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1.
Eur J Endocrinol ; 182(6): 595-605, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32375119

RESUMO

Objective: T2-signal intensity and somatostatin (SST) receptor expression are recognized predictors of therapy response in acromegaly. We investigated the relationship between these predictors and the hormonal and tumoral responses to long-acting pasireotide (PAS-LAR) therapy, which were also compared with responsiveness to first-generation somatostatin receptor ligands (SRLs). Design: The PAPE study is a cohort study. Methods: We included 45 acromegaly patients initially receiving SRLs, followed by combination therapy with pegvisomant, and finally PAS-LAR. We assessed tumor volume reduction (≥25% from baseline), IGF-1 levels (expressed as the upper limit of normal), and T2-weighted MRI signal and SST receptor expression of the adenoma. Results: Patients with significant tumor shrinkage during PAS-LAR showed higher IGF-1 levels during PAS-LAR (mean (S.D.): 1.36 (0.53) vs 0.93 (0.43), P = 0.020), less IGF-1 reduction after first-generation SRLs (mean (S.D.): 0.55 (0.71) vs 1.25 (1.07), P = 0.028), and lower SST2 receptor expression (median (IQR): 2.0 (1.0-6.0) vs 12.0 (7.5-12.0), P = 0.040). Overall, T2-signal intensity ratio was increased compared with baseline (mean (S.D.): 1.39 (0.56) vs 1.25 (0.52), P = 0.017) and a higher T2-signal was associated with lower IGF-1 levels during PAS-LAR (ß: -0.29, 95% CI: -0.56 to -0.01, P = 0.045). A subset of PAS-LAR treated patients with increased T2-signal intensity achieved greater reduction of IGF-1 (mean (S.D.): 0.80 (0.60) vs 0.45 (0.39), P = 0.016). Conclusions: Patients unresponsive to SRLs with a lower SST2 receptor expression are more prone to achieve tumor shrinkage during PAS-LAR. Surprisingly, tumor shrinkage is not accompanied by a biochemical response, which is accompanied with a higher T2-signal intensity.


Assuntos
Acromegalia/tratamento farmacológico , Adenoma/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Hormônios/uso terapêutico , Somatostatina/análogos & derivados , Acromegalia/sangue , Acromegalia/etiologia , Adenoma/sangue , Adenoma/complicações , Adulto , Estudos de Coortes , Preparações de Ação Retardada , Quimioterapia Combinada , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Ligantes , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Receptores de Somatostatina/sangue , Somatostatina/uso terapêutico , Resultado do Tratamento , Carga Tumoral
2.
Eur J Endocrinol ; 183(1): G17-G23, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32369770

RESUMO

Patients with pituitary tumours, ensuing hormonal abnormalities and mass effects are usually followed in multidisciplinary pituitary clinics and can represent a management challenge even during the times of non-pandemic. The COVID-19 pandemic has put on hold routine medical care for hundreds of millions of patients around the globe, while many pituitary patients' evaluations cannot be delayed for too long. Furthermore, the majority of patients with pituitary tumours have co-morbidities potentially impacting the course and management of COVID-19 (e.g. hypopituitarism, diabetes mellitus, hypertension, obesity and cardiovascular disease). Here, we summarize some of the diagnostic and management dilemmas encountered, and provide guidance on safe and as effective as possible delivery of care in the COVID-19 era. We also attempt to address how pituitary services should be remodelled in the event of similar crises, while maintaining or even improving patient outcomes. Regular review of these recommendations and further adjustments are needed, depending on the evolution of the COVID-19 pandemic status. We consider that the utilization of successful models of pituitary multidisciplinary care implemented during the COVID-19 pandemic should continue after the crisis is over by using the valuable and exceptional experience gained during these challenging times.


