Oś hormon wzrostu–insulinopodobny czynnik wzrostu a karcynogeneza

  The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. (Endokrynol Pol 2016; 67 (4): 414–426)    Oś hormon wzrostu (GH)–insulinopodobny czynnik wzrostu (IGF) odgrywa istotną rolę w regulacji proliferacji i różnicowania komórek, apoptozy i angiogenezy. Oś GH–IGF wpływa na regulację cyklu komórkowego przez pobudzenie szlaku wzrostu komórki w stosunku do szlaków sygnałowych prowadzących do śmierci komórki, a ostateczny efekt oddziaływania tych dwóch sił ma podstawowe znaczenie dla prawidłowego lub nieprawidłowego wzrostu komórki. Hipotezy na temat powiązań osi GH–IGF z karcynogenezą pojawiły się wiele lat temu, głównie w oparciu o wyniki badań in vitro oraz badań z wykorzystaniem różnych zwierzęcych modeli raka występującego u ludzi. Chociaż liczne dane doświadczalne potwierdzają rolę osi GH–IGF sprzyjającą rozwojowi i progresji nowotworów, a nad kilkoma składowymi tej osi trwają obecnie badania oceniające ich przydatność jako główne cele terapii przeciwnowotworowej, to jednak siła dowodów uzyskanych u chorych z akromegalią, niedoborem GH lub osób leczonych GH jest znacznie słabsza. W niniejszej pracy przeglądowej spróbowano zebrać wszystkie te dane. (Endokrynol Pol 2016; 67 (4): 414–426)

Novel SUZ12 mutations in Weaver‐like syndrome

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146320/1/cge13415_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146320/2/cge13415-sup-0001-AppendixS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146320/3/cge13415.pd

Short Children with CHARGE Syndrome: Do They Benefit from Growth Hormone Therapy?

AIM: The aim of this study was to evaluate the response to recombinant growth hormone (GH) treatment in short children with CHARGE syndrome. PATIENTS: We identified 51 children (28 boys and 23 girls) in KIGS (Pfizer International Growth Database). The median chronological age was 7.6 years at the start of GH therapy and 13.2 years at the latest visit. Evaluation for GH deficiency (n = 33) was based on the following: peak GH level 7.3 μg/l and IGF-I level -2.01 standard deviation score (SDS). Sixteen subjects (9 boys) were followed longitudinally for 2 years. RESULTS: Birth length (median SDS, -0.47) and weight (-0.97) were slightly reduced. At the start of GH therapy, height was -3.6 SDS, BMI -0.7 SDS, and the GH dose was 0.26 mg/kg/week. At the latest visit after 2.7 years of GH therapy, height had increased to -2.2 SDS and BMI to -0.5 SDS. In the longitudinal group, height increased from -3.72 SDS at the start of GH therapy to -2.92 SDS after 1 year to -2.37 SDS after 2 years of therapy (start - 2 years: p < 0.05), height velocity increased from -1.69 to 2.98 to 0.95 SDS, and BMI and GH dose (mg/kg/week) remained almost unchanged. CONCLUSIONS: Our data show a positive effect of conventional doses of GH on short-term growth velocity for the longitudinal as well as for the total group, without any safety issues.This study was sponsored by Pfizer Inc.This is the author accepted manuscript. The final version is available from Karger via http://dx.doi.org/10.1159/00038201

Insulin-like growth factor 1 gene (CA)n repeats and a variable number of tandem repeats of the insulin gene in Brazilian children born small for gestational age

OBJECTIVE: To investigate the influence of (CA)n repeats in the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene on birth size in children who are small or adequate-sized for gestational age and to correlate these polymorphisms with serum insulin-like growth factor 1 levels and insulin sensitivity in children who are small for gestational age, with and without catch-up growth. PATIENTS AND METHODS: We evaluated 439 infants: 297 that were adequate-sized for gestational age and 142 that were small for gestational age (66 with and 76 without catch-up). The number of (CA)n repeat in the insulin-like growth factor 1 gene and a variable number of tandem repeats in the insulin gene were analyzed using GENESCAN software and polymerase chain reaction followed by enzymatic digestion, respectively. Clinical and laboratory data were obtained from all patients. RESULTS: The height, body mass index, paternal height, target height and insulin-like growth factor 1 serum levels were higher in children who were small for gestational age with catch-up. There was no difference in the allelic and genotypic distributions of both polymorphisms between the adequate-sized and small infants or among small infants with and without catch-up. Similarly, the polymorphisms were not associated with clinical or laboratory variables. CONCLUSION: Polymorphisms of the (CA)n repeats of the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene, separately or in combination, did not influence pre- or postnatal growth, insulin-like growth factor 1 serum levels or insulin resistance

Perfil glicêmico e lipídico em meninos de diferentes classes sociais

Estudos sugerem que o nível socioeconômico (NSE) exerce influência no distúrbio metabólico, desta forma o presente estudo visou verificar as diferenças do perfil glicêmico e lipídico em meninos de diferentes classes sociais da cidade de Curitiba, Paraná. A amostra constituiu-se de 123 meninos (14,0±2,2 anos) sendo avaliado o perfil antropométrico, NSE, perfil glicêmico e lipídico. A análise estatística foi descritiva e para verificar as diferenças entre os níveis foi utilizado a ANOVA one-way com post hoc de Bonferroni com p< 0,05. Meninos de médio e alto NSE apresentaram maiores valores médios de glicemia em jejum, triglicerídeos (TG) e LDL-c do que indivíduos de baixo NSE (

International Consensus Guideline on Small for Gestational Age (SGA): Etiology and Management from Infancy to Early Adulthood

: This International Consensus Guideline was developed by experts in the field of SGA of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Besides, it presents long-term consequences of SGA birth and new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, and the metabolic and cardiovascular health of young adults born SGA after cessation of childhood-GH-treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardio-metabolic health profile in adulthood. Children born SGA with persistent short stature &lt; -2.5 SDS at age 2 years or &lt; -2 SDS at age of 3-4 years, should be referred for diagnostic work-up. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033-0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3-4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle

Cutoff for body mass index in adolescents: comparison with national and international reference standards

OBJETIVO: elaborar uma tabela percentílica para o índice de massa corporal (IMC) para adolescentes na faixa etária de 10 a 14 anos da cidade de Curitiba, Paraná, e comparar os valores encontrados para o sobrepeso (percentil 85) e obesidade (percentil 95) com referências de IMC nacional, regional e internacional. MÉTODO: estudo longitudinal misto com 5231 avaliações, 2471 em meninos e 2760 em meninas, idades entre 10 e 14 anos. Esse número foi obtido a partir de avaliações semestrais realizadas entre os anos de 1998 a 2002, gerando 4321 observações (estudo longitudinal), mais a avaliação de 910 indivíduos no ano de 2006 (estudo transversal). O IMC foi calculado pela razão entre a massa corporal (Kg) dividida pela estatura (m) ao quadrado. Foram elaboradas tabelas de frequência baseadas na distribuição percentílica. Para identificar as diferenças nos pontos de corte para sobrepeso e obesidade com os estudos nacionais de Cintra e de Conde e Monteiro e com o estudo internacional de Cole foi utilizado teste binomial não paramétrico. RESULTADOS: comparando com as referências, os jovens de Curitiba seriam superestimados com sobrepeso se utilizadas a referência de Conde e a de Cole e subestimados na referência regional de Cintra. As mesmas tendências foram observadas com relação ao percentil 95 (obesidade), porém não para todas as faixas etárias. CONCLUSÃO: observamos diferenças nos valores de IMC sugeridos como pontos de corte para sobrepeso e obesidade em relação às referências nacionais e internacionais reforçando a necessidade de utilização de referências específicas para cada população.OBJECTIVE: to develop a scale percentile for body mass index (BMI) for adolescents aged 10 to 14 years from the city of Curitiba, Paraná, and compare the values found for overweight (85th percentile) and obesity (95th percentile) with references to national and international BMI. METHOD: mixed longitudinal study with 5231 evaluation, 2471 in boys and girls in 2760, aged 10 and 14 years. This number was obtained from semester evaluations conducted between the years 1998 to 2002, generating 4321 observations (longitudinal study), further evaluation of 910 individuals in 2006 (cross-sectional study). BMI was calculated as the ratio of body mass (kg) divided by height (m) squared. Frequency tables were prepared based on the percentile distribution. To identify differences in cut-off points for overweight and obesity with the national study of Cintra, and Conde and with the international study of Cole non-parametric binomial test was used. RESULTS: compared with the references, the young people of Curitiba were overestimated overweight if used for the reference of Conde and Cole and underestimated in the regional reference Cintra. The same trends were observed with respect to the 95th percentile (obesity), but not for all ages. CONCLUSION: we observed differences in the values of BMI suggested as cut-off points for overweight and obesity in relation to national and international references emphasizing the need to use specific references for each population

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

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

Objective The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations