Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement.

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors-a review of research and clinical practice.

Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.

Growth hormone deficiency and replacement in children.

Growth hormone deficiency (GHD) is a rare but treatable cause of short stature. The diagnosis requires a careful evaluation of clinical history, physical examination and appropriate interpretation of longitudinal growth, with specific features for each period of life. Other clinical findings, in addition to growth failure, may be present and can be related to the etiology and to associated hormone deficiencies. Despite more than 50 years since the first reports of provocative tests of growth hormone (GH) secretion for the diagnosis of GHD, the interpretation of the results remains a matter of debate. When GHD is confirmed, GH treatment is recommended. Treatment is effective and safe, but requires daily injections during many years, which can affect adherence. At the end of longitudinal growth, during the transition phase, it might be necessary to re-evaluate GH secretion. This review summarizes and updates the recent information related to GHD in children, as well the recommendations for treatment.

Near-Adult Height After Growth Hormone Treatment in Children Born Prematurely-Data From KIGS.

CONTEXT: Children born prematurely have been treated with growth hormone (GH), and a significant improvement in height during the first years of treatment has been described. OBJECTIVE: To evaluate the influence of prematurity on near-adult height (NAH) after GH treatment. DESIGN: KIGS (Pfizer International Growth Database) was queried for children born preterm treated with GH. SETTING: KIGS database. PATIENTS: A total of 586 children short in stature born preterm with various GH status and with available gestational age (GA), birth weight, and NAH, all treated with GH. INTERVENTION: GH treatment. MAIN OUTCOME MEASURE: NAH. RESULTS: Values were expressed as median. From the 586 children included, 482 born appropriate for GA (AGA; median age 8.26 years) and 104 born small for gestational age (SGA) (median age 8.54 years); 66.6% of preterm AGA had GH peak < 7 µg/L during a provocation test, whereas only 8.6% of preterm SGA. Change in height standard deviation scores (SDS) from GH start to NAH after 8.04 years of GH treatment was 1.82 in preterm AGA. Respective values were 7.08 years and 1.08 SDS for preterm SGA (P < 0.001); 57% of the variability of the growth response to NAH could be explained, and the distance to parental height was the strongest predictor. No significant changes in height SDS were observed from puberty start to NAH. No correlation was found with GA. GH treatment was well tolerated. CONCLUSION: GH treatment resulted in significant improvement in height in children born preterm, particularly during prepubertal years and for those with GH deficiency. The degree of prematurity did not influence the growth response.

Postnatal management of growth failure in children born small for gestational age.

OBJECTIVES: To discuss the etiology and growth consequences of small size at birth and the indications, effects, and safety of biosynthetic growth hormone therapy in children born small for gestational age. SOURCE OF DATA: A comprehensive and non-systematic search was carried out in the PubMed, LILACS, and SciELO databases from 1980 to the present day, using the terms "small for gestational age," "intrauterine growth restriction," and "growth hormone". The publications were critically selected by the authors. DATA SYNTHESIS: Although the majority of children born small for gestational age show spontaneous catch-up growth during the first two years of life, some of them remain with short stature during childhood, with high risk of short stature in adult life. Treatment with growth hormone might be indicated, preferably after 2-4 years of age, in those small for gestational age children who remain short, without catch-up growth. Treatment aims to increase growth velocity and to reach a normal height during childhood and an adult height within target height. Response to growth hormone treatment is variable, with better growth response during the pre-pubertal period. CONCLUSIONS: Treatment with growth hormone in short children born small for gestational age is safe and effective to improve adult height. Efforts should be done to identify the etiology of small size at birth before treatment.

