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Glucocorticoids are the final products of the neuroendocrine hypothalamic–pituitary—adrenal axis, and play an important role in the stress response to re-establish homeostasis when it is threatened, or perceived as threatened. These steroid hormones have pleiotropic actions through binding to their cognate receptor, the human glucocorticoid receptor, which functions as a ligand-bound transcription factor inducing or repressing the expression of a large number of target genes. To achieve homeostasis, glucocorticoid signaling should have an optimal effect on all tissues. Indeed, any inappropriate glucocorticoid effect in terms of quantity or quality has been associated with pathologic conditions, which are characterized by short-term or long-lasting detrimental effects. Two such conditions, the primary generalized glucocorticoid resistance and hypersensitivity syndromes, are discussed in this review article. Undoubtedly, the tremendous progress of structural, molecular, and cellular biology, in association with the continued progress of biotechnology, has led to a better and more in-depth understanding of these rare endocrinologic conditions, as well as more effective therapeutic management. [ABSTRACT FROM AUTHOR]

Recent studies have shown a rise in precocious puberty, especially in girls. At the same time, childhood obesity due to overnutrition and energy imbalance is rising too. Nutrition and fertility are currently facing major challenges in our societies, and are interconnected. Studies have shown that high-fat and/or high-glycaemic-index diet can cause hypothalamic inflammation and microglial activation. Molecular and animal studies reveal that microglial activation seems to produce and activate prostaglandins, neurotrophic factors activating GnRH (gonadotropin-releasing hormone expressing neurons), thus initiating precocious puberty. GnRH neurons' mechanisms of excitability are not well understood. In this review, we study the phenomenon of the rise of precocious puberty, we examine the physiology of GnRH neurons, and we review the recent literature regarding the pathophysiological mechanisms that connect diet-induced hypothalamic inflammation and diet-induced phoenixin regulation with precocious puberty. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals (EDCs) are environmental and industrial agents that interfere with hormonal functions. EDC exposure is linked to various endocrine diseases, especially in reproduction, although the mechanisms remain unclear and effects vary among individuals. Neuroinflammation, particularly hypothalamic inflammation, is an emerging research area with implications for endocrine-related diseases like obesity. The hypothalamus plays a crucial role in regulating reproduction, and its inflammation can adversely affect reproductive health. EDCs can cross the blood–brain barrier, potentially causing hypothalamic inflammation and disrupting the reproductive axis. This review examines the existing literature on EDC-mediated hypothalamic inflammation. Our findings suggest that exposure to 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), polychlorinated biphenyl (PCB), tributyltin (TBT), phthalates, bisphenol A (BPA), and chlorpyrifos (CPF) in animals is linked to hypothalamic inflammation, specifically affecting the hypothalamic centers of the gonadotropic axis. To our knowledge, this is the first comprehensive review on this topic, indicating hypothalamic inflammation as a possible mediator between EDC exposure and reproductive dysfunction. Further human studies are needed to develop effective prevention and treatment strategies against EDC exposure. [ABSTRACT FROM AUTHOR]

Leucocyte telomere length (LTL) is a robust marker of biological aging and is associated with obesity and cardiometabolic risk factors in childhood and adolescence. We investigated the effect of a structured, comprehensive, multidisciplinary, personalized, lifestyle intervention program of healthy diet and physical exercise on LTL in 508 children and adolescents (239 males, 269 females; 282 prepubertal, 226 pubertal), aged 10.14 ± 0.13 years. Participants were classified as obese (n = 267, 52.6%), overweight (n = 174, 34.2%), or of normal BMI (n = 67, 13.2%) according to the International Obesity Task Force (IOTF) cutoff points and were studied prospectively for one year. We demonstrated that LTL increased significantly after 1 year of the lifestyle interventions, irrespective of gender, pubertal status, or body mass index (BMI). Waist circumference was the best negative predictor of LTL at initial assessment. The implementation of the lifestyle interventions also resulted in a significant improvement in clinical (BMI, BMI z-score and waist to height ratio) and body composition indices of obesity, inflammatory markers, hepatic enzymes, glycated hemoglobin (HbA1C), quantitative insulin sensitivity check index (QUICKI), and lipid profile in all participants. These findings indicate that the increased LTL may be associated with a more favorable metabolic profile and decreased morbidity later in life. [ABSTRACT FROM AUTHOR]

In recent decades, the prevalence of obesity has risen dramatically worldwide among all age groups. Obesity is characterized by excess fat accumulation and chronic low-grade inflammation. The adipose tissue functions as a metabolically active endocrine organ secreting adipokines. A novel duo of adipokines, the anti-inflammatory secreted frizzled-related protein 5 (Sfrp5) and the proinflammatory wingless type mouse mammary tumor virus (MMTV) integration site family member 5A (Wnt5a), signal via the non-canonical Wnt pathway. Recent evidence suggests that Sfpr5 and Wnt5a play a key role in the pathogenesis of obesity and its metabolic complications. This review summarizes the current knowledge on the novel regulatory system of anti-inflammatory Sfrp5 and pro-inflammatory Wnt5a, and their relation to obesity and obesity-related complications. Future studies are required to investigate the potential role of Sfrp5 and Wnt5a as biomarkers for monitoring the response to lifestyle interventions and for predicting the development of cardiometabolic risk factors. These adipokines may also serve as novel therapeutic targets for obesity-related disorders. [ABSTRACT FROM AUTHOR]

In clinical practice, differences in glucocorticoid sensitivity among healthy subjects may influence the outcome and any adverse effects of glucocorticoid therapy. Thus, a fast and accurate methodology that could enable the classification of individuals based on their tissue glucocorticoid sensitivity would be of value. We investigated the usefulness of untargeted plasma metabolomics in identifying a panel of metabolites to distinguish glucocorticoid-resistant from glucocorticoid-sensitive healthy subjects who do not carry mutations in the human glucocorticoid receptor (NR3C1) gene. Applying a published methodology designed for the study of glucocorticoid sensitivity in healthy adults, 101 healthy subjects were ranked according to their tissue glucocorticoid sensitivity based on 8:00 a.m. serum cortisol concentrations following a very low-dose dexamethasone suppression test. Ten percent of the cohort, i.e., 11 participants, on each side of the ranking, with no NR3C1 mutations or polymorphisms, were selected, respectively, as the most glucocorticoid-sensitive and most glucocorticoid-resistant of the cohort to be analyzed and compared with untargeted blood plasma metabolomics using gas chromatography–mass spectrometry (GC–MS). The acquired metabolic profiles were evaluated using multivariate statistical analysis methods. Nineteen metabolites were identified with significantly lower abundance in the most sensitive compared to the most resistant group of the cohort, including fatty acids, sugar alcohols, and serine/threonine metabolism intermediates. These results, combined with a higher glucose, sorbitol, and lactate abundance, suggest a higher Cori cycle, polyol pathway, and inter-tissue one-carbon metabolism rate and a lower fat mobilization rate at the fasting state in the most sensitive compared to the most resistant group. In fact, this was the first study correlating tissue glucocorticoid sensitivity with serine/threonine metabolism. Overall, the observed metabolic signature in this cohort implies a worse cardiometabolic profile in the most glucocorticoid-sensitive compared to the most glucocorticoid-resistant healthy subjects. These findings offer a metabolic signature that distinguishes most glucocorticoid-sensitive from most glucocorticoid-resistant healthy subjects to be further validated in larger cohorts. Moreover, they support the correlation of tissue glucocorticoid sensitivity with insulin resistance and metabolic syndrome-associated pathways, further emphasizing the need for nutritionists and doctors to consider the tissue glucocorticoid sensitivity in dietary and exercise planning, particularly when these subjects are to be treated with glucocorticoids. [ABSTRACT FROM AUTHOR]

Stress is defined as a state of threatened or perceived as threatened homeostasis. The well-tuned coordination of the stress response system is necessary for an organism to respond to external or internal stressors and re-establish homeostasis. Glucocorticoid hormones are the main effectors of stress response and aberrant glucocorticoid signaling has been associated with an increased risk for psychiatric and mood disorders, including schizophrenia, post-traumatic stress disorder and depression. Emerging evidence suggests that life-stress experiences can alter the epigenetic landscape and impact the function of genes involved in the regulation of stress response. More importantly, epigenetic changes induced by stressors persist over time, leading to increased susceptibility for a number of stress-related disorders. In this review, we discuss the role of glucocorticoids in the regulation of stress response, the mechanism through which stressful experiences can become biologically embedded through epigenetic alterations, and we underline potential associations between epigenetic changes and the development of stress-related disorders. [ABSTRACT FROM AUTHOR]

Previous findings suggest that parental feeding practices may adapt to children's eating behavior and sex, but few studies assessed these associations in toddlerhood. We aimed to study the associations between infant's appetite or children's genetic susceptibility to obesity and parental feeding practices. We assessed infant's appetite (three-category indicator: low, normal or high appetite, labelled 4-to-24-month appetite) and calculated a combined obesity risk-allele score (genetic risk score of body mass index (BMI-GRS)) in a longitudinal study of respectively 1358 and 932 children from the EDEN cohort. Parental feeding practices were assessed at 2-year-follow-up by the CFPQ. Three of the five tested scores were used as continuous variables; others were considered as binary variables, according to the median. Associations between infant's appetite or child's BMI-GRS and parental feeding practices were assessed by linear and logistic regression models, stratified on child's sex if interactions were significant. 4-to-24-month appetite was positively associated with restrictive feeding practices among boys and girls. Among boys, high compared to normal 4-to-24-month appetite was associated with higher use of food to regulate child's emotions (OR [95% CI] = 2.24 [1.36; 3.68]). Child's BMI-GRS was not related to parental feeding practices. Parental feeding practices may adapt to parental perception of infant's appetite and child's sex. [ABSTRACT FROM AUTHOR]

Overweight and obesity in childhood and adolescence represent major public health problems of our century, and account for increased morbidity and mortality in adult life. Irisin and Fibroblast Growth Factor 21 (FGF-21) have been proposed as prognostic and/or diagnostic biomarkers in subjects with obesity and metabolic syndrome, because they increase earlier than other traditional biomarkers. We determined the concentrations of Irisin and FGF-21 in children and adolescents with overweight and obesity before and after one year of a life-style intervention program of diet and physical exercise and explored the impact of body mass index (BMI) reduction on the concentrations of Irisin, FGF-21 and other cardiometabolic risk factors. Three hundred and ten (n = 310) children and adolescents (mean age ± SD: 10.5 ± 2.9 years) were studied prospectively. Following one year of the life-style intervention program, there was a significant decrease in BMI (p = 0.001), waist-to-hip ratio (p = 0.024), waist-to-height ratio (p = 0.024), and Irisin concentrations (p = 0.001), and an improvement in cardiometabolic risk factors. There was no alteration in FGF-21 concentrations. These findings indicate that Irisin concentrations decreased significantly as a result of BMI reduction in children and adolescents with overweight and obesity. Further studies are required to investigate the potential role of Irisin as a biomarker for monitoring the response to lifestyle interventions and for predicting the development of cardiometabolic risk factors. [ABSTRACT FROM AUTHOR]

In children and adolescents, obesity does not seem to depend on a reduction of resting energy expenditure (REE). Moreover, in this young population, the interactions between either age and obesity or between age and gender, or the role of leptin on REE are not clearly understood. To compare the levels of REE in children and adolescents we studied 181 Caucasian individuals (62% girls) classified on the basis of age- and sex-specific body mass index (BMI) percentile as healthy weight (n = 50), with overweight (n = 34), or with obesity (n = 97) and in different age groups: 8–10 (n = 38), 11–13 (n = 50), and 14–17 years (n = 93). REE was measured by indirect calorimetry and body composition by air displacement plethysmography. Statistically significant differences in REE/fat-free mass (FFM) regarding obesity or gender were not observed. Absolute REE increases with age (p < 0.001), but REE/FFM decreases (p < 0.001) and there is an interaction between gender and age (p < 0.001) on absolute REE showing that the age-related increase is more marked in boys than in girls, in line with a higher FFM. Interestingly, the effect of obesity on absolute REE is not observed in the 8–10 year-old group, in which serum leptin concentrations correlate with the REE/FFM (r = 0.48; p = 0.011). In conclusion, REE/FFM is not affected by obesity or gender, while the effect of age on absolute REE is gender-dependent and leptin may influence the REE/FFM in 8–10 year-olds. [ABSTRACT FROM AUTHOR]

As a major public health concern, childhood obesity is a multifaceted and multilevel metabolic disorder influenced by genetic and behavioral aspects. While genetic risk factors contribute to and interact with the onset and development of excess body weight, available evidence indicates that several modifiable obesogenic behaviors play a crucial role in the etiology of childhood obesity. Although a variety of systematic reviews and meta-analyses have reported the effectiveness of several interventions in community-based, school-based, and home-based programs regarding childhood obesity, the prevalence of children with excess body weight remains high. Additionally, researchers and pediatric clinicians are often encountering several challenges and the characteristics of an optimal weight management strategy remain controversial. Strategies involving a combination of physical activity, nutritional, and educational interventions are likely to yield better outcomes compared to single-component strategies but various prohibitory limitations have been reported in practice. This review seeks to (i) provide a brief overview of the current preventative and therapeutic approaches towards childhood obesity, (ii) discuss the complexity and limitations of research in the childhood obesity area, and (iii) suggest an Etiology-Based Personalized Intervention Strategy Targeting Childhood Obesity (EPISTCO). This purposeful approach includes prioritized nutritional, educational, behavioral, and physical activity intervention strategies directly based on the etiology of obesity and interpretation of individual characteristics. [ABSTRACT FROM AUTHOR]

Fast self-reported eating rate (SRER) has been associated with increased adiposity in children and adults. No studies have been conducted among high-school students, and SRER has not been validated vs. objective eating rate (OBER) in such populations. The objectives were to investigate (among high-school student populations) the association between OBER and BMI z-scores (BMIz), the validity of SRER vs. OBER, and potential differences in BMIz between SRER categories. Three studies were conducted. Study 1 included 116 Swedish students (mean ± SD age: 16.5 ± 0.8, 59% females) who were eating school lunch. Food intake and meal duration were objectively recorded, and OBER was calculated. Additionally, students provided SRER. Study 2 included students (n = 50, mean ± SD age: 16.7 ± 0.6, 58% females) from Study 1 who ate another objectively recorded school lunch. Study 3 included 1832 high-school students (mean ± SD age: 15.8 ± 0.9, 51% females) from Sweden (n = 748) and Greece (n = 1084) who provided SRER. In Study 1, students with BMIz ≥ 0 had faster OBER vs. students with BMIz < 0 (mean difference: +7.7 g/min or +27%, p = 0.012), while students with fast SRER had higher OBER vs. students with slow SRER (mean difference: +13.7 g/min or +56%, p = 0.001). However, there was "minimal" agreement between SRER and OBER categories (κ = 0.31, p < 0.001). In Study 2, OBER during lunch 1 had a "large" correlation with OBER during lunch 2 (r = 0.75, p < 0.001). In Study 3, fast SRER students had higher BMIz vs. slow SRER students (mean difference: 0.37, p < 0.001). Similar observations were found among both Swedish and Greek students. For the first time in high-school students, we confirm the association between fast eating and increased adiposity. Our validation analysis suggests that SRER could be used as a proxy for OBER in studies with large sample sizes on a group level. With smaller samples, OBER should be used instead. To assess eating rate on an individual level, OBER can be used while SRER should be avoided. [ABSTRACT FROM AUTHOR]

Primary aldosteronism (PA), a condition characterized by autonomous aldosterone hypersecretion, constitutes the most common cause of secondary hypertension. Over the last decade, major breakthroughs have been made in the field of genetics underpinning PA. The advent and wide application of Next Generation Sequencing (NGS) technology led to the identification of several somatic and germline mutations associated with sporadic and familial forms of PA. Somatic mutations in ion-channel genes that participate in aldosterone biosynthesis, including KCNJ5, CACNA1D, ATP1A1, and ATP2B3, have been implicated in the development of aldosterone-producing adenomas (APAs). On the other hand, germline variants in CLCN2, KCNJ5, CACNA1H, and CACNA1D genes have been implicated in the pathogenesis of the familial forms of PA, FH-II, FH-III, and F-IV, as well as PA associated with seizures and neurological abnormalities. However, recent studies have shown that the prevalence of PA is higher than previously thought, indicating the need for an improvement of our diagnostic tools. Further research is required to recognize mild forms of PA and to investigate the underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1), an incretin hormone, plays an important role in regulating glucose homeostasis. In this study, the applicability of circulating GLP-1 levels as an early indicator of metabolic syndrome (MetS) risk was examined. Women without diagnosed diseases were grouped according to their number of MetS risk factors (MetS RFs) (no RFs as Super-healthy, n = 61; one or two RFs as MetS risk carriers, n = 60; 3 ≤ RFs as MetS, n = 19). The circulating GLP-1 levels and homeostasis model assessment insulin resistance (HOMA-IR) scores were significantly higher in the MetS group than in the other two groups. The GLP-1 levels correlated positively with adiposity, HOMA-IR, blood pressure, and high sensitivity C-reactive protein (hs-CRP), but not with fasting glucose and lipid profiles, whose significances were maintained after adjustments for age, smoking and drinking habits, menopausal status, and total calorie intake. The GLP-1 levels also increased proportionally with the number of MetS RFs. In the MetS group, the GLP-1 levels were much higher in individuals with obesity (body mass index ≥ 25 kg/m2). In conclusion, the circulating GLP-1 level may be applicable as a potential early indicator of MetS risk in women without diagnosed diseases. Further study with a large population is needed to confirm the conclusion. [ABSTRACT FROM AUTHOR]

Obesity represents one of the most challenging public health problems of our century. It accounts for approximately 5% of deaths worldwide, mostly owing to cardiovascular disease and its associated complications. Cardiovascular noninvasive imaging may provide early accurate information about hypertrophy and ischemia/fibrosis in obese subjects. Echocardiography and nuclear cardiology have serious limitations in obese subjects owing to poor acoustic window and attenuation artifacts, respectively. Coronary computed tomography angiography can provide information about obstructive coronary disease; however, the use of radiation is a serious disadvantage. Finally, cardiac magnetic resonance (CMR) holds the promise of an "all in one" examination by combining evaluation of function, wall motion/thickness, stress rest/perfusion, replacement and diffuse fibrosis without radiation. Future studies are required to document the cost/benefit ratio of the CMR in the evaluation of cardiovascular risk in overweight/obese children and adolescents. [ABSTRACT FROM AUTHOR]

Obesity is often associated with cognitive and mood disorders. Recent evidence suggests that obesity may cause hypothalamic inflammation. Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and influence monoaminergic systems. Exercise, healthy diet, and glucagon-like peptide receptor agonists, which can reduce hypothalamic inflammation in obese models, could improve the deleterious effects on cognition and mood. [ABSTRACT FROM AUTHOR]

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70–80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork. Teams should ideally include adult and paediatric endocrinologists, oncologists, cardiologists, surgeons, geneticists, pathologists, radiologists, clinical psychologists and nuclear medicine physicians. Provision of an international Consensus Statement should improve care and outcomes for children and adolescents with these tumours. Phaeochromocytomas and paragangliomas (PPGL) are rare endocrine tumours that can affect paediatric patients as well as adults. In this first international Consensus Statement on PPGL in paediatric patients, the authors discuss the diagnosis, management and long-term surveillance of these tumours in children and adolescents. [ABSTRACT FROM AUTHOR]

Obesity in childhood and adolescence represents one of the most challenging public health problems of the 21st century owing to its epidemic proportions worldwide and the associated significant morbidity, mortality and public health costs. In Greece, the prevalence of overweight and obesity in childhood and adolescence exceeds 30–35%. To address the increasing prevalence of overweight and obesity in children and adolescents in our country, we developed the 'National e-Health Program for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence', which provides specific and detailed guidance to all primary health care physicians about the personalized management of children and adolescents with overweight or obesity. In the present study we evaluated 2400 children and adolescents [mean age ± SEM: 10.10 ± 0.09 years.; Males: 1088, Females: 1312; Obesity (n = 1370, 57.1%), Overweight (n = 674, 28.1%), normal BMI (n = 356, 14.8%)], who followed the personalized multi-disciplinary management plan specified by the 'National e-Health Program for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence', and were studied prospectively for 1 year. We demonstrated that at the end of the first year, the prevalence of obesity decreased by 32.1%, the prevalence of overweight decreased by 26.7%, and the cardiometabolic risk factors improved significantly. These findings indicate that our National e-Health Program is effective at reducing the prevalence of overweight and obesity in childhood and adolescence after one year of intervention in the largest sample size reported to date. [ABSTRACT FROM AUTHOR]

Obesity in childhood and adolescence represents a major health problem. Novel e-Health technologies have been developed in order to provide a comprehensive and personalized plan of action for the prevention and management of overweight and obesity in childhood and adolescence. We used information and communication technologies to develop a "National Registry for the Prevention and Management of Overweight and Obesity" in order to register online children and adolescents nationwide, and to guide pediatricians and general practitioners regarding the management of overweight or obese subjects. Furthermore, intelligent multi-level information systems and specialized artificial intelligence algorithms are being developed with a view to offering precision and personalized medical management to obese or overweight subjects. Moreover, the Big Data against Childhood Obesity platform records behavioral data objectively by using inertial sensors and Global Positioning System (GPS) and combines them with data of the environment, in order to assess the full contextual framework that is associated with increased body mass index (BMI). Finally, a computerized decision-support tool was developed to assist pediatric health care professionals in delivering personalized nutrition and lifestyle optimization advice to overweight or obese children and their families. These e-Health applications are expected to play an important role in the management of overweight and obesity in childhood and adolescence. [ABSTRACT FROM AUTHOR]

Introduction: Although there are some recommendations in the literature on the assessments that should be performed in children on recombinant human growth hormone (rhGH) therapy, the level of consensus on these measurements is not clear. The objective of the current study was to identify the minimum dataset (MDS) that could be measured in a routine clinical setting across the world, aiming to minimise burden on clinicians and improve quality of data collection. Methods: This study was undertaken by the growth hormone (GH) scientific study group in GloBE-Reg, a new project that has developed a common registry platform that can support long-term safety and effectiveness studies of drugs. Twelve clinical experts from 7 international endocrine organisations identified by the GloBE-Reg Steering Committee, 2 patient representatives, and representatives from 2 pharmaceutical companies with previous GH registry expertise collaborated to develop this recommendation. A comprehensive list of data fields routinely collected by each of the clinical and industry experts for children with growth hormone deficiency (GHD) was compiled. Each member was asked to determine the: (1) importance of the data field and (2) ease of data collection. Data fields that achieved 70% consensus in terms of importance qualified for the MDS, provided <50% deemed the item difficult to collect. Results: A total of 246 items were compiled and 27 were removed due to redundancies, with 219 items subjected to the grading system. Of the 219 items, 111 achieved at least 70% consensus as important data to collect when monitoring children with GHD on rhGH treatment. Sixty-nine of the 219 items were deemed easy to collect. Combining the criteria of importance and ease of data collection, 63 met the criteria for the MDS. Several anomalies to the MDS rule were identified and highlighted for discussion, including whether the patients were involved in current or previous clinical trials, need for HbA1c monitoring, other past medical history, and adherence, enabling formulation of the final MDS recommendation of 43 items; 20 to be completed once, 14 every 6 months, and 9 every 12 months. Conclusion: In summary, this exercise performed through the GloBE-Reg initiative provides a recommendation of the MDS requirement, collected through real-world data, for the monitoring of safety and effectiveness of rhGH in children with GHD, both for the current daily preparations and the newer long-acting GH. [ABSTRACT FROM AUTHOR]

Background: Childhood obesity represents a major health problem of our century. The benefits of natural products, such as honey, in the management of obesity have gained renewed interest. In this study, we investigated the effect of honey on glucose and insulin concentrations in obese prepubertal girls. Materials and Methods: Thirty healthy obese girls aged 10.55 (±SEM:0.34) years with a mean body mass index (BMI) above the 97th centile for age (28.58 ± 1.40 kg/m2, BMI z‐score 2.96) underwent a standard oral glucose tolerance test (OGTT) followed by an oral honey tolerance test (OHTT) 2 weeks later. Both solutions contained 75 g of glucose. Subsequently, subjects were randomized to receive either 15 g of honey or 15 g of marmalade daily, while both groups complied with dietetic instructions. Six months later all subjects were re‐evaluated with an OGTT and an OHTT. Results: At the end of the study, all subjects demonstrated a significant reduction in BMI (27.57 ± 1.40, z‐score: 2.54 vs 28.58 ± 1.40 kg/m2, z‐score: 2.96, P < 0.001), however, there were no significant differences in BMI and all parameters tested between the group that received honey and the control group. The areas under the concentration–time curve for glucose and insulin for the entire population were significantly lower following ingestion of honey than glucose solution (P < 0.001) both at the beginning and at the end of study. Conclusions: These findings indicate that honey does not have an effect on stimulated plasma glucose and serum insulin concentrations compared with the standard glucose solution in obese prepubertal girls. [ABSTRACT FROM AUTHOR]

We describe herein the European Reference Network on Rare Endocrine Conditions clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, paediatric endocrinology, and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series. The guideline includes a brief description of the genetics and molecular pathophysiology associated with each condition, the patients to be screened, and how to screen. Diagnostic and treatment approaches for patients with genetically determined diagnosis are presented. The recommendations apply to patients with genetically proven familial hyperaldosteronism and not to families with more than one case of primary aldosteronism without demonstration of a responsible pathogenic variant. [ABSTRACT FROM AUTHOR]

To present the initial assessment of psychosocial adaptation among Greek parents whose children were newly diagnosed with cancer amidst the turmoil of an ongoing financial crisis. This prospective observational study used a quantitative approach. Sixty-one parents of children with cancer treated at a large urban tertiary-care children's hospital were prospectively recruited to participate in our study during the first week of their child's diagnosis (2013–2016). The parents were asked to complete the psychosocial assessment tool (PAT 2.0), Zung Depression Scale, State-Trait Anxiety Inventory, Hospital Anxiety and Depression Scale, and World Health Organization Quality of Life–Bref Instrument; Moreover, three female healthcare providers (the physician oncologist, the head nurse and a senior nurse) completed the relevant PAT 2.0 -Staff Perceptions questionnaire the results of which were then compared to those of the child's parent. The majority of parents had PAT 2.0 scores indicative of increased psychosocial risk :54% were stratified into the "Targeted" (moderate risk) and 15% into the "Clinical" (highest risk) categories, whereas healthcare providers underestimated psychosocial risk in 57%−59% of the cases. The subscales that most contributed to the increased scores were Parental Stress Reaction, Family Structure and Resources, and Family Social Support. The PAT 2.0 had statistically significant correlations with most of the anxiety and depression scales, with Zung having the strongest correlation (r-value: +0.5, p-value <0.01). Our cohort presented more anxiety and depression compared to the general Greek population (14% for depression versus 2,9% for the general population and 46% for anxiety compared to 4,1%) in the years of financial recession in Greece. The parents of children newly diagnosed with cancer in Greece are at increased risk for developing anxiety and depression in the years of financial recession in Greece compared to general population. Parental stress reaction to diagnosis as well as lack of family resources and social support may contribute to this difference. Screening for psychosocial risk factors is essential for the early identification of these families and for the optimal utilization of the limited available resources in times of economic hardship. [ABSTRACT FROM AUTHOR]

Brain-Derived Neurotrophic Factor (BDNF) has been linked to various conditions of the cardiovascular and nervous systems. Scarce data exist about the concentrations of BDNF in children and adolescents in relation with obesity and metabolic syndrome (MetS). The aim of this study was to examine the serum BDNF concentrations in adolescents with metabolic syndrome and according to their body mass index (BMI) status. This was a case-control study, assessing BDNF concentrations between adolescents with MetS (with obesity vs. normal-BMI), in relation to sex, anthropometric, metabolic and endocrine parameters. Participants included male and female adolescents, whose anthropometric and metabolic panel, as well as serum BDNF concentrations were measured. A total of 59 adolescents (obesity: 29; normal-BMI: 30) were included in the study. Increased serum BDNF concentrations were observed in MetS adolescents with obesity when compared with normal-BMI adolescents (p < 0.001). Males exhibited higher concentrations of BDNF than females (p = 0.045). The sample was further divided into four categories by sex and BMI status, with normal-BMI females exhibiting significantly lower BDNF concentrations than females and males with obesity(p = 0.005). In the entire study sample, serum BDNF concentrations correlated positively with BMI z-scores, however, this statistical significance was preserved only in the females of the sample. No statistical difference was observed between males of different BMI z-scores categories. Conclusion: Obesity appeared as a major factor for increased serum BDNF concentrations in adolescents with MetS (vs. normal-BMI), with a higher impact on BDNF concentrations in females than males. What is Known: • The brain-derived neurotrophic factor (BDNF) is involved in metabolic syndrome in adults but data in adolescents are scarce. What is New: • Obesity (vs. normal BMI) was a major factor for increased serum BDNF in adolescents with metabolic syndrome. • Obesity had a higher impact on BDNF concentrations in females than males with metabolic syndrome. [ABSTRACT FROM AUTHOR]

The relation among the various causal factors of obesity is not well understood, and there remains a lack of viable data to advance integrated, systems models of its etiology. The collection of big data has begun to allow the exploration of causal associations between behavior, built environment, and obesity-relevant health outcomes. Here, the traditional epidemiologic and emerging big data approaches used in obesity research are compared, describing the research questions, needs, and outcomes of 3 broad research domains: eating behavior, social food environments, and the built environment. Taking tangible steps at the intersection of these domains, the recent European Union project "BigO: Big data against childhood obesity" used a mobile health tool to link objective measurements of health, physical activity, and the built environment. BigO provided learning on the limitations of big data, such as privacy concerns, study sampling, and the balancing of epidemiologic domain expertise with the required technical expertise. Adopting big data approaches will facilitate the exploitation of data concerning obesity-relevant behaviors of a greater variety, which are also processed at speed, facilitated by mobile-based data collection and monitoring systems, citizen science, and artificial intelligence. These approaches will allow the field to expand from causal inference to more complex, systems-level predictive models, stimulating ambitious and effective policy interventions. [ABSTRACT FROM AUTHOR]

Background: Obesity in childhood and adolescence represents a major health problem of our century. In Greece, 30–35% of children and adolescents are overweight or obese. Objective and Hypotheses: To investigate the effectiveness of a comprehensive multidisciplinary personalized management plan at reducing the prevalence of overweight and obesity in childhood and adolescence. Patients and Methods: One thousand (n = 1,000) children and adolescents aged 2–18 years (mean age ± SD: 10.09 ± 2.86 years; 520 females, 480 males) were studied prospectively. Subjects were classified as obese (n = 579, 57.9%), overweight (n = 295, 29.5%) or having a normal body mass index (BMI) (n = 126, 12.6%) according to the International Obesity Task Force cutoff points. All subjects were evaluated by a multidisciplinary team at frequent intervals, received personalized advice on diet and exercise and were studied prospectively for 1 year. Detailed clinical evaluation and laboratory investigations were performed at the beginning and at the end of the study. Results: At initial evaluation, 57.9% of subjects were obese, 29.5% overweight and 12.6% of normal BMI. Indices of cardiometabolic disease were higher in obese than in overweight and normal-BMI subjects. Following 1 year of multidisciplinary management interventions, the prevalence of obesity decreased by 16.8%, the prevalence of normal BMI increased by 8.2%, and all cardiometabolic indices improved significantly. Conclusions: A personalized multidisciplinary management plan is effective at reducing the prevalence of obesity in childhood and adolescence. [ABSTRACT FROM AUTHOR]

Abstract: Background: Obesity in childhood and adolescence represents a major health problem in our century. In Greece, more than 30%‐35% of children and adolescents are either overweight or obese. Materials and methods: Using information and communication technologies, we developed a “National Registry for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence” for guidance and training of Pediatricians and General Practitioners. The application supports interoperability with other national infrastructures and multi‐layered security spanning preventive, detective and administrative controls. The Patient Summary Dataset includes information on medical history, family history, medications, immunizations, clinical examination and laboratory findings and appointment booking service. Results: The application was launched in September 2015 and is accessible by: http://app.childhood-obesity.gr/. Based on the data that the doctor registers, the system calculates a personalized therapeutic algorithm that provides information on diet, physical exercise and sleep, as well as guidance on laboratory investigations and referral to specialized centres. A pilot study performed in 1270 children and adolescents indicated that using this system resulted in a reduction in obesity rates by 30% and overweight rates by 35% within 1 year. Conclusions: This National e‐Health System appears to be effective in the management of overweight and obesity in childhood and adolescence. [ABSTRACT FROM AUTHOR]

Background The aim of this meta-analysis was to examine differences and predictors of serum 25-hydroxyvitamin D concentrations in women with polycystic ovary syndrome ( PCOS) compared with non- PCOS controls matched for body mass index. Materials and methods Three databases were searched (2003-2015) to retrieve studies that evaluated serum 25-hydroxyvitamin D in PCOS women and controls. Meta-regression analysis was performed with anthropometric and metabolic/endocrine parameters as covariates. Results Fourteen studies that included 2262 women (1150 PCOS patients/1162 controls) were eligible. Serum 25-hydroxyvitamin D, follicle-stimulating hormone and sex hormone-binding globulin were significantly lower in patients with PCOS than controls. Homoeostatic model assessment-insulin resistance index, serum insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, luteinising hormone and testosterone were significantly higher in patients with PCOS compared to controls. Meta-regression analysis demonstrated significant effects of waist-to-hip ratio and glucose in PCOS women (β = −1·60, 95% CI: −2·30 to −0·90, P = 0·003; β = 0·20, 95% CI: 0·80-0·32, P = 0·004, respectively) and controls (β = −2·36, 95% CI: −3·38 to −1·33, P = 0·003; β = 0·11, 95% CI: 0·00-0·21, P = 0·05, respectively) and of total calcium and luteinising hormone in PCOS cases (β = 2·43, 95% CI: 1·67-3·19, P = 0·005; β = −0·37, 95% CI: −0·68 to −0·06, P = 0·03, respectively). Conclusions Serum 25-hydroxyvitamin D may be predicted positively by serum calcium and negatively by luteinising hormone in women with PCOS, and negatively by waist-to-hip ratio and positively by fasting glucose in both PCOS and non- PCOS women, independently of the presence of obesity. [ABSTRACT FROM AUTHOR]

Background Stress is defined as a state of threatened or perceived as threatened homeostasis. A broad spectrum of extrinsic or intrinsic, real or perceived stressful stimuli, called 'stressors', activates a highly conserved system, the 'stress system', which adjusts homeostasis through central and peripheral neuroendocrine responses. Inadequate, excessive or prolonged adaptive responses to stress may underlie the pathogenesis of several disease states prevalent in modern societies. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors and the timing of the stressful event(s), given that prenatal life, infancy, childhood and adolescence are critical periods characterized by increased vulnerability to stressors. Materials and methods We conducted a systematic review of original articles and reviews published in MEDLINE from 1975 through June 2016. The search terms were 'childhood stress', 'pediatric stress', 'stress and disorders' and 'stress management'. Results In this review, we discuss the historical and neuroendocrine aspects of stress, and we present representative examples of paediatric stress system disorders, such as early-life adversity, obesity and bullying. We also discuss the adverse impact of a socio-economic crisis on childhood health. The tremendous progress of epigenetics has enabled us to have a deeper understanding of the molecular mechanisms underlying paediatric stress-related disorders. Conclusions The need for early successful stress management techniques to decrease the incidence of paediatric stress-related diseases, as well as to prevent the development of several pathologic conditions in adolescence and adulthood, is imperative. [ABSTRACT FROM AUTHOR]

Background: The purposes of this study are to examine if the human glucocorticoid receptor (hGR) isoform-α mRNA and hGR protein expressions are deficient in the acute phase of sepsis (S) compared to systemic inflammatory response syndrome (SIRS) and healthy subjects (H) and to evaluate if the hGRα and hGR alterations are associated with cortisol changes and if they are related to (1) extracellular and intracellular heat shock proteins (HSP) 72 and 90α; (2) ACTH, prolactin, and interleukins (ILs); and (3) outcome. Methods: Patients consecutively admitted to a university hospital intensive care unit (ICU) with S ( n = 48) or SIRS ( n = 40) were enrolled in the study. Thirty-five H were also included. Total mRNA was isolated from peripheral blood samples and cDNA was prepared. RT-PCR was performed. Intracellular hGR and HSP expression in monocytes and/or neutrophils was evaluated using four-colour flow cytometry. Serum prolactin, ACTH, and cortisol concentrations were also measured. ELISA was used to evaluate serum ILs and extracellular (e) HSPs (eHSP72, eHSP90α). Results: hGR protein was higher in S compared to H and SIRS; hGRα mRNA was higher in S compared to H ( p < 0.05). In sepsis, hGR protein and eHSP72 were higher among non-survivors compared to survivors ( p < 0.05). The hGR MFI and hGRα mRNA fold changes were significantly related to each other ( r = 0.64, p < 0.001). Monocyte hGR protein expression was positively correlated with extracellular and intracellular HSPs, cortisol, and ILs and negatively to organ dysfunction ( p < 0.05). HSPs, hGR, and cortisol were able to discriminate sepsis from SIRS (AUROC > 0.85, p < 0.05). In sepsis, monocyte-hGR protein and eHSP72 were strong predictors of mortality (AUROC > 0.95, p < 0.04). Conclusions: Acute-phase sepsis is associated with increased hGR expression and cortisol concentrations, possibly implying no need for exogenous steroids. At this stage, hGR is able to predict sepsis and outcome and is related to stress-activated bio-molecules and organ dysfunction. [ABSTRACT FROM AUTHOR]

Background: Chrousos syndrome is a rare pathologic condition characterized by generalized, partial resistance of target tissues to glucocorticoids and caused by inactivating mutations of the human glucocorticoid receptor (hGR) gene. A novel case of Chrousos syndrome has been reported in a patient with adrenal incidentaloma, who harboured a heterozygous point mutation in the hGR gene, which resulted in threonine (T) to isoleucine (I) substitution at amino acid position 556 in the ligand-binding domain of the receptor. Objective: To delineate the molecular mechanisms through which the mutant receptor hGRαT556I causes Chrousos syndrome. Design and Results: Compared with the wild-type receptor, the mutant receptor hGRαT556I demonstrated 50% reduction in its ability to transactivate glucocorticoid-responsive genes and in the affinity for the ligand, 30% increase in the ability to transrepress the nuclear factor-B-target genes and a 3,4-fold delay in the cytoplasmic-to-nuclear translocation. The mutant receptor hGRαT556I did not exert a dominant negative effect upon the hGRα-mediated transcriptional activity; it preserved its ability to bind to DNA and interacted with the glucocorticoid receptor-interacting protein 1 coactivator mostly through its activation function-1 domain. Structural biology studies revealed that the T556I mutation caused disruption of the hydrogen bond formed by the T556 with the =O group of P637 backbone, which resulted in a significant relocation of the P637-bearing loop. This conformational alteration affected the local 3D arrangement of the receptor and hence the electrostatic surface of the region. Conclusions: The hGRαT556I causes Chrousos syndrome by impairing multiple steps of the glucocorticoid signal transduction pathway. [ABSTRACT FROM AUTHOR]

Background Transient generalized glucocorticoid hypersensitivity is a rare disorder characterized by increased tissue sensitivity to glucocorticoids and compensatory hypo-activation of the hypothalamic-pituitary-adrenal axis. The condition itself and the underlying molecular mechanisms have not been elucidated. Objective To present the clinical manifestations, endocrinologic evaluation and transcriptomic profile in a patient with transient generalized glucocorticoid hypersensitivity. Design and Results A 9-year-old girl presented with an 8-month history of clinical manifestations suggestive of Cushing syndrome. Endocrinologic evaluation revealed undetectable 08:00 h ACTH (<1 pg/mL) and cortisol (0·025 μg/dL) concentrations, which remained decreased throughout the 24-h period and did not respond to stimulation with ovine CRH. The disease gradually resolved spontaneously over the ensuing 3 months. Sequencing of the human glucocorticoid receptor gene revealed no mutations or polymorphisms. Western blot analysis in peripheral blood mononuclear cells revealed equal protein expression of hGRa of the patient in the disease and postresolution phases compared with a control subject. Transcriptomic analysis in peripheral blood mononuclear cells in the disease and postresolution phases identified 903 differentially expressed genes. Of these, 106 genes were up-regulated and 797 were down-regulated in the disease compared with the resolution phase. Bioinformatics analysis on the differentially expressed gene networks revealed Nuclear Factor-jB as the predominant transcription factor influencing the expression of the majority of differentially expressed genes. Conclusions Our findings indicate that a transient postreceptor defect, or a virus- or bacterium-encoded molecule, may have enhanced glucocorticoid signal transduction, leading to transient generalized glucocorticoid hypersensitivity and hypo-activation of the HPA axis. [ABSTRACT FROM AUTHOR]

Background Natural mutations in the human glucocorticoid receptor ( hGR, NR3C1) gene cause Chrousos syndrome, a rare condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. Objective To present a new case of Chrousos syndrome caused by a novel mutation in the hGR gene, and to elucidate the molecular mechanisms through which the natural mutant receptor affects glucocorticoid signal transduction. Design and Results The index case presented with hirsutism, acne, alopecia, anxiety, fatigue and irregular menstrual cycles, but no clinical manifestations suggestive of Cushing's syndrome. Endocrinologic evaluation revealed elevated 08:00 h plasma adrenocorticotropic hormone, serum cortisol and androstenedione concentrations and increased urinary free cortisol excretion. The patient harbored a novel A > G transition at nucleotide position 2177, which resulted in histidine (H) to arginine (R) substitution at amino acid position 726 of the receptor (c.2177A > G, p.H726R). Compared with the wild-type receptor, the mutant receptor hGRαH726R demonstrated decreased ability to transactivate glucocorticoid-responsive genes and to transrepress the nuclear factor-κB signalling pathway, displayed 55% lower affinity for the ligand and a four-fold delay in nuclear translocation, and interacted with the glucocorticoid receptor-interacting protein 1 coactivator mostly through its activation function-1 domain. Finally, a 3-dimensional molecular modelling study of the H726R mutation revealed a significant structural shift in the rigidity of helix 10 of the receptor, which resulted in reduced flexibility and decreased affinity of the mutant receptor for binding to the ligand. Conclusions The natural mutant receptor hGRαH726R impairs multiple steps of glucocorticoid signal transduction, thereby decreasing tissue sensitivity to glucocorticoids. [ABSTRACT FROM AUTHOR]

Background Hydrocortisone therapy is based on a dosing regimen derived from estimates of cortisol secretion, but little is known of how the dose should be distributed throughout the 24 h. We have used deconvolution analysis of 24-h serum cortisol profiles to determine 24-h cortisol secretion and distribution to inform hydrocortisone dosing schedules in young children and older adults. Methods Twenty four hour serum cortisol profiles from 80 adults (41 men, aged 60-74 years) and 29 children (24 boys, aged 5-9 years) were subject to deconvolution analysis using an 80-min half-life to ascertain total cortisol secretion and distribution throughout the 24-h period. Results Mean daily cortisol secretion was similar between adults (6·3 mg/m2 body surface area/day, range 5·1-9·3) and children (8·0 mg/m2 body surface area/day, range 5·3-12·0). Peak serum cortisol concentration was higher in children compared with adults, whereas nadir serum cortisol concentrations were similar. Timing of the peak serum cortisol concentration was similar (07·05-07·25), whereas that of the nadir concentration occurred later in adults (midnight) compared with children (22·48) ( P = 0·003). Children had the highest percentage of cortisol secretion between 06·00 and 12·00 (38·4%), whereas in adults this took place between midnight and 06·00 (45·2%). Conclusions These observations suggest that the daily hydrocortisone replacement dose should be equivalent on average to 6·3 mg/m2 body surface area/day in adults and 8·0 mg/m2 body surface area/day in children. Differences in distribution of the total daily dose between older adults and young children need to be taken into account when using a three or four times per day dosing regimen. [ABSTRACT FROM AUTHOR]

Abstract: The characterization of the subfamily of steroid hormone receptors has enhanced our understanding of how a set of hormonally derived lipophilic ligands controls cellular and molecular functions to influence development and help achieve homeostasis. The glucocorticoid receptor (GR), the first member of this subfamily, is a ubiquitously expressed intracellular protein, which functions as a ligand-dependent transcription factor that regulates the expression of glucocorticoid-responsive genes. The effector domains of the GR mediate transcriptional activation by recruiting coregulatory multi-subunit complexes that remodel chromatin, target initiation sites, and stabilize the RNA-polymerase II machinery for repeated rounds of transcription of target genes. This review summarizes the basic aspects of the structure and actions of the human (h) GR, and the molecular basis of its biologic functions. [Copyright &y& Elsevier]

Background: Obesity in childhood and adolescence represents a major public health problem, mostly attributed to dietary and physical activity factors. We aimed to determine the dietary and physical activity habits of participants before and after the implementation of a personalized, multidisciplinary, lifestyle intervention program for the management of obesity in the context of the Horizon Research Project 'BigO: Big Data against Childhood Obesity'., Methods: Three hundred and eighty-six (n = 386) children and adolescents (mean age ± SD: 12.495 ± 1.988 years, 199 males and 187 females) participated in the study prospectively. Based on body mass index (BMI), subjects were classified as having obesity (n = 293, 75.9%) and overweight (n = 93, 24.1%) according to the International Obesity Task Force (IOTF) cut-off points. We implemented a personalized, multidisciplinary, lifestyle intervention program providing guidance on diet, sleep, and exercise, and utilized the BigO technology platform to objectively record data collected via a Smartphone and Smartwatch for each patient., Results: Following the intervention, a statistically significant decrease was noted in the consumption of cheese, cereal with added sugar, savory snacks, pasta, and fried potatoes across both BMI categories. Also, there was an increase in daily water intake between meals among all participants ( p = 0.001) and a reduction in the consumption of evening snack or dinner while watching television ( p < 0.05). Boys showed a decrease in the consumption of savory snacks, fried potato products, and pasta ( p < 0.05), an increase in the consumption of sugar-free breakfast cereal ( p < 0.05), and drank more water between meals daily ( p < 0.001)., Conclusions: Our findings suggest that a personalized, multidisciplinary, lifestyle intervention improves the dietary habits of children and adolescents.

21-hydroxylase deficiency (21-OHD) represents the most common form of congenital adrenal hyperplasia (CAH) due to CYP21A2 gene pathogenic variants. Τhe aim of this study was the identification of CYP21A2 variants in 500 subjects of Greek origin with a suspicion of 21-OHD and, by using the existing hormonal assessment and genotypes of the 500 subjects tested, to identify a biomarker that could differentiate between the heterozygotes and the cases with no pathogenic variants identified. Five hundred subjects with clinical suspicion of 21-OHD underwent CYP21A2 gene sequencing and Multiplex Ligation Dependent Probe Amplification (MLPA). Genetic diagnosis was achieved in 27.4% of the subjects tested, most of which presented with the non-classic form (NC) of 21-OHD. Heterozygotes accounted for 42.6% of cases, whereas no pathogenic variants were identified in 27% of cases. De novo aberrations, duplications, and five novel variants were also identified. Statistical analysis revealed that the difference between the basal and 60' post-ACTH stimulation 17-hydroxyprogesterone concentrations (Δ17-OHP 60-0 ) could be a potential biomarker ( p < 0.05) distinguishing the heterozygotes from the cases with no pathogenic variants identified, although no clear cut-off value could be set. Further analysis revealed overlapping clinical manifestations among all the subjects tested. The presented phenotypic traits of the subjects tested and the inability to identify a discriminative biochemical marker highlight the importance of comprehensive CYP21A2 genotyping to ascertain the correct genetic diagnosis and proper genetic counselling.

Background/Objective: Secreted frizzled-related protein 5 (Sfrp5) is an anti-inflammatory adipokine that has been implicated in the pathophysiology of obesity and its metabolic complications. Despite the fact that numerous studies have been carried out in adults, limited data on Sfrp5 exist for youth, especially in relation to overweight and obesity. Methods: In our study, we assessed the concentrations of Sfrp5, total oxidative (TOS) and antioxidative (TAS) status, high-sensitivity C -reactive protein (hs-CRP), and several cytokines (IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-12, TNF-α) in 120 children and adolescents (mean age ± SE: 11.48 ± 0.25 years; 48 prepubertal, 72 pubertal; 74 males and 46 females) before and 1 year after the implementation of a personalized, structured, lifestyle intervention program of healthy diet, sleep, and physical exercise. Results: Based on the body mass index (BMI), participants were categorized as having morbid obesity ( n = 63, 52.5%), obesity ( n = 21, 17.5%), overweight ( n = 22, 18.33%), or normal BMIs ( n = 14, 11.67%), based on the International Obesity Task Force (IOTF) cut-off points. Following the 1-year lifestyle intervention program, a significant improvement in anthropometric measurements (BMI, BMI-z score, diastolic blood pressure, WHR, and WHtR), body-composition parameters, hepatic enzymes, lipid profile, inflammation markers, and the insulin-sensitivity profile (HbA1C, HOMA index) was observed in all subjects. Sfrp5 decreased in subjects with obesity ( p < 0.01); however, it increased significantly ( p < 0.05) in patients with morbid obesity. Linear regression analysis indicates that TNF-α and systolic blood pressure were the best positive predictors and hs-CRP was the best negative predictor for Sfpr5 concentration at initial assessment and glucose concentration for ΔSfrp5, while TNF-α and TAS were the best positive predictors for Sfpr5 concentration at annual assessment. Conclusions: These results indicate that Sfrp5 is associated with severe obesity and is increased following weight loss in children and adolescents with morbid obesity. It is also related to metabolic homeostasis, as well as inflammation and oxidative status.