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CONTEXT: Reliable estradiol (E2) reference intervals (RIs) are crucial in pediatric endocrinology. OBJECTIVES: This study aims to develop a sensitive ultra-performance liquid chromatographic tandem mass spectrometry (UPLC-MS/MS) method for E2 in serum, to establish graphically represented RI percentiles and annual RIs for both sexes, and to perform a systematic literature comparison. METHODS: First, a UPLC-MS/MS method for E2 was developed. Second, graphically represented RI percentiles and annual RIs covering 0-18 years were computed (cohort of healthy children [1181 girls and 543 boys]). Subsequently, RIs were compared with published data by systematic searches. RESULTS: Lower limit of quantification was 11â pmol/L, indicating high sensitivity. Estradiol first peaked during mini-puberty in both sexes (girls up to 192â pmol/L; boys up to 225â pmol/L). As could be expected, girls showed higher pubertal E2 (up to 638â pmol/L). However, boys' RIs (up to 259â pmol/L) overlapped considerably. We found 4 studies in the literature that also used LC-MS/MS to determine E2 and published RIs for the complete pediatric age range. Reference intervals varied considerably. Pre-pubertal and pubertal phases were present in all studies. Higher E2 during the time of mini-puberty in both sexes was documented in 3 studies including ours. CONCLUSIONS: Variability of RIs for E2 between studies illustrates the importance of laboratory-specific RIs despite using a LC-MS/MS reference method. In boys, the striking E2 peak during mini-puberty as well as high pubertal E2 without phenotypic estrogenization in regular male puberty indicates that the role of E2 in children and, especially in boys, requires better functional understanding.
Assuntos
Estradiol , Puberdade , Espectrometria de Massas em Tandem , Humanos , Masculino , Espectrometria de Massas em Tandem/métodos , Criança , Estradiol/sangue , Feminino , Valores de Referência , Pré-Escolar , Adolescente , Lactente , Cromatografia Líquida/métodos , Cromatografia Líquida/normas , Puberdade/sangue , Puberdade/fisiologia , Recém-Nascido , Maturidade Sexual/fisiologiaRESUMO
OBJECTIVE: The adipokine omentin-1 has been suggested to be inversely associated with obesity and insulin resistance in humans. We studied the relationships between omentin-1, parameters of fat mass, insulin resistance, lipids and blood pressure in children with obesity in a longitudinal study. METHODS: We analysed omentin-1 concentrations in 23 normal-weight children and in 82 children with obesity participating in a one-year lifestyle intervention. In the children with obesity, omentin-1, bioactive and conventional leptin, thyroid hormones (thyroid-stimulating hormone, free thyroxine 4, free triiodothyronine), body mass index, waist circumference, body fat based on skin-fold measurements and bioimpedance analyses, lipids, insulin resistance as homeostatic model assessment of insulin resistance (HOMA-IR) and blood pressure were determined at baseline and 1 year later. Furthermore, we measured omentin-1 concentrations 1 year after the end of the lifestyle intervention. RESULTS: The omentin-1 concentrations were significantly (P = .008) lower in children with obesity compared to normal-weight children (296 ± 108 ng ml-1 vs. 232 ± 99 ng ml-1 ). Omentin-1 concentrations increased significantly (P < .001) in children with obesity and substantial weight loss (35 ± 55 ng ml-1 ), while omentin-1 concentrations did not change significantly (P = .750) in children with obesity without weight loss (-5 ± 108 ng ml-1 ) during the intervention. Substantial weight loss after the end of intervention led to a significant (P < .001) increase of omentin-1 concentrations (+64 ± 14 ng ml-1 ). Omentin-1 was significantly and negatively associated with HOMA-IR both in cross-sectional (r = -.27, P = .006) and longitudinal analyses (r = -.33, P = .001). Omentin-1 concentrations were not related to pubertal stage, sex or thyroid hormones. CONCLUSIONS: Our data do support the hypothesis that omentin-1 is reversibly decreased in obesity and is a link between obesity and insulin resistance.
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Citocinas/sangue , Citocinas/genética , Resistência à Insulina/fisiologia , Lectinas/sangue , Lectinas/genética , Obesidade/sangue , Obesidade/genética , Tecido Adiposo/fisiopatologia , Pressão Sanguínea/fisiologia , Criança , Estudos Transversais , Feminino , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/genética , Alemanha , Humanos , Leptina/sangue , Lipídeos/sangue , Estudos Longitudinais , Masculino , Obesidade/fisiopatologiaRESUMO
BACKGROUND: The inflammatory cytokine progranulin has been proposed to play a role in obesity and its associated comorbidities such as insulin resistance. OBJECTIVE: In a longitudinal study, we analyzed the links between progranulin, parameters of fat mass, insulin resistance, and metabolic syndrome (MetS) in obese children. METHODS: We measured the following parameters in 88 obese children at baseline, at the end of a 1-year lifestyle intervention and 1-year later (=2 years after baseline): progranulin, bioactive leptin, body mass index-SD score (BMI-SDS), waist circumference, body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index homeostasis model assessment (HOMA), and blood pressure. As a control, we determined progranulin in 23 normal-weight children. RESULTS: The progranulin concentrations did not differ significantly (P = .795) between obese and normal-weight children. Progranulin concentrations decreased significantly during and after the lifestyle intervention in children with and without decrease of BMI-SDS. There was no relationship between progranulin concentrations and pubertal stage or gender. Progranulin was not significantly associated with insulin resistance HOMA, parameters of the MetS or transaminases both in cross-sectional and longitudinal multiple linear regression analyses adjusted to multiple confounders. Progranulin was significantly, negatively related to age (b-coefficient -1.24 ± .97, P = .012, r2 = .07). CONCLUSIONS: Our data do not support the hypothesis that progranulin is an important link between obesity, insulin resistance, and MetS in childhood.
Assuntos
Síndrome Metabólica/sangue , Obesidade/sangue , Progranulinas/sangue , Adolescente , Criança , Feminino , Humanos , Estudos Longitudinais , MasculinoRESUMO
OBJECTIVE: Constitutional delay of growth and puberty (CDGP) is a frequent variant of the normal leading to short stature and/or pubertal delay. To distinguish CDGP from hypogonadotropic hypogonadism (HH), we evaluated height, growth and weight pattern of CDGP and HH in the first 5 years of life. DESIGN AND PATIENTS: We studied retrospectively height and weight in the first 5 years (y) of life in 54 boys with CDGP and 8 boys with HH. RESULTS: In boys with CDGP, height-SDS decreased (change -0.94 (interquartile range [IQR] -1.69 to -0.05); P < 0.001) between birth and 2 years. BMI-SDS decreased (change -0.38 (IQR -1.21-0.16); P < 0.001) in the same time period. There were no significant changes in height-SDS or BMI-SDS between 2 years and 5 years, while height-SDS (change + 1.49 (IQR 1.02-1.95); P < 0.001) and BMI-SDS (change + 0.91 (IQR 0.12-1.69); P < 0.001) increased between pubertal and adult age. In boys with HH, height-SDS and BMI-SDS did not change significantly in the first 5 years of life. Height-SDS decreased (change -1.39 (IQR -1.96 to -0.67); P = 0.018) significantly between 5 years of life and puberty, while there were no significant changes in BMI-SDS in this time period. At pubertal age, BMI-SDS was significantly (P = 0.001) higher in boys with HH compared with boys with CDGP. CONCLUSION: Height deflection and weight deflection in CDGP occur already during the first two years of life in contrast to HH. This different pattern of growth and weight might be helpful to distinguish CDGP from HH.
