Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 898
Filtrar
3.
Lancet Diabetes Endocrinol ; 8(8): 683-692, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32707116

RESUMO

BACKGROUND: Recombinant human growth hormone has been used for more than 30 years and its indications have increased worldwide. There is concern that this treatment might increase mortality, but published data are scarce. We present data from the entire dataset of all eight countries of the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) consortium, with the aim of studying long-term overall and cause-specific mortality in young adult patients treated with recombinant human growth hormone during childhood and relating this to the underlying diagnosis. METHODS: This cohort study was done in eight European countries (Belgium, France, Germany, Italy, The Netherlands, Sweden, Switzerland, and the UK). Patients were classified a priori based on pre-treatment perceived mortality risk from their underlying disease and followed up for cause-specific mortality. Person-years at risk of mortality and expected rates from general population data were used to calculate standardised mortality ratios (SMRs). FINDINGS: The cohort comprised 24 232 patients treated with recombinant human growth hormone during childhood, with more than 400 000 patient-years of follow-up. In low-risk patients with isolated growth hormone deficiency or idiopathic short stature, all-cause mortality was not significantly increased (SMR 1·1, 95% CI 0·9-1·3). In children born small for gestational age, all-cause mortality was significantly increased when analysed for all countries (SMR 1·5, CI 1·1-1·9), but this result was driven by the French subcohort. In patients at moderate or high risk, mortality was increased (SMR 3·8, 3·3-4·4; and 17·1, 15·6-18·7, respectively). Mortality was not associated with mean daily or cumulative doses of recombinant human growth hormone for any of the risk groups. Cause-specific mortality from diseases of the circulatory and haematological systems was increased in all risk groups. INTERPRETATION: In this cohort, the largest, to our knowledge, with long-term follow-up of patients treated with recombinant human growth hormone during childhood, all-cause mortality was associated with underlying diagnosis. In patients with isolated growth hormone deficiency or idiopathic short stature, recombinant human growth hormone treatment was not associated with increased all-cause mortality. However, mortality from certain causes was increased, emphasising the need for further long-term surveillance. FUNDING: European Union.


Assuntos
Nanismo Hipofisário/tratamento farmacológico , Nanismo Hipofisário/mortalidade , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Mortalidade/tendências , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Fatores de Tempo , Adulto Jovem
5.
Biomed Res Int ; 2020: 2308124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149088

RESUMO

It has been recognized that people with obesity are more likely to have low growth hormone secretion. Recent studies have also confirmed that the abnormalities of the growth hormone/insulin-like growth factor 1 axis were associated with cardiovascular complications in people with obesity. However, little is known about whether recombinant human growth hormone therapy could improve cardiovascular and metabolic risks in obese children. This study aims to evaluate the effect of one-year growth hormone therapy on obesity-related comorbidities and to assess the safety in Chinese boys with obesity. Eighteen boys with obesity were treated with recombinant human growth hormone for one year. Anthropometric measurements, endocrine testing, and cardiovascular risk markers were performed in all obese boys in baseline, and follow-up visits were performed at 3 months, 6 months, 9 months, and one year, respectively. After one year of recombinant human growth hormone treatment, the body mass index standard deviation scores decreased (P < 0.001) and insulin-like growth factor 1 levels increased (P < 0.001). GH treatment also reduced low density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), triglycerides (P=0.042), and alanine aminotransferase (P=0.027) when compared with the baseline. One-year of recombinant human growth hormone treatment could improve cardiometabolic risk markers, without adverse effects on glucose homeostasis in boys with obesity.


Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Obesidade/complicações , Adolescente , Alanina Transaminase , Índice de Massa Corporal , Criança , Colesterol , Glucose/metabolismo , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Fator de Crescimento Insulin-Like I/uso terapêutico , Lipoproteínas , Masculino , Proteínas Recombinantes/uso terapêutico , Fatores de Risco , Triglicerídeos
6.
BMC Endocr Disord ; 19(1): 138, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829160

RESUMO

BACKGROUND: To evaluate the impact of treatment with recombinant human growth hormone (rhGH; Omnitrope®) on the risk of diabetes mellitus in adults with growth hormone deficiency (GHD), using data from the ongoing PATRO Adults post-marketing surveillance study. METHODS: PATRO Adults is an ongoing post-marketing surveillance study being conducted in hospitals and specialized endocrinology clinics across Europe. All enrolled patients who receive ≥1 dose of Omnitrope® are included in the safety population. Patient profiles, containing all available study database information for each specific patient, were generated for all patients with adverse events (AEs) of diabetes mellitus while participating in the study. Diabetes mellitus was confirmed if fasting plasma glucose was ≥7.0 mmol/L or 2-h plasma glucose ≥11.1 mmol/L during oral glucose tolerance test or glycated hemoglobin ≥6.5%. RESULTS: Up to July 2018, 1293 patients had been enrolled in the study, and 983 (76.0%) remained active. Just under half (n = 687, 49.3%) of the patients were growth hormone (GH) treatment-naïve on entering the study, and most (n = 1128, 87.2%) had multiple pituitary hormone deficiency (MPHD). Diabetes mellitus/inadequate control (worsening) of diabetes mellitus was reported in 21 patients (22 events). The cases were newly diagnosed in 15 patients (age 29-84 years; incidence rate 3.61 per 1000 patient-years) and occurred in 6 patients with pre-existing diabetes mellitus at baseline (age 45-72 years). Most cases of newly diagnosed diabetes mellitus occurred in patients with adult-onset MPHD (n = 13); the remaining cases of new-onset diabetes mellitus occurred in a patient with childhood-onset MPHD who had previously received GH replacement therapy (n = 1), and a patient with adulthood-onset isolated GHD who was naïve to GH replacement therapy (n = 1). All cases of inadequate control/worsening of diabetes mellitus occurred in patients with adult-onset MPHD. CONCLUSIONS: Based on this snapshot of data from PATRO Adults, Omnitrope® treatment is tolerated in adult patients with GHD in a real-life clinical practice setting. No signals of an increased risk for diabetes mellitus have been noted so far, although continued follow-up (both during and after rhGH therapy) is required to confirm this. TRIAL REGISTRATION: Not applicable.


Assuntos
Transtornos do Metabolismo de Glucose/epidemiologia , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Medicamentos Biossimilares , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Europa (Continente)/epidemiologia , Glucose/metabolismo , Hemoglobina A Glicada/análise , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Hormônios Hipofisários/deficiência , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Fatores de Risco
7.
Sci Rep ; 9(1): 15951, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685880

RESUMO

Turner syndrome (TS) is characterized by the partial or complete loss of one sex chromosome and results in growth failure, gonadal insufficiency and cardiac anomalies. Treatment with growth hormone (GH) during childhood has indisputable benefits when taking into account the low stature of TS women. Medical records and biochemical findings of 33 TS women treated with GH in childhood (GH+) were compared to those of 124 TS women who did not receive GH (GH-). It seems that the GH-treated group might have had a more severe initial phenotype than the untreated group, as evidenced by higher FSH, more feeding issues in infancy, more lymphedema cases and urinary system malformations. GH+ women were significantly taller and had a better lipid profile and lower prevalence of arterial hypertension than GH- . However, they also had lower thrombocyte counts, a greater prevalence of retrognathism and nail anomalies, especially when the GH treatment was delayed. Long-term GH use was not as effective for growth as GH treatment during the initial period and seemed to have resulted in elevated creatinine levels. GH treatment in childhood has benefits in adulthood; however, adverse effects may occur, especially in individuals with treatment that is delayed or is too long.


Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Turner/tratamento farmacológico , Fatores Etários , Biomarcadores , Estudos de Casos e Controles , Criança , Gerenciamento Clínico , Feminino , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Cariótipo , Fenótipo , Resultado do Tratamento , Síndrome de Turner/sangue , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética
8.
Pediatr Endocrinol Rev ; 17(1): 41-46, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31599135

RESUMO

The somatotropic axis is intricately involved in normal sleep, as evidenced by the fact that hypothalamic growth hormone-releasing hormone (GHRH) has sleep promoting effects and pituitary growth hormone (GH) release is strongly associated with slow-wave sleep (SWS). Abnormalities in the somatotropic axis, such as GH deficiency of hypothalamic or pituitary origin, result in an alteration of normal sleep patterns which may explain the fatigue reported in these individuals. Sleep disorders such as narcolepsy, in which individuals abnormally enter rapid eye movement (REM) sleep at sleep onset are also associated with an altered GHRH circadian rhythm and abnormal GH secretion. While few studies are available, this review explores what is known about sleep abnormalities in GH deficiency, the effect of treatment on sleep in patients with GH deficiency, and GH secretion in narcolepsy. Emerging evidence suggests a hypothalamic link between narcolepsy and GH secretion. We also describe the unique constellation of isolated idiopathic GH deficiency and severe excessive sleepiness in adopted Nicaraguan siblings, one of which has narcolepsy and the other idiopathic hypersomnia.


Assuntos
Hormônio do Crescimento Humano , Sonolência , Criança , Nanismo Hipofisário/tratamento farmacológico , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Narcolepsia/fisiopatologia
9.
Ann Ig ; 31(6): 590-594, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616903

RESUMO

Hormones with anabolic properties such as growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are commonly abused among professional and recreational athletes to enhance physical ability. Despite their adverse effects are well-documented, the use of GH and IGF-1 has recently grown. This article highlights the anabolic activity related to mechanisms of cancer development and progression. GH/IGF-1 axis is able to activate cellular mechanisms that modulate every key stage of cancer formation and progression, such as inhibition of apoptosis, resistance to treatments, and induction of angiogenesis, metastatic process and cell proliferation. Results from pre-clinical studies and epidemiological observations in patients with an excess of GH and IGF-1 production or treated with these hormones showed a positive association with the risk to develop several types of cancer. In conclusion, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer, especially if associated with other licit or illicit drugs and/or high-protein diet.


Assuntos
Doping nos Esportes , Hormônio do Crescimento Humano/efeitos adversos , Fator de Crescimento Insulin-Like I/efeitos adversos , Neoplasias/induzido quimicamente , Atletas , Progressão da Doença , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Fator de Crescimento Insulin-Like I/administração & dosagem , Neoplasias/epidemiologia , Neoplasias/patologia , Risco , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
10.
Ir Med J ; 112(5): 936, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31411389

RESUMO

Presentation Constant bilateral frontal headache associated with early morning awakenings, two episodes of vomiting and blurred vision. Diagnosis Benign Intracranial Hypertension. Treatment Repeat Lumbar Punctures were performed. GH was stopped and acetazolamide commenced. Later requiring VP shunt due to refractory symptoms with full resolution of symptoms. Conclusion Surgical management involving shunt procedures are reserved for refractory cases and are highly effective at resolving intractable symptoms.


Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Hipertensão Intracraniana/induzido quimicamente , Síndrome de Turner/tratamento farmacológico , Derivação Ventriculoperitoneal , Adolescente , Terapia Combinada , Feminino , Cefaleia/etiologia , Cefaleia/cirurgia , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Hipertensão Intracraniana/cirurgia , Derivação Ventriculoperitoneal/métodos
11.
J Clin Res Pediatr Endocrinol ; 11(4): 329-340, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31284701

RESUMO

It is over sixty years since the first administration of human growth hormone (GH) to children with GH deficiency, and over thirty years since recombinant human GH has been available for treatment of GH deficiency and a wider range of non-GH deficiency disorders. From a diagnostic perspective, genetic analysis, using single gene or Sanger sequencing and more recently next generation or whole exome sequencing, has brought advances in the diagnosis of specific causes of short stature, which has enabled therapy to be targeted more accurately. Genetic discoveries have ranged from defects of pituitary development and GH action to abnormalities in intracellular mechanisms, paracrine regulation and cartilage matrix formation. The strategy of GH therapy using standard doses has evolved to individualised GH dosing, depending on diagnosis and predictors of growth response. Evidence of efficacy of GH in GH deficiency, Turner syndrome and short children born small for gestational age is reviewed. The importance of critical assessment of growth response is discussed, together with the recognition and management of a poor or unsatisfactory growth response and the organisational issues related to prevention, detection and intervention regarding suboptimal adherence to GH therapy.