Assuntos
Adenoma/terapia , Antineoplásicos Hormonais/uso terapêutico , Infecções por Coronavirus , Agonistas de Dopamina/uso terapêutico , Procedimentos Neurocirúrgicos , Pandemias , Apoplexia Hipofisária/terapia , Neoplasias Hipofisárias/terapia , Pneumonia Viral , Adenoma/diagnóstico , Cabergolina/uso terapêutico , Gerenciamento Clínico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Apoplexia Hipofisária/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Guias de Prática Clínica como Assunto , Radioterapia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Telemedicina , Fatores de Tempo , Testes de Campo Visual
4.
Wiad Lek ; 73(2): 266-271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32248157

RESUMO

OBJECTIVE: The aim: to investigate the copper content in blood serum of children with different short stature types. PATIENTS AND METHODS: Materials and methods: In the first stage, a comprehensive survey of 258 school children aged 7-11 was carried out in Chernivtsi to assess the prevalence of short staturechildren of school-age. In the second stage, a comparative study of 42 children aged 3 to 15 years with different types of short stature was conducted. Research: anthropometry, determination of growth hormone, TSH, IGF-1, and copper level in blood plasma. RESULTS: Results: The largest growth rate in children with somatotropic insufficiency, the syndrome of a biologically inactive growth hormone ranged from 4.1 cm/year to 1.6 cm/year, the ones with a family constitutional low-growth - from 5.7 cm/year to 3.3 cm/year. In 57 cases, that makes 1% of children with short stature, the blood plasma level of copper made less and rated 0.89 ± 0.04 µg / ml, which is believed to be lower (pу0,001) the average copper in children of the control group - 1.07 ± 0.02 µg / ml. Indices of copper in blood plasma in children with somatotropic insufficiency were the lowest and averaged 0.75 ± 0.03 µg / l, p<0.05. CONCLUSION: Conclusions: The lack of copper in the blood plasma is observed in most children with short stature, which indicates the need for appropriate correction.


Assuntos
Cobre/sangue , Transtornos do Crescimento , Adolescente , Criança , Pré-Escolar , Hormônio do Crescimento , Hormônio do Crescimento Humano , Humanos , Prevalência
5.
Eur J Endocrinol ; 182(6): D17-D29, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32234975

RESUMO

Current guidelines recommend the use of long-acting somatostatin receptor ligands (SRLs) first when surgery fails to correct GH/IGF-I hypersecretion in patients with acromegaly. In this issue of the journal, a pro- and contra debate will outline which arguments are in favour and which are against positioning pegvisomant (PEGV), a GH receptor antagonist, as the first-line treatment modality of acromegaly. The task of the pros was to promote a paradigm shift towards repositioning PEGV as first-line treatment as PEGV is safe and more effective than the first- and second-generation of SRLs. SRLs, when prescribed together with PEGV can still reduce tumour size when necessary, while they decrease the necessary dose of PEGV by around 50% in the average patient. They conclude that PEGV must move up towards the first-line treatment. For the cons, SRLs remain the first-line medical treatment. Indeed, even if, in recent studies, the remission rate is lower than initially claimed, SRLs are still effective not only for normalizing GH/IGF-I levels in half of the patients but also for inducing tumour shrinkage, improving comorbidities and headaches and reversing excess mortality. They are more convenient for use with their monthly administration and have a remarkable safety profile as demonstrated by the very prolonged experience acquired by more than 30 years of use. Finally, the cost-effectiveness of first-generation SRLs is better than that of PEGV. For all these reasons, cons consider that SRLs remain the best first medical treatment in patients requiring medical therapy.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Receptores da Somatotropina/uso terapêutico , Hormônio do Crescimento Humano/antagonistas & inibidores , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Resultado do Tratamento
6.
Eur J Endocrinol ; 182(6): 559-567, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32337961

RESUMO

Objectives: To report the frequency and characteristics of growth hormone (GH) deficiency (GHD) in adolescents who had normalized GH secretion at mid-puberty and to identify possible factors predictive for GH sufficiency at puberty. Design: Clinical analysis of children affected by GHD at five time points: diagnosis; first year of therapy; intermediate stage of puberty; retesting and end of growth phase. Methods: The study population was 80 children with idiopathic GHD and treated with GH for at least 2 years. Treatment was discontinued at the intermediate stage of puberty. Retesting with an arginine test was performed 12 weeks later. If GH peak at retesting was ≥8 µg/L, the therapy was definitively discontinued, otherwise it was restarted and continued until achievement of near-final height. Results: GH therapy was discontinued in 44 children (55%), and restarted in 36 (45%). No evidence of differences in definitive height and in the delta height between the genetic target and the definitive height was found between the two groups. The only predictive factor for GHD at mid-puberty was the insulin growth factor-1 (IGF-1) level at 1 year of GH treatment. Conclusions: GH secretion should be retested at mid-puberty. Retesting at puberty may reduce potential side effects and minimize costs, without impairing growth potential and final height.


Assuntos
Hormônio do Crescimento Humano/deficiência , Puberdade/metabolismo , Criança , Feminino , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Estudos Retrospectivos
7.
Artigo em Inglês | MEDLINE | ID: mdl-32247186

RESUMO

The quantitative determination of intact proteins in biological samples by LC with high-resolution MS detection can be a useful alternative to ligand-binding assays or LC-MS-based quantification of a surrogate peptide after protein digestion. The 22-kDa biopharmaceutical protein somatropin (recombinant human growth hormone) was quantified down to 10 ng/mL (0.45 nM) in 75 µL of rat plasma by the combination of an immunocapture step using an anti-somatropin antibody and LC-MS on a quadrupole-time of flight instrument. Accuracy and precision of the method as well as its selectivity and sensitivity did not depend on the width of the mass extraction window nor on whether only one or a summation of multiple charge states of the protein analyte were used as the detection response. Quantification based on deconvoluted mass spectra showed equally acceptable method performance but with a less favorable lower limit of quantification of 30 ng/mL. Concentrations in plasma after dosing of somatropin to rats correlated well for the deconvolution approach and the quantification based on the summation of the response of the four most intense charge states (14+ to 17+) of somatropin.


Assuntos
Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/farmacocinética , Proteínas Recombinantes/farmacocinética , Animais , Técnicas Biossensoriais/métodos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Limite de Detecção , Peptídeos/análise , Plasma/química , Ratos , Proteínas Recombinantes/sangue , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
9.
Yonsei Med J ; 61(4): 331-340, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233176

RESUMO

PURPOSE: Osteoarthritis (OA) of the temporomandibular joint (TMJ) elicits cartilage and subchondral bone defects. Growth hormone (GH) promotes chondrocyte growth. The aim of this study was to evaluate the efficacy of intra-articular injections of GH to treat TMJ-OA. MATERIALS AND METHODS: Monosodium iodoacetate (MIA) was used to induce OA in the TMJs of rats. After confirming the induction of OA, recombinant human GH was injected into the articular cavities of rats. Concentrations of GH and IGF-1 were measured in the blood and synovial fluid, and OA grades of cartilage and subchondral bone degradation were recorded by histological examination and micro-computed tomography. RESULTS: MIA-induced OA in the rat TMJ upregulated insulin-like growth factor-1 (IGF-1) rather than GH levels. GH and IGF-1 concentrations were increased after local injection of GH, compared with controls. Locally injected GH lowered osteoarthritic scores in the cartilage and subchondral bone of the TMJ. CONCLUSION: Intra-articular injection of GH improved OA scores in rat TMJs in both cartilage and subchondral bone of the condyles without affecting condylar bone growth. These results suggest that intra-articular injection of human GH could be a suitable treatment option for TMJ-OA patients in the future.


Assuntos
Condrócitos/efeitos dos fármacos , Hormônio do Crescimento/administração & dosagem , Fator de Crescimento Insulin-Like I/administração & dosagem , Osteoartrite/tratamento farmacológico , Articulação Temporomandibular/efeitos dos fármacos , Idoso , Animais , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Hormônio do Crescimento/efeitos adversos , Hormônio do Crescimento Humano , Humanos , Injeções Intra-Articulares , Masculino , Osteoartrite/diagnóstico por imagem , Osteoartrite/patologia , Ratos , Líquido Sinovial , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/fisiopatologia , Microtomografia por Raio-X
10.
Eur J Endocrinol ; 182(6): 583, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32217809

