Long-acting growth hormone in the treatment of growth hormone deficiency in children: a systematic literature review and network meta-analysis.

The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: - 0.031, 95% credibility interval [CrI]: - 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: - 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: - 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: - 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: - 0.15, 95% CrI: - 1.1, 0.66) than somatrogon (MD: - 0.055, 95% CrI: - 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: - 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.

[Growth hormone - 30 years of clinical practice: past, present, future].

The recombinant technologies era, which began in the second half of the XX century, made it possible to produce recombinant growth hormone (rGH) necessary for the treatment of stunting of various genesis. The time of practically unlimited possibilities of rGH production has come, which served as a stimulus for studying the efficacy and safety of rGH application, searching for optimal ways of its use and dosing regimes. Many years of experience in the use of somatropin in clinical practice allowed us to obtain data on its effectiveness primarily in somatotropic insufficiency in children, to study its effect on the functional state of various organs and systems, and to expand the indications for the use of RGR.

Effective growth hormone replacement with once-weekly somapacitan in Japanese children with growth hormone deficiency: Results from REAL4, a phase 3 clinical trial.

OBJECTIVE: Somapacitan is a long-acting growth hormone (GH) derivative developed for the treatment of GH deficiency (GHD). This study evaluates the efficacy and tolerability of somapacitan in Japanese children with GHD after 104 weeks of treatment and after switch from daily GH. DESIGN: Subanalysis on Japanese patients from a randomised, open-labelled, controlled parallel-group phase 3 trial (REAL4, NCT03811535). PATIENTS AND MEASUREMENTS: Thirty treatment-naïve patients were randomised 2:1 to somapacitan (0.16 mg/kg/week) or daily GH (0.034 mg/kg/day) up to Week 52, after which all patients received somapacitan. Height velocity (HV; cm/year) at Weeks 52 and 104 were the primary measurements. Additional assessments included HV SD score (SDS), height SDS, bone age, insulin-like growth factor-I (IGF-I) SDS, and observer-reported outcomes. RESULTS: At Week 52, observed mean HV was similar between treatment groups (10.3 vs. 9.8 cm/year for somapacitan and daily GH, respectively). Similar HVs between groups were also observed at Week 104: 7.4 cm/year after continuous somapacitan treatment (soma/soma) and 7.9 cm/year after 1-year somapacitan treatment following switch from daily GH (switch). Other height-related endpoints supported continuous growth. IGF-I SDS increased in both groups with mean IGF-I SDS within -2 and +2 during the study. Somapacitan was well tolerated, one mild injection site reaction was reported, with no reports of injection site pain. Patient preference questionnaires showed that most patients and their caregivers (90.9%) who switched treatment at Week 52 preferred once-weekly somapacitan over daily GH treatment. CONCLUSIONS: Somapacitan showed sustained efficacy in Japanese children with GHD over 104 weeks and for 52 weeks after switching from daily GH. Somapacitan was well tolerated and preferred over daily GH.

[Pituitary disorders in patients with end-stage chronic renal failure].

Disorders in the kidneys lead to disturbance of homeostasis. As the glomerular filtration rate decreases, the metabolism of numerous biologically active substances, including pituitary hormones, decreases. The article presents an overview of pituitary dysfunction in patients with chronic kidney disease (CKD) and discusses the possible reasons of the pathogenetic mechanisms. Particular focus is being given to the assessment of changes in the concentration of pituitary hormones in patients with end-stage chronic kidney disease (CKD) and discusses the pathogenetic mechanisms of their formation. Particular attention is paid to the assessment of changes in the concentration of pituitary hormones in patients receiving renal replacement therapy (RRT). CKD leads to an increase in the level of prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Concentrations of growth hormone (GH), isulin-like growth factor-1 (IGF-1), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and vasopressin may remain within normal values or increase in this group of patients. RRT does not reduce the levels of prolactin, LH, FSH, while the concentration of growth hormone, IGF-1, TSH tends to normalize. The content of ACTH and vasopressin may remain unchanged or decrease. Kidney transplantation in most cases corrects hormonal disorders. Correction of hormonal changes can improve the clinical outcome and quality of life of patients with end stage CKD.

