RESUMO
There are known geographical differences in growth hormone deficiency (GHD) patient populations and treatment practices. Here, we present a comparison of safety and effectiveness data from patients treated with recombinant human growth hormone (rhGH) in the USA versus other countries. PAtients TReated with Omnitrope® (PATRO) Children is an international, non-interventional study with Omnitrope® (somatropin, Sandoz Inc.). All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope® are given according to country-specific prescribing information. By September 2018, 294 patients had been enrolled in the USA (53% rhGH-naïve) and 6206 patients had been enrolled across 13 other countries (international group; 86% rhGH-naïve). The most common indication in both groups was GHD. Overall, 194 US patients (66%) and 2977 international patients (48%) experienced adverse events (AEs; 886 and 11,716 events, respectively), most of which were of mild or moderate intensity. The AEs were suspected to be treatment-related in five US patients (1.7%) and 452 international patients (7.3%). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No cases of diabetes mellitus or hyperglycemia were reported. In rhGH-naïve GHD patients, after 3 years of rhGH therapy, the improvement in mean height SD score from baseline was + 1.25 and + 1.35 in US and international patients, respectively. CONCLUSION: Omnitrope® treatment appears to be well tolerated and effective in US patients and those from other countries. Across the pediatric indications included, there was no evidence of an increased risk of developing uncommon or unexpected AEs with rhGH. TRIAL REGISTRATION: NA. WHAT IS KNOWN: ⢠Continued monitoring of patients treated with recombinant human growth hormone (rhGH) is important, particularly in terms of diabetogenic potential and the risk of malignancies. ⢠The PAtients TReated with Omnitrope® (PATRO) Children study is a long-term, post-marketing surveillance program for the rhGH Omnitrope®. WHAT IS NEW: ⢠Omnitrope® is well tolerated and effective in US patients, and those from other countries. ⢠Across all indications included, there were no unexpected adverse events and there was no evidence of an increased risk of developing malignancies or diabetes.
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Diabetes Mellitus , Nanismo Hipofisário , Hormônio do Crescimento Humano , Neoplasias , Criança , Nanismo Hipofisário/induzido quimicamente , Nanismo Hipofisário/tratamento farmacológico , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/epidemiologia , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Estudos Longitudinais , Neoplasias/tratamento farmacológico , Vigilância de Produtos Comercializados , Proteínas Recombinantes/efeitos adversosRESUMO
BACKGROUND AND AIMS: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life. METHODS AND RESULTS: For this longitudinal retrospective study, we studied 151 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24-28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired ß-cell function to compensate for insulin-resistance (disposition index: r = -0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized ß = 0.24; p = 0.036). CONCLUSIONS: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity.
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Metabolismo Energético , Doenças Metabólicas/sangue , Neurotensina/sangue , Obesidade Infantil/sangue , Precursores de Proteínas/sangue , Aumento de Peso , Fatores Etários , Biomarcadores/sangue , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/fisiopatologia , Obesidade Infantil/diagnóstico , Obesidade Infantil/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Regulação para CimaRESUMO
BACKGROUND: Obesity in youth is associated with increased risk of metabolic disorders. Adipose tissue hormones are involved in body-weight regulation. Among these, apelin is recognized as an insulin-sensitizer adipokine. Data on apelin levels in obese children and its relation to insulin-sensitivity are limited. OBJECTIVE: We aimed to evaluate apelin levels in relation to obesity and insulin sensitivity in a large cohort of overweight/obese children and adolescents. Furthermore, these youths were reevaluated after a median 6.5 years of follow-up, thus allowing assessing changes in apelin levels in relation to increasing age and weight changes. METHODS: Clinical data in 909 children and adolescents were collected between 2007 and 2010. Two hundred and one were reexamined at a median 6.5 years of follow-up. All subjects at baseline and at follow-up underwent an OGTT. Apelin levels were measured on sera by ELISA method. RESULTS: At baseline, lower apelin levels were associated with increasing age and puberty (Tanner ≥II 0.67 ± 0.96 ng/mL vs. Tanner I 0.89 ± 1.13 ng/mL, p < .002), but not with body-weight. At follow-up, apelin levels in the 201 subjects reexamined were significantly lower than at baseline (0.45 ± 0.77 ng/mL at follow-up, 0.68 ± 0.95 ng/mL baseline, p < .001), confirming the effects of age and puberty. Body-weight did not affect apelin levels. Multiple regression analysis confirmed that sex and puberty were associated with lower apelin levels, independently from age and insulin-sensitivity. CONCLUSIONS: Apelin levels decrease significantly with pubertal development, whilst body-weight in children and adolescents did not determine changes in apelin. Reduced levels of apelin in children and adolescents may therefore represent a necessary response to maintain the "physiological" insulin resistance of puberty. Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; G: glucose; BMI: Body mass index; DBP: Diastolic blood pressure; ELISA: enzyme-linked immunosorbent assay; HDL-C: High-density lipoprotein-cholesterol; HOMA-B: Homeostatic model assessment for beta-cell function; HOMA-IR: Homeostatic model assessment of insulin-resistance; INS: Insulin; ISI: insulin-sensitivity index; LDL-C: Low-density lipoprotein cholesterol; NW: normal weight; OB: obese; OGTT: oral glucose tolerance test; OW: overweight; SBP: Systolic blood pressure; TC: Total cholesterol; TGs: Triglycerides.
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Desenvolvimento do Adolescente/fisiologia , Apelina/sangue , Resistência à Insulina/fisiologia , Sobrepeso/sangue , Puberdade/fisiologia , Adolescente , Fatores Etários , Criança , Feminino , Seguimentos , Teste de Tolerância a Glucose , Humanos , Masculino , Obesidade Infantil/sangue , Fatores SexuaisRESUMO
OBJECTIVE: The diagnosis of growth hormone deficiency (GHD) is currently based on clinical, auxological, biochemical and neuro-radiological investigation. Provocative tests of GH secretion using physiological/pharmacological stimuli are required to confirm GHD. The clonidine test (CT) is widely used to assess GH secretory status. In this retrospective study, we analyzed the reliability of CT and the effect of puberty in a large number of children with short stature who had been evaluated for suspected GHD. DESIGN AND PATIENTS: Data were collected retrospectively from 327 children and adolescents with short stature (204 boys and 123 girls, median age 10.5 years (IQR 7.90-12.40) followed in four Italian Paediatric Endocrine Units (Cagliari, Genova, Napoli and Roma) between 2005 and 2013. MEASUREMENTS: All children underwent CT as the first GH stimulation test after exclusion of other known cause of their short stature. RESULTS: In 73 prepubertal children and 25 pubertal children, the GH peak after CT was <7 µg/L. GHD was confirmed in 87 (37 organic, 50 idiopathic). Six prepubertal and five pubertal patients showed false positive responses. The median BMI-SDS in these children was similar to that of children with GH peak ≥7 µg/L, and none were obese. Overall, the prevalence of false-positive responses was 3.3%. The median (IQR) peak GH after CT was similar between prepubertal and pubertal GHD (3.80 µg/L [1.7-6.00] vs 3.51 µg/L [0.76-5.74]) and non-GHD (13.70 µg/L [10.70-18.40] vs 12.40 µg/L [9.90-19.25]) children. CONCLUSIONS: Our results show that CT is a reliable and safe GH-releasing agent in both prepubertal and pubertal children.
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Nanismo Hipofisário/sangue , Nanismo Hipofisário/diagnóstico , Hormônio do Crescimento Humano/sangue , Índice de Massa Corporal , Criança , Clonidina/farmacologia , Feminino , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Puberdade/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: Apolipoprotein A-V (ApoA-V) is a recognized regulator of plasma triglycerides (TGs), and previous studies have shown associations between variants in APOA5 (apolipoprotein-A5) gene and high TG levels. Recently, a new association between the Arg282Ser missense mutation (rs778114184 G > T) in APOA5 gene and decreased triglyceride levels has been shown in an adult population from Sardinia. In this study we add further insight into the role of APOA5 by exploring whether this association begins early in life in children, or becomes manifest only in adulthood. We performed the genetic association analysis of APOA5 in a cohort of 925 overweight and obese children and adolescents from Sardinia, Italy, to see if the genetic burden is already at play before modifying risk factors are interacting. RESULTS: We identified 24 heterozygous subjects for the Arg282Ser variant and no homozygous subject. Here we show that the Arg282Ser mutation in APOA5 gene is associated with a significant reduction of TG (-15.5 mg/dl), total (-18.1 mg/dl) and LDL-cholesterol (-14.8 mg/dl) levels in overweight/obese children and adolescents, indicating that indeed this association appears early in life. Also, we observed a significant reduction in serum apoA-V levels in heterozygous children. CONCLUSIONS: Our data clearly show that the Arg282Ser mutation in APOA5 gene determines a reduction of TG, total and LDL-cholesterol and apolipoprotein A-V levels in overweight/obese children and adolescents, demonstrating that this mutation has the power to affect lipid levels already since childhood.