RESUMO

Objective: In the Phase III PAOLA study (clinicaltrials.gov: NCT01137682), enrolled patients had uncontrolled acromegaly despite ≥6 months of octreotide/lanreotide treatment before study start. More patients achieved biochemical control with long-acting pasireotide versus continued treatment with octreotide/lanreotide (active control) at month 6. The current work assessed the extent of comorbidities at baseline and outcomes during a long-term extension. Design/methods: Patients receiving pasireotide 40 or 60 mg at core study end could continue on the same dose in an extension phase if biochemically controlled or receive pasireotide 60 mg if uncontrolled. Uncontrolled patients on active control were switched to pasireotide 40 mg, with the dose increased at week 16 of the extension if still uncontrolled (crossover group). Efficacy and safety are reported to 304 weeks (~5.8 years) for patients randomized to pasireotide (core + extension), and 268 weeks for patients in the crossover group (extension only). Results: Almost half (49.5%; 98/198) of patients had ≥3 comorbidities at core baseline. During the extension, 173 patients received pasireotide. Pasireotide effectively and consistently reduced GH and IGF-I levels for up to 5.8 years' treatment; 37.0% of patients achieved GH <1.0 µg/L and normal IGF-I at some point during the core or extension. Improvements were observed in key symptoms. The long-term safety profile was similar to that in the core study; 23/173 patients discontinued treatment because of adverse events. Conclusions: In this patient population with a high burden of comorbid illness, pasireotide was well tolerated and efficacious, providing prolonged maintenance of biochemical control and improving symptoms.


Assuntos
Acromegalia/tratamento farmacológico , Hormônios/administração & dosagem , Somatostatina/análogos & derivados , Fatores de Tempo , Acromegalia/sangue , Adulto , Estudos Cross-Over , Esquema de Medicação , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Estudos Prospectivos , Somatostatina/administração & dosagem , Somatostatina/uso terapêutico , Resultado do Tratamento
11.
Pediatr Endocrinol Rev ; 17(Suppl 1): 191-197, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32208563

RESUMO

Both in vitro and in vivo experimental studies proved that insulin has an important anabolic role. This physiological function of insulin is reflected in its well documented involvement in protein metabolism and in acceleration of cell proliferation. Support for a growth promoting action of insulin is further provided by clinical studies that revealed that children with hypoinsulinemia have a decreased growth rate whereas, on the other hand, children with hyperinsulinemia have an accelerated growth. While it was initially assumed that the growth activities of insulin are facilitated via cross-talk with the closely related insulin-like growth factor-1 receptor (IGF-1R), it is now clear that the vast majority of these activities are mediated via direct interaction with the insulin receptor (IR). The present article provides an overview of the growth and proliferative actions of insulin, with an emphasis on a number of pathological conditions, including cancer.


Assuntos
Insulina/uso terapêutico , Hormônio do Crescimento , Hormônio do Crescimento Humano , Humanos , Fator de Crescimento Insulin-Like I , Receptor IGF Tipo 1
12.
Life Sci ; 253: 117581, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32209424

RESUMO

AIMS: Cisplatin (CDDP) is an effective antineoplastic agent, however, its serious nephrotoxicity limits therapeutic use. Human growth hormone (hGH) has proved antioxidant and anti-inflammatory activities. The present study aimed to investigate the nephroprotective effects of hGH against CDDP-induced nephrotoxicity and the mechanisms underlying this nephroprotection. MAIN METHODS: Male albino rats injected with CDDP (7 mg/kg) and nephrotoxicity indices, oxidative stress and inflammatory biomarkers (high mobility group box protein-1 (HMGB-1), soluble epoxide hydrolase (sEH), and nuclear factor-kappa B (NF-κB)) were assessed. Also, insulin-like growth factor-1 (IGF-1) and Nuclear factor-erythroid-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway were assessed. KEY FINDINGS: hGH (1 mg/kg) improved kidney function and antioxidant systems and showed intact renal tubular epithelium. Cisplatin upregulated the HMGB-1/NF-κB and downregulated Nrf2/HO-1 pathways which were reversed by hGH and aligned with increased renal IGF-1 expression. Also, IGF-1/sEH crosstalk might be involved in hGH nephroprotection. Moreover, hGH downregulated HSP70 and caspase-3 expressions. SIGNIFICANCE: these results concluded that hGH can attenuate the inflammation and oxidative stress attained by CDDP probably through inhibition of Nrf2/HO-1 pathway. We also suggested that Keap1/Nrf2-mediated upregulation of the antioxidant HO-1 might inhibit HMGB-1/NF-κB signaling and thus provide the principal protection mechanism offered by hGH against CDDP-induced kidney injury.