Feline Comorbidities: Hypersomatotropism-induced diabetes in cats.

PRACTICAL RELEVANCE: Diabetes mellitus is the second-most common feline endocrinopathy, affecting an estimated 1/200 cats. While the underlying causes vary, around 15-25% of cats with diabetes mellitus develop the condition secondarily to progressive growth hormone (GH)-induced insulin resistance. This typically results in a form of diabetes that is challenging to manage, whereby the response to insulin is very variable or high doses are required to achieve even minimal diabetic control. CLINICAL CHALLENGES: Although uncontrolled chronic excessive GH may result in phenotypic changes that raise suspicion for acromegaly, many cats with hypersomatotropism (HST) do not have these changes. In these situations, a clinician's index of suspicion may be increased by the presence of less dramatic changes such as marked polyphagia, stertor or uncontrolled diabetes mellitus. The current diagnostic test of choice is demonstration of a markedly increased serum insulin-like growth factor 1 (IGF1) concentration, but some affected cats will have only a marginal increase; additionally, chronic insulin administration in cats results in an increase in serum IGF1, making the diagnosis less clear cut and requiring additional confirmatory tests. EVIDENCE BASE: Over the past two decades, HST has increasingly been recognised as an underlying cause of diabetes mellitus in cats. This review, which focuses on diagnosis and treatment, utilises data from observational studies, clinical trials and case series, as well as drawing on the experience of the authors in managing this condition.

Pituitary Stalk Interruption Syndrome: Analysis of Response to Growth Hormone Therapy.

OBJECTIVE: To analyse the clinical and radiological characteristics of pituitary stalk interruption syndrome (PSIS). METHODS: A retrospective analysis of confirmed cases of PSIS was performed. The development of new pituitary hormonal deficiencies and response to recombinant human growth hormone (rhGH) therapy were assessed during follow-up. RESULTS: This study included 14 children (10 boys) of PSIS with median (range) age of 12.15 years (2 months - 18 years). Short stature was the most common presentation (n = 13), and micropenis (n = 4), cleft lip (n = 1) and single central incisor (n = 1) were other midline defects. Growth hormone (GH) deficiency was present in 14 children and 7 of them also had multiple pituitary hormone deficiencies at baseline. Central hypothyroidism (n = 5), secondary adrenal deficiency (n = 4) and gonadotropin deficiencies (n = 2) were also seen. All children received rhGH. The mean height gain on follow-up was 12.78 cm in first year (n = 14), 6.5 cm in second year (n = 8) and 4.07 cm in third year (n = 7) of rhGH therapy. Four children developed additional pituitary hormone deficiency on follow-up. CONCLUSION: Short stature with isolated GH deficiency was the most common presentation of PSIS that showed good response to rhGH therapy.

Developments in the Management of Growth Hormone Deficiency: Clinical Utility of Somapacitan.

Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily injections. This daily treatment regimen often incurs a burden to patients and caregivers, leading to high rates of non-adherence and, consequently, decreased treatment efficacy outcomes. To address this shortcoming, long-acting growth hormones (LAGHs) have been developed with the aim of reducing the burden of daily injections, thereby potentially improving treatment adherence and outcomes. Somapacitan (Sogroya®) (Novo Nordisk, Bagsværd, Denmark) is a LAGH currently approved for the treatment of adult and childhood GHD (AGHD and CGHD, respectively) in several countries. Other LAGHs, such as somatrogon (Ngenla®) (Pfizer, New York, United States) and lonapegsomatropin/TransCon GH (Skytrofa®) (Ascendis Pharma, Copenhagen, Denmark), are also currently approved and available for the treatment of CGHD in several countries. In this review, we will consider the method of protraction, pharmacokinetics (PK) and pharmacodynamics (PD), efficacy, and safety results of somapacitan in adult and pediatric trials and how these characteristics differ from those of the other aforementioned LAGHs. Additionally, the administration of somapacitan and timing of measurement of serum insulin-like growth factor-I (IGF-I) levels are summarized. Information on administration, advice on missed doses, and clinical guidelines are discussed, as well as identifying which patients are suitable for somapacitan therapy, and how to monitor and adjust dosing whilst on therapy.

Comparative efficacy of different growth hormone supplementation protocols in improving clinical outcomes in women with poor ovarian response undergoing assisted reproductive therapy: a network meta-analysis.

Growth hormone (GH) has a long-standing history of use as an adjunctive therapy in the treatment of poor ovarian response (POR), but the optimal dosage and timing remains unclear. The aim of this study was to evaluate and compare the efficacy of different GH supplementation protocols through a network meta-analysis (NMA) and determine the optimal treatment protocol. This study was reported based on the Preferred Reporting Items for Systematic Reviews for Network Meta-Analysis (PRISMA-NMA) statement. Databases including PubMed, Web of Science, Cochrane Library and Embase were searched until June 2023. A total of 524 records were retrieved in our search, and 23 clinical studies comprising 4889 cycles were involved. Seven different GH protocols were identified. Results showed that compared to the control group, daily administration of 4-8 IU of GH during the follicular phase of the stimulation cycle had the best comprehensive therapeutic effects on improving the number of retrieved oocytes, mature oocytes, endometrial thickness, and reducing gonadotropin requirements in POR patients undergoing assisted reproductive therapy, with a relatively brief treatment duration and a moderate total GH dose. Subgroup analysis demonstrated that this protocol could significantly improve the clinical pregnancy rate of POR patients in the randomized controlled trials (RCT) subgroup and the African subgroup. Therefore, its clinical application is suggested. Besides, the potential advantages of long-term GH supplementation protocol (using GH for at least 2 weeks before oocyte retrieval) has merit for further research. Rigorous and well-designed multi-arm RCTs are needed in the future to confirm the conclusions drawn from this study.

Effect of treatment with growth hormone on body composition and metabolic profile of short children born small for gestational age.

OBJECTIVE: To assess the effect of recombinant growth hormone (rGH) on body composition and metabolic profile of prepubertal short children born small for gestational age (SGA) before and after 18 months of treatment. METHODS: It is a clinical, non-randomized, and paired study. Children born SGA, with birth weight and/or length <-2 standard deviations (SD) for gestational age and sex, prepubertal, born at full term, of both genders, with the indication for treatment with rGH were included. The intervention was performed with biosynthetic rGH at doses ranging from 0.03 to 0.05 mg/kg/day, administered subcutaneously, once a day at bedtime. Total lean mass (LM) and total fat mass (FM) were carried out using dual-energy X-ray absorptiometry (DXA), and the metabolic profile was assessed for insulin, glycemia, IGF-1 levels and lipid profile. RESULTS: Twelve patients (nine girls, 8.17±2.39 y) were evaluated; three patients dropped out of the study. There was an increase of LM adjusted for length (LMI) (p=0.008), LMI standard deviation score (SDS) adjusted for age and sex (p=0.007), and total LM (p<0.001). The percentage of body fat (BF%) and abdominal fat (AF) remained unaltered in relation to the beginning of treatment. Among the metabolic variables, blood glucose remained within normal levels, and there was a reduction in the number of participants with altered cholesterol (p=0.023). CONCLUSIONS: The effect of rGH treatment was higher on LM than in FM, with increased LM adjusted for length and standardized for age and sex. Glycemia remained within the normal limits, and there was a decreased number of children with total cholesterol above the recommended levels.

Insights from an advisory board: Facilitating transition of care into adulthood in brain cancer survivors with acquired pediatric growth hormone deficiency.

OBJECTIVE: Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children with GHD resulting from brain cancer or its treatment, the involvement of oncology care providers and possible disease-related comorbidities add further complexity to this transition. DESIGN: An advisory board of pediatric and adult endocrinologists was convened to help better understand the unique challenges faced by childhood cancer survivors with GHD, and discuss recommendations to optimize continuity of care as these patients proceed to adulthood. Topics included the benefits and risks of growth hormone (GH) therapy in cancer survivors, the importance of initiating GH replacement therapy early in the patient's journey and continuing into adulthood, and the obstacles that can limit an effective transition to adult care for these patients. RESULTS/CONCLUSIONS: Some identified obstacles included the need to prioritize cancer treatment over treatment for GHD, a lack of patient and oncologist knowledge about the full range of benefits provided by long-term GH administration, concerns about tumor recurrence risk in cancer survivors receiving GH treatment, and suboptimal communication and coordination (e.g., referrals) between care providers, all of which could potentially result in treatment gaps or even complete loss of follow-up during the care transition. Advisors provided recommendations for increasing education for patients and care providers and improving coordination between treatment team members, both of which are intended to help improve continuity of care to maximize the health benefits of GH administration during the critical period when childhood cancer survivors transition into adulthood.

Connexin 36 Mediated Intercellular Endoplasmic Reticulum Stress Transmission Induces SSTA Resistance in Growth Hormone Pituitary Adenoma.

Somatostatin analogues (SSTA) are first-line pharmacological treatment choice for acromegaly, which received satisfying tumor shrinkage and normalization of growth hormone. However, there are still patients unresponsive to SSTA, and the underline mechanism remains unknown. Besides, there is no evidence regarding the role of endoplasmic reticulum stress (ERS) and its transmission in SSTA resistance, which also require investigation. Primary growth hormone adenoma cells and cell lines were treated with SSTA; autophagy double-labeled LC3 (mRFP-GFP) adenovirus transfection, flow cytometry sorting, western blotting, calcium imaging as well as immunofluorescence staining were used to determine ERS and autophagy signal transmission; xenograft and syngeneic tumor in vivo model were exploited to confirm the ERS signal transmission mediated effect. Our results revealed that SSTA induces ERS in pituitary growth hormone (GH) adenoma cells. The ERS signals can be intercellularly transmitted, leading to less responsible to SSTA treatment. Moreover, SSTA stimulates inositol triphosphate (IP3) elevation, mediating ERS intercellular transfer. In addition, connexin 36 tunnels ERS transmission, and its blocker, Quinine, exhibits a synergistic effect with SSTA treating GH adenoma. Our study provided insight into ERS intercellular transmission mediated SSTA resistance, which could be translated into clinical usage to improve SSTA efficiency in GH adenoma treatment.

Somatrogon injection for the treatment of pediatric growth hormone deficiency with comparison to other LAGH products.

INTRODUCTION: Somatrogon (NGENLA™) is a long-acting GH (LAGH) formulation that was approved in Canada in October 2021 for the treatment of pediatric growth hormone deficiency (GHD). Somatrogon has also received approval in Australia, Japan, the European Union, the USA, and the UK. Somatrogon is a glycoprotein that utilizes three copies of the C-terminal peptide of human chorionic gonadotropin to delay its clearance allowing for once-weekly administration. AREAS COVERED: The purpose of this article is to describe the development of somatrogon for treatment of individuals with GHD. Trials of somatrogon demonstrated positive efficacy results in adults (Phase 2) and children (Phase 2 and 3) with GHD including non-inferiority of height velocity compared to daily GH, with no concerning side effects. Growth responses, pharmacodynamics and safety data are compared to other LAGH products, lonapegsomatropin and somapacitan, in Phase 3 trials in pediatric GHD. EXPERT OPINION: New LAGH products, including somatrogon, have the potential to increase patient adherence as well as improve quality of life and clinical outcomes. Clinicians will need to identify the best candidates for LAGH therapy and understand how to safely monitor and adjust therapy. Long-term surveillance studies are necessary to demonstrate adherence, efficacy, cost-effectiveness, and safety of LAGH preparations.

Somatrogon for treating growth disturbance in children and young people aged 3 years and over

Evidence-based recommendations on somatrogon (Ngenla) for treating growth disturbance in children and young people aged 3 years and over.