Postnatal management of growth failure in children born small for gestational age / Manejo pós-natal da falha de crescimento em crianças nascidas pequenas para a idade gestacional

Abstract Objectives: To discuss the etiology and growth consequences of small size at birth and the indications, effects, and safety of biosynthetic growth hormone therapy in children born small for gestational age. Source of data: A comprehensive and non-systematic search was carried out in the PubMed, LILACS, and SciELO databases from 1980 to the present day, using the terms "small for gestational age," "intrauterine growth restriction," and "growth hormone". The publications were critically selected by the authors. Data synthesis: Although the majority of children born small for gestational age show spontaneous catch-up growth during the first two years of life, some of them remain with short stature during childhood, with high risk of short stature in adult life. Treatment with growth hormone might be indicated, preferably after 2-4 years of age, in those small for gestational age children who remain short, without catch-up growth. Treatment aims to increase growth velocity and to reach a normal height during childhood and an adult height within target height. Response to growth hormone treatment is variable, with better growth response during the pre-pubertal period. Conclusions: Treatment with growth hormone in short children born small for gestational age is safe and effective to improve adult height. Efforts should be done to identify the etiology of small size at birth before treatment.

Resumo Objetivos: Discutir a etiologia e as consequências para o crescimento e as indicações, os efeitos e a segurança da terapia com hormônio de crescimento biossintético em crianças pequenas para idade gestacional. Fonte dos dados: Uma busca abrangente e não sistemática foi feita nas bases de dados PubMed, LILACS e SciELO de 1980 até a presente data, com os termos "small for gestational age" (pequeno para a idade gestacional), "intrauterine growth restriction" (restrição de crescimento intrauterino) e "growth hormone" (hormônio do crescimento). As publicações foram selecionadas criticamente pelos autores. Síntese dos dados: Embora a maioria das crianças nascidas pequenas para idade gestacional apresente recuperação espontânea do crescimento durante os dois primeiros anos de vida, algumas delas permanecem com baixa estatura durante a infância, com alto risco de baixa estatura na vida adulta. O tratamento com hormônio de crescimento pode ser indicado, preferencialmente após os dois aos quatro anos, naquelas crianças sem recuperação espontânea do crescimento e com baixa estatura. Seus objetivos são aumentar a velocidade de crescimento e atingir uma altura normal durante a infância e uma altura adulta dentro da altura-alvo. A resposta ao tratamento com hormônio de crescimento é variável, com melhor resultado se iniciado durante o período pré-puberal. Conclusões: O tratamento com hormônio de crescimento em crianças baixas nascidas pequenas para idade gestacional é seguro e eficaz para melhorar a estatura adulta. Esforços devem ser feitos para identificar a etiologia do nascimento pequenas para idade gestacional antes do tratamento.

Variability of lipid and lipoprotein concentrations during puberty in Brazilian boys.

BACKGROUND: Evaluation of lipid profile in children and adolescents is important for early diagnosis of dyslipidemias. Physiological changes might be observed in the concentration of the lipid profile components, according to the stage of sexual maturation. OBJECTIVE: To evaluate the variation in lipid and lipoprotein concentrations in boys during puberty. METHODS: The sample consisted of 570 male adolescents with ages between 10 and 17 years. Weight, height, and body mass index (BMI) were assessed. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were determined by the enzymatic method, and low-density lipoprotein cholesterol (LDL-C) was calculated. Puberty was classified according to Tanner references. The percentile criterion was adopted for the distribution and identification of lipoprotein levels. The analysis of variance and description tests with p<0.05 was applied. RESULTS: Participants had similar BMI z-score and physical activity habits in all groups. A significant reduction in TC and HDL-C concentrations between the start and end of puberty was observed. LDL-C levels rose during stage 3 of development, decreasing at the end of the pubertal process. TG levels did not change significantly with pubertal status. CONCLUSION: Lipid and lipoprotein concentrations tend to undergo changes during puberty in boys. The use of percentile values can be very useful to track variations in lipid and lipoprotein levels during the maturation process.

Metabolic risk and television time in adolescent females.