Assuntos
Desenvolvimento do Adolescente/efeitos dos fármacos , Estatura/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/administração & dosagem , Adolescente , Fatores Etários , Estatura/genética , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Transtornos do Crescimento/genética , Transtornos do Crescimento/fisiopatologia , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Humanos , Masculino , Fatores de Tempo , Resultado do Tratamento
12.
BMC Nephrol ; 20(1): 198, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151420

RESUMO

BACKGROUND: Anabolic-androgenic steroids and growth hormone are among the most commonly used supplements by sportsmen and sportswomen. The aim of this systematic review is to collect and report available data about renal safety of anabolic-androgenic steroids and growth hormone (GH). METHODS: The search strategy was in accordance with the PRISMA guideline. Seven databases such as Scopus, Medline, Embase, and ISI Web of Knowledge were searched using keywords, such as "growth hormone", "anabolic-androgenic steroids", and "kidney injury". Articles published from 1950 to December 2017 were considered. Randomized clinical trials, prospective or retrospective human studies, case series as well as case reports, and experimental (in vivo) studies were included. Twenty one clinical and experimental articles were selected (12 for anabolic-androgenic steroids and 9 for GH). RESULTS: Anabolic-androgenic steroids can affect the kidney in different aspects. They can induce or aggravate acute kidney injury, chronic kidney disease, and glomerular toxicity. These adverse effects are mediated through pathways such as stimulating renin-angiotensin-aldosterone system, enhancing the production of endothelin, producing reactive oxygen species, over-expression of pro-fibrotic and pro-apoptotic mediators (e.g., TGF-ß1), as well as inflammatory cytokines (e.g., TNF-α, IL-1b, and IL-6). Although GH may affect the kidney in different aspects, such as size, glomerular filtration rate, and tubule functions, either directly or indirectly, there is no conclusive clinical evidence about its detrimental effects on the kidney in athletes and body builders. CONCLUSION: Evidence regarding effects of anabolic-androgenic steroids exists; However, GH's exact effect on the kidney at doses used by athletes and body builders has not yet been clarified. Cohort clinical studies with long-term follow-up are warranted in this regard.


Assuntos
Atletas , Suplementos Nutricionais , Hormônio do Crescimento Humano/administração & dosagem , Rim/efeitos dos fármacos , Congêneres da Testosterona/administração & dosagem , Suplementos Nutricionais/efeitos adversos , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Rim/fisiologia , Rim/fisiopatologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Estudos Retrospectivos , Esportes/fisiologia , Congêneres da Testosterona/efeitos adversos
13.
J Clin Res Pediatr Endocrinol ; 11(4): 395-399, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117336

RESUMO

Objective: Elevated liver function tests (LFTs) are common in adult Turner syndrome (TS) patients. Data regarding children and adolescents are lacking. To investigate the prevalence of abnormal LFTs in children and adolescents with TS during several years of observation; to evaluate the potential impact of increased body mass index (BMI) and sex hormone replacement therapy (HRT) on LFTs. Methods: The analysis included 100 girls with TS, aged 4-16 years, all of whom were receiving recombinant human growth hormone therapy. A longitudinal study was conducted which included 81 patients. Results: Mean BMI-standard deviation (SD) score of the subjects was 0.63 (SD: 1.53). Forty-four were being treated with HRT. Elevated LFTs were found in 34% of the patients overall (32% not receiving HRT vs 36% on HRT). The relative risk of increased LFTs was not higher in obese vs normal weight [odds ratio (OR): 0.2; 95% confidence interval (CI): 0.1-0.36, p=0.38 vs OR: 0.16; 95% CI: 0.08-0.3, p=0.1]. HRT did not increase the risk of abnormal LFTs activity (OR: 0.8; 95% CI: 0.5-1.2, p=0.37 vs OR: 0.7; 95% CI: 0.4-1.1, p=0.27). During the follow-up period (mean±SD=4.31±0.82 years), no patient developed overt liver disease. There was no significant increase nor decrease of abnormal LFT frequency in the subsequent years of follow up. Conclusion: Constantly elevated LFTs in TS are common in children and adolescents with TS. However the causes and clinical significance remain unclear. This study suggests that obesity and HRT do not increase the risk of elevated LFTs.


