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

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. Resumo: Objetivos: Discutir a etiologia e as consequências para o crescimento e as indicações, os efeitos e 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. Keywords: Small for gestational age, Catch-up, Growth hormone, Short stature, Adult height, Palavras-chave: Pequeno para a idade gestacional, Catch-up, Hormônio de crescimento, Baixa estatura, Estatura adult

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. 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. Keywords: Small for gestational age, Catch‐up, Growth hormone, Short stature, Adult height, Palavras‐chave: Pequeno para a idade gestacional, Catch‐up, Hormônio de crescimento, Baixa estatura, Estatura adult

Potential Effects of Oral Isotretinoin on Growth Plate and Height

Longitudinal growth and puberty are the result of a complex interaction of genetic, hormonal, nutritional, and environmental factors. Acne vulgaris is a chronic disease of the pilosebaceous unit that affects 85% of adolescents worldwide. Isotretinoin is a synthetic vitamin A derivative drug effective and is widely employed for the treatment of moderate and severe acne vulgaris. Premature epiphyseal closure has been reported in patients with neuroblastoma treated with high doses of isotretinoin as well as in patients with acne receiving lower doses. Although the mechanisms for these effects are not clear, it has been suggested that isotretinoin may have a negative impact on the GH-IGF-I axis, leading to a reduction in IGF-I and IGFBP3 serum levels. Although many of the isotretinoin adverse effects in pediatric patients are transient, premature epiphyseal closure and bone abnormalities can lead to transient abnormalities and permanent deformities with a negative impact on longitudinal growth and final height. The aim of this study was to review the potential effects of oral isotretinoin on the growth plate and growth during childhood and adolescence

Clinical and laboratory profile of pediatric and adolescent patients with type 1 diabetes

OBJECTIVE: To evaluate clinical and laboratory profiles of patients with type 1 diabetes mellitus in three public hospitals in São Paulo, Brazil, since type 1 diabetes mellitus is a chronic illness that occurs mainly in the pediatric age group in the Brazilian population. METHODS: Cross-sectional study with patients followed up in reference centers in São José do Rio Preto (FAMERP), Campinas (UNICAMP) and São Paulo (Conjunto Hospitalar do Mandaqui). Data about gender, age, diabetes duration, daily insulin dose, number of daily insulin injections, and glycosylated hemoglobin (HbA1c) were analyzed. RESULTS: Two hundred and thirty-nine patients (131 females) were evaluated; mean age was 13.1±4.7 years and mean diabetes duration was 6.6±4.2 years. Daily insulin doses ranged from 0.1 to 1.78 units/kg/day (0.88±0.28), and 180 (74.7%) patients had two daily injections. HbA1c ranged from 4.6 to 17.9% (10.0±2.3%). CONCLUSIONS: Although the hospitals included in this study are excellence centers for the follow-up of patients with diabetes in three municipalities in the state of São Paulo, one of the most developed states in Brazil, blood glucose control evaluated according to HbA1c was not adequate. Findings confirm that, despite the efforts of all the professionals involved, great challenges still lie ahead.OBJETIVO: Realizar a avaliação clínica e laboratorial dos pacientes com diabetes melito tipo 1 em três hospitais públicos em São Paulo (SP), uma vez que o diabetes melito tipo 1 é uma doença crônica que ocorre principalmente em crianças e adolescentes. MÉTODOS: Estudo transversal com pacientes em acompanhamento em centros de referência em São José do Rio Preto (FAMERP), Campinas (UNICAMP) e São Paulo (Conjunto Hospitalar do Mandaqui). Dados como gênero, idade, duração do diabetes, dose diária de insulina, número de aplicações diárias de insulina e hemoglobina glicosilada (HbA1c) foram analisados. RESULTADOS: Foram avaliados 239 pacientes (131 do sexo feminino); a idade média foi de 13,1±4,7 anos e o tempo médio de duração do diabetes foi de 6,6±4,2 anos. As doses diárias de insulina variaram de 0,1 a 1,78 unidades/kg/dia (0,88±0,28), e 180 (74,7%) pacientes faziam somente duas aplicações por dia. A HbA1c variou de 4,6 a 17,9% (10,0±2,3%). CONCLUSÕES: Embora os hospitais incluídos neste estudo sejam centros de referência para o seguimento de pacientes com diabetes melito em três cidades do estado de São Paulo, um dos estados mais desenvolvidos do Brasil, o controle da glicemia avaliado através da HbA1c não foi adequado. Isso confirma o fato de que, embora haja esforço de todos os profissionais envolvidos, grandes desafios ainda deverão ser vencidos.49049

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