EndoBridge 2023: highlights and pearls.

EndoBridge 2023 took place on October 20-22, 2023, in Antalya, Turkey. Accredited by the European Council, the 3-day scientific program of the 11th Annual Meeting of EndoBridge included state-of-the-art lectures and interactive small group discussion sessions incorporating interesting and challenging clinical cases led by globally recognized leaders in the field and was well attended by a highly diverse audience. Following its established format over the years, the program provided a comprehensive update across all aspects of endocrinology and metabolism, including topics in pituitary, thyroid, bone, and adrenal disorders, neuroendocrine tumors, diabetes mellitus, obesity, nutrition, and lipid disorders. As usual, the meeting was held in English with simultaneous translation into Russian, Arabic, and Turkish. The abstracts of clinical cases presented by the delegates during oral and poster sessions have been published in JCEM Case Reports. Herein, we provide a paper on highlights and pearls of the meeting sessions covering a wide range of subjects, from thyroid nodule stratification to secondary osteoporosis and from glycemic challenges in post-bariatric surgery to male hypogonadism. This report emphasizes the latest developments in the field, along with clinical approaches to common endocrine issues. The 12th annual meeting of EndoBridge will be held on October 17-20, 2024 in Antalya, Turkey.

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.

Physical activity, eating and sleep in athletes one year after the covid-19 pandemic / Actividad física, alimentación y sueño en atletas después de un año de la pandemia del covid-19 / Atividade física, alimentação e sono em atletas após um ano da pandemia de covid-19

ABSTRACT Introduction: The pandemic caused by COVID-19 has resulted in worrying effects related to the "new" habits adopted by the population. The long period of school closures and social isolation have profoundly impacted the learning, health, and protection of children and adolescents. Objective: To re-evaluate school athletes quarantined by COVID-19, highlighting the main physical activity (PA), eating and sleeping habits, and the implications related to physical and mental health after one year of the pandemic in the city of Curitiba, Brazil. Methods: Two surveys were conducted, 342 attended the first assessment, and 222 attended the second. An online questionnaire (Google docs) was applied to the students, consisting of 18 closed and open questions in the first moment (beginning of the pandemic) and 22 at the second moment (after one year of the pandemic). Results: Half of the students (53.2%; 57%) reported eating up to three meals daily. With regard to sleeping hours, the majority of students (80%; 79.5%) were able to sleep at night between 6:00 and 10:00. There was a significant decrease in the time spent on social networks, migrating to school activities (p <0.005). Approximately a quarter of the student-athletes (27%) practiced PA every day and felt fulfilled in the first assessment, and in the second assessment, this number increased to 43% (p = 0.009). Conclusion: Despite the decrease in screen time and the increase in regular PA, there was an increase in body weight in more than a third of the athletes evaluated. Those who maintained their body weight maintained healthier lifestyles with several meals within the recommended range and slept 6 to 10 hours per night. Level of Evidence III; Retrospective comparative study.

RESUMEN Introducción: La pandemia provocada por el COVID-19 trajo efectos preocupantes relacionados con los "nuevos" hábitos adoptados por la población. El largo período de cierre de escuelas y aislamiento social ha impactado profundamente en el aprendizaje, la salud y la protección de niños, niñas y adolescentes. Objetivo: Reevaluar atletas escolares sometidos a cuarentena por COVID-19, destacando los principales hábitos de actividad física (AF), alimentación y sueño y las implicaciones relacionadas con la salud física y mental después de un año de pandemia en la ciudad de Curitiba, Brasil. Métodos: Se realizaron dos encuestas, 342 asistieron a la primera evaluación y 222 a la segunda. Se aplicó un cuestionario en línea (Google docs) a los estudiantes, compuesto por 18 preguntas cerradas y abiertas en el primer momento (inicio de la pandemia) y 22 en el segundo momento (después de un año de pandemia). Resultados: La mitad de los estudiantes (53,2%; 57%) refirió tener hasta tres comidas al día. En cuanto al tiempo de sueño, la mayoría de los estudiantes (80%; 79,5%) pudo dormir por la noche entre las 6:00 y las 10:00. Hubo una disminución significativa en el tiempo dedicado a las redes sociales, migrando a las actividades escolares (p <0,005). Aproximadamente una cuarta parte de los estudiantes deportistas (27%) practicaban AF todos los días y se sentían realizados en la primera evaluación, y en la segunda evaluación este número aumentó al 43% (p = 0,009). Conclusión: A pesar de la disminución del tiempo de pantalla y del aumento de la AF regular, hubo un aumento del peso corporal en más de un tercio de los atletas evaluados. Los que mantuvieron su peso corporal fueron aquellos que mantuvieron estilos de vida más saludables con varias comidas dentro del rango recomendado y que dormían de 6 a 10 horas por noche. Nivel de Evidencia III; Estudio comparativo retrospectivo.

RESUMO Introdução: A pandemia provocada pelo COVID-19 resultou em efeitos preocupantes relacionados aos "novos" hábitos adotados pela população. O longo período de fechamento das escolas e o isolamento social têm impactado profundamente a aprendizagem, a saúde e a proteção de crianças e adolescentes. Objetivo: Reavaliar atletas escolares submetidos à quarentena por COVID-19, destacando os principais hábitos de atividade física (AF), alimentação e sono e as implicações relacionadas à saúde física e mental após um ano de pandemia na cidade de Curitiba, Brasil. Métodos: Foram realizadas duas pesquisas, 342 compareceram à primeira avaliação e 222 à segunda. Foi aplicado aos alunos um questionário online (Google docs), composto por 18 questões fechadas e abertas no primeiro momento (início da pandemia) e 22 no segundo momento (após um ano de pandemia). Resultados: Metade dos alunos (53,2%; 57%) relatou fazer até três refeições ao dia. Quanto ao horário de sono, a maioria dos alunos (80%; 79,5%) conseguiu dormir à noite entre 6h00 e 10h00. Houve diminuição significativa do tempo gasto nas redes sociais, migrando para atividades escolares (p <0,005). Aproximadamente um quarto dos alunos atletas (27%) praticava AF todos os dias e se sentiu realizado na primeira avaliação, e na segunda avaliação esse número aumentou para 43% (p = 0,009). Conclusão: Apesar da diminuição do tempo de tela e do aumento da AF regular, houve aumento do peso corporal em mais de um terço dos atletas avaliados. Os que mantiveram o peso corporal foram os que mantiveram estilos de vida mais saudáveis com várias refeições dentro da faixa recomendada e que dormiam de 6 a 10 horas por noite. Nível de Evidência III; Estudo retrospectivo comparativo.

The science behind the relations among cancer, height, growth patterns, and growth hormone axis.

The association between growth hormone (GH) and carcinogenesis has long been postulated. The rationale for this association is that several components of the GH axis play an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis and have been tested as targets for cancer therapy. Epidemiological and clinical studies have examined the association between height, growth patterns, and insulin-like growth factor 1 (IGF1) levels with the most common types of malignancies, while genome-wide association studies have revealed several height-associated genes linked to cancer and/or metastasis-driving pathways. In this context, a permissive role of the GH-IGF signaling system in the link between height and cancer risk has also been investigated. In animal and human models, genetic defects associated with GH deficiency or resistance are associated with protection from tumor development, while the risk of malignancies in acromegaly or in patients exposed to recombinant GH therapy has long been a matter of concern and scrutiny. In this review, we present a narrative and historical review covering the potential relations among height, growth patterns, GH axis, and cancer.

International Consensus Guideline on Small for Gestational Age: Etiology and Management From Infancy to Early Adulthood.

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

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement.

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors-a review of research and clinical practice.

Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.

Growth hormone deficiency and replacement in children.

Growth hormone deficiency (GHD) is a rare but treatable cause of short stature. The diagnosis requires a careful evaluation of clinical history, physical examination and appropriate interpretation of longitudinal growth, with specific features for each period of life. Other clinical findings, in addition to growth failure, may be present and can be related to the etiology and to associated hormone deficiencies. Despite more than 50 years since the first reports of provocative tests of growth hormone (GH) secretion for the diagnosis of GHD, the interpretation of the results remains a matter of debate. When GHD is confirmed, GH treatment is recommended. Treatment is effective and safe, but requires daily injections during many years, which can affect adherence. At the end of longitudinal growth, during the transition phase, it might be necessary to re-evaluate GH secretion. This review summarizes and updates the recent information related to GHD in children, as well the recommendations for treatment.

Indoor physical activities, eating and sleeping habits among school adolescents during COVID-19 pandemic / Atividades físicas internas, hábitos alimentares e dormir entre escolares adolescentes durante a pandêmica de COVID-19

Social isolation is a strategy to avoid contracting and spreading the coronavirus. This study aimed to evaluate physical activities (PA) performed indoors and other habits among adolescents during social isolation due to the coronavirus pandemic (COVID-19). A cross-sectional study including 342 adolescents, aged 12 to 17 years, all students from a public school who regularly participated in sports activities during the school day. An online questionnaire was sent to the students via a web link with 18 questions about eating habits, sleep, virus protection and PA. The average age of the students was 15 ± 1.36 years, 41.5% of them live with three people at home, 77.5% live in houses, 95% answered that they were following the recommended care for COVID-19. Two thirds of the family members worked outside their homes and 65.2% of them were working in direct exposure to COVID-19 (essential services). More than half (53.2%) of adolescents eat up to three meals a day and 80% meet the recommended hours of rest per night. Most of the day was on social networks and only 27% met the recommendations for PA; 29.8% reported weight gain and among them, 54.9% reported exercising at times and 27.4% no exercise at all (p < 0.001). We concluded that despite recommendations, there were reduction in daily PA and increase in screen time among adolescents during social isolation due to COVID-19. There is an urgent need to review strategies to encourage adolescents to maintain indoor PA in addition to a healthier habit