Assuntos
Terapia de Reposição de Estrogênios , Hormônio do Crescimento Humano/administração & dosagem , Hepatopatias/metabolismo , Testes de Função Hepática , Fígado/efeitos dos fármacos , Progestinas/administração & dosagem , Síndrome de Turner/tratamento farmacológico , Adolescente , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Criança , Pré-Escolar , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Fígado/enzimologia , Fígado/patologia , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Estudos Longitudinais , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/epidemiologia , Valor Preditivo dos Testes , Prevalência , Progestinas/efeitos adversos , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Síndrome de Turner/diagnóstico , Síndrome de Turner/epidemiologia , Regulação para Cima
14.
PLoS One ; 14(5): e0216927, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31095622

RESUMO

PURPOSE: The aim of this registry study was to analyze the long-term safety and effectiveness of recombinant human growth hormone (rhGH) in South Korean pediatric patients (≥2 years of age) with growth hormone deficiency GHD) of idiopathic or organic etiology, idiopathic short stature, Turner syndrome, small for gestational age and chronic renal failure. METHODS: The study patients were followed-up till two years after the epiphyseal closure, with visits scheduled every six months. The outcome measures included the incidence of adverse events (AEs, in particular, neoplasia, glucose intolerance and hypothyroidism), as well as height standard deviation score (Ht SDS) and annual height velocity. The results of the interim analysis of a 5-year accumulated data for 2,024 patients (7,342 patient-years, PY) are presented. RESULTS: A total of 14 neoplasms were diagnosed (191/100,000 PY); 7 out of 9 malignancies were recurrent craniopharyngioma found in patients with organic GHD. Seven cases of glucose intolerance (95/100,000 PY) and 22 cases of hypothyroidism (300/100,000 PY) were detected; about half of the cases (4 and 10 cases each) were considered to be related with rhGH treatment. Most of the growth-retarded patients showed continuous improvement in Ht SDS, with the most prominent effect observed within a year of treatment initiation. The beneficial effect of rhGH on Ht SDS gain was maintained for 2-4 years. CONCLUSIONS: The incidence of AEs of interest in rhGH-treated patients was low, and most of the neoplasms were benign and/or non-related to rhGH. Most patients benefited from the therapy in terms of height increment.


Assuntos
Estatura , Transtornos do Crescimento/terapia , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/uso terapêutico , Adolescente , Glicemia/análise , Criança , Pré-Escolar , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Falência Renal Crônica/terapia , Masculino , Neoplasias/complicações , Neoplasias/diagnóstico , Segurança do Paciente , Proteínas Recombinantes/uso terapêutico , Sistema de Registros , República da Coreia , Tireotropina/sangue , Tiroxina/sangue , Síndrome de Turner/terapia , Adulto Jovem
15.
An. pediatr. (2003. Ed. impr.) ; 90(5): 285-292, mayo 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-186660