Assuntos
Estatura , Peso Corporal , Transtornos do Crescimento/diagnóstico , Hipogonadismo/diagnóstico , Puberdade Tardia/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Transtornos do Crescimento/fisiopatologia , Humanos , Hipogonadismo/fisiopatologia , Lactente , Recém-Nascido , Masculino , Puberdade Tardia/fisiopatologia , Estudos RetrospectivosRESUMO
BACKGROUND: For children with retarded bone ages such as in constitutional delay of growth and puberty (CDGP) there are no specific methods to predict adult height based on bone age. Widely used methods such as Bayley-Pinneau (BP) tend to overestimate adult height in CDGP. OBJECTIVE: We aimed to develop a specific adult height prediction model for teenage boys with retarded bone ages >1 year. METHODS: Based on the adult heights of 68 males (median age 22.5 years) a new height prediction model was calculated based on 105 height measurements and bone age determinations at a median age of 14.0 years. The new model was adapted for the degree of bone age retardation and validated in an independent cohort of 32 boys with CDGP. RESULTS: The BP method overestimated adult height (median +1.2 cm; p = 0.282), especially in boys with a bone age retardation ≥2 years (median +1.6 cm; p = 0.027). In the validation study, there was no significant difference between adult height and predicted adult height based on the new model (p = 0.196), while the BP model led to a significant overestimation of predicted adult height (median +4.1 cm; p = 0.009). CONCLUSIONS: The new model to predict adult height in boys with CDGP provides novel indices for height predictions in bone ages >13 years and is adapted to different degrees of bone age retardation. The new prediction model has a good predictive capability and overcomes some of the shortcomings of the BP model.
Assuntos
Estatura , Transtornos do Crescimento/fisiopatologia , Modelos Biológicos , Puberdade Tardia/fisiopatologia , Adolescente , Adulto , Determinação da Idade pelo Esqueleto , Criança , Pré-Escolar , Seguimentos , Transtornos do Crescimento/patologia , Humanos , Lactente , Masculino , Valor Preditivo dos Testes , Puberdade Tardia/patologiaRESUMO
OBJECTIVE: Chemerin has been suggested as a potential link between obesity and associated comorbidities in humans. Therefore, we studied the relationships between chemerin, parameters of fat mass, and Metabolic Syndrome (MetS) in obese children before and after weight reduction. METHODS: We determined chemerin, bioactive leptin (bioLep), BMI-SDS, waist circumference (WC), body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index HOMA, and blood pressure in 88 obese children participating in a lifestyle intervention at baseline and 1 year later. Furthermore, we determined chemerin concentrations in 23 normal-weight children. RESULTS: Obese children demonstrated significantly (p < 0.001) higher chemerin concentrations compared to normal-weight children (96.2 ± 23.0 versus 63.1 ± 12.4 ng/ml). The chemerin concentrations were not related to age or gender. Prepubertal children had higher (p = 0.024) chemerin concentrations than pubertal children (71.0 ± 13.4 versus 58.0 ± 8.9 ng/ml). Weight loss was associated with a decrease of chemerin (-14.0 ± 22.0 ng/ml; p < 0.001) and an improvement of all parameters of the MetS. Chemerin was significantly related to BMI-SDS, WC, and bioLep in cross-sectional and longitudinal analyses. Chemerin and its changes were significantly related to insulin, HDL-cholesterol, triglycerides and their changes in multiple linear regression analyses adjusted to age, gender, pubertal stage, leptin and BMI. CONCLUSIONS: Since chemerin was related to parameters of central fat mass and MetS both in cross-sectional and longitudinal analyses these findings suggest an impact of chemerin on factors of the MetS in obese children.
Assuntos
Quimiocinas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Síndrome Metabólica/sangue , Obesidade Infantil/sangue , Redução de Peso/fisiologia , Programas de Redução de Peso , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Leptina/sangue , Estudos Longitudinais , Masculino , Síndrome Metabólica/fisiopatologia , Obesidade Infantil/fisiopatologia , Resultado do Tratamento , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
We present a boy with a genetically proven congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. While massively elevated 17-hydroxyprogesterone (17-OHP) concentrations after birth led to the diagnosis, 17-OHP concentrations became immeasurable starting with the second year of life even though the dose of hydrocortisone was continuously decreased to â¼7 mg/m2/day. Furthermore, 17-OHP levels were immeasurable during the ACTH test and after withdrawing hydrocortisone medication. In contrast, ACTH levels increased after cessation of hydrocortisone treatment suggesting complete primary adrenal cortex failure. We discuss this case based on the differential diagnosis of complete adrenal cortex failure including other genetic causes in addition to CAH, prednisolone treatment, autoimmune adrenalitis, adrenoleukodystrophy, CMV infection, and adrenal hemorrhage infarction. The most likely disease in our boy is autoimmune adrenalitis, which is difficult to prove years after the onset of the disease. Treatment of CAH had masked the classical symptoms of complete adrenal cortex insufficiency leading to delayed diagnosis in this case.
Assuntos
17-alfa-Hidroxiprogesterona/sangue , Doenças do Córtex Suprarrenal/diagnóstico , Hiperplasia Suprarrenal Congênita/sangue , Insuficiência Adrenal/diagnóstico , Anormalidades Múltiplas/sangue , Anormalidades Múltiplas/diagnóstico , Doenças do Córtex Suprarrenal/sangue , Doenças do Córtex Suprarrenal/congênito , Hiperplasia Suprarrenal Congênita/diagnóstico , Insuficiência Adrenal/sangue , Insuficiência Adrenal/congênito , Assistência ao Convalescente , Criança , Pré-Escolar , Diagnóstico Tardio , Humanos , Hidrocortisona/uso terapêutico , Lactente , Recém-Nascido , MasculinoRESUMO
OBJECTIVE: This study analyzed the relationships between bioactive leptin, conventionally measured leptin, and parameters of fat mass and distribution in obese children before and after weight reduction. METHODS: We determined bioactive leptin (bioLep), conventional measured leptin (conLep), weight, height, body fat based on skinfold measurements and bioimpedance analyses, waist circumference (wc), and pubertal stage in 88 obese children participating in a lifestyle intervention at baseline and one year later. RESULTS: We identified no child with homozygous or heterozygous status for bioinactive leptin mutations. The baseline associations between bioLep and BMI (râ¯=â¯0.53), BMI-SDS (râ¯=â¯0.48), body fat (bioimpedance: râ¯=â¯0.61, skinfold thickness: râ¯=â¯0.49), wc (râ¯=â¯0.42), and waist to height ratio (whr) (râ¯=â¯0.39) were stronger than the associations between conLep and BMI (râ¯=â¯0.50), BMI-SDS (râ¯=â¯0.44), body fat (bioimpedance: râ¯=â¯0.57, skinfold thickness: râ¯=â¯0.41), wc (râ¯=â¯0.41), and whr (râ¯=â¯0.37). The changes of bioLep were stronger related to changes of BMI-SDS (râ¯=â¯0.54), body fat (bioimpedance râ¯=â¯0.59, skinfold thickness: râ¯=â¯0.37), wc (râ¯=â¯0.22), and whr (râ¯=â¯0.21) than the associations between changes of conLep and changes of BMI-SDS (râ¯=â¯0.48), body fat (bioimpedance: râ¯=â¯0.56, skinfold thickness: râ¯=â¯0.43), wc (râ¯=â¯0.20), and whr (râ¯=â¯0.20). The same findings were observed in multiple linear regression analyses adjusted to multiple confounders. In contrast to changes of conLep (râ¯=â¯0.22), the changes of bioLep during intervention were not related to weight regain after the end of intervention. BioLep concentrations did not differ between prepubertal girls and boys, but were higher in pubertal girls compared to pubertal boys (pâ¯=â¯0.031). CONCLUSIONS: Bioactive leptin was stronger related to fat mass and distribution compared to conventionally measured leptin.
