Vitamin D-Dependent Rickets Type 3: A Case Report and Systematic Review.

Although vitamin D deficiency resulting from insufficient sunlight exposure or inadequate dietary vitamin D intake is the most common cause of rickets, mutations in genes involved in vitamin D metabolism can cause genetic forms of rickets termed Vitamin D-Dependent Rickets (VDDR). In 2018, Roizen et al. described a new type of VDDR, named VDDR3, caused by a recurrent missense mutation in the CYP3A4 gene that leads to accelerated inactivation of vitamin D metabolites. Here, we describe the third case of VDDR3 due to the same CYP3A4 mutation in a 2-year-old boy with bone deformities associated with poor growth. As in the previously reported cases, this patient had no family history of rickets. Serial measurements of vitamin D metabolites after a single 150,000 IU dose of cholecalciferol demonstrated an accelerated inactivation of 25(OH)D and 1,25(OH)2D. Significant improvement in growth velocity and healing of bone deformities were achieved after a short period of treatment with 10.000 IU of cholecalciferol daily, showing the importance of early recognition and prompt precision therapy of this condition.

Diagnostic yield of a multigene sequencing approach in children classified as idiopathic short stature.

Objective: Most children with short stature remain without an etiologic diagnosis after extensive clinical and laboratory evaluation and are classified as idiopathic short stature (ISS). This study aimed to determine the diagnostic yield of a multigene analysis in children classified as ISS. Design and methods: We selected 102 children with ISS and performed the genetic analysis as part of the initial investigation. We developed customized targeted panel sequencing, including all genes already implicated in the isolated short-stature phenotype. Rare and deleterious single nucleotide or copy number variants were assessed by bioinformatic tools. Results: We identified 20 heterozygous pathogenic (P) or likely pathogenic (LP) genetic variants in 17 of 102 patients (diagnostic yield = 16.7%). Three patients had more than one P/LP genetic alteration. Most of the findings were in genes associated with the growth plate differentiation: IHH (n = 4), SHOX (n = 3), FGFR3 (n = 2), NPR2 (n = 2), ACAN (n = 2), and COL2A1 (n = 1) or involved in the RAS/MAPK pathway: NF1 (n = 2), PTPN11 (n = 1), CBL (n = 1), and BRAF (n = 1). None of these patients had clinical findings to guide a candidate gene approach. The diagnostic yield was higher among children with severe short stature (35% vs 12.2% for height SDS ≤ or > -3; P = 0.034). The genetic diagnosis had an impact on clinical management for four children. Conclusion: A multigene sequencing approach can determine the genetic etiology of short stature in up to one in six children with ISS, removing the term idiopathic from their clinical classification.

Achondroplasia in Latin America: practical recommendations for the multidisciplinary care of pediatric patients.

BACKGROUND: Achondroplasia is the most common bone dysplasia associated with disproportionate short stature, and other comorbidities, such as foramen magnum stenosis, thoracolumbar kyphosis, lumbar hyperlordosis, genu varum and spinal compression. Additionally, patients affected with this condition have higher frequency of sleep disorders, ear infections, hearing loss and slowed development milestones. Considering these clinical features, we aimed to summarize the regional experts' recommendations for the multidisciplinary management of patients with achondroplasia in Latin America, a vast geographic territory with multicultural characteristics and with socio-economical differences of developing countries. METHODS: Latin American experts (from Argentina, Brazil, Chile and Colombia) particiáted of an Advisory Board meeting (October 2019), and had a structured discussion how patients with achondroplasia are followed in their healthcare centers and punctuated gaps and opportunities for regional improvement in the management of achondroplasia. RESULTS: Practical recommendations have been established for genetic counselling, prenatal diagnosis and planning of delivery in patients with achondroplasia. An outline of strategies was added as follow-up guidelines to specialists according to patient developmental phases, amongst them neurologic, orthopedic, otorhinolaryngologic, nutritional and anthropometric aspects, and related to development milestones. Additionally, the role of physical therapy, physical activity, phonoaudiology and other care related to the quality of life of patients and their families were discussed. Preoperative recommendations to patients with achondroplasia were also included. CONCLUSIONS: This study summarized the main expert recommendations for the health care professionals management of achondroplasia in Latin America, reinforcing that achondroplasia-associated comorbidities are not limited to orthopedic concerns.

Growth hormone deficiency and the transition from pediatric to adult care

Abstract Objective: To discuss the approach to patients diagnosed with growth hormone deficiency (GHD) in childhood during the transition period from puberty to adulthood, focusing on the following: (1) physiology; (2) effects of recombinant human GH (rhGH) interruption/reinstitution after adult height achievement; (3) re-evaluation of somatrotropic axis; (4) management of rhGH reinstitution, when necessary. Source of data: Narrative review of the literature published at PubMed/MEDLINE until September 2020 including original and review articles, systematic reviews and meta-analyses. Synthesis of data: Growth hormone is crucial for the attainment of normal growth and for adequate somatic development, which does not end concomitantly with linear growth. Retesting adolescents who already meet the criteria that predict adult GHD with high specificity is not necessary. Patients with isolated GHD have a high likelihood of normal response to GH testing after puberty. Adolescents with confirmed GHD upon retesting should restart rhGH replacement and be monitored according to IGF-I levels, clinical parameters, and complementary exams. Conclusion: Patients with isolated idiopathic GHD in childhood are a special group who must be reevaluated for GHD as many of them have normal GH provocative tests upon retesting after puberty. Patients who confirm the persistence of GHD in the transition period should maintain rhGH replacement in order to reach an ideal peak bone mass, satisfactory body composition, lipid and glucose profiles, and quality of life.

Growth hormone deficiency and the transition from pediatric to adult care.

OBJECTIVE: To discuss the approach to patients diagnosed with growth hormone deficiency (GHD) in childhood during the transition period from puberty to adulthood, focusing on the following: (1) physiology; (2) effects of recombinant human GH (rhGH) interruption/reinstitution after adult height achievement; (3) re-evaluation of somatrotropic axis; (4) management of rhGH reinstitution, when necessary. SOURCE OF DATA: Narrative review of the literature published at PubMed/MEDLINE until September 2020 including original and review articles, systematic reviews and meta-analyses. SYNTHESIS OF DATA: Growth hormone is crucial for the attainment of normal growth and for adequate somatic development, which does not end concomitantly with linear growth. Retesting adolescents who already meet the criteria that predict adult GHD with high specificity is not necessary. Patients with isolated GHD have a high likelihood of normal response to GH testing after puberty. Adolescents with confirmed GHD upon retesting should restart rhGH replacement and be monitored according to IGF-I levels, clinical parameters, and complementary exams. CONCLUSION: Patients with isolated idiopathic GHD in childhood are a special group who must be reevaluated for GHD as many of them have normal GH provocative tests upon retesting after puberty. Patients who confirm the persistence of GHD in the transition period should maintain rhGH replacement in order to reach an ideal peak bone mass, satisfactory body composition, lipid and glucose profiles, and quality of life.

Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing.

OBJECTIVE: To perform a prospective genetic investigation using whole exome sequencing of a group of patients with syndromic short stature born small for gestational age of unknown cause. STUDY DESIGN: For whole exome sequencing analysis, we selected 44 children born small for gestational age with persistent short stature, and additional features, such as dysmorphic face, major malformation, developmental delay, and/or intellectual disability. Seven patients had negative candidate gene testing based on clinical suspicion and 37 patients had syndromic conditions of unknown etiology. RESULTS: Of the 44 patients, 15 (34%) had pathogenic/likely pathogenic variants in genes already associated with growth disturbance: COL2A1 (n = 2), SRCAP (n = 2), AFF4, ACTG1, ANKRD11, BCL11B, BRCA1, CDKN1C, GINS1, INPP5K, KIF11, KMT2A, and POC1A (n = 1 each). Most of the genes found to be deleterious participate in fundamental cellular processes, such as cell replication and DNA repair. CONCLUSIONS: The rarity and heterogeneity of syndromic short stature make the clinical diagnosis difficult. Whole exome sequencing allows the diagnosis of previously undiagnosed patients with syndromic short stature.

Physical fitness and activity, metabolic profile, adipokines and endothelial function in children / Aptidão e atividade física, perfil metabólico, adipocinas e função endotelial em crianças

Abstract Objectives: The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. Method: Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). Results: A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (p < 0.01). HDL cholesterol and adiponectin levels were higher in the eutrophic group compared to the obese and excess-weight groups (p < 0.01). Flow-mediated vasodilation after hyperemia was higher in the eutrophic group in comparison to obese and excess-weight subjects (p < 0.05). There was no difference in the physical activity levels among groups measured by PAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho = −0.41; p = 0.01), and this association remained after adjusting for body mass index z-score (rho = 0.28; p = 0.03). Conclusion: This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index.