RESUMO

Introducción: El crecimiento en pacientes con déficit aislado de hormona del crecimiento (GH) es heterogéneo a pesar del tratamiento, debido a la baja especificidad de las pruebas diagnósticas, por lo que es necesario definir las variables de eficacia. Objetivos: Evaluar la eficacia de la terapia de reemplazo hormonal en niños con déficit aislado de GH. Métodos: Estudio observacional-ambispectivo de pacientes tratados en nuestro servicio en los últimos 14 años por déficit aislado de GH, definido como GH inferior a 7,4 mg/dl en 2 pruebas de estímulo, en pacientes con talla < -2DE y velocidad de crecimiento disminuida. Resultados: Se estudiaron 97 pacientes. El 69% eran varones. Con el tratamiento hubo una ganancia de talla de 1,17DE. El 79,31% alcanzaron la talla diana. El 71,13% fueron reevaluados en la edad adulta, de los cuales el 39,4% mantuvo el déficit. La talla diana, el pronóstico de talla adulta y la ganancia puberal total se correlacionaron positivamente con la talla adulta, mientras que la relación edad ósea/edad cronológica y factor de crecimiento insulínico tipo 1 inicial mostraron una correlación negativa. Ninguno tuvo efectos secundarios. Conclusiones: La mayoría de los pacientes alcanzaron la talla diana, aunque no todos mostraron permanencia del déficit en edad adulta. La talla diana, el pronóstico de talla adulta y las variables de pubertad están directamente relacionados con la talla adulta; mientras que la edad ósea/edad cronológica y factor de crecimiento insulínico tipo 1 están inversamente relacionadas, pudiendo utilizarse estas como variables de eficacia. No se han observado efectos adversos en la muestra con las dosis utilizadas


Introduction: Growth in patients with isolated growth hormone (GH) deficiency is heterogeneous despite treatment due to the low specificity of diagnostic tests, making it necessary to define efficacy variables. Aims: To evaluate efficacy of hormone replacement therapy in children with isolated GH deficiency. Methods: Observational-ambispective study of patients treated in our department in the last 14 years for isolated GH deficiency. This was defined as a GH level less than 7.4 mg/dl in response to 2 stimulation tests in patients with height < 2SD and a decreased growth rate. Results: The study included a total 97 patients, of whom 69% were boys. The large majority (89.58%) achieved final height. None of them had side effects. The median dose of GH used was 0.028 mg/kg/day (0.03-0.025). There was a gain of 1.17 SD in final height. Around three-quarters (71.13%) of the patients were reassessed in adulthood, of whom 39.4% maintained the deficiency, and 79.31% achieved target range height. Target height, estimated height, and the total pubertal gain were positively correlated with final height, while the bone age/chronological age ratio and the initial insulin-like growth factor-1 showed a negative correlation. Conclusions: A majority of patients reached target size, although only a few of them maintained the deficiency in adulthood. Target size, estimated adult height, and pubertal variables are directly related to adult height, while bone age/chronological age and insulin-like growth factor-1 were inversely related, and these can be used as efficacy variables. No adverse effects were observed in the sample with the doses used for the treatment


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Nanismo Hipofisário/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Hormônio do Crescimento Humano/administração & dosagem , Fator de Crescimento Insulin-Like I/metabolismo , Fatores Etários , Estatura/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hormônio do Crescimento Humano/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos
16.
Medicine (Baltimore) ; 98(14): e14962, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946320

RESUMO

To investigate the progression rate of bone age (BA) and associated factors during the first 3 years of growth hormone (GH) treatment in children with idiopathic GH deficiency (iGHD) and idiopathic short stature (ISS).Data for prepubertal children with iGHD and ISS who were treated with recombinant human GH were obtained from the LG Growth Study Database and analyzed. Height, weight, BA, insulin-like growth factor-1 (IGF-1) level, and GH dose were recorded every 6 months. Differences between BA and chronological age (CA), BA-CA, were calculated at each measurement. This study included 92 (78 iGHD and 14 ISS) subjects.After 3 years of GH treatment, the height z-score was -1.09 ±â€Š0.71 (P < .001 compared to baseline), BA-CA was -1.21 ±â€Š1.18 years (P < .001), and IGF-1 standard deviation score (SDS) was 0.43 ±â€Š1.21 (P < .001) in the iGHD subjects; the change in BA over the 3 years was 3.68 ±â€Š1.27 years. In the ISS subjects, the height z-score was -1.06 ±â€Š0.59 (P < .001), BA-CA was -0.98 ±â€Š1.23 years (P = .009), and IGF-1 SDS was 0.16 ±â€Š0.76 (P = .648); the change in BA over the 3 years was 3.88 ±â€Š1.36 years. The only significant factor associated with the BA progression was the BA-CA at 1 year of GH treatment (OR = 2.732, P = .001). The baseline BA-CA, IGF-1 SDS, and GH dose did not influence BA progression.Prepubertal subjects with iGHD and ISS showed height improvement and mild BA acceleration over the first 3 years of GH treatment. However, because the BA progression rate was considered to be clinically acceptable, GH treatment may increase the predicted adult height during this period.