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Apolipoproteína A-V/sangue , LDL-Colesterol/sangue , Mutação de Sentido Incorreto , Obesidade/genética , Triglicerídeos/sangue , Adolescente , Alelos , Apolipoproteína A-V/genética , Criança , HDL-Colesterol/sangue , Estudos de Coortes , Feminino , Expressão Gênica , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Heterozigoto , Humanos , Masculino , Obesidade/sangue , Obesidade/patologiaRESUMO
Chronic kidney disease (CKD) is a significant challenge for pediatric endocrinologists, as children with CKD may present a variety of endocrine complications. Growth failure is common in CKD, and its severity is correlated with the degree of renal insufficiency. Management strategies include addressing reversible comorbidities, optimizing nutrition, and ensuring metabolic control. Kidney replacement therapy, including transplantation, determines a significant improvement in growth. According to a recent Consensus Statement, children with CKD stage 3-or on dialysis older >6 months-are eligible for treatment with recombinant growth hormone (rGH) in the case of persistent growth failure. Treatment with rGH may be considered for those with height between the 3rd and 10th percentile and persistent growth deceleration. In children who received kidney transplantation but continue to experience growth failure, initiation of GH therapy is recommended one year post-transplantation if spontaneous catch-up growth does not occur and steroid-free immunosuppression is not an option. In children with CKD, due to nephropathic cystinosis and persistent growth failure, GH therapy should be considered at all stages of CKD. Potential adverse effects and benefits must be regularly assessed during therapy. Treatment with GH is safe in children with CKD. However, its general efficacy is still controversial. All possible problems with a negative impact on growth should be timely addressed and resolved, whenever possible with a personalized approach to the patient. GH therapy may be useful in promoting catch-up growth in children with residual growth potential. Future research should focus on refining effective therapeutic strategies and establishing consensus guidelines to optimize growth outcomes in this population.
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Silver-Russell syndrome (SRS, OMIM, 180860) is a rare genetic disorder with a wide spectrum of symptoms. The most common features are intrauterine growth retardation (IUGR), poor postnatal development, macrocephaly, triangular face, prominent forehead, body asymmetry, and feeding problems. The diagnosis of SRS is based on a combination of clinical features. Up to 60% of SRS patients have chromosome 7 or 11 abnormalities, and <1% show abnormalities in IGF2 signaling pathway genes (IGF2, HMGA2, PLAG1 and CDKN1C). The underlying genetic cause remains unknown in about 40% of cases (idiopathic SRS). We report a novel IGF2 variant c.[-6-2A>G] (NM_000612) in a child with severe IUGR and clinical features of SRS and confirm the utility of targeted exome sequencing in patients with negative results to common genetic analyses. In addition, we report that long-term growth hormone treatment improves height SDS in this patient.
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Hormônio do Crescimento Humano , Síndrome de Silver-Russell , Criança , Feminino , Humanos , Síndrome de Silver-Russell/tratamento farmacológico , Síndrome de Silver-Russell/genética , Síndrome de Silver-Russell/diagnóstico , Hormônio do Crescimento/genética , Herança Paterna , Fenótipo , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento Humano/genética , Retardo do Crescimento Fetal/genética , Fator de Crescimento Insulin-Like II/genéticaRESUMO
Purpose: Omnitrope® (somatropin) was approved as a biosimilar recombinant human growth hormone (rhGH) in 2006. Here, we report final data from the PAtients TReated with Omnitrope® (PATRO) Children study, a post-marketing surveillance study designed to monitor the long-term safety and effectiveness of this treatment in pediatric patients. Methods: The study population included all pediatric patients treated with Omnitrope® (biosimilar rhGH), administered via daily injection, in routine clinical practice. The primary objective was to assess long-term safety, with effectiveness assessed as a secondary objective. Results: In total, 7359 patients were enrolled and treated in the PATRO Children study; 86.0% were treatment-naïve at baseline. Growth hormone deficiency was the most frequent indication (57.9%), followed by patients born small for gestational age (SGA; 26.6%). The mean (SD) duration of exposure to biosimilar rhGH was 3.66 years (2.39). A total of 16,628 adverse events (AEs) were reported in 3981 (54.1%) patients, most of which were mild/moderate. AEs suspected to be treatment related occurred in 8.3% of patients, most frequently headache (1.6%), injection-site pain (1.1%), or injection-site hematoma (1.1%). The incidence rate (IR) of type 2 diabetes mellitus was 0.11 per 1000 person-years (PY) across all patients, and 0.13 per 1000 PY in patients born SGA. The IR of newly diagnosed primary malignancies was 0.22 per 1000 PY across all patients. In the 6589 patients included in the effectiveness population, a sustained catch-up growth was observed across all indications. After 5 years of treatment, height SDS increased from baseline by a median (range) of +1.79 (-3.7 to 6.2) in treatment-naïve patients and +0.73 (-1.4 to 3.7) in pretreated patients. Conclusion: This final analysis of the PATRO Children study indicates that biosimilar rhGH is well tolerated and effective in real-world clinical practice. These data are consistent with the well-characterized safety profile of rhGH treatment in pediatric patients.
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Medicamentos Biossimilares , Diabetes Mellitus Tipo 2 , Hormônio do Crescimento Humano , Humanos , Criança , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento , Medicamentos Biossimilares/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Proteínas Recombinantes/efeitos adversos , Vigilância de Produtos ComercializadosRESUMO
BACKGROUND: Childhood obesity is a growing epidemic worldwide, and it is associated with metabolic complications, such as insulin resistance. Recently, a genetic variation (rs7607980) in the COBLL1 gene has been associated with lower insulin resistance in adults. The aim of the study was to investigate if the association between COBLL1 rs7607980 genetic variant and lower insulin resistance was present early in life. METHODS: This sequence variant was genotyped in 878 overweight and obese children (mean age: 10 years) from Sardinia, Italy, from the outpatient clinic of the Pediatric Endocrine Unit, at the Regional Hospital for Microcitaemia in Cagliari. Insulin resistance was assessed by measurement of fasting circulating insulin levels before and after an oral glucose tolerance test and by HOMA-IR. RESULTS: The COBLL1 rs7607980 C allele was associated with lower fasting insulin and HOMA-IR levels (p = 0.002 and p = 0.035, respectively) in overweight and obese children. Importantly, lower insulin levels were also observed 2 h after oral glucose tolerance test in C allele carriers (p = 0.009). CONCLUSIONS: The present study shows for the first time, the association between COBLL1 rs7607980 C allele, lower serum insulin levels and lower insulin resistance in overweight and obese children.
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Regulação para Baixo , Resistência à Insulina , Insulina/sangue , Obesidade/genética , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Adolescente , Adulto , Alelos , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Estudos de Associação Genética , Heterozigoto , Homozigoto , Humanos , Itália , Masculino , Obesidade/sangue , Obesidade/metabolismo , Sobrepeso/sangue , Sobrepeso/metabolismo , Fatores de Transcrição/metabolismo , Adulto JovemRESUMO
AIM: We aimed to study the influence of the fat mass and obesity-associated (FTO) gene on eating behavior in 412 obese Sardinian children and adolescents. Genome-wide association studies (GWAS) have identified several susceptibility loci for obesity. Among these, the polymorphisms in the intron 1 of the FTO gene has been found associated to weight gain and obesity in various populations. METHODS: All obese patients were genotyped for the FTO single nucleotide polimorphysm (SNP) rs9939609. In all subjects we evaluated eating behavior using the Child Eating Behaviour Questionnaire (CEBQ). RESULTS: We found no differences in eating behavior according to the genotype, either in the entire cohort, or when subjects were subdivided into four different age groups. CONCLUSIONS: FTO genotype is associated with body mass index but does not influence eating behavior in a selected cohort of obese children from the isolated genetic population of Sardinia.
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Comportamento Alimentar/fisiologia , Obesidade/genética , Proteínas/genética , Adolescente , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Íntrons/genética , Itália , Masculino , Obesidade/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Prevalência , Adulto JovemRESUMO
OBJECTIVE: The natural history of Hashimoto's thyroiditis (HT) and isolated hyperthyrotropinaemia (IH) is not well defined. We therefore studied the natural course of patients with HT and IH and looked for possible prognostic factors. DESIGN: This is retrospective cross-sectional study. PATIENTS: Three hundred and twenty-three patients with HT (88 boys and 235 girls) and 59 with IH (30 boys and 29 girls), mean age 9·9 ± 3·8 years were included in the study. When first examined, 236 of the children with HT had a normal TSH (G0) and in 87, it was elevated but <100% of the upper limit (G1). All IH subjects had elevated TSH. Potential risk factors for thyroid failure were evaluated after 3 years and included the presence or familiarity for endocrine/autoimmune diseases, premature birth, signs and symptoms of hypothyroidism, TSH levels, antithyroid antibodies and thyroid volume. RESULTS: HT: Of those with HT, 170 G0 patients remained stable, 31 moved to G1 and 35 to G2 (hypothyroidism). Thirty-six G1 children moved to G0, 17 remained stable and 34 moved to G2. Of patients with IH: 23 normalized, 28 remained stable and eight became overtly hypothyroid. In patients with HT, the presence of coeliac disease, elevated TSH and thyroid peroxidase antibodies (TPOAb) increased the risk of developing hypothyroidism by 4·0-, 3·4- and 3·5-fold, respectively. The increase in TSH levels during follow-up was strongly predictive of the development of hypothyroidism. In patients with IH, no predictive factor could be identified. CONCLUSIONS: Coeliac disease, elevated TSH and TPOAb at presentation and a progressive increase in TSH are predictive factors for thyroid failure in HT patients.
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Doença de Hashimoto/sangue , Tireotropina/sangue , Adolescente , Autoanticorpos/sangue , Criança , Feminino , Seguimentos , Subunidade alfa de Hormônios Glicoproteicos/sangue , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/imunologia , Masculino , Tamanho do Órgão , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Glândula Tireoide/imunologia , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Tireotropina Subunidade beta/sangue , Tiroxina/sangue , Fatores de Tempo , Tri-Iodotironina/sangueRESUMO
Growth hormone deficiency (GHD) is the most commonly affected pituitary hormone in childhood with a prevalence of 1 in 4000-10000 live births. GH stimulation testing (GHST) is commonly used in the diagnostic workup of GHD. However, GHD can be diagnosed in some clinical conditions without the need of GHST. The diagnosis of GHD in newborns does not require stimulation testing. Likewise infants/children with delayed growth and/or short stature associated with neuroradiological abnormalities and one or more additional pituitary hormone deficiencies may not need GHST. This review summarizes the current evidence on the diagnosis of GHD without stimulation tests.
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Nanismo Hipofisário , Hormônio do Crescimento Humano , Hipopituitarismo , Criança , Nanismo Hipofisário/diagnóstico , Humanos , Hipopituitarismo/diagnóstico , Recém-Nascido , Fator de Crescimento Insulin-Like I , Hormônios HipofisáriosRESUMO
Objective: This retrospective study aimed to evaluate children observed for suspected precocious puberty in five Italian centers of Pediatric Endocrinology during the first wave of coronavirus disease 2019 pandemic (March-September 2020), compared to subjects observed in the same period of the previous year. Design: The study population (490 children) was divided according to the year of observation and final diagnosis: transient thelarche, non-progressive precocious puberty, central precocious puberty (CPP), or early puberty. Results: Between March and September 2020, 338 subjects were referred for suspected precocious puberty, compared to 152 subjects in the same period of 2019 (+122%). The increase was observed in girls (328 subjects in 2020 vs 140 in 2019, P < 0.05), especially during the second half of the period considered (92 girls from March to May vs 236 girls from June to September); while no difference was observed in boys (10 subjects in 2020 vs 12 in 2019). The percentage of girls with confirmed CPP was higher in 2020, compared to 2019 (135/328 girls (41%) vs 37/140 (26%), P < 0.01). Anthropometric and hormonal parameters in 2019 and 2020 CPP girls were not different; 2020 CPP girls showed more prolonged use of electronic devices and a more sedentary lifestyle both before and during the pandemic, compared to the rest of the 2020 population. Conclusions: The present findings corroborate the recently reported association between the complex lifestyle changes related to the lockdown and a higher incidence of CPP in Italian girls.
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Several studies have reported an association of the intronic single nucleotide polymorphism (SNP) rs9939609 of the fat mass and obesity-associated (FTO) gene with obesity and with a number of obesity-related features. We studied the association of rs9939609 with obesity in 912 obese children and adolescents (426 males and 486 females, mean ± SD age 10.5 ± 3.3 years) and in 543 normal weight subjects. A number of biochemical and clinical parameters was also evaluated in 700 of these patients. In the obese group, mean body mass index standard deviation score (BMI-SDS) was similar between the three genotypes. The A allele was present in 55% of the patients' and in 43% of controls' chromosomes. The distribution of heterozygotes was similar between patients and controls (47%), while the distribution of AA homozygotes was significantly higher in patients (31% vs. 20%). Logistic regression analysis on the genotypes yielded a χ(2) of 35.5 with an odds ratio of 1.6 (CI = 1.3-1.8), P < 1 × 10(-5) . None of the clinical and metabolic parameters tested was associated with the genotype. In conclusion, we have confirmed the strong association between FTO and obesity, and shown that only AA homozygotes are predisposed to develop obesity while TT homozygotes might be protected. Finally, we found no association between rs9939609 and a number of obesity-related abnormalities.
Assuntos
Obesidade/genética , Proteínas/genética , Adolescente , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Estudos de Casos e Controles , Criança , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Itália , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVES: An inverse relationship has been shown between body mass index (BMI) and the peak growth hormone (GH) response to stimulation in adults and in children with short stature. This relation is observed even within a normal range of BMI. The aim of this study was to investigate the effect of BMI on the GH response to clonidine in a large number of children with short stature. DESIGN: We conducted a retrospective study on the GH response to clonidine in a single centre. METHODS: We studied 202 children with short stature (135 M and 67 F) who underwent clonidine testing from 2007 to 2009. RESULTS: One hundred and twenty-eight patients had a GH peak >10 µg/l. In univariate regression analysis, the peak GH after clonidine was negatively correlated with BMI-standard deviation score (BMI-SDS) and positively correlated with height velocity-SDS and IGF-I-SDS. Only the relationship between peak GH and BMI-SDS remained significant in children with a BMI-SDS from -2 to +2. In the multivariate stepwise regression analysis, BMI-SDS and IGF-I-SDS were the only significant variables in the entire cohort, explaining 19·5% of the variance in peak GH. When only subjects with BMI-SDS between -2·0 and +2·0 were included in the analysis (n = 173), BMI-SDS alone explained 21·4% of the variability in peak GH. The number of patients who failed the clonidine test increased with increasing BMI-SDS. CONCLUSIONS: BMI affects the GH response to clonidine in children with short stature and should be considered when interpreting the results to the stimulation test.
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Índice de Massa Corporal , Clonidina/farmacologia , Transtornos do Crescimento/sangue , Hormônio do Crescimento Humano/sangue , Adolescente , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Adulto , Análise de Variância , Criança , Feminino , Transtornos do Crescimento/diagnóstico , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Análise de Regressão , Estudos Retrospectivos , Taxa Secretória/efeitos dos fármacosRESUMO
Although there are guidelines for treatment of short stature, open questions regarding optimal management of growth hormone therapy still exist. Experts attending six international meetings agree that successful therapy results in the patient attaining mid-parental height, and relies on correct diagnosis and early intervention. Experts advocate patient followup every 3-6 months, and that growth and adherence should be monitored at each visit. Growth response is variable, and an accepted definition of good/poor response is lacking. Combined with patient education and regular patient follow-up, a definition of treatment response could lead to improved treatment outcomes. Few experts use prediction models in clinical practice, but all agree that pharmacogenetics might improve prediction, enable early therapy modulation, and promote growth. Poor growth is often due to low adherence. Guidance on optimal management of growth hormone therapy is required, with focus on early diagnosis, dosing, treatment monitoring, adherence, and motivation.
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Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Prova Pericial , Transtornos do Crescimento/diagnóstico , Crescimento e Desenvolvimento/efeitos dos fármacos , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Cooperação do Paciente/estatística & dados numéricos , Prática Profissional/estatística & dados numéricos , Prática Profissional/tendências , Prognóstico , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Paediatric disorders of impaired linear growth are challenging to manage, in part because of delays in the identification of pathological short stature and subsequent referral and diagnosis, the requirement for long-term therapy, and frequent poor adherence to treatment, notably with human growth hormone (hGH). Digital health technologies hold promise for improving outcomes in paediatric growth disorders by supporting personalisation of care, from diagnosis to treatment and follow up. The value of automated systems in monitoring linear growth in children has been demonstrated in Finland, with findings that such a system is more effective than a traditional manual system for early diagnosis of abnormal growth. Artificial intelligence has potential to resolve problems of variability that may occur during analysis of growth information, and augmented reality systems have been developed that aim to educate patients and caregivers about growth disorders and their treatment (such as injection techniques for hGH administration). Adherence to hGH treatment is often suboptimal, which negatively impacts the achievement of physical and psychological benefits of the treatment. Personalisation of adherence support necessitates capturing individual patient adherence data; the use of technology to assist with this is exemplified by the use of an electronic injection device, which shares real-time recordings of the timing, date and dose of hGH delivered to the patient with the clinician, via web-based software. The use of an electronic device is associated with high levels of adherence to hGH treatment and improved growth outcomes. It can be anticipated that future technological advances, coupled with continued 'human interventions' from healthcare providers, will further improve management of paediatric growth disorders.
Assuntos
Inteligência Artificial , Tecnologia Digital , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/análise , Adesão à Medicação/estatística & dados numéricos , HumanosRESUMO
The Italian Cancer Registry Association has estimated that for the five-year period 2016-2020, in line with the previous five years, approximately 7000 neoplasms have been diagnosed among children and 4000 among adolescents. Leukemias, brain tumors and lymphomas together account for more than two-thirds of all pediatric cancers. Fortunately, the five-years survival rate has progressively improved reaching 80% thanks to the continuing improvement of therapeutic protocols but most of these cancer survivors will have at least one chronic health condition by 40 years of age. Long-term complications concern various organs and systems and have a multifactorial etiopathogenesis. Obesity, diabetes, and metabolic syndrome represent chronic diseases that affect life expectancy. Cardiovascular risk partly linked to therapies and genetic susceptibility and partly linked to the presence of obesity, diabetes and metabolic syndrome predispose childhood cancer survivors to heart failure, coronary artery disease, valvular disease, arrhythmia. Hence the cardio- metabolic risk of childhood cancer survivors can have a significant impact on their lives, families, and on society at-large. Therefore, it is very important to know the risk factors that predispose to the development of cardio-metabolic pathologies in childhood cancer survivors, the possible primary and secondary prevention strategies, the methods of surveillance and the therapeutic approaches.
Assuntos
Neoplasias Encefálicas , Sobreviventes de Câncer , Doenças Cardiovasculares , Adolescente , Criança , Humanos , Sistema de Registros , Taxa de SobrevidaRESUMO
Growth hormone (GH) deficiency (GHD) in children is defined as impaired production of GH by the pituitary gland that results in growth failure. This disease might be congenital or acquired, and occurs in isolation or in the setting of multiple pituitary hormone deficiency. Isolated GHD has an estimated prevalence of 1 patient per 4000-10,000 live births and can be due to multiple causes, some of which are yet to be determined. Establishing the correct diagnosis remains key in children with short stature, as initiating treatment with recombinant human GH can help them attain their genetically determined adult height. During the past two decades, our understanding of the benefits of continuing GH therapy throughout the transition period from childhood to adulthood has increased. Improvements in transitional care will help alleviate the consequent physical and psychological problems that can arise from adult GHD, although the consequences of a lack of hormone replacement are less severe in adults than in children. In this Review, we discuss the differential diagnosis in children with GHD, including details of clinical presentation, neuroimaging and genetic testing. Furthermore, we highlight advances and issues in the management of GHD, including details of transitional care.