Eficácia e segurança de Somatropina para o tratamento de crianças nascidas pequenas para a idade gestacional: revisão rápida de evidências / Efficacy and safety of Somatropine for the treatment of children born small for gestational age: a rapid response review of evidence

Tecnologia: Somatropina. Indicação: Transtorno de crescimento em crianças nascidas pequenas para a idade gestacional (PIG). Pergunta: A somatropina é eficaz e segura para promover aumento da curva de crescimento em crianças nascidas PIG? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED, seguindo estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews version 2). Resultados: Foi selecionada uma revisão sistemática que atendeu aos critérios de inclusão. Conclusão: evidências de moderada certeza indicam que somatropina é eficaz e segura para tratamento de crianças nascidas PIG, pois promove recuperação do crescimento e não há relatos de eventos adversos graves na literatura científica

Technology: Somatropin. Indication: Growth disorder in children born small for gestational age (SGA). Question: Is somatropin effective, safe and cost effective for promoting height gain in children born SGA? Methods: A bibliographic search was done in PUBMED database, following predefined search strategies. The methodological quality of systematic reviews was evaluated using the AMSTAR-2 tool (A MeaSurement Tool to Assess systematic Reviews version 2). Results: Only a systematic review met the inclusion criteria and was selected. Conclusion: Evidence of moderate certainty indicates that somatropin is effective and safe for the treatment of children born SGA, because the treatment improve the growth and there are no reports of serious adverse events in the scientific literature

Perspectives on long-acting growth hormone therapy in children and adults

ABSTRACT Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7

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.

Effects of the use of growth hormone in children and adolescents with juvenile idiopathic arthritis: a systematic review / Efeitos do uso do hormônio de crescimento em crianças e adolescentes com artrite idiopática juvenil: revisão sistemática

Abstract Introduction: Children with juvenile idiopathic arthritis (JIA) often have impaired growth and short stature. There is evidence that the therapeutic use of growth hormone (GH) is useful and safe in these patients. Objective: To analyze the effects of GH use in patients with JIA. Method: A systematic review of the literature over the last 18 years in Medline and Embase databases. The criteria were analyzed independently by the researchers. We used the following keywords: "growth hormone", "arthritis, juvenile", "arthritis, rheumatoid", "child" and "adolescent". Results: Among the 192 identified articles, 20 corresponded to the inclusion criteria. Seventeen longitudinal studies and 3 case reports were found. Most studies analyzed observed increased growth, muscle mass and bone mass using GH. Adverse effects observed were glucose intolerance, diabetes, bone deformities, osteonecrosis, reactivation of the disease and low final height. Conclusion: The majority of studies reported positive effects after the therapeutic use of GH, but some variability in response to treatment was observed. The combination of growth hormone with other drugs seems to be a good option.

Resumo Introdução: Crianças com artrite idiopática juvenil (AIJ) frequentemente apresentam prejuízo no crescimento e baixa estatura. Existem evidências de que o uso terapêutico do hormônio de crescimento (GH) é útil e seguro nesses pacientes. Objetivo: Analisar os efeitos do uso de GH em pacientes com AIJ. Método: Fez-se revisão sistemática da literatura nos últimos 18 anos, nas bases de dados Medline e Embase. Os critérios foram analisados pelos pesquisadores de forma independente. Usaram-se os seguintes descritores: growth hormone, arthritis, juvenile, arthritis, rheumatoid, child e adolescent. Resultados: Entre os 192 artigos identificados, 20 corresponderam aos critérios de inclusão. Foram encontrados 17 estudos longitudinais e três relatos de casos. A maioria dos estudos analisados observou um aumento de crescimento, massa muscular e massa óssea com o uso do GH. Os efeitos adversos observados foram intolerância à glicose, diabetes, deformidades ósseas, osteonecrose, reativação da doença e altura final baixa. Conclusão: A maioria dos estudos relatou efeitos positivos após uso terapêutico do GH, porém certa variabilidade na resposta ao tratamento foi observada. A combinação do hormônio de crescimento com outros medicamentos parece ser uma boa opção.

Eje somatotrópico y marcadores moleculares del metabolismo mineral en niños en diálisis / Somatotropic axis and molecular markers of mineral metabolism in children undergoing chronic peritoneal dialysis

El retraso del crecimiento de los niños con enfermedad renal crónica es de origen multifactorial, incluyendo la resistencia a hormona de crecimiento (GH) y alteraciones en el metabolismo mineral óseo. Objetivos: 1) Caracterizar marcadores del metabolismo mineral: FGF23-Klotho y del eje somatotrópico: IGF1, IGFBP3 y GHBP, en niños en diálisis peritoneal (DP); 2) Evaluar la evolución de la talla en aquellos pacientes tratados con rhGH. Pacientes y Método: Niños prepuberales en DP seguidos durante 12 meses. Criterios exclusión fueron Tanner > 1, síndrome nefrótico activo, tratamiento esteroidal, malabsorción gastrointestinal, enfermedades endocrinas, síndromes genéticos, uso de rhGH al ingreso del estudio. Se evaluaron variables demográficas, antropométricas: Z talla/edad, (ZT/E), velocidad de crecimiento (VC), bioquímicas (calcio, fósforo, PTH), marcadores del metabolismo mineral (25OHvitD, 1,25OHvitD, FGF23, Klotho), y de crecimiento (IGF-1, IGFBP-3, GHBP). Resultados: Quince pacientes, 7 varones, edad 6,9 ± 3,0 años, tiempo en DP 14,33 ± 12,26 meses. Puntaje ZT/E al mes 1= -1,69 ± 1,03. FGF23: 131,7 ± 279,4 y Klotho: 125,9 ± 24,2 pg/ml. Durante los 12 meses de seguimiento no hubo diferencia significativa en el promedio de las variables. El uso de rhGH en 8 pacientes no mostró mejoría significativa del ZT/E ni la VC. El análisis bivariado mostró correlación positiva entre niveles de Klotho y delta ZT/E, y entre GHBP y VC (p < 0,05). Conclusiones: Los valores de FGF23 se encuentran elevados y los de Klotho disminuidos en niños con enfermedad renal crónica en DP en comparación con niños sanos. Las variables de eje somatotrópico, se encuentran normales o elevadas. rhGH tiende a mejorar la talla y GHBP se correlaciona positivamente con VC en estos niños.

Growth failure is one of the most relevant complications in children with chronic kidney disease (CKD). Among others, growth hormone (GH) resistance and bone mineral disorders have been identified as the most important causes of growth retardation. Objectives: 1. To characterize bone mineral metabolism and growth hormone bio-markers in CKD children treated with chronic peritoneal dialysis (PD). 2. To evaluate height change with rhGH treatment. Patients and Method: A longitudinal 12-month follow-up in prepuberal PD children. Exclusion criteria: Tanner stage >1, nephrotic syndrome, genetic disorders, steroids, intestinal absorption disorders, endocrine disturbances, treatment with GH to the entry of the study. Demographic and anthropometric data were registered. FGF23, Klotho, VitD, IGF-1, IGFBP3, and GHBP were measured to evaluate mineral and growth metabolism. Results: 15 patients, 7 male, age 6.9 ± 3.0 y were included. Time on PD was 14.33 ± 12.26 months. Height/age Z score at month 1 was -1.69 ± 1.03. FGF23 and Klotho: 131.7 ± 279.4 y 125.9 ± 24.2 pg/ml, respectively. 8 patients were treated with GH during 6-12 months, showing a non-significant increase in height/age Z-score during the treatment period. Bivariate analysis showed a positive correlation between Klotho and delta ZT/E, and between GHBP vs growth velocity index (p < .05). Conclusions: FGF23 values were high and Klotho values were reduced in children with CKD in PD, comparing to healthy children. Somatotropic axis variables were normal or elevated. rhGH tends to improve height and there is a positive correlation of GHBP and growth velocity in these children.

Análisis de impacto presupuestal de somatropina para el tratamiento de la restricción del crecimiento en niñas con síndrome de Turner en Colombia / Orçamento somatropina análise de impacto para o tratamento de restrição do crescimento em meninas com síndrome de Turner na Colômbia

Tecnologías evaluadas: Somatropina. Población: Niñas entre 4 y 18 años de edad con restricción del crecimiento por síndrome de Turner en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costo promedio ponderado de la somatropina en Colombia; Costo de la dosis representativa de somatropina de una niña promedio con restricción del crecimiento por síndrome de Turner en Colombia. Fuente de costos: Precios de la somatropina reportados por SISMED. Escenarios: Escenario 1: Dado que la tecnología tiene efectividad decreciente en el tiempo se postula un escenario de adopción de 100% de la tecnología. Escenario 2: Debido a que hay barreras de implementación logísticas, administrativas y presupuestales se propone un escenario alternativo con niveles de adopción de 50% en el primer año, 75% en el segundo y 100% en el tercero. Resultados: El gobierno nacional deberá hacer un esfuerzo financiero de 27.9 mil millones COP en el primer año de adopción de la somatropina como tecnología para el tratamiento del ST y de 28.7 y 29.5 mil millones en cada uno de los dos años siguientes, asumiendo que a totalidad de las niñas con ST se les suministra el medicamento.(AU)

Análisis de impacto presupuestal de somatropina para el tratamiento de niños con déficit de la hormona del crecimiento en Colombia / Budgetary impact analysis of somatropin for the treatment of children with growth hormone deficiency in Colombia

Tecnologías evaluadas: Somatropina. Población: Infantes entre 4 y 18 años de edad con déficit de la hormona\r\ndel crecimiento en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costo promedio ponderado de la somatropina en Colombia; Costo de la dosis representativa de somatropina de un niño y una niña promedio con déficit de la hormona del crecimiento. Fuente de costos: Precios de la somatropina en sus diferentes CUM reportados por SISMED. Escenarios: Escenario 1: Dado que la tecnología tiene efectividad decreciente en el tiempo se postula un escenario de adopción de 100% de la tecnología; Escenario 2: Debido a que hay barreras de implementación logísticas, administrativas y presupuestales se propone un escenario alternativo con niveles de adopción de 50% en el primer año, 75% en el segundo y 100% en el tercero. Resultados: El gobierno nacional deberá hacer un esfuerzo financiero entre 25.9 y 27.3 mil millones COP en el primer año de adopción de la somatropina como tecnología para el tratamiento del DHC y de 26.5 y 27.3 mil millones en cada uno de los dos años siguientes, asumiendo que a totalidad de las infantes con DHC se les suministra el medicamento. (AU)

Reported shoes size during GH therapy: is foot overgrowth a myth or reality?

Objectives To describe population reference values for shoes size, and to identify possible disproportional foot growth during GH therapy.Materials and methods Construction of percentile chart based on 3,651 controls (male: 1,838; female: 1,813). The GH treated group included 13 children with idiopathic short stature (ISS) and 50 children with normal height, but with height prediction below their target height; male: 26 and female: 37 mean ± SD age 13.3 ± 1.9 and 12.9 ± 1.5 years, respectively. GH (0.05 mg/kg/day) was used for 3.2 ± 1.6 years, ranging from 1.0-10.3 years. Height expressed as SDS, target height (TH) SDS, self-reported shoes size and target shoes size (TSS) SDS were recorded.Results Reference values were established showed as a foot SDS calculator available online at www.clinicalcaselearning.com/v2. Definitive shoes size was attained in controls at mean age of 13y in girls and 14y in boys (average values 37 and 40, respectively). In the study group, shoes size was -0.15 ± 0.9 and -0.02 ± 1.3 SDS, with target feet of 0.08 ± 0.8 and -0.27 ± 0.7 SDS in males and females, respectively. There was a significant positive correlation between shoes size and familial TSS, between shoes size and height and between TSS and TH. There was no correlation between duration of GH treatment and shoes size. Our data suggest that during long-term treatment with GH, patients maintain proportional growth in shoes size and height, and the expected correlation with the familial target.Conclusions We conclude that there is no excessive increase in the size of foot as estimated by the size of shoes in individuals under long term GH therapy.

Indicaciones actuales para el uso de la hormona de crecimiento / Growth hormone treatment update

La baja talla en la infancia es una causa frecuente de derivación al endocrinólogo infantil, y corresponde la mayoría de las veces a variantes normales del crecimiento. Inicialmente la terapéutica con hormona de crecimiento humana estaba circunscripta a los niños que presentaban deficiencia de dicha hormona. A partir de la producción de la hormona recombinante humana por ingeniería genética se pudo ampliar su uso a otras patologías.

Short stature in children is a common cause for referral to pediatric endocrinologists, corresponding most times to normal variants of growth. Initially growth hormone therapy was circumscribed to children presenting growth hormone deficiency. Since the production of recombinant human hormone its use had spread to other pathologies.

Utilización de la hormona de crecimiento en niños y adolescentes / [Use of growth hormone in children and adolescents].

Growth hormone treatment for children and adolescents with growth disorders has been used for more than five decades. Since 1985 recombinant human growth hormone (rhGH) is the only drug approved for treatment. In most of the countries rhGH is licensed for the treatment of children with growth hormone deficiency, Turner syndrome, Prader-Willi syndrome, chronic renal failure, and children born small for gestational age. The objective of the treatment is to improve the growth of these patients. The efficacy of rhGH treatment based on auxologic parameters has shown that growth response is variable and mostly dependent on each particular indication. Most of the reports on drug safety obtained from different databases that included thousands of patients, have shown that rhGH is a safe drug and that serious adverse events are rare. Regarding new indications to improve height in children, data on efficacy remains controversial, so we believe their ultimate indication must take into account potential risk versus benefits of this treatment.

Adverse effects of growth hormone replacement therapy in children / Efeitos adversos da reposição de hormônio do crescimento em crianças

Human growth hormone (hGH) replacement therapy has been widely available for clinical purposes for more than fifty years. Starting in 1958, hGH was obtained from cadaveric pituitaries, but in 1985 the association between hGH therapy and Creutzfeldt-Jakob disease was reported. In the same year, the use of recombinant hGH (rhGH) was approved. Side effects of rhGH replacement therapy in children and adolescents include rash and pain at injection site, transient fever, prepubertal gynecomastia, arthralgia, edema, benign intracranial hypertension, insulin resistance, progression of scoliosis, and slipped capital femoral epiphysis. Since GH stimulates cell multiplication, development of neoplasms is a concern. We will review the side effects reported in all rhGH indications.

A terapia de reposição de hormônio de crescimento (hGH) tem sido amplamente disponível para uso clínico por mais de 50 anos. Inicialmente, em 1958, hGH era obtido de hipófises de cadáveres, mas em 1985 foi relatada a associação entre terapia com hGH e doença de Creutzfeldt-Jakob. No mesmo ano o uso de hGH recombinante (rhGH) foi aprovado. Os efeitos adversos que crianças e adolescentes em terapia de reposição de rhGH podem apresentar incluem erupção cutânea e dor no local da aplicação, febre transitória, ginecomastia pré-puberal, artralgia, edema, hipertensão intracraniana benigna, resistência insulínica, progressão de escoliose e epifisiólise da cabeça do fêmur. Como o GH estimula a multiplicação celular, o desenvolvimento de neoplasias é uma preocupação. Neste artigo, revisaremos os possíveis efeitos adversos do rhGH em cada uma de suas indicações clínicas.

Growth response of Egyptian children with idiopathic short stature during four years of growth hormone therapy.

BACKGROUND: Multiple factors affect the growth response to recombinant human growth hormone (rhGH) in children with idiopathic short stature (ISS). AIM: To evaluate the growth responses of children with ISS treated with rhGH, aiming to identify the predictors of growth response. MATERIALS AND METHODS: We studied 120 cases, 90 males (75%), with a mean age of 13.8±2.7 years and 30 females (25%), with a mean age of 12.3±2.5 years. All patients received rhGH with a standard dose of 20 IU/m2/week. The calculated dose per week was divided into six days and given subcutaneous at night. RESULTS: A significant positive trend was detected in the delta changes of all anthropometric data. For the first year, the growth response was positively correlated to CA and BA delay and negatively correlated to height, weight and IGF-1 SDSs. For the second year, the growth response was correlated positively to first year growth velocity, BA, triceps skin fold thickness SDS and deviation from target height, and negatively correlated to weight, IGFBP3 SDS and target height SDS. For the third year, the growth response was positively correlated to five variables namely target height, 2nd year growth velocity, IGF-1 SDS, weight SDS and triceps skin fold thickness SDS. For the fourth year, growth response was positively correlated to 2nd and 3rd year growth velocity, BA, deviation from target height and weight/ height SDS. CONCLUSION: Our study showed multiplicity of predictors that is responsible for response in ISS children treated with rhGH, and BA was an important predictor.

