BACKGROUND: Thymic neuroendocrine tumor as a cause of Cushing syndrome is extremely rare in children. CASE PRESENTATION: We report a case of a 10-year-old girl who presented with typical symptoms and signs of hypercortisolemia, including bone fractures, growth retardation, and kidney stones. The patient was managed with oral ketoconazole, during which she experienced adrenal insufficiency, possibly due to either cyclic adrenocorticotropic hormone (ACTH) secretion or concurrent COVID-19 infection. The patient underwent a diagnostic work-up which indicated the possibility of an ACTH-secreting pituitary neuroendocrine tumor. However, after a transsphenoidal surgery, the diagnosis was not confirmed on histopathological examination. Subsequent bilateral inferior petrosal sinus sampling showed strong indications of the presence of ectopic ACTH syndrome. Detailed rereading of functional imaging studies, including 18F-FDG PET/MRI and 68Ga DOTATOC PET/CT, ultimately identified a small lesion in the thymus. The patient underwent videothoracoscopic thymectomy that confirmed a neuroendocrine tumor with ACTH positivity on histopathological examination. CONCLUSION: This case presents some unique challenges related to the diagnosis, management, and treatment of thymic neuroendocrine tumor in a child. We can conclude that ketoconazole treatment was effective in managing hypercortisolemia in our patient. Further, a combination of functional imaging studies can be a useful tool in locating the source of ectopic ACTH secretion. Lastly, in cases of discrepancy in the results of stimulation tests, bilateral inferior petrosal sinus sampling is highly recommended to differentiate between Cushing disease and ectopic ACTH syndrome.

• Klíčová slova
• 18F-FDG PET/MRI, 68Ga-DOTATOC PET/CT, Ectopic Cushing syndrome, Ketoconazole, Thymic neuroendocrine tumor,
• MeSH
• Cushingův syndrom etiologie   diagnóza   chirurgie   MeSH
• dítě MeSH
• ektopický ACTH syndrom * diagnóza   chirurgie   MeSH
• ketokonazol terapeutické užití   MeSH
• lidé MeSH
• nádory brzlíku * komplikace   diagnóza   chirurgie   patologie   MeSH
• neuroendokrinní nádory * komplikace   diagnóza   chirurgie   patologie   MeSH
• thymektomie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• ketokonazol MeSH

OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (CUL7). Hypogonadism and hypospadias have been described in only a few males. We report a patient with CUL7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome.

• Klíčová slova
• 3-M syndrome, CUL7 gene pathogenic variant, hypergonadotropic hypogonadism, recombinant human growth hormone, short stature,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The rising prevalence of obesity in children calls for new strategies for the provision of effective care by a multidisciplinary team. Telemedicine has overall proven to be an effective tool for promoting a healthy lifestyle. The main objective of the current paper is to present the protocol of our ongoing CardioMetabolic Prevention (CAMP) study and compare its design with published studies on telemedicine in paediatric obesity. Additionally, we analysed the preliminary anthropometric and laboratory data to test the efficacy of our 12-week intensive program that combines in-person and telemedicine support. The program demonstrated a positive impact on body mass index (BMI) and its z-scores in 21 adolescents, and BMI in 18 participating parents. However, we found no effect on body composition, waist circumference, cardiometabolic parameters, or fitness evaluated via a 6-min walk test in adolescents. In conclusion, the combination of in-person and telemedicine intensive support over 35 h delivered by a multidisciplinary team can be beneficial not only for adolescents with obesity but also for their parents. The ongoing CAMP study serves as a platform for precision medicine in future decisions regarding anti-obesity medication in adolescents with obesity.

• Klíčová slova
• adolescents, cardiometabolic prevention, healthy lifestyle support, mental health, obesity, parental involvement, telemedicine, weight reduction,
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND AIMS: A subset of obese individuals lacks cardiometabolic impairment. We aimed to analyze hormonal profiles of insulin-sensitive obese (ISO) and insulin-resistant obese (IRO) adolescents and determine hormonal predictors of homeostasis model of insulin resistance (HOMA-IR). MATERIALS AND METHODS: A threshold of 3.16 of HOMA-IR was used to classify ISO (<3.16) IRO (≥3.16). In 702 individuals aged 13-18years (55.8% girls) anthropometric and laboratory [blood glucose, insulin, thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), sex hormone-binding globulin (SHBG), steroid hormones, luteinizing hormone, follicle stimulating hormone, prolactin, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like-peptide 1glucagon, leptin, resistin, visfatin, leptin, adiponectin and adipsin] assessments were performed. Orthogonal projections to latent structures and Mann-Whitney tests with Bonferroni correction were applied for statistical analysis. RESULTS: 52.6% girls and 42.9% boys were insulin sensitive. In the predictive model of HOMA-IR thyroid function tests, adiponectin, ghrelin and leptin concentrations played an important role in both genders. Prolactin, testosterone and glucagon contributed to the model only in boys, while progesterone and dehydroepiandrosterone sulfate levels only in girls. After Bonferroni correction levels of leptin, adiponectin, leptin/adiponectin ratio, SHBG and fT4/TSH ratio in both genders, testosterone and glucagon levels in boys and levels of TSH and fT3 in girls were related to insulin sensitivity. CONCLUSION: Metabolic health defined by HOMA-IR is partly predicted by various hormones. Some of them are gender specific. Free T4/TSH and leptin/adiponectin ratios are related to insulin sensitivity in both genders.

• Klíčová slova
• Homeostasis model of insulin resistance, Hormones, Insulin-resistant/sensitive obese, Metabolically healthy obesity, Predictors of insulin sensitivity,
• MeSH
• biologické modely MeSH
• homeostáza MeSH
• hormony krev   MeSH
• index tělesné hmotnosti MeSH
• inzulinová rezistence * MeSH
• lidé MeSH
• mladiství MeSH
• obezita patofyziologie   MeSH
• pohlavní dimorfismus MeSH
• prediktivní hodnota testů MeSH
• tělesná hmotnost MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hormony MeSH

CONTEXT: Metabolically healthy obesity (MHO) is found in a subset of obese individuals. OBJECTIVE: This study sought to examine possible determinants of MHO related to the length of exposure to obesity, lifestyle factors, and dietary intake in adolescent boys. DESIGN: This was a cross-sectional Childhood Obesity Prevalence And Treatment study. Participants and Main Measures: Of 313 boys age 13.0-17.9 years with a body mass index (BMI) ≥ 97th percentile for age, two study cohorts were established based on two definitions of metabolically unhealthy obesity (MUO). Cohort 1 included 18 boys with at least three risk factors (hypertension, dyslipidemia, dysglycemia) who were matched for age, weight, height, and BMI with 18 boys with MHO. Cohort 2 included 35 boys with at least two risk factors who were compared with 31 boys with MHO. MHO was defined by the absence of cardiometabolic risk factors (excluding waist). Data on lifestyle factors and BMI growth trajectories were compared (MHO vs MUO). RESULTS: Boys with MUO (Cohort 1) presented with an earlier onset (4.3 vs 9.1 y; P = .005) and a longer duration of obesity (11.2 vs 6.4 y; P = .003) compared with those with MHO in both group comparisons using different MUO definitions. We found an overall trend toward higher BMI z scores (significant from 3-7 y; P < .001) in metabolically unhealthy compared with their healthy counterparts (Cohort 1). Boys with MHO had higher carbohydrate intake (P < .001). No additional determinants of MHO were observed. CONCLUSIONS: Increased cardiometabolic risk in boys is related to an earlier onset and a longer duration of obesity.

• MeSH
• časové faktory MeSH
• kardiovaskulární nemoci epidemiologie   metabolismus   MeSH
• lidé MeSH
• metabolické nemoci epidemiologie   metabolismus   MeSH
• metabolicky zdravá obezita epidemiologie   metabolismus   MeSH
• mladiství MeSH
• obezita dětí a dospívajících epidemiologie   metabolismus   MeSH
• pilotní projekty MeSH
• prevalence MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• věk při počátku nemoci MeSH
• životní styl MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Specific targets for most obesity candidate genes discovered by genomewide association studies remain unknown. Such genes are often highly expressed in the hypothalamus, indicating their role in energy homeostasis. We aimed to evaluate the associations of selected gene variants with adiposity and dietary traits. Anthropometric parameters, fat mass, dietary intake (total energy, fat, protein, carbohydrate, fiber, and calcium) and 10 gene variants (in/near TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R and FTO) were analyzed in 1953 Czech individuals aged 10.0 to 18.0 years (1035 nonoverweight and 918 overweight: body mass index [BMI] ≥90th percentile). Obesity risk alleles of TMEM18 rs7561317, SEC16B rs10913469, and FTO rs9939609 were related to increased body weight and BMI (P < .005). The FTO variant also showed a significant positive association with waist circumference and fat mass (P < .001). Overweight adolescents had a lower total energy intake (P < .001) but a higher percentage of fat (P = .009) and protein intake (P < .001) than the nonoverweight subjects. There was also a lower calcium intake in the overweight group (P < .001). An association with at least one component of dietary intake was found in 3 of 10 studied gene variants. The MC4R rs17782313 was associated negatively with protein (P = .012) and positively associated with fiber (P = .032) intakes. The obesity risk alleles of BDNF rs925946 and FTO rs9939609 were related to a lower calcium intake (P = .001 and .037). The effects of FTO and MC4R variants, however, disappeared after corrections for multiple testing. Our results suggest that the common BDNF variant may influence dietary calcium intake independent of BMI.

• Klíčová slova
• Adolescence, BDNF, Dietary intake, FTO, Obesity, Single nucleotide polymorphism,
• MeSH
• alely MeSH
• dítě MeSH
• energetický příjem * MeSH
• genotyp MeSH
• index tělesné hmotnosti * MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• mladiství MeSH
• mozkový neurotrofický faktor genetika   MeSH
• nadváha MeSH
• obezita etiologie   genetika   MeSH
• receptor melanokortinový typ 4 genetika   MeSH
• stravovací zvyklosti * MeSH
• tělesná hmotnost MeSH
• vápník dietní aplikace a dávkování   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• BDNF protein, human MeSH Prohlížeč
• MC4R protein, human MeSH Prohlížeč
• mozkový neurotrofický faktor MeSH
• receptor melanokortinový typ 4 MeSH
• vápník dietní MeSH

Common obesity is a result of interaction between genes and environmental/lifestyle factors, with heritability estimates 40-70%. Not only the susceptibility to obesity but also the success of weight management depends on the genetic background of each individual. This paper summarizes the up-to-date knowledge on genetic causes of common obesities. Introduction of genome-wide association studies (GWAS) led to an identification of a total of 32 variants associated with obesity/BMI and 14 with body fat distribution. Further, a great progress in revealing the mechanisms regulating the energy balance was also noted. However, the proportion of explained variance for BMI is still low, suggesting other mechanisms such as gene-gene and gene-environment interactions, rare gene variants, copy number variants polymorphisms, or epigenetic modifications and microRNAs regulating gene transcription. In summary, we present results of our studies on obesity risk variants in Czech adults, children and adolescents including those evaluating the influence of selected gene variants on the outcomes of weight management.

• MeSH
• celogenomová asociační studie * MeSH
• distribuce tělesného tuku MeSH
• dítě MeSH
• dospělí MeSH
• energetický metabolismus genetika   MeSH
• genetická epistáze genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• index tělesné hmotnosti MeSH
• interakce genů a prostředí MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• mladiství MeSH
• nemoci u dvojčat genetika   MeSH
• obezita genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• mikro RNA MeSH

Obesity and its comorbidities represent one of the major health problems worldwide. A positive energy balance due to inappropriate life-style changes plays a key role in the current obesity epidemic. The influence of genetic factors is also significant - several studies concluded that genes contribute to the development of obesity by 40-70%. Genetic variability predisposes an individual to tendency or resistance to increase body weight in obesogenic environment. Polygenic type of inheritance is responsible in most of obese individuals. However, an intensive research of the past 20 years has led to an identification of several genes causing monogenic forms of obesity. To date, several monogenic genes (leptin, leptin receptor, prohormon convertase 1, proopiomelanocortin, melanocortin 4 receptor, single-minded homolog 1, brain-derived neurotrophic factor, neurotrophic tyrosine kinase receptor type 2) that are either involved in the neuronal differentiation of the paraventricular nucleus or in the leptin-melanocortin pathway are known to cause obesity. Mutation carriers apart from severe early onset obesity manifest with additional phenotypic characteristics as adrenal insufficiency, impaired immunity and impaired fertility. This review provides an overview of molecular-genetic and clinical research in the field of monogenic obesities including therapeutical approaches.

• MeSH
• detekce genetických nosičů MeSH
• energetický metabolismus genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• genetický výzkum MeSH
• interakce genů a prostředí * MeSH
• lidé MeSH
• mutační analýza DNA MeSH
• obezita genetika   MeSH
• tělesná hmotnost genetika   MeSH
• životní styl MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Adolescence, due to transient pubertal insulin resistance (IR), is associated with a higher risk for disturbances of glucose metabolism. The aim of our study was 1) to investigate the prevalence of disturbances of glucose metabolism, 2) to define gender specific homeostasis model assessment of insulin resistance (HOMA-IR) thresholds associated with increased cardiometabolic risks and 3) to provide predictors of HOMA-IR. METHODS: The studied cohort consisted of Czech adolescents aged 13.0-17.9 years: 1,518 individuals of general population and three studied groups according weight category (615 normal weight, 230 overweight and 683 obese). The prevalence of IR, impaired fasting glucose (IFG) and type 2 diabetes was assessed. Risky HOMA-IR thresholds based on components of metabolic syndrome were investigated. HOMA-IR prediction was calculated taking into account age, blood pressure, multiple anthropometric, biochemical and hormonal parameters. RESULTS: In general population cohort, the prevalence of IFG and type 2 diabetes was 7.0% and <0.5%, respectively. Boys regardless of weight presented significantly higher levels of blood glucose and higher prevalence of IFG than girls. Obese boys were found more insulin resistant than obese girls. HOMA-IR thresholds of 3.6 for girls and 4.4 for boys were associated with increased cardiometabolic risks. For both genders, the model of HOMA-IR prediction was composed of age, BMI, ratio of free triiodthyronine to free thyroxine, gamma-glutamyltransferase activity and levels of triglycerides and sex hormone-binding globulin. CONCLUSIONS: The type 2 diabetes in adolescents, including those who were obese, was rarely diagnosed. Obese adolescent boys were at greater risk for IR and for IFG than obese girls. In adolescence, thresholds of HOMA-IR in contrast to predictors were found gender specific.

• Klíčová slova
• Adolescence, Glucose homeostasis, HOMA-IR prediction, Insulin resistance, Metabolic syndrome, Obesity, Type 2 diabetes,
• Publikační typ
• časopisecké články MeSH

Worldwide obesity prevalence has nearly doubled since 1980. Due to numerous co-morbidities, obesity represents a serious health and socioeconomic problem worldwide. Pharmacotherapy should be an integral part of comprehensive obesity management. Drug therapy can assist in weight loss and its maintenance in those individuals who do not achieve appropriate weight loss through lifestyle interventions alone. After the withdrawal of sibutramine from the market in 2010, orlistat, a lipase inhibitor, was the only remaining prescription drug approved for the long-term treatment of obesity. In 2012, phentermine/topiramate extended-release (PHEN/TPM ER) combination and lorcaserin were approved by the US FDA as novel medications for long-term weight management. Three major phase III trials conducted with each drug confirmed their efficacy in terms of weight loss/maintenance and improvement of cardiometabolic risks. No head-to-head studies between the two new anti-obesity drugs have been carried out. However, in the existing studies PHEN/TPM ER had a superior weight loss profile to lorcaserin but the incidence of adverse effects was lower with lorcaserin. Both drugs were well-tolerated, and adverse events were modest in intensity, dose dependent, rather rare, and tended to decrease with the duration of treatment. Major safety concerns regarding PHEN/TPM ER include elevations in resting pulse rate, teratogenicity, mild metabolic acidosis, and psychiatric and cognitive adverse events. Valvulopathy, cognitive impairment, psychiatric disorders, and hypoglycemia represent major safety concerns for lorcaserin. Although existing trials have not demonstrated any significant issues with PHEN/TPM ER-induced heart rate elevation and lorcaserin-induced valvulopathy, all safety concerns should be seriously taken into account in patients treated with either of these novel anti-obesity medications.

• MeSH
• benzazepiny škodlivé účinky   MeSH
• benzoxaziny škodlivé účinky   MeSH
• bupropion škodlivé účinky   MeSH
• chemie farmaceutická MeSH
• fentermin aplikace a dávkování   škodlivé účinky   MeSH
• fruktosa aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• glukagonu podobný peptid 1 škodlivé účinky   analogy a deriváty   MeSH
• látky proti obezitě aplikace a dávkování   škodlivé účinky   MeSH
• lidé MeSH
• liraglutid MeSH
• naltrexon škodlivé účinky   MeSH
• nežádoucí účinky léčiv MeSH
• obezita farmakoterapie   MeSH
• topiramat MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• benzazepiny MeSH
• benzoxaziny MeSH
• bupropion MeSH
• cetilistat MeSH Prohlížeč
• fentermin MeSH
• fruktosa MeSH
• glukagonu podobný peptid 1 MeSH
• látky proti obezitě MeSH
• liraglutid MeSH
• lorcaserin MeSH Prohlížeč
• naltrexon MeSH
• topiramat MeSH