Assuntos
Nanismo/tratamento farmacológico , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento/deficiência , Hormônio do Crescimento Humano/efeitos adversos , Determinação da Idade pelo Esqueleto/métodos , Fenômenos Biológicos , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Nanismo/diagnóstico , Feminino , Transtornos do Crescimento/diagnóstico , Hormônio do Crescimento/sangue , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Estudos Prospectivos , Estudos Retrospectivos
17.
J Clin Res Pediatr Endocrinol ; 11(4): 350-357, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-30819016

RESUMO

Objective: To evaluate glucose metabolism and insulin sensitivity in children with idiopathic growth hormone (GH) deficiency, treated with recombinant human GH (rhGH), and to identify possible risk factors for the development of glucose abnormalities in this population. Methods: We retrospectively collected data from 101 patients (60 males, median age 10.4 years, 77 prepubertal), with confirmed GH deficiency, enrolled before starting rhGH and followed up during the first three years of treatment. Glucose metabolism was evaluated annually by oral glucose tolerance test (OGTT) and glycated hemoglobin A1c (HbA1c). OGTT was used to calculate insulin sensitivity (HOMA-S) and insulin resistance (HOMA-IR), defined as HOMA-IR >3. Results: RhGH was effective in improving growth and dosages significantly reduced after the first year of therapy. No patient developed diabetes mellitus. After one year of therapy, a significant increase in HbA1c (p=0.0042) and insulin levels (fasting p<0.0001, 60 min p=0.0018, 120 min p=0.0003) was observed, with a higher prevalence of IR (p<0.05). These indices did not alter further during the follow-up and were not related to GH dose or to family history of diabetes. A significant correlation was found only for IR indices and pubertal status, weight and age (p<0.05). Conclusion: In this retrospective study on a large GH deficient pediatric population, conventional use of replacement therapy resulted in an increase in HbA1c and IR after one year of therapy, regardless of rhGH dosage. These alterations did not worsen significantly in the following two years and were not associated with overt diabetes.


Assuntos
Glicemia/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/efeitos adversos , Resistência à Insulina , Insulina/sangue , Biomarcadores/sangue , Glicemia/metabolismo , Criança , Feminino , Transtornos do Crescimento/sangue , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/fisiopatologia , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/deficiência , Humanos , Masculino , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
18.
Diabet Med ; 36(10): 1276-1281, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30690790

RESUMO

AIMS: To determine the long-term risk of diabetes in a cohort of children treated with recombinant human growth hormone in Israel, using data from the Israeli National Diabetes Register. METHODS: Between 1988 and 2009, 2513 children were approved for growth hormone treatment. They were assigned to one of two groups. The first group included children treated for isolated growth hormone deficiency and who were small for gestational age and the second included those treated for multiple pituitary hormone deficiency, chronic renal failure, Turner syndrome or Prader-Willi syndrome. The cohort was cross-linked with the Israeli National Diabetes Register for 2014 (mean follow-up duration 12.1±5.3 years), and prevalent cases of diabetes were identified. Standardized prevalence ratios for diabetes were calculated for people aged 10-29 years. RESULTS: In 2014, a total of 23 individuals were identified with diabetes (four with pre-existing diabetes, seven developed diabetes before age 17 years and 12 developed it at a later age). In the isolated growth hormone deficiency and small-for-gestational-age group there was no difference in the prevalence of diabetes compared with the general population (standardized prevalence ratio 2.05, 95% CI 0.94-3.89). In the group that included people with multiple pituitary hormone deficiency, chronic renal failure, Turner syndrome and Prader-Willi syndrome there was a significantly higher diabetes prevalence (standardized prevalence ratio 11.94, 95% CI 6.53-20.00) compared with the general population. CONCLUSIONS: No difference in diabetes prevalence was found in the isolated growth hormone deficiency and small-for-gestational-age group, compared with the general population. Children treated with growth hormone with pre-existing risk factors had an increased prevalence of diabetes. It is advisable to monitor blood glucose levels closely during and after growth hormone treatment, especially in such children.


Assuntos
Diabetes Mellitus/epidemiologia , Hormônio do Crescimento Humano/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Israel/epidemiologia , Falência Renal Crônica/tratamento farmacológico , Masculino , Hormônios Hipofisários/deficiência , Síndrome de Prader-Willi/tratamento farmacológico , Prevalência , Proteínas Recombinantes/uso terapêutico , Fatores de Risco , Síndrome de Turner/tratamento farmacológico
19.
J Clin Res Pediatr Endocrinol ; 11(4): 419-425, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-30630810

RESUMO

Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked disease caused by PHF6 mutations. Classic BFLS has been associated with intellectual disability (ID), developmental delay (DD), obesity, epilepsy, typical facial features and anomalies of fingers and toes. Endocrinological phenotypes and outcome of treatment in this condition remain to be delineated. Here we report a patient who exhibited complete growth hormone deficiency who responded to hormonal treatment but with adverse effects. Horseshoe kidney was present in this patient, which is also atypical in BFLS. A heterozygous nonsense mutation c.673C>T (p.R225X) of PHF6 gene was identified in the patient, inherited from her unaffected mother. Both the patient and her mother showed highly skewed X-inactivation. We reviewed the phenotypes of all reported BFLS cases, and summarized their endocrine presentations. This first report of an Asian patient with BFLS further delineated the genetic and phenotypic spectrum of the syndrome. The adverse effect experienced by the patient suggests caution in the use of growth hormone treatment in this condition.


Assuntos
Códon sem Sentido , Epilepsia/genética , Face/anormalidades , Dedos/anormalidades , Transtornos do Crescimento/genética , Hipogonadismo/genética , Retardo Mental Ligado ao Cromossomo X/genética , Obesidade/genética , Proteínas Repressoras/genética , Criança , Comportamento Infantil , Desenvolvimento Infantil , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Feminino , Predisposição Genética para Doença , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/tratamento farmacológico , Hereditariedade , Heterozigoto , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/tratamento farmacológico , Retardo Mental Ligado ao Cromossomo X/diagnóstico , Retardo Mental Ligado ao Cromossomo X/tratamento farmacológico , Obesidade/diagnóstico , Obesidade/tratamento farmacológico , Linhagem , Fenótipo
20.
J Clin Endocrinol Metab ; 104(3): 658-664, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137467

RESUMO

Context: There has been concern that GH treatment of children might increase meningioma risk. Results of published studies have been inconsistent and limited. Objective: To examine meningioma risks in relation to GH treatment. Design: Cohort study with follow-up via cancer registries and other registers. Setting: Population-based. Patients: A cohort of 10,403 patients treated in childhood with recombinant GH in five European countries since this treatment was first used in 1984. Expected rates from national cancer registration statistics. Main Outcome Measures: Risk of meningioma incidence. Results: During follow-up, 38 meningiomas occurred. Meningioma risk was greatly raised in the cohort overall [standardized incidence ratio (SIR) = 75.4; 95% CI: 54.9 to 103.6], as a consequence of high risk in subjects who had received radiotherapy for underlying malignancy (SIR = 658.4; 95% CI: 460.4 to 941.7). Risk was not significantly raised in patients who did not receive radiotherapy. Risk in radiotherapy-treated patients was not significantly related to mean daily dose of GH, duration of GH treatment, or cumulative dose of GH. Conclusions: Our data add to evidence of very high risk of meningioma in patients treated in childhood with GH after cranial radiotherapy, but suggest that GH may not affect radiotherapy-related risk, and that there is no material raised risk of meningioma in GH-treated patients who did not receive radiotherapy.


Assuntos
Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/efeitos adversos , Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Irradiação Craniana/efeitos adversos , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Neoplasias Meníngeas/etiologia , Meningioma/etiologia , Segunda Neoplasia Primária/etiologia , Proteínas Recombinantes/efeitos adversos , Sistema de Registros/estatística & dados numéricos , Medição de Risco , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...