Resumo: Objetivos: A prevalência da obesidade está aumentando. O objetivo deste estudo foi investigar se há disfunção endotelial nas crianças com peso normal ou excesso de peso e se o perfil metabólico, as adipocinas e a disfunção endotelial seriam mais fortemente associados à aptidão física ou aos níveis de atividade física. Método: Estudo transversal que envolve crianças de 5-12 anos. A avaliação incluiu pletismografia de oclusão venosa, níveis séricos de adiponectina, leptina, insulina e lipidograma, escore de atividade física (questionário PAQ-C) e avaliação da aptidão física (teste Yo-yo). Resultados: Um total de 62 crianças participou deste estudo. Com base no índice de massa corporal, 27 eram eutróficos, 10 estavam acima do peso e 25 estavam obesos. Os níveis de triglicerídeos, colesterol LDL, HOMA-RI e leptina estavam mais elevados nas crianças obesas e com excesso de peso que o grupo de eutróficos (p < 0,01). Os níveis de colesterol HDL e adiponectina estavam mais elevados no grupo de eutróficos em comparação ao grupo de obesos e com excesso de peso (p < 0,01). A vasodilatação mediada pelo fluxo após hiperemia foi maior no grupo de eutróficos em comparação aos indivíduos obesos e com excesso de peso (p < 0,05). Não houve nenhuma diferença nos níveis de atividade física entre os grupos medidos pelo PAQ-C. O teste de ida e volta foi significativamente associado ao colesterol HDL (ró = −0,41; p = 0,01) e essa associação continuou após ajustar o escore z do índice de massa corporal (ró = 0,28; p = 0,03). Conclusão: Este estudo mostrou que a disfunção endotelial já está presente nas crianças obesas, sugeriu uma predisposição à doença aterosclerótica. Além disso, os níveis de colesterol HDL foram correlacionados à aptidão física, independentemente do índice de massa corporal.

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.

Physical fitness and activity, metabolic profile, adipokines and endothelial function in children.

OBJECTIVES: The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. METHOD: Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). RESULTS: A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (p<0.01). HDL cholesterol and adiponectin levels were higher in the eutrophic group compared to the obese and excess-weight groups (p<0.01). Flow-mediated vasodilation after hyperemia was higher in the eutrophic group in comparison to obese and excess-weight subjects (p<0.05). There was no difference in the physical activity levels among groups measured by PAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho=-0.41; p=0.01), and this association remained after adjusting for body mass index z-score (rho=0.28; p=0.03). CONCLUSION: This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index.

Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children.

BACKGROUND: Early exposure to cardiovascular risk factors creates a chronic inflammatory state that could damage the endothelium followed by thickening of the carotid intima-media. OBJECTIVE: To investigate the association of cardiovascular risk factors and thickening of the carotid intima. SUBJECTS/METHODS: Media in prepubertal children. In this cross-sectional study, carotid intima-media thickness (cIMT) and cardiovascular risk factors were assessed in 129 prepubertal children aged from 5 to 10 year. Association was assessed by simple and multivariate logistic regression analyses. RESULTS: In simple logistic regression analyses, body mass index (BMI) z-score, waist circumference, and systolic blood pressure (SBP) were positively associated with increased left, right, and average cIMT, whereas diastolic blood pressure was positively associated only with increased left and average cIMT (p<0.05). In multivariate logistic regression analyses increased left cIMT was positively associated to BMI z-score and SBP, and increased average cIMT was only positively associated to SBP (p<0.05). CONCLUSIONS: BMI z-score and SBP were the strongest risk factors for increased cIMT.

Evaluation of sublingual microcirculation in children with dengue shock.

