 1.39-3.60; P = .001). For primary adrenal insufficiency and insulin-deficient diabetes no statistical inferences were made due to the smaller number of events. CONCLUSIONS AND RELEVANCE: Our study provides more precise data on the incidence of endocrine dysfunctions among patients receiving ICI regimens. Patients on combination therapy are at increased risk of thyroid dysfunction and hypophysitis.

Gastrointestinal Endocrinology in Bariatric Surgery.

The long-lasting weight-reducing effect of bariatric surgical procedures cannot simply be explained by the malabsorption of nutrients and the subsequent energy deficit due to this malabsorption. Clinical studies have shown that the reorganization of the anatomy of the gut and the subsequent alterations of gastrointestinal physiology have a large impact on the secretion and function of gastrointestinal hormones, which regulate hunger and satiety. These changes have been named the BRAVE effect: bile flow alteration, reduction of gastric size, anatomical gut rearrangement and altered flow of nutrients, vagal manipulation, and enteric gut modulation. In addition, the metabolic improvements, for example, increased insulin secretion and improved glucose sensitivity after bariatric surgery cannot simply be explained by the weight loss achieved by the operation. Several metabolic improvements occur directly after bariatric surgery even before significant weight loss has occurred. Clinical studies revealed that the altered gastrointestinal physiology and the postoperative profile of gastrointestinal hormones are responsible for these metabolic alterations. Further insights into the changes of gastrointestinal hormone profiles before and after bariatric surgery may open new ways to prevent the surgical procedure and probably obtain equivalent results by nutraceuticals.

[Endocrine and metabolic features of female children with Prader-Willi syndrome: an analysis of 4 cases].

This article reports the clinical features and endocrine and metabolic features of 4 children with Prader-Willi syndrome (PWS). All the patients were female and aged 6-12 years at diagnosis. All of them had clinical manifestations of obesity, unusual facies, developmental retardation, and intellectual disability. Genetic detection showed that 2 patients had paternal deletion of the 15q11.2-q13 region, one patient had maternal autodiploid in the 15q11.2-q13 region, and one patient had no abnormality in the 15q11.2-q13 region. All patients had varying degrees of endocrine and metabolic disorders: 2 patients had short stature, among whom one had delayed appearance of secondary sex characteristics and the other one had type 2 diabetes; one patient had insulin resistance and no mammary gland development; one patient had a body height of P3-P10 and precocious puberty. Patients with PWS have various endocrine disorders, so long-term endocrine follow-up and management is very important.

Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy.

Anti-VEGF-based antiangiogenic drugs are designed to block tumor angiogenesis for treatment of cancer patients. However, anti-VEGF drugs produce off-tumor target effects on multiple tissues and organs and cause broad adverse effects. Here, we show that vasculatures in endocrine organs were more sensitive to anti-VEGF treatment than tumor vasculatures. In thyroid, adrenal glands, and pancreatic islets, systemic treatment with low doses of an anti-VEGF neutralizing antibody caused marked vascular regression, whereas tumor vessels remained unaffected. Additionally, a low dose of VEGF blockade significantly inhibited the formation of thyroid vascular fenestrae, leaving tumor vascular structures unchanged. Along with vascular structural changes, the low dose of VEGF blockade inhibited vascular perfusion and permeability in thyroid, but not in tumors. Prolonged treatment with the low-dose VEGF blockade caused hypertension and significantly decreased circulating levels of thyroid hormone free-T3 and -T4, leading to functional impairment of thyroid. These findings show that the fenestrated microvasculatures in endocrine organs are more sensitive than tumor vasculatures in response to systemic anti-VEGF drugs. Thus, our data support the notion that clinically nonbeneficial treatments with anti-VEGF drugs could potentially cause adverse effects.

Endocrine dysfunction in hereditary hemochromatosis.

Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies.

Improved versus worsened endocrine function after transsphenoidal surgery for nonfunctional pituitary adenomas: rate, time course, and radiological analysis.