Assuntos
Lesão Renal Aguda/prevenção & controle , Cisplatino/efeitos adversos , Hormônio do Crescimento/metabolismo , Heme Oxigenase-1/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Animais , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/metabolismo , Antineoplásicos/efeitos adversos , Antineoplásicos/metabolismo , Antioxidantes/efeitos adversos , Antioxidantes/farmacologia , Caspase 3/metabolismo , Cisplatino/metabolismo , Modelos Animais de Doenças , Epóxido Hidrolases/metabolismo , Hormônio do Crescimento/farmacologia , Proteínas HMGB/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Hormônio do Crescimento Humano , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Transdução de Sinais
13.
Arch Endocrinol Metab ; 64(1): 82-88, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32187262

RESUMO

Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8.


Assuntos
Teste de Tolerância a Glucose/métodos , Hormônio do Crescimento Humano/sangue , Hidrocortisona/sangue , Hipoglicemia/sangue , Hipoglicemiantes/administração & dosagem , Fator de Crescimento Insulin-Like I/análise , Insulina/administração & dosagem , Adulto , Automonitorização da Glicemia , Feminino , Teste de Tolerância a Glucose/efeitos adversos , Humanos , Hipoglicemia/diagnóstico , Hipoglicemia/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/metabolismo , Estudos Retrospectivos
14.
J Comput Assist Tomogr ; 44(2): 255-261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32195805

RESUMO

OBJECTIVE: We aimed to determine the effects of recombinant human growth hormone (rhGH) replacement on cognitive function in subjects with poststroke cognitive impairment using resting-state functional magnetic resonance imaging. METHODS: We included 60 patients with a first-ever stroke for 3 months and a diagnosis of cognitive impairment who were randomized 1:1 to receive either rhGH subcutaneously or placebo injection for 6 months. All subjects were required to receive the same rehabilitative therapy program. Both groups were subjected to pretreatment and posttreatment neuropsychological assessment using the Montreal Cognitive Assessment, serum neurotrophic factors, biomarkers of glucose and lipid metabolism, and functional magnetic resonance imaging during 6 months of the study period. The pattern of brain activity was determined by examining the functional connectivity and amplitude of low-frequency fluctuations (ALFF) of blood oxygen level dependent signal. RESULTS: Forty-three (82.7%) completed the study. Treatment with rhGH reduced levels of triglycerides and low-density lipoprotein cholesterol but did not significantly altered plasma concentrations of glucose and glycated hemoglobin. We found a significant increase in serum insulin-like growth factor 1 levels (32.6%; P < 0.001) in the rhGH-treated group compared with that in the controls. After 6 months of rhGH treatment, mean Montreal Cognitive Assessment score improved from 16.31 (5.32) to 21.19 (6.54) (P < 0.001). The rhGH group showed significant increased area of activation with increased ALFF values in the regions of the frontal lobe, putamen, temporal lobe, and thalamus (P < 0.05), relative to the baseline conditions. The correlation analysis revealed that the ALFF and functional connectivity of default mode network was positively correlated with the ΔMoCA score and ΔIGF-1 levels; that is, the more the scale score increased, the higher the functional connection strength. No undesirable adverse effects were observed. CONCLUSIONS: The rhGH replacement has a significant impact on global and domain cognitive functions in poststroke cognitive impairment.


Assuntos
Disfunção Cognitiva/complicações , Disfunção Cognitiva/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Imagem por Ressonância Magnética/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Resultado do Tratamento
15.
Endocr Pract ; 26(4): 454-462, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32045295