OBJECTIVE: To report the sublingual microcirculation observed using Sidestream Dark Field imaging in two children with dengue shock. METHOD: Two children, aged 9 and 10 years, were admitted to the pediatric intensive care unit with dengue shock and multiple organ dysfunction. Sublingual microcirculation was assessed in each patient on the first and second days of shock and was assessed a final time when the patients were no longer in shock (on the day prior to extubation) using Sidestream Dark Field technology. The De Backer score and microvascular flow index were used for the analyses. RESULTS: Both patients had reduced perfused small vessel density in the first two days and showed predominantly intermittent or no microcirculation flow, as demonstrated by a low microvascular flow index. The blood flow in the large vessels was not affected. Prior to the extubation, the microvascular flow index had increased, although the perfused small vessel density remained diminished, suggesting persistent endothelial dysfunction. CONCLUSIONS: Severe microcirculation changes may be involved in the pathophysiological mechanisms that lead to the final stages of dengue shock, which is frequently irreversible and associated with high mortality rates. Microcirculatory monitoring may help elucidate the physiopathology of dengue shock and prove useful as a prognostic tool or therapeutic target.

Evaluation of sublingual microcirculation in children with dengue shock

OBJECTIVE: To report the sublingual microcirculation observed using Sidestream Dark Field imaging in two children with dengue shock. METHOD: Two children, aged 9 and 10 years, were admitted to the pediatric intensive care unit with dengue shock and multiple organ dysfunction. Sublingual microcirculation was assessed in each patient on the first and second days of shock and was assessed a final time when the patients were no longer in shock (on the day prior to extubation) using Sidestream Dark Field technology. The De Backer score and microvascular flow index were used for the analyses. RESULTS: Both patients had reduced perfused small vessel density in the first two days and showed predominantly intermittent or no microcirculation flow, as demonstrated by a low microvascular flow index. The blood flow in the large vessels was not affected. Prior to the extubation, the microvascular flow index had increased, although the perfused small vessel density remained diminished, suggesting persistent endothelial dysfunction. CONCLUSIONS: Severe microcirculation changes may be involved in the pathophysiological mechanisms that lead to the final stages of dengue shock, which is frequently irreversible and associated with high mortality rates. Microcirculatory monitoring may help elucidate the physiopathology of dengue shock and prove useful as a prognostic tool or therapeutic target. .

Leydig cell tumour in a 46,XX child with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

CASE REPORT: A 10-year-old male was referred to our institution due to short stature and bilateral cryptorchidism and reported pubic hair development and acne since the age of 4 years. Laboratory and molecular genetic tests indicated congenital adrenal hyperplasia due to 21-hydroxylase deficiency. After treatment with prednisone, adrenal hormones normalised but testosterone remained elevated. Magnetic resonance imaging of the abdomen due to cryptorchidism revealed uterus and adnexal attachments, a prostate and poorly defined nodules on the iliac chains. Upon exploratory laparotomy, a hysterectomy, bilateral oophorectomy and resection of a peri-adnexal nodular lesion on the patient's right side were performed. Histopathology of the nodule mass was compatible with a Leydig cell tumour with a low proliferation rate according to Ki67.

Hipoglicemia hiperinsulinêmica da infância: Análise de dados clínicos de uma amostra brasileira / Hyperinsulinemic hypoglycemia of the infancy: Analysis of clinical data from a Brazilian sample

OBJETIVO: Rever a apresentação dos casos de hipoglicemia hiperinsulinêmica da infância (HHI), tratamento e histologia nos serviços de endocrinologia pediátrica no Brasil. MATERIAIS E MÉTODO: Os serviços receberam protocolo para resgatar dados de nascimento, resultados laboratoriais, tipo de tratamento instituído, necessidade de pancreatectomia e histologia. RESULTADOS: Vinte e cinco casos de HHI de seis centros foram resgatados, 15 do sexo masculino, 3/25 nascidos de parto normal. A mediana de idade do diagnóstico foi 10,3 dias. As dosagens de glicose e insulina na amostra sérica crítica apresentaram mediana de 24,7 mg/dL e 26,3 UI/dL. A velocidade de infusão de glicose endovenosa foi superior a 10 mg/kg/min em todos os casos (M:19,1). Diazóxido foi utilizado em 15/25, octreotide em 10, corticoide em 8, hormônio de crescimento em 3, nifedipina em 2 e glucagon em 1. Quarenta por cento (10/25) foram pancreatectomizados, nos quais a análise histológica revelou a forma difusa da patologia. CONCLUSÃO: Primeira análise crítica de uma amostra brasileira de portadores de HHI congênita. Arq Bras Endocrinol Metab. 2012;56(9):666-71.

OBJECTIVE: To review the presentation of hyperinsulinemic hypoglycemia of the infancy (HHI), its treatment and histology in Brazilian pediatric endocrinology sections. MATERIALS AND METHOD: The protocol analyzed data of birth, laboratory results, treatment, surgery, and pancreas histology. RESULTS: Twenty-five cases of HHI from six centers were analyzed: 15 male, 3/25 born by vaginal delivery. The average age at diagnosis was 10.3 days. Glucose and insulin levels in the critical sample showed an average of 24.7 mg/dL and 26.3 UI/dL. Intravenous infusion of the glucose was greater than 10 mg/kg/min in all cases (M:19,1). Diazoxide was used in 15/25 of the cases, octreotide in 10, glucocorticoid in 8, growth hormone in 3, nifedipine in 2 and glucagon in 1. Ten of the cases underwent pancreatectomy and histology results showed the diffuse form of disease. CONCLUSION: This is the first critic review of a Brazilian sample with congenital HHI. Arq Bras Endocrinol Metab. 2012;56(9):666-71.

[Hyperinsulinemic hypoglycemia of the infancy: analysis of clinical data from a Brazilian sample]. / Hipoglicemia hiperinsulinêmica da infância: Análise de dados clínicos de uma amostra brasileira.

OBJECTIVE: To review the presentation of hyperinsulinemic hypoglycemia of the infancy (HHI), its treatment and histology in Brazilian pediatric endocrinology sections. MATERIALS AND METHOD: The protocol analyzed data of birth, laboratory results, treatment, surgery, and pancreas histology. RESULTS: Twenty-five cases of HHI from six centers were analyzed: 15 male, 3/25 born by vaginal delivery. The average age at diagnosis was 10.3 days. Glucose and insulin levels in the critical sample showed an average of 24.7 mg/dL and 26.3 UI/dL. Intravenous infusion of the glucose was greater than 10 mg/kg/min in all cases (M:19,1). Diazoxide was used in 15/25 of the cases, octreotide in 10, glucocorticoid in 8, growth hormone in 3, nifedipine in 2 and glucagon in 1. Ten of the cases underwent pancreatectomy and histology results showed the diffuse form of disease. CONCLUSION: This is the first critic review of a Brazilian sample with congenital HHI.

Endocrine diseases, perspectives and care in Turner syndrome / Doenças endócrinas, perspectivas e cuidados na síndrome de Turner

Turner syndrome is a frequent chromosome disorder in clinical practice. It is characterized by short stature, gonadal dysgenesia and multisystemic involvement, responsible for a high morbidity and reduced life expectancy. The aim of the present paper is to describe the endocrinopathies and major problems at different ages, and to present suggestion for follow-up care in these patients.

A síndrome de Turner é uma doença cromossômica frequente na prática clínica. É caracterizada pela baixa estatura, disgenesia gonadal e alterações em diversos sistemas, o que leva a uma alta morbidade e diminuição da expectativa de vida. O objetivo do presente estudo é descrever as endocrinopatias e outros problemas em cada idade e apresentar uma sugestão de cuidados e segmentos dessas pacientes.

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.

Update in growth hormone therapy of children.

Although recombinant human GH (rhGH) has been available since 1985, there are several questions related to its use that remain unanswered. The Entrez-PubMed search engine was used to conduct a review of publications appearing since 2007 that address growth and GH treatment. Recent publications related to the diagnosis of GH deficiency, genetics of growth, the use of rhGH in different genetic conditions, in idiopathic short stature, and in puberty, and strategies to adjust rhGH dose were reviewed. New studies investigating the genetics of growth and the response to rhGH therapy in different groups are helping in the understanding of the physiology of normal growth. Although in most children treated with rhGH there is a short-term benefit, the clinical relevance of the benefits after long-term treatment in some conditions remains unclear. The challenges are to define milder forms of GH deficiency and to assess the relevance of the benefits, if any, caused by rhGH in different patient populations and the best therapeutic approach for these patients. Well-designed long-term studies using anthropometric, genetic, and laboratory data that will also assess long-term quality of life benefits are needed to help clinicians select patients to initiate treatment with rhGH and to adjust treatment to improve outcome.

Endocrine diseases, perspectives and care in Turner syndrome.

Turner syndrome is a frequent chromosome disorder in clinical practice. It is characterized by short stature, gonadal dysgenesia and multisystemic involvement, responsible for a high morbidity and reduced life expectancy. The aim of the present paper is to describe the endocrinopathies and major problems at different ages, and to present suggestion for follow-up care in these patients.

Adverse effects of growth hormone replacement therapy in children.

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.