RESUMO
The global decline in malaria has stalled1, emphasizing the need for vaccines that induce durable sterilizing immunity. Here we optimized regimens for chemoprophylaxis vaccination (CVac), for which aseptic, purified, cryopreserved, infectious Plasmodium falciparum sporozoites (PfSPZ) were inoculated under prophylactic cover with pyrimethamine (PYR) (Sanaria PfSPZ-CVac(PYR)) or chloroquine (CQ) (PfSPZ-CVac(CQ))-which kill liver-stage and blood-stage parasites, respectively-and we assessed vaccine efficacy against homologous (that is, the same strain as the vaccine) and heterologous (a different strain) controlled human malaria infection (CHMI) three months after immunization ( https://clinicaltrials.gov/ , NCT02511054 and NCT03083847). We report that a fourfold increase in the dose of PfSPZ-CVac(PYR) from 5.12 × 104 to 2 × 105 PfSPZs transformed a minimal vaccine efficacy (low dose, two out of nine (22.2%) participants protected against homologous CHMI), to a high-level vaccine efficacy with seven out of eight (87.5%) individuals protected against homologous and seven out of nine (77.8%) protected against heterologous CHMI. Increased protection was associated with Vδ2 γδ T cell and antibody responses. At the higher dose, PfSPZ-CVac(CQ) protected six out of six (100%) participants against heterologous CHMI three months after immunization. All homologous (four out of four) and heterologous (eight out of eight) infectivity control participants showed parasitaemia. PfSPZ-CVac(CQ) and PfSPZ-CVac(PYR) induced a durable, sterile vaccine efficacy against a heterologous South American strain of P. falciparum, which has a genome and predicted CD8 T cell immunome that differs more strongly from the African vaccine strain than other analysed African P. falciparum strains.
Assuntos
Anticorpos Neutralizantes/imunologia , Fígado/imunologia , Fígado/parasitologia , Vacinas Antimaláricas/imunologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/imunologia , Vacinas Atenuadas/imunologia , Adulto , Animais , Formação de Anticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Estágios do Ciclo de Vida/imunologia , Malária/sangue , Malária/imunologia , Malária/parasitologia , Malária/prevenção & controle , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/química , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/crescimento & desenvolvimento , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fatores de Tempo , Vacinação/efeitos adversos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/químicaRESUMO
IoT has seen remarkable growth, particularly in healthcare, leading to the rise of IoMT. IoMT integrates medical devices for real-time data analysis and transmission but faces challenges in data security and interoperability. This research identifies a significant gap in the existing literature regarding a comprehensive ontology for vulnerabilities in medical IoT devices. This paper proposes a fundamental domain ontology named MIoT (Medical Internet of Things) ontology, focusing on cybersecurity in IoMT (Internet of Medical Things), particularly in remote patient monitoring settings. This research will refer to similar-looking acronyms, IoMT and MIoT ontology. It is important to distinguish between the two. IoMT is a collection of various medical devices and their applications within the research domain. On the other hand, MIoT ontology refers to the proposed ontology that defines various concepts, roles, and individuals. MIoT ontology utilizes the knowledge engineering methodology outlined in Ontology Development 101, along with the structured life cycle, and establishes semantic interoperability among medical devices to secure IoMT assets from vulnerabilities and cyberattacks. By defining key concepts and relationships, it becomes easier to understand and analyze the complex network of information within the IoMT. The MIoT ontology captures essential key terms and security-related entities for future extensions. A conceptual model is derived from the MIoT ontology and validated through a case study. Furthermore, this paper outlines a roadmap for future research, highlighting potential impacts on security automation in healthcare applications.
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Segurança Computacional , Internet das Coisas , Humanos , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Telemedicina/métodosRESUMO
The current method for sampling aerosols using the 37-mm closed-face cassette (CFC) sampler is based on the orientation of the cassette at â¼45° from horizontal. There is some concern as to whether this method is appropriate and may be underestimating exposures. An alternative orientation at â¼0° (horizontal) has been discussed. This research compared the CFC's orientation at 45° from horizontal to the proposed orientation at horizontal, 0° in a controlled laboratory setting. The particles used in this study were fused alumina oxide in four sizes, approximately 9.5 µm, 12.8 µm, 18 µm, and 44.3 µm in aerodynamic diameter. For each test, one aerosol was dispersed in a wind tunnel operating at 0.2 m/s with samplers mounted in the breathing zone of a rotating mannequin. A sampling event consisted of four pairs of samplers, placed side by side (one pair at 45° and another at 0° cassette orientation), and exposed for a period of 45 minutes. A total of 12 sampling events, 3 sample events per particle size, were conducted with a total of 94 samples collected. Mass concentration measurements were compared to assess the relationship between the sampler orientations of the cassettes. In addition, the relationship between the mass collected on the cassette filter and on the interior walls of the cassette was also assessed. The results indicated that there was no significant difference between the measured concentrations based on the orientation of the CFCs. The amount of mass collected on the interior walls of the cassettes was relatively low (<5%) compared to expected (up to 100%) wall losses for both orientations.
Assuntos
Poluentes Ocupacionais do Ar/análise , Monitoramento Ambiental/métodos , Tamanho da Partícula , Material Particulado/análise , Aerossóis/análise , Movimentos do Ar , Óxido de Alumínio/análise , Monitoramento Ambiental/instrumentação , Filtração/instrumentação , ManequinsRESUMO
OBJECTIVE: Growth hormone (GH) replacement may increase bone mineral density (BMD) in GH-deficient (GHD) adults. The goal of this study was to identify predictors of BMD response to GH replacement in GH naïve adults. DESIGN AND MEASUREMENTS: This was a retrospective analysis of data extracted from KIMS (Pfizer International Metabolic Database), an international pharmacoepidemiological survey of adult GHD patients from 31 countries. PATIENTS: A total of 231 GH naive adults were identified (115 women and 116 men) who had BMD measured on the same densitometer in the lumbar spine (LS) and/or femoral neck (FN) both at baseline and after 4 years of GH replacement. RESULTS: After 4 years, there was a median (10th, 90th percentile) 4·6% (-5·2%, 12·2%) increase in LS BMD over baseline (P = 0·0001). There was a positive correlation between per cent change in LS BMD and age at the onset of pituitary disease (r = 0·25, P = 0·001). There was no change in FN BMD over baseline [0·0% (-7·3%, 8·5%)]. On multivariate analysis, older age at the onset of pituitary disease predicted a greater increase in LS BMD on GH replacement (r = 0·55, P < 0·0001). CONCLUSIONS: In a population of GH naïve adults, GH replacement led to a significant increase in LS BMD over baseline, but no change in FN BMD. The potential for greater BMD improvement on GH replacement therapy in adults with disease of later onset should be considered when making treatment decisions in this patient population.
Assuntos
Densidade Óssea , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Vértebras Lombares/metabolismo , Adulto , Idade de Início , Bases de Dados Factuais , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/metabolismo , Terapia de Reposição Hormonal , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos RetrospectivosRESUMO
The weekly sustained-release recombinant human GH formulation LB03002, showed beneficial effects in GH-deficient (GHD) adults in a previous 26-week double-blind study. Prior studies of long-acting GH preparations in adults have only been conducted for 6 or 8 months, so the effects of longer-term use are unknown; this is important to address, as replacement is given for many years in GHD adults. This open-label, 26-week study extension evaluated longer-term safety and efficacy of LB03002 over 52 weeks in adults with GHD who had previously been randomized to GH, and provides additional safety and efficacy data over 26 weeks in the cohort who had previously been randomized to placebo. Of 147 adults with GHD who completed a preceding study, 136 patients continued in this open-label study to receive LB03002 over an additional 26 weeks. This represented a continuation of long-acting GH for 26 weeks in the cohort who took this medication in the prior study (LB03002 Throughout group), and describes the first use of long-acting GH in the cohort that was randomized to placebo in the prior study (Switched to LB03002 group). The LB03002 dose was adjusted according to serum insulin-like growth factor-I (IGF-I) levels. LB03002 treatment demonstrated mean significant decreases from baseline in fat mass (FM) for both 26 (Switched group, P = 0.001) and 52 weeks (Throughout group, P = 0.002) of 1.11 (1.95) kg and 1.06 (3.16) kg, respectively. Prolonged GH treatment was effective in sustaining the increase in lean body mass (LBM), serum IGF-I and IGFBP-3 levels achieved during the first 26 weeks. Long-term treatment with the sustained-release weekly GH preparation over both 26 and 52 weeks in adults with GHD demonstrated a sustained reduction of FM with a favorable safety profile. This study extends prior knowledge about long-acting GH because it reports the most prolonged treatment of adults with any long-acting GH preparation, thereby confirming the value and safety of such agents for long-term GH replacement.
Assuntos
Hormônio do Crescimento/uso terapêutico , Hormônio do Crescimento Humano/deficiência , Adulto , Esquema de Medicação , Feminino , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Weight-based (WB: 0.03 mg/kg) and fixed dose (FD: 1-1.5 mg) regimens of the glucagon stimulation test (GST) have been used to evaluate GH and cortisol secretion in children and adults, respectively. However, experience of the WB regimen in assessing GH and cortisol secretion in adults are limited. We describe a multicenter experience using WB and FD regimens in evaluating GH and cortisol secretion in adults suspected of GH deficiency and central adrenal insufficiency. Retrospective case series of GSTs (n = 515) performed at five tertiary centers. Peak and nadir glucose, and peak GH and peak cortisol responses occurred later with WB (mean dose: 2.77 mg) compared to FD (mean dose: 1.20 mg) regimens. Main side-effects were nausea and vomiting, particularly in younger females. Nausea was comparable but vomiting was more frequent in the WB regimen (WB: 10.0 % vs FD: 2.4 %; P < 0.05). Peak and nadir glucose, ΔGH, and peak and Δcortisol were higher in the WB regimen. In both regimens, age correlated negatively with peak cortisol levels, and body mass index (BMI), fasting, peak and nadir glucose correlated negatively with peak GH levels. WB and FD regimens can induce adult GH and cortisol secretion, but peak responses occur later in the WB regimen. Both regimens are relatively safe, and vomiting was more prevalent in the WB regimen. As age, BMI, and glucose tolerance negatively correlated with peak GH and cortisol levels, the WB regimen may be more effective than the FD regimen in older overweight glucose intolerant patients.
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Glucagon/metabolismo , Hormônio do Crescimento Humano/metabolismo , Hidrocortisona/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite. AREAS COVERED: Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving >90% efficacy against Pf infection. This review describes >30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.' EXPERT OPINION: First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers exposed to Pf in Africa, with licensure for these populations possible within 5 years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.
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Vacinas Antimaláricas , Malária Falciparum , Malária , Gravidez , Criança , Animais , Humanos , Feminino , Esporozoítos , Ciência Translacional Biomédica , Vacinas Atenuadas , Malária/prevenção & controle , Malária Falciparum/prevenção & controle , Plasmodium falciparum , ImunizaçãoRESUMO
The optimal dosing of growth hormone (GH) therapy is challenging due to high inter-individual variability in subcutaneous GH absorption and sensitivity to the drug. Optimal dosing would maximize patient gains in height, body composition, and metabolic outcomes while minimizing GH adverse events. The pulsatile secretion of GH, however, does not allow direct assessment of circulating GH levels as a measure of response to GH therapy. Insulin-like growth factor (IGF-I), a key marker of GH activity, has been shown to be useful in monitoring and adjusting GH dose during treatment of GH deficiency (GHD). Traditionally, monitoring IGF-I levels in response to GH therapy has been recommended for assessment of treatment compliance and safety. More recently, GH treatment guidelines have stated that IGF-I levels should also be used to guide GH dosing. This review examines whether individualized GH dosing based on the IGF-I response to GH therapy provides a better method for determining the GH replacement needs of pediatric and adult patients compared with conventional GH dosing, and whether IGF-I-based dosing improves outcomes such as height and body composition, with reduced side effects. Because IGF-I measurement presents its own difficulties, the current state of IGF-I assays is also discussed. The reviewed studies show that the use of GH dose adjustments based on IGF-I responses to GH therapy successfully reduces adverse events in adults with GHD and results in greater positive height attainment in children, without increasing adverse events. Long-term outcome studies are needed, as are internationally accepted guidelines for IGF-I measurement.
Assuntos
Terapia de Reposição Hormonal/métodos , Hormônio do Crescimento Humano/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Growth hormone (GH) is approved by the US Food and Drug Administration (FDA) for use in pediatric patients with disorders of growth failure or short stature and in adults with growth hormone deficiency (GHD) and HIV/AIDS wasting and cachexia. For pediatric patients, guidelines for the use of GH have been developed by several organizations that have identified specific criteria for initiating GH therapy for each FDA-approved indication. Guidelines for adults have also been developed and include recommendations for transition (adolescent) patients with GHD. These patients are often treated with GH as children but may require continued treatment as young adults to attain full skeletal mineralization and improve cardiovascular risk factors. Adult and pediatric guidelines are supported by efficacy and safety studies, which show that, when started at an early age, GH treatment can increase growth velocity and that GH is safe and well-tolerated. We summarize the guidelines that are available for all FDA-approved indications among pediatric and transition patients. Adherence to these guidelines will help to ensure that patients with disorders of growth failure or short stature receive the necessary therapy to increase linear growth and transition smoothly to healthy adulthood.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Adolescente , Adulto , Pré-Escolar , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Síndrome de Noonan/tratamento farmacológico , Guias de Prática Clínica como Assunto , Síndrome de Prader-Willi/tratamento farmacológico , Síndrome de Turner/tratamento farmacológicoRESUMO
Whether or not all foods marketed to consumers as organic meet specified standards for use of that descriptor, or are nutritionally different from conventional foods, is uncertain. In a retail market study in a Western US metropolitan area, differences in mineral composition between conventional potatoes and those marketed as organic were analysed. Potatoes marketed as organic had more copper and magnesium (p < 0.0001), less iron (p < 0.0001) and sodium (p < 0.02), and the same concentration of calcium, potassium and zinc as conventional potatoes. Comparison of individual mineral concentrations between foodstuffs sold as organic or conventional is unlikely to establish a chemical fingerprint to objectively distinguish between organic and conventional produce, but more sophisticated chemometric analysis of multi-element fingerprints holds promise of doing so. Although statistically significant, these differences would only minimally affect total dietary intake of these minerals and be unlikely to result in measurable health benefits.
Assuntos
Comércio , Dieta , Alimentos Orgânicos/análise , Minerais/análise , Tubérculos/química , Solanum tuberosum/química , Oligoelementos/análise , Humanos , Valor Nutritivo , Estados UnidosRESUMO
Surgical resection is often not curative in patients with acromegaly and long-acting somatostatin analogues (lanreotide or octreotide) are often needed. This study assessed the efficacy and safety of self- or partner-administration of lanreotide in patients with acromegaly. This was a six-month, single-arm, open-label study conducted at 13 endocrinology clinics. Fifty-nine patients received deep subcutaneous lanreotide injections every 28 days. Twelve patients started on 120 mg lanreotide and forty-seven started on 90 mg lanreotide. At week 16, the dose was adjusted to 60, 90 or 120 mg based on insulin-like growth factor-1 (IGF-1) levels at week 12. Fifty-nine patients with acromegaly either switched from long-acting octreotide (switch; n = 33) or were somatostatin analogue treatment-naïve or not currently taking long-acting octreotide ("other"; n = 26). The key endpoints included the percentage of patients/partners able to self- or partner-inject lanreotide and those with normal IGF-1 or growth hormone (GH) levels at week 24/early termination. 100% of patients/partners correctly self- (n = 41) or partner-injected (n = 18) lanreotide by week 4. By week 24/early termination, IGF-1 levels were controlled in 93.7% of switch and 46.2% of "other" patients, while GH levels were controlled in 76.9% and 39.1% of patients, respectively. Both IGF-1 and GH were controlled in 73.1% of switch and 30.4% of "other" patients. Most switch patients (81%) reported they preferred lanreotide over long-acting octreotide for future use (P = 0.0001). Self- or partner-administration of lanreotide is generally well tolerated and associated with IGF-1 and GH control in many lanreotide-naïve patients with acromegaly.
Assuntos
Acromegalia/tratamento farmacológico , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/efeitos adversos , Somatostatina/análogos & derivados , Acromegalia/metabolismo , Adulto , Idoso , Esquema de Medicação , Feminino , Hormônio do Crescimento Humano/metabolismo , Humanos , Injeções Subcutâneas , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/uso terapêutico , Somatostatina/administração & dosagem , Somatostatina/efeitos adversos , Somatostatina/uso terapêutico , Resultado do TratamentoRESUMO
Acromegaly is a disease that results from a growth hormone (GH)secreting pituitary tumor. Clinically, the disease is characterized by excessive skeletal growth, soft tissue enlargement with disfigurement, and increased risk of cardiovascular death. The goals of treatment are the removal or reduction of the tumor mass via surgery and normalization of GH secretion. Another treatment goal is the preservation of normal pituitary function if possible. Transsphenoidal surgery by an experienced neurosurgeon is usually the first line of therapy, especially for small tumors. Surgeon expertise is crucial for outcome, with dedicated pituitary surgeons having better results. However, overall cure rates remain low because patients with these tumors usually present at an incurable stage. Therefore, medical therapy to control excess GH secretion plays a significant role in a large proportion of patients with acromegaly who are not cured by surgery or other forms of therapy, such as radiotherapy, and/or are awaiting the effects of radiotherapy. If surgery is not curative, lifelong monitoring and the control of excess GH is usually necessary by a care team experienced in handling this chronic disease. In the past decade major progress has occurred in the development of highly specific and selective pharmacological agents that have greatly facilitated more aggressive management of active acromegaly. Treatment approach should be individualized and take into consideration a patient's tumor size and location, symptoms, comorbid conditions, and preferences. Because a surgical cure can be difficult to achieve, all patients, even those with what seems to be a clinically and biochemically inactive disease, should undergo long-term biochemical testing and pituitary MR imaging.
Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/cirurgia , Adenoma/tratamento farmacológico , Adenoma/cirurgia , Hormônio do Crescimento Humano/metabolismo , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/cirurgia , Acromegalia/sangue , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Octreotida/uso terapêutico , Neoplasias Hipofisárias/sangue , Radioterapia Adjuvante/métodosRESUMO
This study retrospectively analyzed demographic factors that may affect the prevalence of intestinal parasites among Guatemalan school children. The findings of the study showed that young age, wet season, female gender, and severe malnutrition all correlated positively with increased rates of infection. Clinical visits were performed on 10,586 school children aged 5-15 years over a four-year period (2004-2007) in the Palajunoj Valley of Guatemala, during which 5,705 viable stool samples were screened for infection with the following parasites: Ascaris lumbricoides, Giardia lamblia, Entamoeba histolytica, Hymenolepis nana, and Blastocystis hominis. The average overall prevalences of infection for specific parasites were A. lumbricoides 17.7%, E. histolytica 16.1%, G. lamblia 10.9%, H. nana 5.4%, and B. hominis 2.8%. Statistical analysis showed significantly higher rates of infection among younger children with G. lamblia (odds ratio [OR]=0.905, 95% confidence interval [CI] 0.871-0.941, p<0.0001) and E. histolytica (p=0.0006), greater prevalence of H. nana among females (OR=1.275, CI 1.010-1.609, p=0.0412), higher infection rates during the wet season for E. histolytica (p=0.0003) and H. nana (OR=0.734, CI 0.557-0.966, p=0.0275), and greater rates of infection with G. lamblia among malnourished children (for moderately malnourished children OR=1.498, CI 1.143-1.963, p<0.0001) and E. histolytica (for mildly malnourished children OR=1.243, CI 1.062-1.455, p=0.0313). The results suggest that the prevalence of gastrointestinal parasites among young Guatemalan children is highly dependent on the specific species of the parasite.
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Transtornos da Nutrição Infantil/complicações , Fezes/parasitologia , Enteropatias Parasitárias/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Guatemala/epidemiologia , Humanos , Masculino , Contagem de Ovos de Parasitas , Prevalência , Estudos Retrospectivos , Estações do Ano , Fatores Sexuais , Especificidade da EspécieRESUMO
OBJECTIVE: GH is usually the first pituitary hormone to be affected following a pathological insult to the pituitary; however, data on the prevalence of GH deficiency in patients with nonsecreting pituitary microadenomas and normal serum IGF-1 levels are scarce. This study aims to evaluate the prevalence of GH and other anterior pituitary hormone deficiencies, and to determine whether microadenomas per se could be associated with reduced GH response rates to GHRH-arginine stimulation. DESIGN: Analytical, retrospective, two-site case-control study. PATIENTS AND METHODS: Thirty-eight patients with nonsecreting pituitary microadenomas (mean size 4.2 mm) and normal serum IGF-1 levels were studied. Anterior pituitary function testing, including the GHRH-arginine test to examine GH reserve, was performed in all patients. Serum IGF-1 levels and peak GH levels in the patients that passed the GHRH-arginine test were compared with 22 age- and BMI-matched healthy controls. RESULTS: Nineteen patients (50%) failed the GHRH-arginine test and had higher body mass index (BMI) than those that passed the GHRH-arginine test and healthy controls. Peak GH levels in patients that passed the GHRH-arginine test were lower compared to healthy controls and 19 patients (50%) had at least one other pituitary hormone deficit. A negative correlation (r = -0.42, P < 0.01) between peak GH levels and BMI was identified, but no correlations were found between peak GH and serum IGF-1 levels. CONCLUSIONS: Our data demonstrated that a substantial number of patients with nonsecreting pituitary microadenomas failed the GHRH-arginine test despite normal serum IGF-1 levels, and had at least one other pituitary hormone deficiency, suggesting that nonsecreting microadenomas may not be clinically harmless. We therefore recommend long-term follow-up with periodic basal pituitary function testing, and to consider dynamic pituitary testing should clinical symptoms arise in these patients.
Assuntos
Adenoma/epidemiologia , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/epidemiologia , Fator de Crescimento Insulin-Like I/metabolismo , Hormônios Adeno-Hipofisários/deficiência , Neoplasias Hipofisárias/epidemiologia , Adenoma/sangue , Adenoma/complicações , Adenoma/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/etiologia , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/metabolismo , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND/AIM: The insulin tolerance test (ITT) remains the gold standard for evaluating the pituitary function, but has potential risks when hypoglycaemia is induced. There are scarce data using short-acting insulin analogs for ITTs. This pilot study compares the effects of insulin lispro (LPI) with regular insulin (RGI) during an ITT. METHODS: Patients with suspected hypopituitarism (n = 103) randomly received either LPI (n = 51) or RGI (n = 52). RESULTS: All patients reported signs and symptoms when hypoglycaemia was induced. In the LPI group, hypoglycaemia occurred sooner (23.6 +/- 1.6 vs. 28.3 +/- 1.4 min, p < 0.05), and duration of hypoglycaemia (25.0 +/- 1.7 vs. 31.9 +/- 1.9 min, p < 0.05) and time for blood glucose levels to return to a 'safe' level (>3.3 mmol/l; 56.5 +/- 2.3 vs. 76.0 +/- 2.1 min, p < 0.001) were shorter as compared with the RGI group. No differences in peak growth hormone and cortisol levels were observed between the two groups. CONCLUSIONS: Our data suggest that despite inducing similar symptomatology, LPI exerted a quicker onset and a shorter duration of hypoglycaemia as compared with RGI. Thus, using LPI might reduce the potential risks associated with an ITT by shortening the hypoglycaemic phase of the test.
Assuntos
Hipoglicemia/induzido quimicamente , Hipoglicemia/fisiopatologia , Hipoglicemiantes/efeitos adversos , Insulina/análogos & derivados , Insulina/efeitos adversos , Testes de Função Hipofisária/efeitos adversos , Hipófise/fisiopatologia , Adulto , Glicemia/metabolismo , Relação Dose-Resposta a Droga , Feminino , Hormônio do Crescimento/sangue , Humanos , Hidrocortisona/sangue , Hipoglicemiantes/farmacologia , Hipopituitarismo/sangue , Hipopituitarismo/diagnóstico , Hipopituitarismo/fisiopatologia , Insulina/farmacologia , Insulina Lispro , Resistência à Insulina/fisiologia , Masculino , Projetos Piloto , Hipófise/efeitos dos fármacos , Fatores de RiscoRESUMO
UNLABELLED: To determine if replacement of GH improves BMD in adult-onset GHD, we administered GH in physiologic amounts to men and women with GHD. GH replacement significantly increased spine BMD in the men by 3.8%. INTRODUCTION: Growth hormone (GH) deficiency (GHD) acquired in adulthood results in diminished BMD; the evidence that replacement of GH improves BMD is not conclusive. We therefore performed a randomized, placebo-controlled trial to determine whether GH replacement would increase lumbar spine BMD in a combined group of men and women with adult-onset GHD. MATERIALS AND METHODS: We randomized 67 men and women to receive GH (n=33) or placebo (n=34) for 2 yr. The GH dose was initially 2 microg/kg body weight/d, increased gradually to a maximum of 12 microg/kg/d and adjusted to maintain a normal IGF-I concentration for age and sex. BMD was assessed before treatment and at 6, 12, 18, and 24 mo of treatment. Fifty-four subjects completed the protocol. RESULTS: BMD of the lumbar spine in the entire group increased by 2.9 +/- 3.9% above baseline in the GH-treated subjects, which was significantly (p=0.037) greater than the 1.4 +/- 4.5% increase in the placebo-treated subjects. In a secondary analysis, spine BMD in GH-treated men increased 3.8 +/- 4.3% above baseline, which was significantly (p=0.001) greater than that in placebo-treated men (0.4 +/- 4.7%), but the change in GH-treated women was not significantly different from that in placebo-treated women. Treatment with GH did not increase total hip BMD more than placebo treatment after 2 yr. CONCLUSIONS: We conclude that GH replacement in men who have adult-onset GHD improves their spine BMD, but we cannot draw any conclusions about the effect of GH replacement on spine BMD in women with adult-onset GHD.
Assuntos
Densidade Óssea/efeitos dos fármacos , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/uso terapêutico , Terapia de Reposição Hormonal , Vértebras Lombares , Adulto , Biomarcadores/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipopituitarismo/complicações , Hipopituitarismo/tratamento farmacológico , Vértebras Lombares/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
OBJECTIVE: Fibromyalgia (FM) is characterized by diffuse pain, fatigue, and sleep disturbances; symptoms that resemble the adult growth hormone (GH) deficiency syndrome. Many FM patients have low serum GH levels, with a hypothesized aetiology of dysregulated GH/insulin-like growth factor (IGF)-I axis. The aim of this study was to assess the GH reserve in FM patients with low serum IGF-I levels using the GH-releasing hormone (GHRH)-arginine test. DESIGN: We retrospectively reviewed the GHRH-arginine data of 77 FM patients with low serum IGF-I levels referred to our tertiary unit over a 4-year period. RESULTS: Of the 77 FM patients, 13 patients (17%) failed the GHRH-arginine test. Further evaluation with pituitary imaging revealed normal pituitary glands (n=7), coincident microadenomas (n=4), empty sella (n=1) and pituitary cyst (n=1), and relevant medical histories such as previous head injury (n=4), Sheehan's syndrome (n=1), and whiplash injury (n=1). In contrast, the remaining 64 patients (83%) that responded to the GHRH-arginine test demonstrated higher peak GH levels compared to age and BMI-matched controls (n=24). CONCLUSION: Our data shows that a subpopulation of FM patients with low serum IGF-I levels will fail the GHRH-arginine test. We, thus, recommend that the GH reserve of these patients should be evaluated further, as GH replacement may potentially improve the symptomatology of those with true GH deficiency. Additionally, the increased GH response rates to GHRH-arginine stimulation in the majority of FM patients with low serum IGF-I levels further supports the hypothesis of a dysregulated GH/IGF-I axis in the pathophysiology of FM.
Assuntos
Nanismo Hipofisário/diagnóstico , Fibromialgia/sangue , Fator de Crescimento Insulin-Like I/análise , Adulto , Idoso , Estudos de Casos e Controles , Diagnóstico Diferencial , Nanismo Hipofisário/sangue , Nanismo Hipofisário/complicações , Feminino , Fibromialgia/complicações , Hormônio do Crescimento/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Hipofisária , Estudos RetrospectivosRESUMO
The use of growth hormone (GH) replacement for GH-deficient adults is now in its 10th year of FDA-approved use in the United States; it has been used for a longer period of time in some European countries. Despite widespread experience, there is still lack of consensus regarding the best approach to GH initiation and titration in adults with growth hormone deficiency. Several factors must be considered prior to dose selection, including patient age, gender, symptoms, and the use and route of estrogen replacement therapy. We retrospectively examined GH dosing practices within our institution over a 5-year period to define GH dose requirements during the initial titration and maintenance phases, the frequency of dose adjustments, and the reasons behind the dose adjustments in young and older adults. Based on this review, we offer practical recommendations for endocrinologists in the management of adults with hypopituitarism and long-term GH treatment.
Assuntos
Relação Dose-Resposta a Droga , Nanismo Hipofisário/tratamento farmacológico , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/uso terapêutico , Adulto , Seguimentos , Humanos , Visita a Consultório Médico/estatística & dados numéricos , População , Titulometria , Resultado do TratamentoRESUMO
In patients with childhood-onset growth hormone (GH) deficiency who have reached adult height, the transition from pediatric to adult healthcare is an appropriate time for reassessment of GH status. For patients in whom persistent GH deficiency (GHD) is established by appropriate testing, reinstitution of GH therapy or its continuation can improve quality of life, optimize body composition and bone mineral density, as well as reduce cardiovascular risks associated with GHD. Ongoing GH therapy should be individualized with attention paid to changes in serum insulin-like growth factor (IGF)-I concentrations, body composition, and occurrence of adverse effects such as edema and arthralgia. GH deficient patients who discontinue childhood GH replacement therapy and are not restarted as adults should undergo long-term surveillance to detect possible adverse consequences (e.g. reduced bone mineral density) typically associated with interruption of GH treatment.
Assuntos
Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/terapia , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Adolescente , Adulto , Idade de Início , Criança , HumanosRESUMO
Growth hormone as therapy for adults with growth hormone deficiency has not been universally accepted by endocrinologists who treat adult patients. The following are addressed in this commentary: the evidence on safety and efficacy in the literature supporting the idea that growth hormone should be offered as replacement therapy to adults who are growth hormone deficient; common concerns of the average prescribing endocrinologist, including the purported association between insulin-like growth factor-I and malignant neoplasms and quality-of-life issues with long-term therapy; and controversial subjects, such as differences in dosing for adults versus children and diagnostic issues. This analysis should encourage reluctant practitioners to at least consider growth hormone replacement therapy for patients with definite growth hormone deficiency--that is, patients with symptomatic panhypopituitarism.