RESUMO
OBJECTIVES: To conduct a cost-utility analysis comparing drug strategies involving octreotide, lanreotide, pasireotide, and pegvisomant for the treatment of patients with acromegaly who have failed surgery, from a Brazilian public payer perspective. METHODS: A probabilistic cohort Markov model was developed. One-year cycles were employed. The patients started at 45 years of age and were followed lifelong. Costs, efficacy, and quality of life parameters were retrieved from the literature. A discount rate (5%) was applied to both costs and efficacy. The results were reported as costs per quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated when applicable. Scenario analyses considered alternative dosages, discount rate, tax exemption, and continued use of treatment despite lack of response. Value of information (VOI) analysis was conducted to explore uncertainty and to estimate the costs to be spent in future research. RESULTS: Only lanreotide showed an ICER reasonable for having its use considered in clinical practice (R$ 112,138/US$ 28,389 per QALY compared to no treatment). Scenario analyses corroborated the base-case result. VOI analysis showed that much uncertainty surrounds the parameters, and future clinical research should cost less than R$ 43,230,000/US$ 10,944,304 per year. VOI also showed that almost all uncertainty that precludes an optimal strategy choice involves quality of life. CONCLUSIONS: With current information, the only strategy that can be considered cost-effective in Brazil is lanreotide treatment. No second-line treatment is recommended. Significant uncertainty of parameters impairs optimal decision-making, and this conclusion can be generalized to other countries. Future research should focus on acquiring utility data.
Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/economia , Antineoplásicos , Análise Custo-Benefício , Hormônios , Hormônio do Crescimento Humano/análogos & derivados , Octreotida , Avaliação de Resultados em Cuidados de Saúde , Peptídeos Cíclicos , Somatostatina/análogos & derivados , Antineoplásicos/economia , Antineoplásicos/farmacologia , Brasil , Hormônios/economia , Hormônios/farmacologia , Hormônio do Crescimento Humano/economia , Hormônio do Crescimento Humano/farmacologia , Humanos , Programas Nacionais de Saúde , Octreotida/economia , Octreotida/farmacologia , Avaliação de Resultados em Cuidados de Saúde/economia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Peptídeos Cíclicos/economia , Peptídeos Cíclicos/farmacologia , Somatostatina/economia , Somatostatina/farmacologiaRESUMO
Background The relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy. Methods We retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3). Results In groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy. Conclusions GH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Hipotireoidismo/diagnóstico , Recém-Nascido Pequeno para a Idade Gestacional , Glândula Tireoide/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/fisiopatologia , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/farmacologia , Humanos , Hipotireoidismo/fisiopatologia , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Japão , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/fisiopatologia , Testes de Função Tireóidea/métodos , Glândula Tireoide/fisiopatologia , Hormônio Liberador de Tireotropina/farmacologia , Fatores de TempoRESUMO
PURPOSE: The effects of growth hormone (GH) treatment on linear growth and body composition have been studied extensively. Little is known about the GH effect on energy expenditure (EE). The aim of this study was to investigate the effects of GH treatment on EE in children, and to study whether the changes in EE can predict the height gain after 1 year. METHODS: Total EE (TEE), basal metabolic rate (BMR), and physical activity level (PAL) measurements before and after 6 weeks of GH treatment were performed in 18 prepubertal children (5 girls, 13 boys) born small for gestational age (n = 14) or with growth hormone deficiency (n = 4) who were eligible for GH treatment. TEE was measured with the doubly labelled water method, BMR was measured with an open-circuit ventilated hood system, PAL was assessed using an accelerometer for movement registration and calculated (PAL = TEE/BMR), activity related EE (AEE) was calculated [AEE = (0.9 × TEE) - BMR]. Height measurements at start and after 1 year of GH treatment were analysed. This is a 1-year longitudinal intervention study, without a control group for comparison. RESULTS: BMR and TEE increased significantly (resp. 5% and 7%). Physical activity (counts/day), PAL, and AEE did not change. 11 out of 13 patients (85%) with an increased TEE after 6 weeks of GH treatment had a good first-year growth response (∆height SDS > 0.5). CONCLUSIONS: GH treatment showed a positive effect on EE in prepubertal children after 6 weeks. No effect on physical activity was observed. The increase in TEE appeared to be valuable for the prediction of good first-year growth responders to GH treatment.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/farmacologia , Metabolismo Basal/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Índice de Massa Corporal , Criança , Pré-Escolar , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Feminino , Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Resultado do TratamentoRESUMO
Children born small for gestational age (SGA) are at a higher risk for metabolic disorders later in life. In this study, we aimed to characterize young SGA children without catch-up growth and evaluate the effects of GH treatment on endocrinological, metabolic, and immunological parameters. Study design is a one-year single hospital-based study included prospective observation of SGA patients during 12 months of GH treatment. Clinical and laboratory profiles of SGA children at baseline were compared with controls born appropriate size for age. Twenty-six SGA children (median age, 3.4 years) and 26 control children (median age, 3.8 years) were enrolled. Anthropometric, hematologic, biochemical, immunological, and endocrinological parameters were assessed at baseline and 1, 3, 6, 9, and 12 months after the start of GH treatment. As a result, median height SD score (SDS) of SGA children increased by +0.42 with 12-month GH treatment. Body mass index SDS was lower in SGA children than in controls. Serum apolipoprotein A1 increased, whereas apolipoprotein B decreased during GH treatment. Serum leptin and resistin levels, which were lower in SGA children than in controls at baseline, did not change remarkably with GH treatment. Monocyte counts, which were lower in SGA patients at baseline, increased after GH treatment. Neutrophil counts significantly increased after GH treatment. Natural killer cell ratios, which were higher in SGA patients, decreased after GH treatment. In conclusion, there was no evidence suggesting metabolic abnormalities in SGA children. Serum apolipoprotein changes might predict the beneficial role of GH treatment in lowering cardiometabolic risk.
Assuntos
Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Transtornos do Crescimento/sangue , Hormônio do Crescimento Humano/farmacologia , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Leptina/sangue , Masculino , Estudos Prospectivos , Resistina/sangue , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Dietary management is a difficult but key aspect of care in children with Prader-Willi syndrome (PWS). We therefore investigated the effect of growth hormone (GH) treatment on reported energy intake in children with PWS, in relation with body composition, resting energy expenditure (REE) and hormone levels. METHODS: In a randomized controlled GH trial including 47 children with PWS, we assessed 5-day dietary records and dual-energy X-ray absorptiometry for body composition. REE was calculated by Müller's equation, based on fat mass, fat free mass and gender. RESULTS: Baseline energy intake of children with PWS was lower than normal daily energy requirements (p < 0.001), and decreased with age to 50% in prepubertal children. Energy intake in infants [m/f: 11/8; median (interquartile range [IQR]) age 2.7 years (1.5-3.2)] increased after 1 year of GH treatment (p = 0.008); this tended to be higher in the GH group than in the untreated group (p = 0.07). In prepubertal children [m/f: 14/14; median (IQR) age 6.8 years (5.1-8.1)], the increase in energy intake was higher in the GH group, but this was not different compared to the untreated group. REE was not different between the GH group and the untreated group. Increase in energy intake during 2 years of GH treatment was correlated with lower fat percentage standard deviation scores (p = 0.037) and higher adiponectin levels (p = 0.007). CONCLUSION: Our study demonstrates that parents of children with PWS are very well capable of restricting energy intake up to 50% compared to daily energy requirements for age- and sex-matched healthy children. GH treatment was associated with a slight increase in energy intake, but also improved body composition and adiponectin levels, which suggests a protective effect of GH treatment.
Assuntos
Composição Corporal/fisiologia , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Prader-Willi/tratamento farmacológico , Composição Corporal/efeitos dos fármacos , Criança , Pré-Escolar , Dieta , Ingestão de Energia/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Feminino , Hormônio do Crescimento Humano/farmacologia , Humanos , Lactente , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Síndrome de Prader-Willi/fisiopatologia , Resultado do TratamentoRESUMO
Sustained treatment adherence, usually over long periods of time, is critical to the success of growth hormone (GH) therapy. However, adherence rates are often poor which may result in suboptimal clinical outcomes. The type of device used by patients to administer their GH can influence adherence. Offering patients a choice of device maximizes the chance of adherence to treatment. Multiple factors will influence a patient's choice of device, depending on individual priorities. This study evaluated the most preferred features of GH injection devices by parents using a web-based questionnaire and as assessed by their willingness to pay for specific device features. The results show that parents are willing to pay for device features facilitating ease of use.
Assuntos
Comportamento de Escolha , Gastos em Saúde , Hormônio do Crescimento Humano/administração & dosagem , Injeções/economia , Injeções/instrumentação , Adesão à Medicação , Pais , Adolescente , Adulto , Estatura/efeitos dos fármacos , Criança , Feminino , Hormônio do Crescimento Humano/farmacologia , Humanos , Masculino , Inquéritos e Questionários , SuíçaRESUMO
There are 9 recombinant human growth hormone (rhGH) products currently available for 10 US Food and Drug Administration-approved indications; each rhGH product is approved for 1 or more indications. Adult and pediatric patients with the various conditions for which rhGH is indicated, from idiopathic short stature (ISS) and growth hormone (GH) deficiency to short bowel syndrome and HIV/AIDS wasting, may benefit from rhGH treatment. In clinical practice, pediatric patients with GH deficiency or ISS make up the majority of the population receiving treatment with rhGH. Most rhGH products are provided through specialty pharmacies that often have to balance the needs of the patient, their own utilization objectives, and the availability of the rhGH on formulary from a particular payer. Often, a payer will prefer only 2 or 3 rhGH products to cover all 10 indications. As such, managed care professionals need to be more informed about the options available and should be familiar with the different indications to help educate patients about treatment. Additionally, healthcare providers should endeavor to identify and manage the care of appropriate patients who would potentially benefit from rhGH therapy, and should be aware of formulary options. Because many of the patients are children and young adults, adherence to treatment is a concern; patient education on the importance of treatment adherence should be ongoing. Various mechanisms are in place (eg, prior authorization requirements and case manager follow-up) to help ensure that rhGH products are used, and used appropriately. This publication includes highlights from a roundtable discussion by key opinion leaders (clinicians and managed care professionals) on how managed care policies and clinical guidelines on appropriate use of rhGH translate into real-world practice. Also discussed are the efficacy and safety of rhGH therapy for its pediatric indications, and the role of specialty pharmacies in managing patient access to therapy.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/economia , Hormônio do Crescimento Humano/uso terapêutico , Programas de Assistência Gerenciada/economia , Guias de Prática Clínica como Assunto , Adulto , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Aprovação de Drogas , Feminino , Transtornos do Crescimento/diagnóstico , Hormônio do Crescimento Humano/farmacologia , Humanos , Masculino , Padrões de Prática Médica , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration , Adulto JovemAssuntos
Biotecnologia/história , Endocrinologia/história , Biologia Molecular/história , Animais , História do Século XX , História do Século XXI , Hormônio do Crescimento Humano/biossíntese , Hormônio do Crescimento Humano/genética , Hormônio do Crescimento Humano/farmacologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Pesquisa Translacional Biomédica/economia , Pesquisa Translacional Biomédica/história , Estados UnidosRESUMO
AIM: The optimal GH regimen, in terms of cost-effectiveness, in children with normal GH immunoreactivity but reduced bioactivity is still debated. METHODS: In 12 GH-deficient (GHD) and 12 bioinactive GH children undergoing GH treatment we evaluated the increase in growth velocity, the difference between target height and final stature and the incremental cost-effectiveness ratio. RESULTS: We found a significant (p < 0.05) increase in growth velocity in both groups during the first year of GH treatment (non- GHD: from -1.7 to 5.4 SDS; GHD: from -1.46 to 4.74 SDS). There was no statistically significant variation between the two groups in the difference between final height and target height. We did not find any significant difference in cost/height gain between GHD (1925.28 ± 653.15 euro) and bioinactive GH children (1639.55 ± 631.44 euro). There were also no significant differences in cost/year of therapy between GHD (12347.68 ± 2018.1 euro) and bioinactive GH children (11355.08 ± 1747.61 euro). CONCLUSION: In children with reduced GH biological activity, confirmed by the increase of serum IGF-I levels during generation test, the cost of GH treatment is justified by the positive results obtained in growth and adult height as in classical GHD patients.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Adolescente , Adulto , Estatura/efeitos dos fármacos , Criança , Análise Custo-Benefício , Feminino , Hormônio do Crescimento Humano/economia , Hormônio do Crescimento Humano/farmacologia , Humanos , Masculino , Resultado do TratamentoRESUMO
Growth hormone (GH) is a commonly used drug aimed at improving sport performance. The aim of this study is to evaluate the immunomodulatory effects of short-term administration of recombinant GH (rhGH) in healthy young males. NK cell number, activity and phenotype, T cell number, CD4(+) (Th1/Th2) cytokine production of IL2, IL4, IL6, IL10, TNF-α and IFN-γ and CD4(+)/CD8(+) ratio with particular attention to the possible correlation to IGF-I production were investigated. 30 males (27 ± 9 years) were randomly assigned to placebo (n = 15) or drug (rhGH) 1 mg/day groups (n = 15) with daily injection for 7 days. IGF-I plasma concentration and flow cytometry data were generated at baseline and days 8, 15, 22 and 29 post injection. Data analysis used General Linear Model with repeated measures, Bonferroni correction factor and significance at p ≤ 0.05. Serum IGF-I levels (ng/mL) increased significantly (p ≤ 0.01) on day 8 (0.48 ± 0.78) after injections compared to baseline (0.31 ± 0.07) and days 15 (0.33 ± 0.06), 22 (0.29 ± 0.05) and 29 (0.29 ± 0.06). A significant time effect was noted in IL10 secretion (pg/mL) from day 15 (P = 35.14 ± 19.93, rhGH = 26.63 ± 16.39) to days 22 (P = 61.32 ± 20.41, rhGH = 74.99 ± 46.91) and 29 (P = 101.98 ± 67.25, rhGH = 107.74; ± 122.58). There was no correlation between IGF-I and NK activity, phenotype or number along with T lymphocyte number, CD4(+)/CD8(+) ratio or Th1 and Th2 cytokine production. In conclusion, cytokine secretion spectrum was not affected by short-term rhGH administration in young males.
Assuntos
Hormônio do Crescimento Humano/farmacologia , Sistema Imunitário/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Adulto , Esquema de Medicação , Saúde , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Sistema Imunitário/fisiologia , Fator de Crescimento Insulin-Like I/análise , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Contagem de Linfócitos , Masculino , Placebos , Proteínas Recombinantes/administração & dosagem , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Fatores de Tempo , Adulto JovemRESUMO
Despite major progress in dialysis, nutrition and drug treatment in the past 20 years, growth of infants and toddlers with chronic kidney disease (CKD) remains a major challenge in paediatric nephrology. Our hypothesis is that early growth deficit is one of the most important factors for impaired final height in children with CKD, and we conclude that early implementation of recombinant human growth hormone (rhGH) therapy should be offered to infants with growth failure. Infants with delayed growth, adequate caloric intake and stable parameters of bone metabolism are candidates for rhGH therapy. One predictive factor for the selection of infants for rhGH treatment may be growth retardation at birth. Our conclusion from the limited published data is that the use of rhGH in young children with CKD is effective and safe. Compared with its use in older children, the early use of growth hormone requires lower absolute dosages of rhGH, which therefore reduce the annual treatment costs and allow earlier renal transplantation. Furthermore, an early start on rhGH improves the psychosocial situation later in childhood and may lead to a further improvement in adult height. A multi-centre randomised controlled study should be initiated to analyse the short-term and long-term effects of early rhGH therapy on infants with CKD.
Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Falência Renal Crônica/terapia , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Transtornos do Crescimento/terapia , Hormônio do Crescimento Humano/economia , Hormônio do Crescimento Humano/genética , Hormônio do Crescimento Humano/farmacologia , Humanos , Lactente , Recém-Nascido , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/economia , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêuticoRESUMO
OBJECTIVE: Measurement of plasma C2 glucose enrichment is cumbersome. Therefore, the plasma C5 glucose-to-(2)H(2)O rather than the plasma C5-to-C2 glucose ratio commonly has been used to measure gluconeogenesis and glycogenolysis during hyperinsulinemic-euglycemic clamps. The validity of this approach is unknown. RESEARCH DESIGN AND METHODS: Ten nondiabetic and 10 diabetic subjects ingested (2)H(2)O the evening before study. The following morning, insulin was infused at a rate of 0.6 mU . kg(-1) . min(-1) and glucose was clamped at approximately 5.3 mmol/l for 5 h. Plasma C5 glucose, C2 glucose, and (2)H(2)O enrichments were measured hourly from 2 h onward. RESULTS: Plasma C2 glucose and plasma (2)H(2)O enrichment were equal in both groups before the clamp, resulting in equivalent estimates of gluconeogenesis and glycogenolysis. In contrast, plasma C2 glucose and plasma C5 glucose enrichments fell throughout the clamp, whereas plasma (2)H(2)O enrichment remained unchanged. Since the C5 glucose concentration and, hence, the C5 glucose-to-(2)H(2)O ratio is influenced by both gluconeogenesis and glucose clearance, whereas the C5-to-C2 glucose ratio is only influenced by gluconeogenesis, the C5 glucose-to-(2)H(2)O ratio overestimated (P < 0.01) gluconeogenesis during the clamp. This resulted in biologically implausible negative (i.e., calculated rates of gluconeogenesis exceeding total endogenous glucose production) rates of glycogenolysis in both the nondiabetic and diabetic subjects. CONCLUSIONS: Plasma C5 glucose-to-(2)H(2)O ratio does not provide an accurate assessment of gluconeogenesis in nondiabetic or diabetic subjects during a traditional (i.e., 2-3 h) hyperinsulinemic-euglycemic clamp. The conclusions of studies that have used this approach need to be reevaluated.
Assuntos
Glicemia/metabolismo , Óxido de Deutério/sangue , Diabetes Mellitus/sangue , Gluconeogênese , Técnica Clamp de Glucose/métodos , Hiperinsulinismo/sangue , Insulina/farmacologia , Glicemia/efeitos dos fármacos , Glucagon/análogos & derivados , Glucagon/farmacologia , Glicogênio/metabolismo , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/farmacologia , Humanos , Infusões Intravenosas , Insulina/administração & dosagem , Cinética , Valores de Referência , Reprodutibilidade dos Testes , Somatostatina/administração & dosagem , Somatostatina/farmacologia , ÁguaAssuntos
Indústria Farmacêutica/tendências , Sistema Endócrino/fisiologia , Hormônio do Crescimento Humano/metabolismo , Adulto , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/farmacologia , Humanos , Cooperação Internacional , Estados UnidosRESUMO
Children and adults with Prader-Willi syndrome are usually overweight, if not obese. Nevertheless, it is now thought that the body composition exhibited by such individuals is markedly dissimilar to that found in simple obesity. In fact, the body composition typical of Prader-Willi syndrome is actually more characteristic of that found in individuals with growth hormone (GH) deficiency, namely an increased level of adiposity in the limbs in comparison with the trunk and an overall reduction in fat-free mass. This variation in body composition may impact upon the assumptions inherent in many techniques used to measure body size and body composition, such as the use of body mass index and skinfolds. Therefore, it is important that the potential error in body composition assessment is understood by professionals evaluating patients with Prader-Willi syndrome. Accurate assessment of body composition is critical in Prader-Willi syndrome, as a number of recent studies have revealed extremely similar findings relating to the effect of exogenous GH on the body composition of patients with this syndrome. Other notable findings of these studies include significant increases in muscle strength and exercise capacity, which probably result from the changes in body composition. The routine use of exogenous GH to treat this extremely debilitating syndrome should now be considered.
Assuntos
Composição Corporal/efeitos dos fármacos , Hormônio do Crescimento Humano/farmacologia , Síndrome de Prader-Willi/fisiopatologia , Criança , Impedância Elétrica , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Síndrome de Prader-Willi/tratamento farmacológico , Dobras CutâneasRESUMO
We assessed whether the increased growth in parenterally fed rats treated with growth hormone (GH) or insulin-like growth factor I (IGF-I) or both is associated with alterations in energy expenditure or macronutrient oxidation or both. Surgically stressed male rats (approximately 235 g) were given total parenteral nutrition (TPN) and treated with recombinant human GH (rhGH) (800 micrograms/d), rhIGF-I (800 micrograms/d), rhGH+rhIGF-I (800 micrograms/d of each), or TPN alone for 3 d. Treatment with GH or IGF-I or both resulted in significantly greater body weight gain, nitrogen retention, and serum total IGF-I concentrations compared with TPN alone (P < 0.0001). Assessment of respiratory gas exchange and motor activity for 23 h on day 3 indicated no significant differences between groups in either total or activity-related rates of energy expenditures (kJ/kg0.75). Estimates based on the nitrogen-free respiratory quotient (RQ) revealed fat oxidation to be significantly increased by GH (P < 0.001) and IGF-I (P < 0.03), whereas protein oxidation was significantly reduced (P < 0.0001) by these growth factors. GH and IGF-I combined further enhanced fat oxidation while reducing protein catabolism. Serum insulin concentrations were significantly increased by GH but decreased by IGF-I. GH significantly decreased serum total triiodothyronine concentrations and IGF-I significantly decreased serum corticosterone concentrations. These results suggest that treatment with GH or IGF-I can increase fat oxidation and spare protein for growth without altering energy expenditure in surgically stressed rats maintained with TPN.