Assuntos
Tecido Adiposo , Imunoensaio , Leptina/sangue , Obesidade/sangue , Índice de Massa Corporal , Criança , Feminino , Humanos , Estilo de Vida , Estudos Longitudinais , MasculinoRESUMO
BACKGROUND: While the main role of growth hormone (GH) replacement therapy in children is to promote linear growth, GH has also an effect on lipids and body composition. There is an ongoing discussion whether discontinuation of GH treatment is associated with deterioration of lipids. METHODS: We analyzed weight status [as body mass index-standard deviation score (BMI-SDS)], insulin like growth factor (IGF)-1, triglycerides, total, low-density liporptoein (LDL)- and high-density lipoprotein (HDL)-cholesterol at the end of GH treatment and in mean 6 months later in 90 adolescents (53 with GH deficiency, 16 with Turner syndrome [TS] and 21 born small-for-gestational age [SGA]). RESULTS: After stopping GH treatment, total cholesterol (+10±24 mg/dL vs. -4±13 mg/dL) and LDL-cholesterol (+15±20 mg/dL vs. -6±12 mg/dL) increased significantly higher in severe (defined by GH peak in stimulation test <3 ng/mL) compared to moderate GHD. In patients with TS, total cholesterol (+19±9 mg/dL), LDL-cholesterol (+9±12 mg/dL) and HDL-cholesterol (+4.3±3.5 mg/dL) increased significantly. In adolescents born SGA, triglycerides increased (+34±51 mg/dL) and HDL-cholesterol decreased significantly (-3.8±7.1 mg/dL). In multiple linear regression analyses, changes of total and LDL-cholesterol were significantly negatively related to peak GH in stimulation tests, but not to gender, age at GH start, duration of GH treatment, observation time, changes of BMI-SDS or IGF-1 after the end of GH treatment. The BMI-SDS did not change after the end of GH treatment. CONCLUSIONS: Discontinuation of GH treatment leads to a deterioration of lipids in TS, SGA and severe but not moderate GHD.
Assuntos
Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento Humano/administração & dosagem , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Lipídeos/análise , Síndrome de Turner/fisiopatologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/deficiência , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Fatores de Risco , Triglicerídeos/metabolismo , Síndrome de Turner/tratamento farmacológicoRESUMO
OBJECTIVE: The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. DESIGN: This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13-16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. METHODS: We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S), estrone and estradiol by LC-MS/MS steroid profiling at baseline and one year later. RESULTS: At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. CONCLUSIONS: The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS.
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OBJECTIVE: The Anti-Muellerian Hormone (AMH) has been reported as surrogate marker of antral follicles, which are the origins of hyperandrogenism in polycystic ovarian syndrome (PCOS). Therefore, AMH may be useful for the diagnosis of PCOS. The objective was to study the longitudinal changes in AMH concentrations in girls with and without PCOS. DESIGN: This is a longitudinal study of obese girls participating in a 1-year lifestyle intervention. PATIENTS: Forty obese girls aged 13-16 years (50% with PCOS) were included in the study. Girls with and without PCOS were matched to age, BMI and change in weight status. MEASUREMENTS: AMH, gonadotropins, androstenedione, testosterone, oestradiol and sex hormone-binding globulin (SHBG) were determined. RESULTS: Obese girls with PCOS demonstrated significantly (P<.001) higher AMH concentrations (5.8±3.1 ng/mL) compared to obese girls without PCOS (2.4±1.4 ng/mL). None of the girls without PCOS had AMH concentrations ≥6 ng/mL and none of the PCOS girls showed AMH concentrations ≤3 ng/mL. Weight loss in girls with PCOS was associated with a significant drop in AMH concentrations (-1.4±1.8 ng/mL, P=.045). AMH was significantly related to testosterone (cross-sectional: b-coefficient 3.7±1.7, P=.001, longitudinal: b-coefficient 0.54±0.47, P=.026) and luteinizing hormone (LH) (cross-sectional: b-coefficient 0.05±0.04, P=.039, longitudinal: b-coefficient 0.005±0.004, P=.039), but not to any other analysed parameter in multiple linear regression analyses adjusted to multiple confounders. CONCLUSIONS: AMH was increased in adolescent girls with PCOS and normalized with weight loss. AMH was cross-sectionally and longitudinally related to hyperandrogenism.