OBJECTIVES: A sedentary lifestyle is increasingly implicated in a negative metabolic health profile among youth. The present study examined relationships between clustered metabolic risk factors and TV viewing in female adolescents. METHODS: The sample comprised 262 girls 14-17 years. Height, weight, fasting glucose, insulin, HDL cholesterol, triglycerides, and blood pressure were measured. Body mass index (BMI) was calculated. TV viewing time and moderate-to-vigorous physical activity (MVPA) were estimated from a 3-day diary. Outcome variables were normalized and expressed as Z scores which were summed into a metabolic risk score. Multiple linear regression analysis was used. RESULTS: TV viewing was independently associated with increased prevalence of clustered metabolic risk in girls after adjustment for several confounders (i.e., chronological age, BMI, MVPA, and parental education). The final model also indicated that lower levels of MVPA, higher BMI, and lower mother education were associated with higher metabolic risk. CONCLUSIONS: Increased TV viewing had an adverse effect on metabolic health of adolescent girls. The findings highlight the potential importance of preventive actions to ameliorate metabolic risk in youth which target both sedentary and physically active behaviors.

Relationship between metabolic syndrome and moderate-to-vigorous physical activity in youth.

BACKGROUND: Associations of metabolic syndrome (MetS) with lifestyle behaviors in youth is potentially important for identifying subgroups at risk and encourage interventions. This study evaluates the associations among the clustering of metabolic risk factors and moderate-to-vigorous physical activity (MVPA) in youth. METHODS: The sample comprised 522 girls and 402 boys (N = 924) aged 11 to 17 years. Height, weight, waist circumference (WC), fasting glucose, high-density lipoprotein cholesterol, triglycerides, and blood pressures were measured. Cardiorespiratory fitness (CRF) was assessed using the 20-m shuttle run test. MVPA was estimated with a 3-day diary. Outcome variables were statistically normalized and expressed as z scores. A clustered metabolic risk score was computed as the mean of z scores. Multiple linear regression was used to test associations between metabolic risk and MVPA by sex, adjusted for age, WC, and CRF. RESULTS: After adjustment for potential confounders, MVPA was inversely associated with the clustering of metabolic risk factors in girls, but not in boys; in addition, after adjusting for WC, the statistical model of that relationship was substantially improved in girls. CONCLUSION: MVPA was independently associated with increased risk of MetS in girls. Additional efforts are needed to encourage research with different analytical approach and standardization of criteria for MetS in youth.

Independent association of clustered metabolic risk factors with cardiorespiratory fitness in youth aged 11-17 years.

BACKGROUND: Although the prevalence of metabolic syndrome (MetS) has increased in youth, the potential independent contribution of cardiorespiratory fitness (CRF) to the clustering of metabolic risk factors has received relatively little attention. AIM: This study evaluated associations between the clustering of metabolic risk factors and CRF in a sample of youth. SUBJECTS AND METHODS: Height, weight, BMI, fasting glucose, insulin, HDL-cholesterol, triglycerides and blood pressures were measured in a cross-sectional sample of 924 youth (402 males, 522 females) of 11-17 years. CRF was assessed using the 20-metre shuttle run test. Physical activity (PA) was measured with a 3-day diary. Outcome variables were statistically normalized and expressed as Z-scores. A MetS risk score was computed as the mean of the Z-scores. Multiple linear regression was used to test associations between CRF and metabolic risk, adjusted for age, sex, BMI, PA and parental education. RESULTS: CRF was inversely associated with MetS after adjustment for potential confounders. After adjusting for BMI, the relationship between CRF and metabolic risk has substantially improved. CONCLUSION: CRF was independently associated with the clustering of metabolic risk factors in youth of 11-17 years of age.

Reappraisal of serum insulin-like growth factor-I (IGF-1) measurement in the detection of isolated and combined growth hormone deficiency (GHD) during the transition period / Reavaliação da dosagem sérica do fator de crescimento insulina-símile-1 (IGF-1) para o diagnóstico da deficiência isolada e combinada de hormônio de crescimento no período de transição

OBJECTIVE: To evaluate the accuracy of serum IGF-1 in the detection of isolated (IGHD) or combined growth hormone deficiency (CGHD) at the transition phase. SUBJECTS AND METHODS: Forty nine patients with GHD during childhood [16 with IGHD (10 men) and 33 with CGHD (24 men); age 23.2 ± 3.5 yrs.] were submitted to an insulin tolerance test (ITT) with a GH peak < 5 µg/L used for the diagnosis of GHD at the transition phase. Pituitary function and IGF-1 measurements were evaluated in the basal sample of the ITT. Transition patients were reclassified as GH-sufficient (SGH; n = 12), IGHD (n = 7), or CGHD (n = 30). RESULTS: Five (31%) patients with IGHD and 32 (97%) with CGHD at childhood persisted with GHD at retesting. One patient with IGHD was reclassified as CGHD, whereas 3 patients with CGHD were reclassified as IGHD. Mean GH peak was 0.2 ± 0.3 µg/L in the CGHD, 1.3 ± 1.5 µg/L in the IGHD, and 18.1 ± 13.1 µg/L in the SGH group. Serum IGF-1 level was significantly higher in the SGH (272 ± 107 ng/mL) compared to IGHD (100.2 ± 110) and CGHD (48.7 ± 32.8) (p < 0.01). All patients reclassified as CGHD, 86% reclassified as IGHD, and 8.3% reclassified as SGH had low IGF-1 level, resulting in 97.3% sensitivity and 91.6% specificity in the detection of GHD at the transition period; the cutoff value of 110 ng/mL showed 94.5% sensitivity and 100% specificity. Mean IGF-1 values did not differ in IGHD or CGHD associated with one, two, three, or four additional pituitary deficiencies. CONCLUSION: IGF-1 measurement is accurate to replace ITT as initial diagnostic test for IGHD and CGHD detection at the transition phase.

OBJETIVO: Avaliar a acurácia da dosagem sérica de IGF-1 no diagnóstico da deficiência de hormônio de crescimento isolada (DGHI) ou combinada (DGHC) na fase de transição. SUJEITOS E MÉTODOS: Quarenta e nove pacientes com DGH na infância [16 DGHI (10 homens) e 33 DGHC (24 homens); idade 23,2 ± 3,5 anos] realizaram teste de tolerância à insulina (TTI), com pico de GH < 5 µg/L considerado diagnóstico de DGH na transição. Função hipofisária e níveis de IGF-1 foram determinados na amostra basal do TTI e os pacientes foram reclassificados em GH suficientes (SGH; n = 12), DGHI (n = 7) ou DGHC (n = 30). RESULTADOS: Cinco (31%) pacientes com DGHI e 32 (97%) com DGHC na infância persistiram com DGH no reteste. Um paciente com DGHI foi reclassificado como DGHC e três com DGHC como DGHI. Os picos médios de GH foram 0,2 ± 0,3 µg/L (DGHC), 1,3 ± 1,5 µg/L (DGHI) e 18,1 ± 13,1 µg/L (SGH). O nível médio de IGF-1 foi maior no grupo SGH (272 ± 107 ng/mL) comparado com DGHI (100,2 ± 110) e DGHC (48,7 ± 32,8) (p < 0,01). IGF-1 baixo foi observado em todos os pacientes reclassificados como DGHC, 86% dos DGHI e 8,3% dos SGH, resultando em sensibilidade de 97,3% e especificidade de 91,6% para detecção de DGH na transição; valor de corte de 110 ng/mL mostrou 94,5% sensibilidade e 100% especificidade. O nível médio de IGF-1 foi similar nos pacientes com DGHI ou DGHC com uma, duas, três ou quatro deficiências hipofisárias associadas. CONCLUSÃO: A dosagem sérica de IGF-1 mostrou-se acurada para substituir o TTI na detecção tanto de DGHI como DGHC na transição.

Variations in the vitamin D-binding protein (DBP) gene are related to lower 25-hydroxyvitamin D levels in healthy girls: a cross-sectional study.

BACKGROUND/AIMS: Vitamin D deficiency has been recognized as a worldwide epidemic affecting several pediatric and adolescent populations. We determined the genotype and haplotype distribution of the rs4588 and rs7041 polymorphisms of the GC gene encoding vitamin D-binding protein (DBP) and investigated the associations between these gene variants and their haplotypes with 25-hydroxyvitamin D [25(OH)D] levels in girls from South Brazil. METHODS: Cross-sectional study including 198 apparently healthy girls aged 10-18 years. Plasma levels of 25(OH)D were assessed by radioimmunoassay. Participants were genotyped for rs4588 and rs7041 by real-time PCR, with allelic discrimination assays. RESULTS: Mean chronological age and BMI percentile were 13.17 ± 1.74 years and 57.81 ± 29.03, respectively. Sufficient circulating 25(OH)D levels (≥30 ng/ml) were found in 9.1% of the overall group, insufficient levels (20-29.9 ng/ml) in 59.6%, and deficient levels (<20 ng/ml) in 31.3%. The AA genotype of rs4588, TT genotype of rs7041 and CT-AT/AT-AT (GC 1f-2/2-2) diplotypes were significantly associated with lower 25(OH)D levels, even after adjustment for age and season at the time of blood collection. CONCLUSIONS: The GC gene genotype may be related to the susceptibility to low 25(OH)D levels in female children and adolescents.

Reappraisal of serum insulin-like growth factor-I (IGF-1) measurement in the detection of isolated and combined growth hormone deficiency (GHD) during the transition period.

OBJECTIVE: To evaluate the accuracy of serum IGF-1 in the detection of isolated (IGHD) or combined growth hormone deficiency (CGHD) at the transition phase. SUBJECTS AND METHODS: Forty nine patients with GHD during childhood [16 with IGHD (10 men) and 33 with CGHD (24 men); age 23.2 ± 3.5 yrs.] were submitted to an insulin tolerance test (ITT) with a GH peak < 5 µg/L used for the diagnosis of GHD at the transition phase. Pituitary function and IGF-1 measurements were evaluated in the basal sample of the ITT. Transition patients were reclassified as GH-sufficient (SGH; n = 12), IGHD (n = 7), or CGHD (n = 30). RESULTS: Five (31%) patients with IGHD and 32 (97%) with CGHD at childhood persisted with GHD at retesting. One patient with IGHD was reclassified as CGHD, whereas 3 patients with CGHD were reclassified as IGHD. Mean GH peak was 0.2 ± 0.3 µg/L in the CGHD, 1.3 ± 1.5 µg/L in the IGHD, and 18.1 ± 13.1 µg/L in the SGH group. Serum IGF-1 level was significantly higher in the SGH (272 ± 107 ng/mL) compared to IGHD (100.2 ± 110) and CGHD (48.7 ± 32.8) (p < 0.01). All patients reclassified as CGHD, 86% reclassified as IGHD, and 8.3% reclassified as SGH had low IGF-1 level, resulting in 97.3% sensitivity and 91.6% specificity in the detection of GHD at the transition period; the cutoff value of 110 ng/mL showed 94.5% sensitivity and 100% specificity. Mean IGF-1 values did not differ in IGHD or CGHD associated with one, two, three, or four additional pituitary deficiencies. CONCLUSION: IGF-1 measurement is accurate to replace ITT as initial diagnostic test for IGHD and CGHD detection at the transition phase.

GH-releasing hormone receptor gene: a novel splice-disrupting mutation and study of founder effects.

BACKGROUND: Mutations in GH-releasing hormone receptor gene (GHRHR) are emerging as the most common cause of autosomal recessive isolated GH deficiency (IGHD). OBJECTIVE: To search for GHRHR mutations in patients with familial or sporadic IGHD and to investigate founder effects in recurring mutations. METHODS: The coding region of GHRHR was entirely amplified and sequenced from DNA of 18 patients with IGHD (16 unrelated) with topic posterior pituitary lobe on MRI. Haplotypes containing promoter SNPs and microsatellites flanking GHRHR were analyzed in patients with c.57+1G>A (IVS1+1G>A) mutation of our previously published kindred and also a Brazilian patient and 2 previously reported Japanese sisters with c.1146G>A (p.E382E) mutation. RESULTS: A novel homozygous intronic GHRHR c.752-1G>A (IVS7-1G>A) mutation, predicting loss of the constitutive splice acceptor site, was identified in two siblings with IGHD. A compound heterozygous c.[57+1G>A];[1146G>A] and a heterozygous c.527C>T (p.A176V) were found in two sporadic cases. Haplotype analysis provided evidence for a founder effect for the c.57+1G>A mutation and independent recurrence for the c.1146G>A mutation. CONCLUSION: We report a novel splice-disrupting mutation in GHRHR in 2 siblings and provide evidence that all c.57+1G>A (IVS1+1G>A) mutant chromosomes have the same haplotype ancestor, indicating the occurrence of a founder effect in Brazilian patients with IGHD.

Vitamin D deficiency in girls from South Brazil: a cross-sectional study on prevalence and association with vitamin D receptor gene variants.

BACKGROUND: Vitamin D deficiency has been associated with a multitude of disorders including diabetes, defective insulin secretion as well as rickets and poor bone health. Vitamin D is also a concern during childhood and adolescence and has been reported in girls from South Brazil. We determined the prevalence of vitamin D deficiency in girls from South Brazil and investigated whether the genotypic distribution of the BsmI, ApaI and TaqI polymorphisms of the VDR gene and their haplotypes were associated with vitamin D levels. METHODS: Cross-sectional study including 234 apparently healthy girls aged 7 to 18 years. Height and weight were measured for calculation of body mass index (BMI) percentiles for age. Plasma levels of 25-hydroxyvitamin D [25(OH)D] were assessed. Participants were genotyped for ApaI (rs7975232), TaqI (rs731236), and BsmI (rs1544410) SNPs. RESULTS: The median and interquartile range (25-75%) of BMI percentile was 62.0 (33.3 - 84.9). The frequency of overweight/obesity was 24.9%. Circulating levels of 25(OH)D (≥ 30 ng/mL) were adequate in 9.4%; insufficient in 54.3% (20-29 ng/mL); and deficient in 36.3% (< 20 ng/mL). Genotype frequencies were GG = 47.0%, GA = 41.5%, and AA = 11.5% for BsmI; GG = 16.7%, GT = 52.6%, and TT = 30.8% for ApaI; TT = 46.2%, TC = 44.9% and CC = 9.0% for TaqI. Genotypes with no gene variance (ancestral wild genotype) of BsmI (GG vs. GA + AA, two-tailed Student's t-test p < 0.001), ApaI (GG vs. GT + TT, two-tailed Student's t-test p = 0.031) and TaqI (TT vs. TC + CC, two-tailed Student's t-test p = 0.005) SNPs and the GGT haplotype (two-tailed Student's t-test p = 0.036) were significantly associated with lower 25(OH)D levels. CONCLUSIONS: 25-hydroxyvitamin D deficiency and insufficiency were highly prevalent in this sample. The BsmI, ApaI and TaqI wild variants of the VDR gene, as well as the GGT haplotype, were associated with lower vitamin D levels, suggesting that VDR gene polymorphisms could be linked to higher susceptibility to vitamin D deficiency in a sub-population of children and adolescents.

Correlation of cardiorespiratory fitness with risk factors for cardiovascular disease in children with type 1 diabetes mellitus.

UNLABELLED: The objective of this study was to correlate CRF with cardiovascular risk factors in T1DM children. METHODS: Fifty children and adolescents aged between 9 and 17 years with no diabetes complications and a mean diabetes duration of 4.6 years were selected. Antropometric, sexual maturation and blood pressure data were evaluated. CRF level was assessed with a 20-m shuttle run test. Laboratory tests were performed to verify fasting lipids and glycated hemoglobin. Statistical analyses were made with Pearson partial correlation, t test, and one-way ANOVA, with p≤0.05. RESULTS: After adjustment for body adiposity and sexual maturity, inverse correlations among CRF and TC, TG, TC/HDL-C, TG/HDL-C, non-HDL-C, and SBP were statistically significant. Variables differing by sex included weight Z score, BMI Z score, skinfold thickness, percentage of body fat, and DBP. Boys had higher CRF compared to girls. CRF and TC differed significantly by sexual maturation status. CONCLUSION: An inverse and significant relationship between CRF and most lipid profile's components and SBP in poor controlled T1DM children and adolescents was found, independently of body adiposity.

GH deficiency during the transition period: clinical characteristics before and after GH replacement therapy in two different subgroups of patients.

OBJECTIVE: To study two subsets of patients with GH deficiency (GHD) during the transition period: childhood onset GHD (CO-GHD) and patients who develop GHD during the transition phase (TO-GHD) before and after GH replacement. PATIENTS AND MEASUREMENTS: In 1340 GHD subjects from KIMS (Pfizer International Metabolic Database), CO (n=586) or TO (n=754), background characteristics, anthropometric measurements, IGF-1, lipids and quality of life (QoL) were evaluated at baseline and after 3 years of GH replacement. RESULTS: Both groups responded similarly to GH treatment. Changes of clinical outcomes were mainly determined by their value at baseline. Onset of the disease in childhood or transition period did not appear to be a significant predictor of response in any of the clinical outcomes. CONCLUSIONS: Age at GHD diagnosis was a significant predictor for many outcomes at baseline, but disease onset did not appear as an independent predictor concerning changes after 3 years of GH treatment. The results suggest that GH replacement during the transition period should be considered independently of the onset of the deficiency.

Physical activity, cardiorespiratory fitness, and metabolic syndrome in adolescents: a cross-sectional study.

BACKGROUND: In adults, there is a substantial body of evidence that physical inactivity or low cardiorespiratory fitness levels are strongly associated with the development of metabolic syndrome. Although this association has been studied extensively in adults, little is known regarding this association in adolescents. The aim of this study was to analyze the association between physical activity and cardiorespiratory fitness levels with metabolic syndrome in Brazilian adolescents. METHODS: A random sample of 223 girls (mean age, 14.4 ± 1.6 years) and 233 boys (mean age, 14.6 ± 1.6 years) was selected for the study. The level of physical activity was determined by the Bouchard three-day physical activity record. Cardiorespiratory fitness was estimated by the Leger 20-meter shuttle run test. The metabolic syndrome components assessed included waist circumference, blood pressure, HDL-cholesterol, triglycerides, and fasting plasma glucose levels. Independent Student t-tests were used to assess gender differences. The associations between physical activity and cardiorespiratory fitness with the presence of metabolic syndrome were calculated using logistic regression models adjusted for age and gender. RESULTS: A high prevalence of metabolic syndrome was observed in inactive adolescents (males, 11.4%; females, 7.2%) and adolescents with low cardiorespiratory fitness levels (males, 13.9%; females, 8.6%). A significant relationship existed between metabolic syndrome and low cardiorespiratory fitness (OR, 3.0 [1.13-7.94]). CONCLUSION: The prevalence of metabolic syndrome is high among adolescents who are inactive and those with low cardiorespiratory fitness. Prevention strategies for metabolic syndrome should concentrate on enhancing fitness levels early in life.