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.

Hormona de crecimiento humana recombinante para el tratamiento de niños con deficiencia de hormona de crecimiento / Recombinant human growth hormone for the treatment of children with growth hormone

INTRODUCCIÓN: Este documento técnico se realiza a solicitud de la Dirección Regional de Salud Cusco; la cual motivó la realización de la pregunta PICO por parte de médicos y especialistas de la siguiente manera, P: Niños de 0-18 años con deficiencia de hormona de crecimiento; I: Hormona de crecimiento humana recombinante; C: placebo o no intervención; O: Ganancia de talla, diferencias en la talla durante la adultez, calidad de vida, mortalidad, neoplasias. a. Cuadro clínico: La deficiencia de la hormona del crecimiento (GHD) es un trastorno poco frecuente con una prevalencia estimada a nivel mundial de 1 de cada 4000 durante la infancia (1). En Perú, no se cuenta con datos epidemiológicos respecto a esta condición. En los niños, la principal manifestación de la deficiencia de hormona de crecimiento es la falla en el crecimiento. Sin embargo, su deficiencia también produce efectos sobre el metabolismo, incrementando la masa grasa y disminuyendo la masa magra, y sobre el neurodesarrollo, afectando principalmente el funcionamiento cognitivo. b. Tecnología sanitaria: La hormona de crecimiento es una proteína que interviene en la regulación del crecimiento y en el metabolismo de los carbohidratos, proteínas y lípidos, tanto de forma directa como indirecta a través de los factores de crecimiento similares a la insulina. En niños con deficiencia de GH, el tratamiento sustitutivo con hormona de crecimiento estimula el crecimiento lineal y mejora la velocidad de crecimiento. El evento adverso más común es el dolor de cabeza, aunque puede existir un riesgo ligeramente mayor de hipertensión intracraneal idiopática, aumento de la presión intraocular, deslizamiento de la epífisis femoral capital y empeoramiento de la escoliosis existente. Cuenta con aprobación de la Food and Drug Administration (FDA) desde 1985. En Perú, cuenta con cinco registros sanitarios vigentes y seis registros sanitarios con vigencia prorrogada provisional, bajo diferentes denominaciones comerciales. OBJETIVO: Describir la evidencia científica disponible sobre la eficacia y seguridad de la hormona de crecimiento humana recombinante para el tratamiento de niños con deficiencia de hormona de crecimiento. METODOLOGÍA: Se realizó una búsqueda sistemática en Medline (Pubmed), The Cochrane Library y LILACS utilizando la estrategia de búsqueda descrita en el Anexo 01. Ésta se complementó con la búsqueda de evidencia en páginas institucionales de agencias gubernamentales y buscadores genéricos. Se priorizó la identificación y selección de ensayos clínicos aleatorizados controlados, revisiones sistemáticas (RS) con o sin meta-análisis (MA) de ensayos clínicos aleatorizados controlados, guías de práctica clínica (GPC), evaluaciones de tecnología sanitaria (ETS) y evaluaciones económicas (EE) de América Latina. La calidad de la evidencia se valoró usando las siguientes herramientas: AMSTAR 2 para la valoración de la calidad de RS, la herramienta propuesta por la colaboración Cochrane para ensayos clínicos y AGREE II para valorar el rigor metodológico de las GPC. RESULTADOS: Se identificó tres revisiones sistemáticas (RS), una guía de práctica clínica (GPC) y una evaluación de tecnología sanitaria (ETS) que respondieron a la pregunta PICO de interés. CONCLUSIONES: El uso de hormona de crecimiento en niños produjo un incremento significativo de la talla durante un periodo de tratamiento de 4 a 6 años, comparado con un grupo de control. Estas diferencias se mantuvieron hasta la adultez, con una estatura aproximadamente 4 cm superior en los niños tratados con hormona de crecimiento respecto a los niños en el grupo control. Se reportó un incremento significativo de la mortalidad por cualquier causa en pacientes tratados con hormona de crecimiento, mientras que el riesgo de neoplasias no fue consistente, una revisión sistemática reportó un incremento del riesgo de neoplasias en la población general, mientras que otra no encontró diferencias significativas en niños sobrevivientes de cáncer. Una ETS recomienda el uso de hormona de crecimiento humana recombinante para la falla de crecimiento asociada, entre otras condiciones, a la deficiencia de hormona de crecimiento. La GPC de la Sociedad de Endocrinología Pediátrica de los Estados Unidos recomienda el uso de la hormona de crecimiento en niños y adolescentes con la finalidad de normalizar la estatura adulta y evitar la talla baja extrema. Dos RS fueron consideradas como nivel de confianza baja, y la restante como nivel de confianza medio. La GPC incluida obtuvo una puntuación superior al 57,4% en la valoración global de la calidad metodológica.

Características auxológicas en pacientes pediátricos con déficit aislado permanente o transitorio de hormona del crecimiento. Respuesta al tratamiento y talla final / Auxological characteristics of pediatric patients with permanent or transient isolated growth hormone deficiency. Response to treatment and final height

Introducción: El tratamiento con hormona de crecimiento recombinante (rhGH) ha demostrado mejorar la talla adulta de los pacientes pediátricos con déficit de GH (DGH). Sin embargo, cuando los pacientes son reevaluados al llegar a la talla final, se evidencia que existen pacientes en los que el déficit de GH es permanente (DPGH) y otros en los que el déficit ha sido transitorio (DTGH). El objetivo es evaluar, en una cohorte de pacientes pediátricos con DGH, si existen diferencias en la respuesta al tratamiento con GH en función de que dicho déficit sea permanente o transitorio. Materiales y métodos: Estudio retrospectivo de 89 pacientes con DGH, que fueron seguidos desde el diagnóstico y durante todo el seguimiento hasta la talla adulta. Se obtuvieron parámetros clínicos, auxológicos, radiológicos y analíticos al diagnóstico, así como tras el primer año de tratamiento y en la revisión de la talla final. Resultados: El 28% de los pacientes presentaron un DPGH. Talla inicial de −2,46 ± 0,86 DE en el DPGH y −2,24 ± 0,68 DE en el DTGH. El valor pico de GH al diagnóstico fue de 4,26 ± 2,78 y 6,20 ± 2,01 ng/mL, respectivamente (p < 0,01). Tras el primer año de tratamiento el incremento de la velocidad de crecimiento fue mayor en el grupo de DPGH: 4,33 ± 3,53 DE vs. 2,95 ± 2,54 DE (p = 0,043). Talla final de −0,81 ± 0,87 DE los DPGH y de −0,95 ± 0,83 DE los DTGH (p = 0,47). Conclusiones: Los pacientes con DPGH obtienen un mayor beneficio del tratamiento con rhGH tanto a corto como a largo plazo. Además, muestran niveles más bajos de GH en las pruebas de estímulo al diagnóstico, como ha sido descrito previamente

Introduction: Treatment with recombinant human growth hormone (rhGH) has been shown to improve adult height in pediatric patients with GH deficiency (GHD). However, reassessment of patients after they reach their final height shows some of them have permanent GH deficiency (PGHD), while others had a transient deficiency (TGHD). The study objective was to assess, in a cohort of pediatric patients with GHD, potential differences in response to treatment with rhGH depending on whether deficiency is permanent or transient. Materials and methods: A retrospective study of 89 patients with GHD, who were monitored from diagnosis to adult height. Clinical, auxological, radiographic and laboratory variables were collected at diagnosis, after the first year of treatment, and when they had reached their adult height. Results: PGHD was found in 28% of patients. Initial height was −2.46 ± 0.86 SD and −2.24 ± 0.68 SD in subjects with PGHD and TGHD respectively. Peak GH level at diagnosis was 4.26 ± 2.78 and 6.20 ± 2.01 ng/mL (p < 0.01) in the PGHD and TGHD groups respectively. After the first year of treatment, increase in growth velocity was greater in the PGHD group: 4.33 ± 3.53 SD vs. 2.95 ± 2.54 SD in the PGHD group (p = 0.043). Final height was −0.81 ± 0.87 SD in the PGHD and −0.95 ± 0.83 SD in the TGHD group (p = 0.47). Conclusions: Patients with PGHD had a better short- and long-term response to rhGH. They also showed lower GH levels in stimulation tests at diagnosis, as previously reported

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)

Hipertensión intracraneal idiopática: casuística y revisión de la bibliografía / Idiopathic intracranial hypertension: epidemiology and current literature review

Introducción: se analizan las características de la hipertensión intracraneal idiopática; clínica al inicio, pruebas realizadas, tratamiento y evolución que presentaron. Material y métodos: estudio descriptivo retrospectivo de los pacientes diagnosticados de hipertensión intracraneal idiopática en los últimos siete años (2011-2017) en un hospital de tercer nivel. Resultados: se estudiaron 40 pacientes (55% mujeres) con una edad media de 9,6 años. Como factores asociados, el 5% seguían tratamiento con hormona del crecimiento. Solo el 25% presentaban sobrepeso u obesidad. El síntoma principal fue cefalea opresiva, asociando vómitos (27,5%) o alteraciones visuales (22%). Tres pacientes presentaron hallazgo casual de papiledema bilateral. La exploración física fue anodina (65%), se observó estrabismo por parálisis del VI par craneal (35%). Presentaron papiledema el 62,5%. La campimetría solo se realizó en el 55% de los pacientes y estaba alterada en el 50% de estos. El tiempo hasta el diagnóstico fue 44,8 días. Obtuvimos una presión de apertura media 29,7 cm H2O (± 8,2). Se realizó tomografía computarizada al 85% de los pacientes y fue normal en el 88,2% de estos. Se hizo resonancia magnética craneal al 7,5%, y fue normal en el 70% de estos. Se practico angio-RM al 5%, y fue normal en todos los casos. Se solicitó analítica, con función renal y hepática (62,5%, todos normal), hormonal (65%), estudio de trombofilias y autoinmunidad (10% y 20% respectivamente, anodinas). Se inició tratamiento con acetazolamida (95%), y hubo que añadir corticoterapia por falta de respuesta en el 24% de los casos. En el 5% se autolimitó espontáneamente. Como último escalón, el 7,5% requirió válvula de derivación lumboperitoneal. Evolucionaron favorablemente el 95%, con recidivas en el 15% de los casos. El tiempo medio hasta la resolución fue de 3,9 meses. Conclusión: el diagnóstico y tratamiento precoz de la hipertensión intracraneal idiopática es importante para evitar posibles secuelas irreversibles. El estudio oftalmológico, especialmente la campimetría, es esencial para el diagnóstico, seguimiento y determinación de la agresividad del tratamiento

Introduction: the characteristics of idiopathic intracranial hypertension are analyzed; epidemiology, clinic at the beginning, tests performed, treatment and evolution that presented the analyzed cases. Material and methods: a retrospective descriptive study was conducted on patients with idiopathic intracra­nial hypertension in the last seven years (2011-2017), in a third level hospital. Results: forty patients (55% women) were studied, with a mean age of 9.6 years. As associated factors, 5% had a treatment with growth hormone. It is important to note that only 25% were overweight or obese. The main symptom was oppressive headache, without predominance hours, associating vomiting (27.5%), or visual alterations (22%). Three asymptomatic patients presented a chance finding of bilateral papilledema. The physical examination was anodyne (65%), showing strabismus due to cranial nerve palsy VI (35%). 62,5% presented papilledema, and the campimetry was only performed in 55% of the patients, altered in 50% of them. The time to diagnosis was 44.8 days. We obtained an average opening pressure of 29.7 cm H2O (± 8.2). CT was performed (85%), being normal (88.2%). MRI of the skull (7.5%), normal (70%). Angio-NMR (5%), all normal. Analytical was requested, with renal and hepatic function (62.5%, all normal), hormonal (65%), thrombophilic study and autoimmunity (10% and 20% respectively, anodyne). Treatment was started with acetazolamide (95%), requiring the addition of corticotherapy due to lack of response 24%. In 5%, it spontaneously self-limited. As a last step, 7.5% required a lumboperitoneal bypass valve. They evolved favora­bly 95%, relapsing 15%. Redialing the average time to resolution was 3.9 months. Conclusion: idiopathic intracranial hypertension is rare, but its diagnosis and early treatment is essential to avoid possible irreversible sequelae. The ophthalmological study, by fundus and especially campimetry, is es­sential for the diagnosis, monitoring and determination of the aggressiveness of the treatment

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.

Respuesta clínica al tratamiento con hormona de crecimiento en niños con retraso de crecimiento intrauterino sin recuperación posnatal de talla en Castilla y León / Clinical response to growth hormone in children with intrauterine growth retardation without catch-up growth in Castilla y León (Spain)

Introducción y objetivos: La hormona de crecimiento recombinante humana (rhGH) se utiliza en niños con crecimiento intrauterino retardado sin recuperación posnatal de talla. En 2010 se inició el Comité Asesor de Castilla y León para aplicar de forma homogénea los criterios de utilización de la rhGH. El objetivo es valorar la evolución antropométrica y clínica de niños sometidos a tratamiento. Pacientes y métodos: Estudio retrospectivo, longitudinal, con pacientes de Castilla y León diagnosticados de crecimiento intrauterino retardado sin crecimiento recuperador a partir del año 2010, con al menos 3 años de tratamiento. Se evaluaron las modificaciones en diferentes parámetros antropométricos, clínicos y analíticos. Resultados: Se incluyeron 43 niños con una edad media de 6,06 años (58,14%<5 años), tratados con una dosis media de 0,038mg/kg/día. Se observó un aumento significativo en la talla (−3,05 hasta −1,58DE). El peso se incrementó durante todo el estudio, así como el IMC (14,51 hasta 15,80kg/m2). La velocidad de crecimiento alcanzó su pico máximo durante el primer año de tratamiento (0,74DE). Los valores de IGF-1 se incrementaron durante todo el estudio (99,96 hasta 392,88ng/ml). Se observaron incrementos significativos de la glucohemoglobina en el primer año y de la glucemia y de la insulinemia basal durante el segundo año, así como un descenso en el cociente LDL/HDL (1,70 hasta 1,50). Conclusión: El tratamiento con hormona de crecimiento favorece el crecimiento de niños con crecimiento intrauterino retardado, observándose su máximo efecto en los primeros 12 meses, siendo mayor si la edad de comienzo es anterior a los 5 años de edad

Introduction and objectives: Growth hormone (rhGH) is used in children with intrauterine growth retardation without catch-up growth. The Advisory Committee of Castilla y León was implemented in 2010 to watch for consistent application of the criteria for using rhGH. The aim is to assess anthropometric and clinical changes in children treated with growth hormone. Patients and methods: A retrospective, longitudinal study of patients diagnosed with intrauterine growth retardation without catch-up growth in Castilla y León since 2010 who have received treatment for at least 3 years. Changes in anthropometric, clinical, and laboratory parameters were assessed. Results: Forty-three children with a mean age of 6.06 years (58.14%<5 years) were enrolled and treated with a mean dose of 0.038mg/kg/day. A significant increase was seen in height (−3.05 to −1.58SD). Both weight and BMI (14.51 to 15.80kg/m2) increased throughout the study. Growth rate peaked during the first year of treatment (0.74SD). IGF-1 levels increased throughout the study (99.96 to 392.88ng/mL). There were significant increases in glycosylated hemoglobin levels in the first year, and in basal blood glucose and insulin levels during the second year. The LDL/HDL ratio decreased during the study period (1.70 to 1.50). Conclusion: Treatment with rhGH promotes growth in children with intrauterine growth retardation. Peak effect occurs in the first 12 months of treatment, and is greater when growth hormone is started before the age of 5 years