O isolamento social é estratégia para evitar o contágio e transmissão do coronavírus. Este estudo teve como objetivo avaliar as atividades físicas (AF) realizadas em ambientes fechados e hábitos de saúde entre adolescentes durante o isolamento social devido à pandemia de COVID-19 (COVID-19). Estudo transversal com 342 adolescentes, de 12 a 17 anos de idade, estudantes de escola pública e participantes de atividades esportivas escolares. Um questionário on-line foi enviado para os estudantes com 18 perguntas sobre hábitos alimentares, sono, comportamentos de proteção ao COVID-19 e AF. A idade média dos estudantes foi de 15 ± 1,36 anos, 41,5% vivem com três pessoas, 77,5% moram em casas, 95% responderam que estão tomando as medidas de proteção recomendadas. Dois terços dos familiares trabalham fora de casa sendo que 65,2% deles em exposição direta ao COVID-19 (serviços essenciais). Mais da metade (53,2%) dos adolescentes fazem até três refeições por dia e 80% cumprem as horas de descanso recomendadas por noite. A maior parte do dia é usada em redes sociais e penas 27% atenderam às recomendações para AF e 29,8% relataram ganho de peso. Entre os adolescentes que relataram ganho de peso, 54,9% relataram fazer exercícios às vezes e 27,4% não fazem nenhum exercício (p < 0,001). Concluímos que, apesar das recomendações, houve redução nas AF diárias e aumento no tempo de tela entre adolescentes durante o período de isolamento social. Faz-se necessária reavaliação das maneiras de incentivar os adolescentes a manter a AF em ambientes fechados e hábitos de saúde mais saudáveis

Near-Adult Height After Growth Hormone Treatment in Children Born Prematurely-Data From KIGS.

CONTEXT: Children born prematurely have been treated with growth hormone (GH), and a significant improvement in height during the first years of treatment has been described. OBJECTIVE: To evaluate the influence of prematurity on near-adult height (NAH) after GH treatment. DESIGN: KIGS (Pfizer International Growth Database) was queried for children born preterm treated with GH. SETTING: KIGS database. PATIENTS: A total of 586 children short in stature born preterm with various GH status and with available gestational age (GA), birth weight, and NAH, all treated with GH. INTERVENTION: GH treatment. MAIN OUTCOME MEASURE: NAH. RESULTS: Values were expressed as median. From the 586 children included, 482 born appropriate for GA (AGA; median age 8.26 years) and 104 born small for gestational age (SGA) (median age 8.54 years); 66.6% of preterm AGA had GH peak < 7 µg/L during a provocation test, whereas only 8.6% of preterm SGA. Change in height standard deviation scores (SDS) from GH start to NAH after 8.04 years of GH treatment was 1.82 in preterm AGA. Respective values were 7.08 years and 1.08 SDS for preterm SGA (P < 0.001); 57% of the variability of the growth response to NAH could be explained, and the distance to parental height was the strongest predictor. No significant changes in height SDS were observed from puberty start to NAH. No correlation was found with GA. GH treatment was well tolerated. CONCLUSION: GH treatment resulted in significant improvement in height in children born preterm, particularly during prepubertal years and for those with GH deficiency. The degree of prematurity did not influence the growth response.

The challenge of long-term follow-up of survivors of childhood acute leukemia after hematopoietic stem cell transplantation in resource-limited countries: A single-center report from Brazil.

With the number of long-term HSCT survivors steadily increasing, attention needs to be focused on the late complications and quality of life. We therefore analyzed the outcome of 101 pediatric patients (<18 years old at the time of HSCT) transplanted for acute leukemia between 1981 and 2015 at Complexo Hospital de Clínicas, Federal University of Paraná, Brazil, and who survived at least two years after HSCT. The median follow-up was 5.9 years (2.0-29.0); median age at follow-up was 17.5 years (2.98-39.0). The 5-year cumulative incidence of relapse was 27.5% (95% CI 18.6%-36.4%). Two-year cumulative incidence of chronic GVHD was 21.8% (95% CI 13.7%-29.8%). Of the 101 patients, 72 patients (71.3%) presented with late effects. Those surviving longer after HSCT experienced more complications. Patients who received TBI-based regimen developed more late effects (P = .013) and more endocrinological complications (P = .024). Endocrinological complications were the most common late sequelae found in this study. For childhood survivors, quality of life was not influenced by age (at HSCT or at last visit), time from HSCT, gender, donor, or GVHD. For survivors that no longer were children, only age at last visit impacted financial domain measures, irrespective of gender, donor, or GVHD. The current study confirms the high burden late complications after pediatric HSCT have on the survivors and underlines the importance of extended follow-up.

From dwarves to giants: South American's contribution to the history of growth hormone and related disorders.

The aim of this article is to present a historical review on giants and dwarves living in South America and the contribution of South America's researchers to scientific advances on growth hormone (GH) and human disorders related to GH excess and GH deficiency (GHD). We went back in time to investigate facts and myths stemming from countless reports of giants who lived in the Patagonia region, focusing on what is currently known about gigantism in South America. Additionally, we have reviewed the exceptional work carried out in two of the world's largest cohorts of dwarfism related to GH-IGF axis: one living in Itabaianinha, Brazil, suffering from severe GHD due to a mutation in the GHRH receptor (GHRHR) gene, and the other living in El Oro and Loja provinces of Ecuador, who are carriers of GH receptor gene mutation that causes total GH insensitivity (Laron syndrome). Importantly, we present an overview of the outstanding medical contribution of Jose Dantas de Souza Leite, a Brazilian physician that described the first cases of acromegaly, and Bernardo Alberto Houssay, an Argentine researcher graced with the Nobel Prize, who was one the first scientists to establish a link between GH and glucose metabolism.

Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective.

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.

Growth hormone therapy in children; research and practice - A review.

Short stature remains the most common reason for referral to a pediatric Endocrinologist and its management remains a challenge. One of the main controversies is the diagnosis of idiopathic short stature and the role of new technologies for genetic investigation of children with inadequate growth. Complexities in management of children with short stature includes selection of who should receive interventions such as recombinant human growth hormone, and how should this agent dose be adjusted during treatment. Should anthropometrical data be the primary determinant or should biochemical and genetic data be used to improve growth response and safety? Furthermore, what is considered a suboptimal response to growth hormone therapy and how should this be managed? Treatment of children with short stature remains a "hot" topic and more data is needed in several areas. These issues are reviewed in this paper.

Postnatal management of growth failure in children born small for gestational age.

OBJECTIVES: To discuss the etiology and growth consequences of small size at birth and the indications, effects, and safety of biosynthetic growth hormone therapy in children born small for gestational age. SOURCE OF DATA: A comprehensive and non-systematic search was carried out in the PubMed, LILACS, and SciELO databases from 1980 to the present day, using the terms "small for gestational age," "intrauterine growth restriction," and "growth hormone". The publications were critically selected by the authors. DATA SYNTHESIS: Although the majority of children born small for gestational age show spontaneous catch-up growth during the first two years of life, some of them remain with short stature during childhood, with high risk of short stature in adult life. Treatment with growth hormone might be indicated, preferably after 2-4 years of age, in those small for gestational age children who remain short, without catch-up growth. Treatment aims to increase growth velocity and to reach a normal height during childhood and an adult height within target height. Response to growth hormone treatment is variable, with better growth response during the pre-pubertal period. CONCLUSIONS: Treatment with growth hormone in short children born small for gestational age is safe and effective to improve adult height. Efforts should be done to identify the etiology of small size at birth before treatment.

Growth Hormone's Links to Cancer.

Several components of the GH axis are involved in tumor progression, and GH-induced intracellular signaling has been strongly associated with breast cancer susceptibility in genome-wide association studies. In the general population, high IGF-I levels and low IGF-binding protein-3 levels within the normal range are associated with the development of common malignancies, and components of the GH-IGF signaling system exhibit correlations with clinical, histopathological, and therapeutic parameters in cancer patients. Despite promising findings in preclinical studies, anticancer therapies targeting the GH-IGF signaling system have led to disappointing results in clinical trials. There is substantial evidence for some degree of protection against tumor development in several animal models and in patients with genetic defects associated with GH deficiency or resistance. In contrast, the link between GH excess and cancer risk in acromegaly patients is much less clear, and cancer screening in acromegaly has been a highly controversial issue. Recent studies have shown that increased life expectancy in acromegaly patients who attain normal GH and IGF-I levels is associated with more deaths due to age-related cancers. Replacement GH therapy in GH deficiency hypopituitary adults and short children has been shown to be safe when no other risk factors for malignancy are present. Nevertheless, the use of GH in cancer survivors and in short children with RASopathies, chromosomal breakage syndromes, or DNA-repair disorders should be carefully evaluated owing to an increased risk of recurrence, primary cancer, or second neoplasia in these individuals.