RESUMO

Objective: Comprehensive evidence comparing different medications for acromegaly is scarce. The aim of this study was to perform a network meta-analysis based on evidence from both randomized trials and observational studies of medical treatments for acromegaly. Methods: Electronic databases were searched for both observational studies and randomized trials that enrolled acromegaly patients treated with medications of interest. Simulated trials were generated by a machine learning algorithm and then synthesized with Bayesian random-effects network meta-analyses. The main outcome was the rate of insulin-like growth factor 1 (IGF-1) control after medical treatment. Results: We included 90 studies (100 arms, 4,523 patients) before matching. After matching, 28 simulated trials were generated. Balance of matched arms was checked by spatial distance and correlation matrix. Cotreatment with somatostatin receptor ligands and pegvisomant was the most effective treatment compared with other treatments. In unselected patients, pegvisomant was better than octreotide long-acting release (logOR, 0.85; 95% credible interval [CrI], 0.05 to 1.65) or lanreotide (logOR, 1.09, 95% CrI, 0.05 to 2.14), and the mean absolute IGF-1 control rate ranged from 40 to 60%. In partially responsive patients, cotreatment with somatostatin receptor ligands and pegvisomant was similar to pegvisomant monotherapy, ranking as the most two effective treatments, and the mean absolute IGF-1 control rate was over 60%. Conclusion: Our analysis suggested that the combination of data from observational studies and randomized trials in network meta-analysis was feasible. The findings of this network meta-analysis provided robust evidence supporting the current guidelines in treatment strategy for acromegaly. Abbreviations: CrI = credible interval; DA = dopamine agonist; GH = growth hormone; IGF-1 = insulin-like growth factor 1; ITT = intention-to-treat; LAN = lanreotide; LAN-ATG = lanreotide autogel; OCT = octreotide; OCT-LAR = octreotide long acting repeatable; OR = odds ratio; PEG = pegvisomant; PP = per-protocol; SRL = somatostatin receptor ligand.


Assuntos
Acromegalia , Hormônio do Crescimento Humano , Teorema de Bayes , Humanos , Fator de Crescimento Insulin-Like I , Metanálise em Rede , Estudos Observacionais como Assunto , Octreotida , Peptídeos Cíclicos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Clin Chim Acta ; 505: 130-135, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32084383

RESUMO

BACKGROUND: Biotin is an interference in many streptavidin-biotin based immunoassays, causing falsely decreased results with sandwich immunoassays and falsely increased results with competitive immunoassays. It has been discussed that premixing streptavidin coated beads and biotinylated capturing molecules may prevent biotin interference. This study was designed to test whether such modification could mitigate biotin interference in two originally susceptible sandwich immunoassays. METHODS: Roche C-peptide and human growth hormone (hGH) immunoassays utilize three reagent containers for streptavidin coated beads (M), biotinylated capturing antibody (R1) and ruthenylated antibody (R2). The reagents were modified by premixing reagent M and R1. Following incubation, the beads were placed back in the M-container and R1-supernatant back to R1-container. Patient specimens were selected, spiked with biotin to 1055 ng/mL, and measured by both the original, unmodified reagent and modified reagent on Roche cobas e411 analyzer. The biotin interference dose response curves were also compared using pooled patient specimen spiked with different concentrations of biotin. RESULTS: For the original reagent, 1055 ng/mL of biotin decreased C- peptide results by 88% and hGH results by 97%. After reagent modification, this interference effect was nearly eliminated for C- peptide but remained about 20% decreased for hGH. CONCLUSION: Premixing streptavidin beads and biotinylated capturing molecules is an effective approach to mitigate biotin interference for certain immunoassays.


Assuntos
Biotina/análise , Biotina/química , Imunoensaio/métodos , Estreptavidina/química , Biotinilação , Peptídeo C/análise , Reações Falso-Positivas , Hormônio do Crescimento Humano/análise , Humanos , Indicadores e Reagentes
17.
Metabolism ; 105: 154188, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32084431

RESUMO

OBJECTIVES: Lipoprotein lipase (LPL) catalyzes the hydrolysis of circulating triglycerides into free fatty acids (FFA) and thereby promotes FFA uptake in peripheral tissues. LPL is negatively regulated by angiopoietin-like protein 4 (ANGPTL4) presumably by an FFA-dependent mechanism. Growth hormone (GH) suppresses LPL activity, but it is unknown whether this is mediated by FFA and ANGPTL4. Therefore, we investigated the concerted effect of GH on ANGPTL4 and LPL in the presence and absence of lipolysis in two in vivo studies in human subjects. METHODS: In a randomized, placebo-controlled, cross-over study, nine obese men were examined after injection of 1) a GH bolus, and 2) a GH-receptor antagonist followed by four adipose tissue biopsies obtained over a 5-h period. In a second study, nine hypopituitary men were examined in a 2 × 2 factorial design including GH and acipimox (an anti-lipolytic agent), with biopsies from adipose tissue and skeletal muscle obtained during a basal period and a subsequent hyperinsulinemic-euglycemic clamp. The mRNA expression of ANGPTL4 and LPL as well as LPL activity were analyzed in the biopsies. RESULTS: In both studies, GH increased serum FFA levels, upregulated ANGPTL4 mRNA expression and suppressed LPL activity. In study 2, acipimox completely suppressed FFA levels and antagonized the effects of GH on ANGPTL4 and LPL. CONCLUSIONS: These human in vivo studies demonstrate that GH upregulates ANGPTL4 mRNA and suppresses LPL activity via an FFA-dependent mechanism.


Assuntos
Proteína 4 Semelhante a Angiopoietina/biossíntese , Ácidos Graxos/metabolismo , Hormônio do Crescimento Humano/farmacologia , Lipase Lipoproteica/antagonistas & inibidores , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adulto , Idoso , Estudos Cross-Over , Ácidos Graxos não Esterificados/sangue , Hormônio do Crescimento Humano/antagonistas & inibidores , Humanos , Hipolipemiantes/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/patologia , Pirazinas/uso terapêutico , RNA Mensageiro/biossíntese , Método Simples-Cego , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
18.
Eur J Endocrinol ; 182(5): R67-R82, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32069216

RESUMO

Gonadal steroids modulate the effects of GH, with oestrogens attenuating and androgens augmenting GH action. Whether these divergent effects influence the clinical manifestation, management and prognosis of acromegaly have not been carefully reviewed. This review examines whether there is a gender difference in epidemiology, presentation, quality of life (QoL), morbidity, treatments and mortality of acromegaly. Acromegaly is more common in women who present at an older age with longer diagnostic delay. At presentation, women have a higher GH relative to IGF-1 level than men. QoL is more adversely affected in women both before and after treatment. Prevalence of hypertension and diabetes are greater in women than in men with acromegaly. Treatment outcomes with SSAs are comparable between sexes, but women may require a higher dose of pegvisomant for equivalent response. Mortality in untreated acromegaly is more profoundly affected in women; however, improved treatments in recent decades have resulted in normalisation of standard mortality ratios in both sexes. We conclude that gender does matter in the management of acromegaly, with women presenting later in life, with greater diagnostic delay, higher prevalence of comorbidities and experiencing worse QoL.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Fatores Etários , Gerenciamento Clínico , Relação Dose-Resposta a Droga , Feminino , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Qualidade de Vida , Fatores Sexuais , Resultado do Tratamento
19.
Eur J Endocrinol ; 182(4): 405-411, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31961800

RESUMO

Objective: Children with Prader-Willi syndrome (PWS) have mild to moderate cognitive impairment. Short-term studies showed positive effects of growth hormone (GH) on cognitive development. This study investigated the effects of 8 years of GH on cognitive development in children with PWS. We also investigated whether starting GH during infancy results in higher cognitive functioning after 8 years of GH. Design: Longitudinal study in 43 children with PWS during 8 years of GH (median age at GH start 8.1 years). Cognitive functioning after 8 years was compared to another group of 22 children with PWS (median age at GH start 1.4 years). Methods: Cognitive functioning was measured by Wechsler Intelligence Scale for Children. Vocabulary, Similarities and Block Design subtests were expressed as standard deviation scores (SDS) and total IQ (TIQ) calculated. Results: Estimated mean (95%CI) Block Design SDS changed from -2.2 (-2.6; -1.8) at GH start to -1.8 (-2.2; -1.4) after 8 years of GH (P = 0.18), similarly SDS from -1.5 (-2.1; -0.9) to -1.3 (-1.9; -0.7, P = 0.66) and TIQ from 66 (60; 72) to 69 (63; 75, P = 0.57). Vocabulary SDS remained similar, being -1.9 (-2.3; -1.4) at GH start and -1.9 (-2.4; -1.5) after 8 years (P = 0.85). After 8 years of GH Vocabulary, SDS and TIQ were higher in the children who started GH during infancy, compared to those who started GH later in childhood (P < 0.01, P = 0.04, respectively). Conclusions: Cognitive functioning in children with PWS remains similar during long-term GH and develops at the same pace as healthy peers.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Prader-Willi/tratamento farmacológico , