Clinical characteristics of four children with 3M syndrome and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical features of 3M syndrome and effect of growth hormone therapy.@*METHODS@#Clinical data of four children diagnosed with 3M syndrome by whole exome sequencing at Hunan Children's Hospital from January 2014 to February 2022 were retrospectively analyzed, which included clinical manifestation, results of genetic testing and recombinant human growth hormone (rhGH) therapy. A literature review was also carried our for Chinese patients with 3M syndrome.@*RESULTS@#The clinical manifestations of the 4 patients included severe growth retardation, facial dysmorphism and skeletal malformations. Two patients were found to harbor homozygous variants of CUL7 gene, namely c.4717C>T (p.R1573*) and c.967_993delinsCAGCTGG (p.S323Qfs*33). Two patients were found to harbor 3 heterozygous variants of the OBSL1 gene including c.1118G>A (p.W373*), c.458dupG (p.L154Pfs*1002) and c.690dupC (p.E231Rfs*23), among which c.967_993delinsCAGCTGG and c.1118G>A were unreported previously. Eighteen Chinese patients with 3M syndrome were identified through the literature review, including 11 cases (11/18, 61.1%) carrying CUL7 gene variants and 7 cases (7/18, 38.9%) carrying OBSL1 gene variants. The main clinical manifestations were in keeping with previously reported. Four patients were treated with growth hormone, 3 showed obvious growth acceleration, and no adverse reaction was noted.@*CONCLUSION@#3M syndrome has a typical appearance and obvious short stature. To attain accurate diagnosis, genetic testing should be recommended for children with a stature of less than -3 SD and facial dysmorphism. The long-term efficacy of growth hormone therapy for patients with 3M syndrome remains to be observed.

Uso do hormônio do crescimento associado à fibrina rica em plaquetas e leucócitos injetável (I-PRF) / Use of the growth hormone associated with injectable platelet-rich fibrin (I-PRF)

Objetivo: demonstrar, por meio de uma revisão de literatura, a utilização do hormônio do crescimento (GH) e concentrados plaquetários e sugerir técnica de associação de uso para odontologia em processos de preservação de osso alveolar. Revisão de literatura: enxertos ósseos são uma necessidade na área da saúde, por diversas razões. A utilização de osso autógeno apresenta grande desvantagem em ter um segundo sítio cirúrgico, entretanto, os substitutos ósseos não possuem as características ideais. Assim, existe a busca por alternativas que otimizem a cicatrização e a incorporação dos substitutos ósseos, dentre elas os concentrados sanguíneos, ricos em fatores de crescimento derivados das plaquetas e o hormônio do crescimento. É possível encontrar uma vasta literatura utilizando os concentrados sanguíneos, inclusive utilizando esses como veículos para outras substâncias. Os concentrados sanguíneos são ricos em fatores de crescimento derivados das plaquetas, como fator de crescimento semelhante à insulina (IGF), Fator de crescimento derivado de plaquetas (PDGF) e outros. Além disso, também é possível encontrar, na literatura, o uso tópico de hormônio do crescimento em enxertos ósseos, fraturas e implantes dentários. Entretanto, o GH possui uma meia-vida de 20 minutos, assim, quando utilizado em conjunto com a I-PRF, espera-se um aumento no tempo de ação local. Considerações finais: é possível otimizar os enxertos ósseos utilizando-se L-PRF/I-PRF e hormônio do crescimento. Porém, são necessárias mais pesquisas.(AU)

Objective: this study aims to show through a literature review the use of the growth hormone and platelet concentrates and to suggest an association technique for dentistry use in alveolar bone preservation processes. Literature review: bone grafts are a health requirement for a number of reasons. The use of autogenous bone has the main disadvantage of a second surgical site, while bone substitutes do not present optimal characteristics. Thus, there is a search for alternatives that optimize the healing and incorporation of bone substitutes, which include blood concentrates that are rich in platelet-derived growth factors and the growth hormone. A vast literature can be found on blood concentrates, including their use as vehicles to other substances. Blood concentrates are rich in platelet-derived growth factors such as IGF, PDGF, and others. Moreover, the literature also shows the topical use of the growth hormone in bone grafts, fractures, and dental implants. However, the growth hormone presents a half-life of 20 minutes; therefore, when combined with I-PRF, an increased time in local action is expected. Final considerations: it is possible to optimize bone grafts by using L-PRF/I-PRF and the growth hormone. However, further research is required.(AU)

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.

Aplicación del Heberprot-P® en un paciente con pie diabético neuroinfeccioso / Application of Heberprot-P® in a patient with neuroinfectious diabetic foot

Se describe el caso clínico de un paciente de 51 años de edad, con diabetes mellitus de tipo 2 desde hacía alrededor de 26 años, al que se le diagnosticó pie diabético neuroinfeccioso. Inicialmente fue ingresado en el Servicio de Angiología del Hospital Provincial Docente Clinicoquirúrgico Saturnino Lora Torres de Santiago de Cuba, donde se le indicó Heberprot-P® como parte del tratamiento, primero 3 bulbos de 75 mg cada uno y luego 8 bulbos de 25 mg; estos últimos fueron aplicados de forma ambulatoria en el policlínico de su área de salud. A las 11 semanas de comenzada la terapéutica se logró la cicatrización total de la lesión

The case report of a 51 years patient with type 2 diabetes mellitus for around 26 years is described, to whom neuroinfectious diabetic foot was diagnosed. Initially, he was admitted to the Angiology Service of Saturnino Lora Torres Teaching Clinical Surgical Provincial Hospital in Santiago de Cuba, where Heberprot-P® was indicated as part of the treatment, first 3 bulbs of 75 mg each and then 8 bulbs of 25 mg; the latter were applied in an ambulatory way in the polyclinic of his health area. After 11 weeks of beginning the therapy the total scaring of the lesion was achieved

Hormônio do crescimento como adjuvante à estimulação ovariana de pacientes más respondedoras candidatas à fertilização in vitro / Growth hormone as an adjuvant to ovarian stimulation of poor responder IVF candidates

A má resposta ovariana em fertilização in vitro apresenta uma prevalência de 2 a 30% dos ciclos de estimulação ovariana. Diversos tratamentos adjuvantes são encontrados na literatura, no entanto, a utilização de hormônio de crescimento (GH) adjuvante foi o que apresentou os resultados mais promissores, com elevação da taxa de gravidez em até 17% nestas pacientes. O objetivo deste estudo foi realizar uma revisão da literatura para esclarecer como o GH atua na estimulação ovariana e para investigar as formas de utilização em más respondedoras. Foram encontrados estudos que relacionam a utilização de GH com o aumento no número de oócitos, na sua qualidade, na redução do tempo de êxito na concepção, na taxa de nascimentos, no estímulo de secreção de progesterona e de gonadotrofina coriônica humana (hCG). Foram discutidas as limitações dos estudos anteriores e de que forma limitam ou condicionam os resultados encontrados. Apesar dos estudos revisados terem diferido na dosagem e na forma de utilização do GH, seus resultados suportaram a proposta de utilização de GH no protocolo de estimulação de pacientes más respondedoras.(AU)

Between 2 and 30% of the patients submitted to ovarian stimulation present poor ovarian response. Several adjuvant treatments were found in the literature, however, the use of growth hormone (GH) as adjuvant presented the most promising results, increasing pregnancy rates in up to 17% in these patients. The objective of this study was to review the literature in order to clarify how GH acts on ovarian stimulation and to investigate ways to use it in poor responders. Studies that relate the use of GH with increase in the number of oocytes, on its quality, in the reduction of time to conception, life birth rate, in the stimulus of progesterone and human corionic gonadotropin (hCG) secretion were found.. The limitations found on previous studies and the way in which they limit or condition the founded results were discussed. Although the dosage and ways of use of GH have differed on the reviewed studies, their results supported the proposal of GH use on the stimulation protocols for poor responder patients.(AU)

Doença periodontal em adultos com Deficiência Isolada do Hormônio do Crescimento: aspectos clínicos, microbiológicos e imunológicos / Periodontal disease in adults with isolated growth hormone deficiency: clinical, microbiological and immunological aspects

Indivíduos com Deficiência Isolada do Hormônio do Crescimento (IGHD), homozigotos para a mutação c.57+1G>A no gene do receptor do hormônio liberador do hormônio de crescimento (GHRH), apresentam maior chance de apresentarem perda de inserção periodontal devido a possível efeito direto da IGHD sobre os tecidos periodontais e/ou a repercussões locais ou sistêmicas da IGHD sobre a resposta imune. Este estudo teve como objetivos avaliar as repercussões locais e sistêmicas da IGHD sobre a resposta imune e comparar os níveis dos patógenos periodontais. Material e Métodos: Foi composto por uma amostra de 19 indivíduos com IGHD e 19 indivíduos no grupo controle, pareados por idade, gênero, condição sócio-econômica, tabagismo e diabetes. Todos foram submetidos a exame periodontal completo, em 6 sítios por dente, e entrevistados por meio de um questionário estruturado. Foi realizada coleta de biofilme subgengival (em sítios rasos e profundos, pareados pela PCS) para verificar os níveis dos microorganismos. Além disso, foram realizadas coletas do fluido gengival (dos mesmos sítios) e do sangue, de ambos os grupos, com a finalidade de analisar o perfil das citocinas inflamatórias. Resultados: Indivíduos com IGHD apresentaram maior quantidade de MMP-8 e CRP (p=0,026 e 0,002) no fluido gengival coletado dos sítios profundos, maior quantidade de IL-17 (p=0,02) no soro e mesmos níveis dos patógenos periodontais, em comparação com os controles (p>0,05). Conclusões: Mesmo com um perfil microbiológico semelhante, indivíduos com a IGHD apresentam alterações imunológicas moderadas (aumento de Interleucina 17 no soro e de metaloproteinase-8 e Proteína C-Reativa no fluido gengival coletado de sítios profundos), comparados aos controles.

Isolated Growth Hormone Deficiency (IGHD) subjects, homozygous to a mutation c.57+1G>A in the growth hormone releasing hormone receptor (GHRHR) gene, have a greater chance of having periodontal attachment loss (PAL) due to a possible direct effect of IGHD on the periodontal tissues and/or locals and systemic effects of IGHD on immune response. This aims of this study was evaluate local and systemic effects of IGHD on immune response and compare periodontal pathogens levels. Material and Methods: The sample was composed of 19 IGHD individuals and 19 controls, matched by age, gender, socio-economic condition, smoking and diabetes. Participants were submitted to a clinical full-mouth periodontal examination of six sites per tooth and were interviewed using a structured questionnaire. Subgingival biofilm was collected (in shallow and deep sites matched by probing clinical depth) to check the periodontal pathogens levels. Futhermore, gingival crevicular fluid (same sites) and blood samples were also collected from both groups to analyze inflammatory cytokines profile. Results: IGHD subjects had significantly higher amounts of MMP-8 and CRP (p= 0.026 e 0.002) in the gingival crevicular fluid collected from deep sites, higher amounts of IL-17 (p=0.02) in serum, and same levels of periodontal pathogens, compairing to the control group (p>0.05). Conclusions: Despite the same microorganism profile, IGHD subjects had moderate immunological alterations (increased serum Interleukin 17 and metalloproteinase 8 and C - reactive protein in deep sites gingival fluid), comparing to controls.

Efficacy of Short-Term Growth Hormone Treatment in Prepubertal Children with Idiopathic Short Stature

PURPOSE: It has been reported that daily recombinant human growth hormone (GH) treatment showed beneficial effects on growth in prepubertal children with idiopathic short stature (ISS). The present study aimed to validate the GH (Eutropin(R)) effect on growth promotion and safety after short-term GH treatment. MATERIALS AND METHODS: This study was an open-label, multicenter, interventional study conducted at nine university hospitals in Korea between 2008 and 2009. Thirty six prepubertal children with ISS were enrolled in this study to receive 6-month GH treatment. Yearly growth rate, height standard deviation score (SDS), and adverse events were investigated during treatment. RESULTS: After 26 weeks of GH treatment, the height velocity significantly increased by 6.36+/-3.36 cm/year (p<0.001). The lower end of one-sided 95% confidence interval was 5.22 cm/year, far greater than the predefined effect size. The gain in height SDS at week 26 was 0.57+/-0.27 (p<0.0001). Bone age significantly increased after GH treatment, however, bone maturation rate (bone age for chronological age) showed limited advancement. This 26-week GH treatment was effective in increasing serum levels of insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 from baseline (p<0.0001). Eutropin was well tolerated and there were no withdrawals due to adverse events. No clinically significant changes in laboratory values were observed. CONCLUSION: This 6-month daily GH treatment in children with ISS demonstrated increased height velocity, improved height SDS, and increased IGF-I and IGFBP-3 levels with a favorable safety profile.

Efectividad y seguridad de somatropina para el tratamiento del retardo de crecimiento en niños menores de 18 años con insuficiencia renal crónica / Effectiveness and safety of somatropin for the treatment of growth retardation in children under 18 years of age with chronic renal failure

Antecedentes: Descripción de la condición de salud de interés: La Insuficiencia Renal Crónica (IRC) es un síndrome clínico complejo, resultante de un deterioro progresivo e irreversible de la función renal, que se traduce en la incapacidad del riñón para remover los productos de desecho y mantener la homeostasis orgánica. Puede producirse por una variedad de condiciones, incluyendo trastornos congénitos, glomerulares o infecciones. Descripción de la tecnología: La HC es una hormona no sexual, producida en el lóbulo anterior de la glándula pituitaria o hipófisis, en respuesta fundamentalmente, al factor liberador de HC producido por el hipotálamo. La somatropina es la HC obtenida por tecnología de ADN recombinante; actúa como agente anabólico y anticatabólico, estimulando el crecimiento de los huesos largos e incrementando el número y tamaño de las células musculares en niños con deficiencia de HC, con lo cual se consigue un aumento de la talla final del paciente. Evaluación de efectividad y seguridad: Pregunta de evaluación: En niños menores de 18 años con insuficiencia renal crónica, ¿cuál es la efectividad y seguridad de la somatropina comparada con placebo o no intervención, para el tratamiento del retardo de crecimiento? La pregunta de investigación fue refinada y validada con base en: autorización de mercadeo de la tecnología para la indicación de interés (registro sanitario INVIMA), listado de medicamentos vitales no disponibles, cobertura de la tecnología en el Plan Obligatorio de Salud (POS) (Acuerdo 029 de 2011), revisión de grupos terapéuticos (código ATC: Anatomical, Therapeutic, Chemical classification system), recomendaciones de guías de práctica clínica actualizadas, disponibilidad de evidencia sobre efectividad y seguridad (reportes de evaluación de tecnologías, revisiones sistemáticas de la literatura), uso de las tecnologías (listas nacionales de recobro, estadísticas de prescripción, etc), estudios de prevalencia/incidencia y carga de enfermedad, y consulta con un experto temático (especialista clínico) representante de la Asociación Colombiana de Endocrinología Pediátrica. Población: Niños menores de 18 años con insuficiencia renal crónica. Metodología: Búsqueda de literatura, Búsqueda en bases de datos electrónicas. Conclusiones: -Efectividad: en niños menores de 18 años con insuficiencia renal crónica, somatropina comparada con placebo o no intervención, es más efectiva para el aumento de la talla (después de 1 año de tratamiento) y de la velocidad de crecimiento (después de 6 meses y 1 año de tratamiento). La calidad global de la evidencia es baja (metodología GRADE), -Seguridad: los eventos adversos reportados con somatropina son poco comunes y su frecuencia es generalmente similar al grupo control.

Estudio preliminar sobre el tratamiento con hormona de crecimiento humana recombinante en el síndrome de Turner / Preliminary study on the recombinant human growth hormone treatment of Turner's syndrome

Introducción: los pacientes con síndrome de Turner presentan una monosomía parcial o total del gonosoma X, disgenesia gonadal, diversos rasgos físicos típicos, baja talla e infantilismo sexual. Objetivo: evaluar el efecto del tratamiento con hormona de crecimiento recombinante sobre la talla en las pacientes con el diagnóstico clínico y cromosómico de síndrome de Turner. Métodos: se realizó un estudio de tipo descriptivo y retrospectivo a pacientes con síndrome de Turner atendidas en consultas externas en el Departamento de Endocrinología Pediátrica del Instituto Nacional de Endocrinología, desde mayo de 2003 hasta mayo de 2004. La muestra estuvo constituida por 19 niñas. Se confeccionaron dos grupos, uno con aquellas pacientes que recibieron tratamiento con hormona de crecimiento recombinante (n= 9) a una dosis de 0,14 UI/kg/día, administrada vía subcutánea entre las 8:30 y 9:30 pm, que se conoció como grupo A. El segundo quedó conformado con las pacientes que no recibieron dicha hormona (n= 10), denominado grupo B. Los datos necesarios para la investigación fueron obtenidos de la revisión de las historias clínicas. Resultados: un incremento de la talla en el grupo A, que inició el estudio con una talla basal media de 131,7 ± 7,5 cm, para alcanzar una talla media, después de un año de tratamiento, de 137,9 ± 7,1 cm, con una velocidad de crecimiento media en ese año de 6,2 ± 2,3 cm/año. La comparación de ambos grupos después de un año de estudio mostró diferencias significativas en la talla media al año (p= 0,0071) y la velocidad de crecimiento media al año (p= 0,0032). Conclusiones: el tratamiento con hormona de crecimiento recombinante durante el primer año resultó efectivo, al acelerar significativamente la velocidad de crecimiento en las niñas con síndrome de Turner. La ganancia de peso corporal resultó adecuada durante el periodo de estudio, pues se logró mantener una valoración nutricional estable sin modificaciones en el canal percentilar. La inducción de la pubertad no cambió el pronóstico de la talla al final del estudio(AU)

Introduction: Turner's syndrome patients present with total or partial monosomy of X gonosome, general disgenesia, several typical physical traits, short height and sexual infantilism. Objective: to evaluate the effect of recombinant human growth hormone-based treatment on the height of patients clinically and chromosomally diagnosed as Turner's syndrome subjects. Methods: a retrospective and descriptive study was conducted in Turner's syndrome patients, who had been seen from May 2003 to May 2004 at the pediatric endocrinology department of the National Institute of Endocrinology. The sample was made up of 19 girls divided into 2 groups. Group A comprised patients who were treated with recombinant human growth hormone (n= 9) at a dose of 0.14 IU/kg/day subcutaneously administered from 8:30 to 9:30 pm. Group B included the patients who did not receive this treatment (n= 10). The required data for the research stemmed from the medical history check-ups. Results: increase of the Group A patients' height, whose mean basal height at the beginning of the study was just 131.7 ± 7.5 cm and after one year of treatment, they reached 137.9 ± 7.1 cm, at a rate of average growth of 6.2 ± 2.3 cm/year. The comparison of both groups after one year showed significant differences in mean height (p= 0.0071) and mean growth a year (p= 0.0032). Conclusions: the treatment of these patients with the recombinant growth hormone during the first year was effective, since it markedly accelerated the rate of growth in girls with Turner's syndrome. The body weight gain proved to be adequate in the study period, because it managed to keep steady nutritional assessment without changes in the percentile canal. Inducement to puberty did not alter the final height prognosis at the end of the study(AU)

Ética en enfermería: incertidumbre en la efectividad de un tratamiento en un lactante con síndrome de intestino corto / Ethics in nursing: uncertainty in the effectiveness of treatment in an infant with short bowel syndrome

Enfermería como profesión y disciplina debe utilizar el patrón de conocimiento ético para solucionar los problemas a los que se ve enfrentada(o) la (el) enfermera(o) durante el desempeño de sus funciones. En el presente artículo se plantea como objetivo realizar un análisis ético clínico, utilizando para esto el procedimiento de toma de decisiones de Galveston, el cual considera: las indicaciones médicas, las preferencias del paciente, la calidad de vida y los factores no clínicos o contextuales. El análisis corresponde al caso de un lactante de siete meses hospitalizado desde su nacimiento. El menor actualmente se encuentra con diagnósticos principales de síndrome de intestino corto y daño hepático crónico secundario al uso de nutrición parenteral. En este contexto, el equipo de salud se cuestiona sobre continuar con un tratamiento (hormona del crecimiento) que no está alcanzando el restablecimiento de la salud del menor. A partir de la situación del lactante se plantea la siguiente pregunta: ¿es éticamente correcto continuar con un tratamiento que no beneficia al paciente ni mejora su calidad de vida? Se concluye que esta metodología de análisis es una excelente herramienta que puede ser utilizada por la (el) enfermera(o) y los demás miembros del equipo de salud, ya que considera y analiza desde diversas aristas el caso clínico, permitiendo tomar una decisión bien informada, con una visión amplia del problema y su contexto.

Nursing as profession and discipline, must use the pattern of ethical knowledge to solve problems that confront the nurse in the performance of their duties. This paper has like objective to make a clinical ethical analysis, using for this the decision-making procedure of Galveston, which considers: medical indications, patient preferences, quality of life and contextual features. The analysis is about a 7-month infant case hospitalized since birth. The child is now with principal diagnoses of short bowel syndrome and chronic liver damage secondary to parenteral nutrition. In this context, the health team questioned about continuing a treatment (growth hormone) that is not achieving restoring the health of the child. Given the current status of the infant, the health team raises the following question: Is it ethically corrects to continue with a treatment that not benefits the patient and not improves their quality of life? It is concluded that this method of analysis is an excellent tool that can be used by nurses and other health team members because it considers and analyzes from different edges the clinical case, allowing taking an informed decision, with a broad vision´s problem and its context.

A Case of 9.7 Mb Terminal Xp Deletion Including OA1 Locus Associated with Contiguous Gene Syndrome

Terminal or interstitial deletions of Xp (Xp22.2-->Xpter) in males have been recognized as a cause of contiguous gene syndromes showing variable association of apparently unrelated clinical manifestations such as Leri-Weill dyschondrosteosis (SHOX), chondrodysplasia punctata (CDPX1), mental retardation (NLGN4), ichthyosis (STS), Kallmann syndrome (KAL1), and ocular albinism (GPR143). Here we present a case of a 13.5 yr old boy and sister with a same terminal deletion of Xp22.2 resulting in the absence of genes from the telomere of Xp to GPR143 of Xp22. The boy manifested the findings of all of the disorders mentioned above. We began a testosterone enanthate monthly replacement therapy. His sister, 11 yr old, manifested only Leri-Weill dyschondrosteosis, and had engaged in growth hormone therapy for 3 yr. To the best of our knowledge, this is the first report of a male with a 9.7 Mb terminal Xp deletion including the OA1 locus in Korea.

Hormônio de crescimento em crianças e adolescentes com fibrose cística / Growth hormone in children and adolescents with cystic fibrosis

O hormônio de crescimento recombinante humano (rhGH) pode melhorar o ganho ponderal, o crescimento físico e as condições clínicas e pulmonares na fibrose cística (FC). Entretanto, o uso rotineiro, embora promissor, não está estabelecido na literatura. O objetivo deste trabalho foi verificar os benefícios do rhGH em crianças e adolescentes com FC. Realizou-se uma revisão sistemática nas bases de dados PubMed, Lilacs, SciELO, Cochrane, no período de 20002010, utilizando-se as palavras-chave: "fibrose cística", "hormônio de crescimento", "crianças" e "adolescentes". Foram encontrados 77 artigos, sendo incluídos 11 estudos randomizados controlados, com 290 crianças e adolescentes com FC. O uso em curto prazo (1-24 meses) do rhGH melhorou estatura, peso, velocidade de crescimento, massa óssea e componentes da função pulmonar. Efeitos adversos como diabetes não foram observados nos estudos. O uso em curto prazo do rhGH melhorou o crescimento e a composição corporal em pacientes com FC.

The recombinant human growth hormone (rhGH) can improve weight gain, physical growth, clinical and lung in cystic fibrosis (CF). However, the routine use, although promising, is not established in the literature. The objective of this study was to assess the benefits of rhGH in children and adolescents with CF. We conducted a systematic review in the database PubMed, Lilacs, SciELO and Cochrane, in the period 2000-2010, using the keywords: "cystic fibrosis", "growth hormone", "children" and "adolescents". We found 77 articles and included 11 randomized controlled trials, with 290 children and adolescents with CF. The short-term use (1-24 months) of rhGH improved the height, weight, growth rate, bone mineral content and components of pulmonary function. Adverse effects, like diabetes, were not observed in the studies. The short-term use of rhGH improved growth and body composition in patients with CF.

Talla baja idiopática y uso de hormona de crecimiento: documento del consenso de la Sociedad Chilena de Endocrinología y Diabetes / Consensus recommendations of the Chilean Society of Endocrinology an Diabetes on growth hormone use in idiopathic short stature

The diagnosis of idiopathic short stature (ISS) is common among patients with short stature, especially those with a height lower than 2 standard deviations (SD) of the mean. The diagnosis of ISS is considered in children with short stature in whom no recognizable causes are found after a proper evaluation by pediatric endocrinologists. The professional must perform a complete personal and family history, appropriate anthropometry and physical examination and confirm that general and specific laboratory studies including supraphysiological stimuli to measure growth hormone, are normal. Growth hormone (GH) treatment is safe and effective in patients with ISS. Its effects are very similar to those observed in other conditions that affect growth as Turner Syndrome and Small for Gestational Age Short Children. However, treatment is still controversial because ethical, psychological, social, cultural and economic issues, wich are difficult to evaluate, must be taken into account. Individual patient differences and their family environment must also be considered. The hormone is more often indicated to fulfil parent or social environment needs rather than the wish of the patients. Although the treatment is safe, it is not free of complications and its results are often poorer than those expected by patients or their parents. The Chilean Society of Endocrinology and diabetes commissioned a panel of experts among its members, to generate a consensus document on ISS and the use of growth hormone, to provide information and recommendations to the Chilean community.

Response to growth hormone therapy in indian patients.

Objective. To analyse response to growth hormone therapy on Indian patients with short stature. Methods. Data were collected on 71 patients of short stature on GHT. All patients underwent clinical and hormonal evaluation. GHD was diagnosed in the presence of short stature (height SDS < 2) and peak GH levels < 10 ng/ml. Bone age was estimated using Tanner Whitehouse 3 method (TW3). Results. Primary GHD (73%) was the commonest diagnosis among patients on GHT, followed by organic GHD (12.6%), genetic syndromes (8.4%) and systemic diseases (5.4%). Mean chronological age at presentation was 10.07±3.26 years (median-11 years, range 3-15 years), mean height age was 6.98±2.82 years (median 7.5 years, range 1-13 years) and mean bone age (available for 55 patients) was 7.19±3.1 years (median 8.2 years, range 1.3 - 13 years). Patients with systemic diseases (6.75±3.5 years) presented earlier, compared to patients with GHD (10.27±3.16 years) and genetic syndromes (10.18±3.20 years) (p=0.349). Most of the patients on GHT were in the age group 9-15 years (60.6%). Mean height gain with GHT was 8.7±2.7 cm (median 8.3 cm, range 3.0-13cm) during 1st year then decreased to 6.9±2.4 cm (median 7.0 cm, range 3.0-12.5 cm) in the second year, and was maintained through the third year (mean 7.1±3.0 cm, median 7.0, range 3.0-13 cm). Among patients with GHD, those with primary deficiency had significantly better response to GHT in 1st year than secondary deficiency (9.0±2.65 vs 6.8±3.03 cm, p = 0.026). Response to GHT was negatively correlated with CA (r-0.27, p = 0.05), HA (r-0.47, p = 0.027) and BA (r-0.31, p=0.022) at presentation. Four patients (5.6%) developed hypothyroidism and one patient each developed disseminated tuberculosis and rickets. One patient of Turner's syndrome died of adrenal carcinoma. Short follow up and absence of measurement of IGF-1 and IGFBP3 were major limitations of this study. Conclusions. Response to GHT in Indian patients is comparable to western counterparts. Maximum height gain on GHT is during the first year than decreases in second year, but is maintained through third year. Patients with primary GHD had better response than secondary GHD. Response to GHT is negatively correlated with chronological, height and bone age at presentation.

Turner syndrome and its variants.

Case records of female patients with karyotype proven turner syndrome were analyzed. 11 patients had classic Turner karyotype (Group 1) and 13 patients had karyotype suggestive of one of the variants of Turner syndrome (Group 2). There was a median difference of 3 years between the age of presentation and the age of diagnosis in Group 2. Out of the thirteen patients in Group 2, 4 had no clinical stigmata of Turner Syndrome; the rest (n=9) had one or more of the typical clinical stigmata of Turner Syndrome. One patient with a complex mosaic karyotype also had an intracranial medulloblastoma. One patient in each group had coarctation of the aorta. 5 patients in Group 1 and 3 patients in Group 2 had primary hypothyroidism and received levothyroxine. The median Thyroid Stimulating Hormone levels were significantly higher among patients in group 1 than in group 2.

Tratamiento con hormona de crecimiento en niños menores de 6 años de edad, con talla baja, nacidos pequeños para la edad gestacional / Growth hormone treatment in younger than six years of age short children born small for gestational age

Introducción. Un 10 por ciento de los niños nacidos pequeños para la edad gestacional no presentan un crecimiento compensador y permanecen bajos. El tratamiento con hormona de crecimiento, aprobado en los países desarrollados, ha demostrado su eficacia en estos niños. Objetivo. Determinar la eficacia y la seguridad del tratamiento con hormona de crecimiento durante dos años en niños nacidos pequeños para la edad gestacional sin deficiencia de hormona de crecimiento. Material y métodos. Se trataron 14 niños menoresde 6 años con hormona de crecimiento a 1,0 UI/kg/semana. Resultados. Se observó un aumento significativo en la velocidad de crecimiento (media más sobre menos DE) de 5,4 más sobre menos 1,7 cm/año a 9,8 1,5 cm/año y 7,6 más sobre menos 1,5 cm/año durante el primer y segundo años, respectivamente, (p= 0,00058). Ello resultó en una mejoría significativa en el puntaje z de talla(media más sobre menos DE) de -2,79 más sobre menos 0,3 a -1,27 más sobre menos 0,5 en 2 años (p < 0,0001). Se observó un incremento significativo en las concentraciones de IGF-I y su proteína transportadora BP3 a los 12 y 24 meses del tratamiento. Las concentraciones de glucosa e insulina aumentaron significativamente durante el estudio (ANOVA, p = 0,0006 y p = 0,036, respectivamente). Dos de los índices de sensibilidad a la insulina utilizados revelaron una leve alteración en la sensibilidad a la insulina. Conclusiones. El tratamiento durante 2 años con hormona del crecimiento produjo un aumento significativo de la talla de los pacientes nacidos pequeños para la edad gestacional y permitió alcanzar una talla dentro de los límites normales. No se informaron episodios adversos mayores durante el tratamiento.

Introduction. Approximately 10 percent of children born small for gestational age (SGA) do not show spontaneous catch-up growth. Objective. Our objective was to assess the efficacy and safety of 2 years growth hormone treatment in children younger than 6 years of age, born SGA. Material and methods. Fourteen patients, mean age 4.2 more about less 1.1 years were treated with growth hormone at 1.0 UI/kg/wk for two years. Results. Growth velocity increased from a mean more about less SD of 5.4 more about less 1.7 cm/yr to 9.8 more about less 1.50 cm/yr and 7.6 more about less 1.5 cm/yr during the first year and second year, respectively (p 0.00058). Serum IGF-I and its binding protein BP3 increased significantly throughout treatment. Basal glucose and insulin levels increased significantly during treatment, p= 0.0006 and p= 0.036, respectively, without significant changes in postprandial glucose or insulin levels. A mild change in insulin sensitivity was observed along treatment. Conclusion. Two years growth hormone treat-ment induced a significant growth acceleration in children born small for gestational age, allowing them to attain a normal height. No serious adverse events were reported.

Turner syndrome: searching for better outcomes

OBJECTIVES: To assess the results of growth hormone on the growth of girls with Turner Syndrome and identify relevant parameters to improve outcomes. METHODS: Growth velocity and final height were studied in a historical cohort of 41 girls, regularly followed up for hormone distribution at three referral centers. The influence of oxandrolone and of estrogens on the final height was analyzed. The girls (initial chronological age=8.9±3.4years; initial bone age=7.0±3.1years) used 0.19 mg/kg/week of growth hormone for 4.0 ± 2.0 years. RESULTS: In the first year, growth velocity increased by 71.5 percent in 41 girls and 103.4 percent in those who reached final height (11 girls). The whole group had a gain in the height SDS of 0.8 ± 0.7 (p<0.01) and for those who reached a final height of 1.0 ± 0.8 (p<0.01). Final height (143.6 ±6.3 cm) was 3.9 ± 5.3 cm higher than the predicted height, and the height gain occurred before estrogen therapy. Oxandrolone had no significant influence on height gain. The significant variables contributing to the final height were the duration of growth hormone used and its use prior to starting estrogens, the initial height SDS, and the growth velocity during the first year of treatment. CONCLUSIONS: We concluded that the use of growth hormone significantly increased the final height, which remained lower than the target. Results point to a need for starting growth hormone use as early as possible and to maximize treatment before estrogen replacement. It has been observed that even moderate doses of growth hormone may significantly increase early growth velocity.

Diagnosis and growth hormone (GH) therapy in children with GH deficiency: experience in King Chulalongkorn Memorial Hospital, Thailand.

BACKGROUND: Diagnosis of growth hormone deficiency (GHD) needs both clinical and biological aspects such as auxological data and GHprovocative tests, and active metabolites of GH including IGF-I and IGFBP-3. In GHD children, rhGH has been used worldwide with minimal serious side effects. The aims of the present study were to describe the experience in King Chulalongkorn Memorial Hospital regarding diagnosis and treatment with rhGH in GHD children. MATERIAL AND METHOD: Clinical data of 173 short children was retrospectively reviewed. Two GH provocative tests used in the present study were insulin tolerance test (ITT) and clonidine test. To make the diagnosis of GHD, the children had to fail both GH provocative tests (peak GH < 10 ng/ml). Baseline clinical data, IGF-I, and IGFBP-3 were compared between the group with true positive test and the group with false positive test. Thirty-five children with GHD, who had been treated with rhGH, were evaluated in terms of growth response, changes of IGF-I SDS and the relationship between these parameters. RESULTS: From the present study, ITT could diagnose GHD with true positive 57% and false positive 43% and clonidine could diagnose with true positive 67% and false positive 33%. Clinical data including chronological age, bone age, HtSDS, WtSDS, IGF-I SDS, and IGFBP-3 SDS were not different between the true positive and false positive group. rhGH with a mean dose of 29.3 +/- 4.6 microg/kg/day increased height velocity (HV) from 3.9 +/- 2.5 to 9.3 +/- 2.5, 8.1 +/- 1.5, 7.2 +/- 2.2, 6.8 +/- 2.2, 7.6 +/- 2.4, and 6.5 +/- 1.8 cm/yr after 6 months, 1, 2, 3, 4, and 5 years after treatment, respectively. This also improved HtSDS during treatment and brought the HtSDS into the target range after 3 years of treatment. At the end of the first year of treatment, the difference of IGF-I SDS (DeltaIGF-I SDS) > or = 1 could predict a good response (DeltaHtSDS > or = 0.5) with sensitivity of 88.9% and specificity of 60% respectively. At the end of the second year, DeltaIGF-I SDS > or = 1 could predict a good response with sensitivity and specificity of 100% and 29%, respectively. CONCLUSION: From the present study, the authors demonstrated the investigation and treatment practices of short children with GHD. The growth response is satisfactory even with a lower dose than suggested. In addition, measurement of IGF-I and IGFBP-3 cannot be used in diagnosing GHD but can predict the height outcome at least by the first 2 years of the treatment. However long-term outcome need to be clarified.