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.

Talla final en pacientes transplantados renales bajo tratamiento con hormona de crecimiento / Final height in renal transplant patients after growth hormone treatment

El retardo de crecimiento es un importante problema clínico aun no resuelto ni correctamente manejado en niños con insuficiencia renal crónica (IRC). La optimización de todos los parámetros metabólicos y nutricionales no siempre lleva a una mejoría del crecimiento en estos pacientes. Desde hace aproximadamente 20 años se utiliza el tratamiento con rhGH para mejorar la talla en este grupo de niños. La bibliografía internacional muestra mejoría de la velocidad de crecimiento en estos pacientes sin embargo la experiencia publicada en la talla final (TF) alcanzada por los mismos es escasa. Los objetivos de este estudio fueron:1) evaluar la talla final alcanzada por pacientes transplantados renales(TxR) que recibieron tratamiento con rhGH (GrGH) comparándolos con un grupo control (GrC) con similares características clínicas, 2) evaluar los factores predictores de la TF, y 3) la repercusión de dicho tratamiento en la función renal. La TF en el GrGH fue significativamente mayor que la TF del GrC (-1.96 ± 1.13 vs -3.48 ± 1.19 SDS respectivamente, p <0.05). La talla (SDS) al inicio del tratamiento con rhGH fue la única variable significativa para predecir la respuesta al tratamiento (p= 0.001). Se observó una disminución significativa ClCr final en ambos grupos (GrGH: 76 ± 18 vs 66 ± 14 ml/min/m2 sup p<0.05; GrC: 72 ± 19 vs 56 ± 9 ml/min/m2 sup, p<0.05) lo que sugiere una caída similar del filtrado glomerular en ambos grupos independiente del tratamiento. Conclusión: Nuestros hallazgos permiten confirmar que el tratamiento con rhGH es efectivo para mejorar la talla final en pacientes TxR sin afectar la función renal (AU)

Growth retardation is a common and significant clinical problem that is not adequately managed in children with chronic renal disease. Despite optimization of metabolic parameters the growth of this patients not always amelioreted. About 20 years ago rhGH treatment became to be used for this group of children to optimization final height.The international experience show that rhGH treatment improve growth velocity but the results about final heigth are scarse. The aims of our trial were: 1) to evaluate final height in renal transplant patients treated with rhGH (n=23) comparing with a control group not treated with rhGH (n=14) with similar characteristics, 2) to evaluate the effect of rhGH on creatinine clearance,3) to establish predictive variables for final height. Final Heigth was significantly greater in treated group vs control group (-1.9±1.1 vs -3.5±1.2, p<0.05). Initial height was the only significant variable to predict final height (p=0.001). We described a significantly decrease of creatinine clearence in both groups during follow up (GH Group 76±9 vs 66±14 ml/min/m2 sup, p<0.05 and Control Group 72.5±19 vs 56±9 ml/min/m2 sup, p= p<0.05).This suggest a similar decrese of creatinine clearence in both groups. Conclution: Our data confirm that rhGH treatment was effective in improving final height in renal transplant patients and did not decline allograft function (AU)

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.

Prepubertal gynecomastia a rare complication of growth hormone therapy.

We report a case of prepubertal gynecomastia diagnosed during growth hormone (GH) treatment. In our patient gynecomastia appeared 6 months after GH was started. This condition appears to be self-limited and benign. In our patient gynaecomastia resolved on its own.

Preditores clínicos do ganho estatural do primeiro ano de tratamento com dose fixa de hormônio de crescimento em crianças nascidas pequenas para idade gestacional / Clinical predictors of growth response in the first year of treatment with a fixed dose of growth hormone in children born small for gestational age

OBJETIVO: Identificar preditores clínicos associados à recuperação do crescimento no primeiro ano de tratamento com somatropina (rhGH) em um grupo de crianças nascidas pequenas para a idade gestacional (PIG). SUJEITOS E MÉTODOS: Foram avaliadas 39 crianças que estavam em terapia com rhGH por pelo menos um ano (0,33 mg/kg/semana). As variáveis analisadas foram idade cronológica (IC), idade óssea (IO), altura-alvo e escores de desvios-padrão (Z-escore) do peso e comprimento ao nascer, altura, peso e velocidade de crescimento pré e pós-rhGH. RESULTADOS: A terapia com rhGH foi associada a incremento significativo de 0,67 Z-escore (p < 0,01) na estatura nesse primeiro ano. IO e Z-escore de peso ao nascimento foram reconhecidos como preditores dessa resposta, com diferença significativa na variação do Z-escore de estatura entre pré-púberes e púberes (p = 0,016). CONCLUSÃO: Esses dados mostram ganho estatural significativo com dose fixa de rhGH, observando-se melhores resultados quando a terapia foi iniciada na fase pré-puberal.

OBJECTIVE: To identify clinical predictors associated with catch-up growth in the first year of treatment with somatropin (rhGH) in a group of children born small for gestational age (SGA). SUBJECTS AND METHODS: Thirty nine children who have been on rhGH therapy for at least one year (0.33 mg/kg/week) were evaluated. The clinical parameters analyzed were chronological age (CA), bone age (BA), target height and standard deviations scores (SDS) of birth weight and length, height, weight and growth rate. RESULTS: rhGH therapy was associated with a first year height increment of 0.67 SDS (p < 0.01). BA and birth weight SDS were predictive of growth response, with statistical difference in height SDS variation between prepubertal and pubertal subgroups (p = 0.016). CONCLUSION: These data show a significant growth response with a fixed rhGH dose, those children who started rhGH in prepubertal ages presented the best outcomes.

Conseqüências em longo prazo da deficiência do hormônio de crescimento / Long time consequences of the growth hormone deficiency

Este artigo descreve as conseqüências puras, em longo prazo, da deficiência isolada e vitalícia do hormônio de crescimento (GH) porque usa um modelo único de resistência ao hormônio liberador do GH (GHRH), em virtude da mutação homozigótica no gene do receptor do GHRH, em uma centena de indivíduos acometidos. Elas incluem baixa estatura grave com estatura final entre -9,6 a -5,2 desvios-padrão abaixo da média, com redução proporcional das dimensões ósseas, redução do volume da adenohipófise corrigido para o volume craniano e da tireóide, do útero, do baço e da massa ventricular esquerda, todos corrigidos para a superfície corporal, em contraste com o tamanho de pâncreas e fígado, maior que o de controles, quando igualmente corrigidos. As alterações características da composição corporal incluem redução acentuada da quantidade de massa magra (kg) e aumento do percentual de gordura com depósito predominante no abdome. Nos aspectos metabólicos são encontrados aumento de colesterol total e LDL, redução de insulina e do índice de resistência à insulina homeostasis model assessment, acompanhados de aumento da proteína C reativa de alta sensibilidade e da elevação da pressão arterial sistólica nos adultos, embora sem evidências de aterosclerose precoce. Outros achados incluem resistência óssea menor, embora acima do limiar de fraturas, puberdade atrasada, fertilidade normal, paridade diminuída, climatério antecipado e qualidade de vida normal.

This article describes the long time consequences of the isolated and lifetime growth hormone (GH) deficiency using a single model of GH releasing hormone resistance (GHRH) due to a homozygous mutation in the GHRH receptor gene, in a hundred of subjects. These consequences include severe short stature with final height between -9.6 and -5.2 standard deviations below of the mean, with proportional reductions of the bone dimensions; reduction of the anterior pituitary corrected to cranial volume and the thyroid, the uterus, the spleen and left ventricular mass volume, all corrected to body surface, in contrast of pancreas and liver size, bigger than in controls, when equally corrected. Body composition features included marked reduction in the amount of fat free mass (kg) and increase of fat mass percentage, with predominant abdominal deposit. In the metabolic aspects, we find increase in the total cholesterol and LDL cholesterol; reduction of the insulin and the insulin resistance assessed by Homeostasis model assessment; increase of ultra sensitive C reactive protein and systolic body pressure in adults, although without evidences of premature atherosclerosis. Other findings include smaller bone resistance, although above of the threshold of fractures, delayed puberty, normal fertility, small parity, anticipated climacteric and normal quality of life.