OBJECTIVE: The impact of transsphenoidal surgery for nonfunctional pituitary adenomas (NFAs) on preoperative hypopituitarism relative to the incidence of new postoperative endocrine deficits remains unclear. The authors investigated rates of hypopituitarism resolution and development after transsphenoidal surgery. METHODS: Over a 5-year period, 305 transsphenoidal surgeries for NFAs performed at The California Center for Pituitary Disorders were retrospectively reviewed. RESULTS: Patients with preoperative endocrine deficits (n = 153, 50%) were significantly older (mean age 60 vs 54 years; p = 0.004), more frequently male (65% vs 44%; p = 0.0005), and had larger adenomas (2.4 cm vs 2.1 cm; p = 0.02) than patients without preoperative deficits (n = 152, 50%). Of patients with preoperative endocrine deficits, 53% exhibited symptoms. Preoperative deficit rates were 26% for the thyroid axis; 20% and 16% for the male and female reproductive axes, respectively; 13% for the adrenocorticotropic hormone (ACTH)/cortisol axis, and 19% for the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. Laboratory normalization rates 6 weeks and 6 months after surgery without hormone replacement were 26% and 36% for male and 13% and 13% for female reproductive axes, respectively; 30% and 49% for the thyroid axis; 3% and 3% for the cortisol axis; and 9% and 22% for the IGF-1 axis (p < 0.05). New postoperative endocrine deficits occurred in 42 patients (13.7%). Rates of new deficits by axes were: male reproductive 3% (n = 9), female reproductive 1% (n = 4), thyroid axis 3% (n = 10), cortisol axis 6% (n = 19), and GH/IGF-1 axis 4% (n = 12). Patients who failed to exhibit any endocrine normalization had lower preoperative gland volumes than those who did not (0.24 cm(3) vs 0.43 cm(3), respectively; p < 0.05). Multivariate analyses revealed that no variables predicted new postoperative deficits or normalization of the female reproductive, cortisol, and IGF-1 axes. However, increased preoperative gland volume and younger age predicted the chances of a patient with any preoperative deficit experiencing normalization of at least 1 axis. Younger age and less severe preoperative hormonal deficit predicted normalization of the thyroid and male reproductive axes (p < 0.05). CONCLUSIONS: After NFA resection, endocrine normalization rates in this study varied with the hormonal axis and were greater than the incidence of new endocrine deficits. Low preoperative gland volume precluded recovery. Patient age and the severity of the deficiency influenced the recovery of the thyroid and male reproductive axes, the most commonly impaired axes and most likely to normalize postoperatively. This information can be of use in counseling patients with hypopituitarism who undergo NFA surgery.

Immune stimulation improves endocrine and neural fetal outcomes in a model of maternofetal thyrotoxicosis.

The potentiation of the immune system in pregnant rats was performed with Complete Freund's Adjuvant [CFA; 20µl, subcutaneous at gestation day (GD) 18] in experimentally-induced hyperthyroidism by Levo-thyroxine (L-T4; 10µg/100g of b.w., intraperitoneal from GD 2 to 17). The potential effects on the fetal neuroendocrine function were evaluated by observing some histopathological investigations in pregnant rats and measuring some biochemical parameters in dams and their fetuses at GD 20. In hyperthyroid group, an increase in maternofetal serum thyroxine (T4), triiodothyronine (T3) and a decrease in thyrotropin (TSH) levels were noticed, while the concentrations of fetal serum growth hormone (GH) and insulin-like growth factor-1 (IGF1) levels were increased at tested GD with respect to control and CFA groups. Moreover, the activity of uterine and placental myeloperoxidase (MPO) was increased (P<0.001) in CFA and CFA-treated hyperthyroid groups in respect to control or hyperthyroid groups, respectively. The gestational thyrotoxicosis led to some histopathological lesions in uterine and placental tissues characterized by severe degeneration in trophoblast spongioblast cell layer with congestion, mild congested blood vessels in the endometrium and deficient in spiral artery remodeling. Although, the elevation in fetal serum transforming growth factor-beta (TGFß) and cerebellar monoamines [norepineprine (NE), epinephrine (E), dopamine (DA) and 5-hydroxytryptamine (5-HT)] was observed, the reduction in fetal serum tumor necrosis factor-alpha (TNFα) and adipokines (Leptin and adiponectin) was detected. Treatment of dams with CFA showed an obviously reversing and protecting effect against hyperthyroid perturbations. Thus, the maternal CFA can be used in treatment of the fetal neuroendocrine dysfunctions.

Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility.