Assuntos
Hormônio Antimülleriano/sangue , Obesidade , Síndrome do Ovário Policístico/complicações , Redução de Peso/fisiologia , Adolescente , Estudos Transversais , Feminino , Humanos , Hiperandrogenismo/sangue , Estudos Longitudinais , Hormônio Luteinizante , TestosteronaRESUMO
OBJECTIVE: To assess the impact of weight changes on the onset of puberty in overweight children. STUDY DESIGN: We evaluated the timing of puberty onset in 160 prepubertal overweight children (aged 11.2 ± 1.0 years) depending on the changes of their weight status in a 1-year lifestyle intervention. We determined body mass index (BMI), pubertal stage, luteinizing hormone (LH), follicle-stimulating hormone, insulin-like growth factor (IGF)-1, insulin-like growth factor binding protein-3, insulin resistance index homeostatic model assessment, and serum gonadotropins at baseline and 1 year later. RESULTS: Puberty onset during the 1-year follow-up was significantly (P = .014) more frequent in girls without BMI-SDS reduction (75.0%) compared with girls with BMI-SDS reduction (45.7%). The start of puberty was significantly (P = .024) more frequent in boys with BMI-SDS reduction (76.9%) compared with boys without BMI-SDS reduction (53.6%). In logistic regression analyses adjusted for baseline age and BMI-SDS, BMI-SDS reduction was associated with a decreased likelihood for puberty onset in girls (OR 0.24; 95% CI 0.07-0.85) and an increased likelihood in boys (OR 3.77; 95% CI 1.34-10.52). Central onset of puberty was confirmed by an increase of LH concentration and LH/follicle-stimulating hormone ratio in both boys and girls. Homeostatic model assessment, IGF-1, and IGF-1/insulin-like growth factor binding protein-3 ratio as marker for free IGF-1 at baseline or their changes were not associated with the onset of puberty. CONCLUSIONS: BMI-SDS reduction in overweight children was associated with earlier gonadotropin-dependent onset of puberty in boys and later onset of puberty in girls, suggesting earlier puberty in obese girls and later puberty in obese boys. We found no evidence that insulin resistance or IGF-1 have an impact on the start of puberty in obese children. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00435734.
Assuntos
Sobrepeso/fisiopatologia , Puberdade , Redução de Peso , Adolescente , Criança , Feminino , Humanos , Masculino , Sobrepeso/sangue , Puberdade/sangueRESUMO
BACKGROUND: There is an ongoing discussion whether high doses of growth hormone (GH) may lead to cardiovascular diseases. Therefore, we studied the longitudinal relationships between GH treatment and carotid intima-media thickness (cIMT), which is predictive of the development of atherosclerosis. METHODS: We measured blood pressure, lipids, hemoglobin HbA1c, IGF-1, IGFBP-3, and cIMT in 28 children treated with supraphysiological doses of GH (mean age 9.8 ± 2.2 years, 39% males) and 36 children suffering from GH deficiency (GHD) and treated with physiological doses of GH (mean age 9.7 ± 2.2 years, 72% males) in a longitudinal study over 3 years. RESULTS: The cIMT values did not change significantly in the observation period in children with GHD (Δmaximum and Δmean cIMT 0.0 ± 0.1 mm). The mean (+0.1 ± 0.1 mm) but not the maximum cIMT (0.0 ± 0.1 mm) increased significantly (p = 0.049) in the children treated with supraphysiological doses of GH. Blood pressure, lipids, and HbA1c were not related to cIMT, while IGF-1, IGFBP-3, body mass index expressed as a standard deviation score, and treatment duration correlated significantly with cIMT. CONCLUSIONS: We did not find any robust evidence that GH treatment is associated with changes in cIMT. Further studies are necessary to analyze the impact of IGF-1 and IGFBP-3 concentrations on cIMT.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Espessura Intima-Media Carotídea , Hemoglobinas Glicadas/metabolismo , Hormônio do Crescimento Humano/administração & dosagem , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Criança , Feminino , Seguimentos , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Humanos , MasculinoRESUMO
Growth hormone (GH) has a large number of metabolic effects, involving lipid and glucose homoeostasis, lean and fat mass. Growth hormone deficiency (GHD) is associated with a metabolic profile similar to the Metabolic Syndrome which is characterized by dyslipidemia, insulin resistance, haemostatic alterations, oxidative stress, and chronic inflammation. GH replacement treatment in GHD children improves these cardiovascular risk factors, while cessation of GH is associated with a deterioration of most of these risk factors. However, it is unclear whether the changes of these risk factors are associated with an increased risk of cardiovascular diseases especially after discontinuing GH treatment. GH treatment itself can lead to insulin resistance, which probably also influences the cardiovascular health status. Therefore, longitudinal studies with the primary outcome cardiovascular diseases are needed in GHD children. Furthermore, new approaches such as metabolomic studies might be helpful to understand the relationship between GHD, GH treatment, and cardiovascular diseases.
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Nanismo Hipofisário/metabolismo , Hormônio do Crescimento/deficiência , Criança , Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/tratamento farmacológico , Glucose/metabolismo , Hormônio do Crescimento/metabolismo , Hemodinâmica , Humanos , Metabolismo dos Lipídeos , Estresse OxidativoRESUMO
OBJECTIVE: Copeptin has been reported to be associated with stress, obesity and the metabolic syndrome (MetS) in adults. However, data in childhood are scarce. Therefore, we studied the relationships between copeptin, cortisol, puberty and parameters of the MetS in children. DESIGN: Cross-sectional study. PATIENTS: A total of 51 obese children (10·8 ± 3·2 years, 39% male, 45% prepubertal, body mass index standard deviation score (BMI-SDS) 2·77 ± 0·56) and 24 lean children of similar age, gender and pubertal stage. MEASUREMENTS: Copeptin, serum cortisol, 24-h urinary free cortisol, BMI-SDS and, as parameters of the MetS, insulin resistance index (HOMA), HbA1c, uric acids, blood pressure and lipids. RESULTS: Copeptin levels were significantly (P = 0·047) higher in obese children (5·8 ± 2·8pmol/l) compared to lean children (4·6 ± 2·2pmol/l). BMI-SDS (ß-coefficient 0·38 ± 0·35, P =0·033), but not any parameter of the MetS, was significantly related to copeptin in multiple linear regression analyses adjusted for age, gender and pubertal stage. A 24-h urinary free cortisol (ß-coefficient 0·13 ± 0·06, P < 0·001), but not serum cortisol, was significantly related to copeptin in multiple linear regression analyses adjusted for age, gender, pubertal stage and BMI-SDS. Pubertal boys (6·6 ± 2·8pmol/l) demonstrated significantly (P = 0·042) higher copeptin levels compared to pubertal girls (4·8 ± 2·6pmol/l), while copeptin concentrations did not differ between prepubertal girls and boys. CONCLUSIONS: Copeptin levels are related to 24-h urinary free cortisol in obese children. Pubertal boys, but not prepubertal boys, demonstrated higher copeptin levels than girls, suggesting that sex hormones are involved in the regulation of copeptin levels. Further studies are necessary to understand the relationship between obesity, cortisol, gender, pubertal stage and copeptin levels.
Assuntos
Glicopeptídeos/sangue , Obesidade , Adolescente , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Hidrocortisona/análise , Masculino , Síndrome Metabólica , Puberdade , Fatores SexuaisRESUMO
BACKGROUND: Familial short stature (FSS) and constitutional delay of growth (CDG) are the most frequent norm variants in children presenting with short stature. Knowing the growth patterns of these entities in the first years of life might be helpful to distinguish them from growth hormone deficiency (GHD) or other chronic diseases. METHODS: We studied the height in the first 5 years of life in 26 children with FSS, in 38 children with CDG and in 14 children with idiopathic GHD. RESULTS: Height standard deviation scores (SDS) did not change between birth and 6 months of life, while height SDS decreased significantly afterwards in GHD, FSS, and CDG. The loss of height SDS was higher in the first 2 years of life than between 2 and 5 years of life in children with CDG (-0.92 vs. -0.11; p = 0.003) or FSS (-0.79 vs. -0.01; p = 0.002). In idiopathic GHD, the loss of height SDS did not differ between the first 2 years of life and the next 3 years (-0.78 vs. -0.77; p = 0.821). CONCLUSION: Children with FSS and CDG showed a decline in height SDS mainly in the first 2 years of life, whereas the height SDS of children with idiopathic GHD decreased almost continuously over the first 5 years of life.
Assuntos
Estatura , Desenvolvimento Infantil , Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento Humano/deficiência , Criança , Pré-Escolar , Feminino , Seguimentos , Transtornos do Crescimento/patologia , Humanos , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
CONTEXT: Knowing the changes of cardiovascular risk factors (CRFs) in relation to weight loss would be helpful to advise overweight children and their parents and to decide whether drugs should be prescribed in addition to lifestyle intervention. OBJECTIVE: The objective of the study was to determine the body mass index (BMI)-SD score (SDS) reduction to improve CRFs in overweight children. DESIGN: This was a prospective observation study. SETTING: The study was conducted at a specialized outpatient obesity clinic. PATIENTS: A total of 1388 overweight children (mean BMI 27.9 ± 0.1 kg/m(2), mean age 11.4 ± 0.1 y, 43.8% male, 45.5% prepubertal) participated in the study. INTERVENTION: The study included a 1-year lifestyle intervention. MAIN OUTCOME MEASURES: We studied changes of blood pressure (BP), fasting high-density lipoprotein- and low-density lipoprotein-cholesterol, triglycerides, glucose, and homeostasis model assessment (HOMA) of insulin resistance index. Change of weight status was determined by δBMI-SDS based on the recommended percentiles of the International Task Force of Obesity. RESULTS: BMI-SDS change was associated with a significant improvement of all CRFs except fasting glucose and low-density lipoprotein-cholesterol after adjusting for multiple confounders such as baseline CRFs, age, gender, BMI, pubertal stage, and its changes. BMI-SDS reduction of 0.25-0.5 was related to a decrease of systolic blood pressure (BP) (-3.2 ± 1.4 mm Hg), diastolic BP (-2.2 ± 1.1 mm Hg), triglycerides (-6.9 ± 5.8 mg/dL), HOMA (-0.5 ± 0.3), and triglyceride/high-density lipoprotein)-cholesterol (-0.3 ± 0.2), whereas high-density lipoprotein (HDL)-cholesterol increased (+1.3 ± 1.2 mg/dL). A reduction of greater than 0.5 BMI-SDS led to more pronounced improvement (systolic BP -6.0± 1.3 mm Hg, diastolic BP -5.1 ± 1.3 mm Hg, triglycerides -16.4 ± 7.1 mg/dL, HDL-cholesterol +1.6 ± 1.5 mg/dL, HOMA -0.9 ± 0.3). Per 0.1 BMI-SDS reduction in systolic BP (-1.0 mm Hg), diastolic BP (-0.8 mm Hg), triglycerides (-2.3 mg/dL), HOMA (-0.2), and triglyceride/HDL-cholesterol (-0.5) decreased significantly, whereas HDL-cholesterol (0.2 mg/dL) increased significantly in linear regression analyses and accounted for multiple confounders. CONCLUSIONS: A BMI-SDS reduction of 0.25 or greater significantly improved hypertension, hypertriglyceridemia, and low HDL-cholesterol, whereas a BMI-SDS greater than 0.5 doubled the effect.