Worldwide obesity rates have nearly doubled since 1980 and currently over 10% of the population is obese. In 2008, over 1.4 billion adults aged 20 years and older had a body mass index or BMI above a healthy weight and of these, over 200 million men and nearly 300 million women were obese. While obesity can have many ramifications upon adult life, one growing area of concern is that of reproductive capacity. Obesity affects male infertility by influencing the hypothalamic-pituitary-gonadal axis, thus causing detrimental effects upon spermatogenesis and subsequent fertility. In particular, evidence indicates that excess adipose tissue can alter the relative ratio of testosterone and oestrogen. Additional effects involve the homeostatic disruption of insulin, sex-hormone-binding-globulin, leptin and inhibin B, leading to diminished testosterone production and impairment to spermatogenesis. Aberrant spermatogenesis arising from obesity is associated with downstream changes in key semen parameters, defective sperm capacitation and binding, and deleterious effects on sperm chromatin structure. More recent investigations into trans-generational epigenetic inheritance further suggest that molecular changes in sperm that arise from obesity-related impaired spermatogenesis, such as modified sperm RNA levels, DNA methylation, protamination and histone acetylation, can impact upon the development of offspring. Here, we summarise our current understanding of how obesity exerts influence over spermatogenesis and subsequent fertility status, and make recommendations for future investigative research.

Quality of survival assessment in European childhood brain tumour trials, for children aged 5 years and over.

INTRODUCTION: There is increasing recognition of the long-term sequelae of brain tumours treated in childhood. Five year survival rates now exceed 75% and assessing the quality of survival (QoS) in multiple domains is essential to any comparison of the benefits and harms of treatment regimens. AIM: The aim of this position statement is to rationalise assessments and facilitate collection of a common data set across Europe. Sufficient numbers of observations can then be made to enable reliable comparisons between outcomes following different tumour types and treatments. METHODS: This paper represents the consensus view of the QoS working group of the Brain Tumour group of the European Society of Paediatric Oncology regarding domains of QoS to prioritise for assessment in clinical trials. This consensus between clinicians and researchers across Europe has been arrived at by discussion and collaboration over the last eight years. RESULTS: Areas of assessment discussed include core medical domains (e.g. vision, hearing, mobility, endocrine), emotion, behaviour, adaptive behaviour and cognitive functioning. CONCLUSIONS: A 'core plus' approach is suggested in which core assessments (both direct and indirect tests) are recommended for all clinical trials. The core component is a relatively brief screening assessment that, in most countries, is a sub-component of routine clinical provision. The 'plus' components enable the addition of assessments which can be selected by individual countries and/or tumour-, age-, and location-specific groups. The implementation of a QoS protocol common to all European clinical studies of childhood brain tumours is also discussed.

Mechanisms of aging-related impairment of brown adipocyte development and function.

Aging is one of the primary risk factors for the development of obesity, a pathology that develops due to an imbalance of increased energy consumption over reduced expenditure. Brown adipocytes are responsible for thermogenesis and could therefore counter obesity by increasing energy expenditure. It is by now well established that humans possess thermogenesis-competent brown adipocytes throughout life, and recent findings indicate that brown fat is actively involved in metabolic control and body weight regulation in adults. Aging is accompanied by a loss of classical brown adipocytes as well as the brown-like adipocytes found in white adipose tissue, suggesting that loss of their energy-expending capacity might contribute to an obesity-prone phenotype with increased age. We here discuss the hypothesis that the age-related loss of brown adipocyte regenerative capacity is a result of dysfunctional stem/progenitor cells. The possible molecular mechanisms that lead to an age-related decline in brown adipogenic stem/progenitor cell function include cell-autonomous and external effects. General loss of mitochondrial biogenesis and function has repeatedly been linked to age-related perturbation of metabolic processes. We also discuss the possibility that alterations in neuronal control by the sympathetic nervous system may contribute to impaired regeneration and thermogenesis in aged brown adipocytes. Finally, age-related changes of endocrine signals have been proposed to exacerbate the loss of brown adipose tissue. In conclusion, age-induced impairment of brown adipogenic stem/progenitor cell function could contribute to the loss of brown adipocyte regeneration, thereby promoting the development of obesity and other metabolic disorders with age.

[Changes in serum hormone levels in the middle and gerontic aged inhabitants of Arkhangelsk due to the gender identity].

The serum hormone levels were studied among middle and gerontic aged residents of Arkhangelsk by enzyme immunoassay and radioimmunoassay. The significant increase of follicle-stimulating and luteinizing hormones levels in gerontic aged men was recorded in the presence of higher concentrations of these hormones in women. There was a statistical tendency of decrease in the level of testosterone in gerontic aged women compared to middle aged. Regardless of gender the lowering of the dehydroepiandrosterone sulfate content was observed in gerontic aged residents compared to middle aged. The criteria of functional activity reduction of the thyroid gland were a decrease in serum free thyroxine fraction levels in gerontic aged women and low concentrations of common triiodothyronine in middle aged men living in Arkhangelsk. Serum cortisol, insulin, estradiol, growth hormone had no significant age and sex differences in the present groups. The number of correlations was greater among the gerontic aged people in comparison with the middle aged, especially among women.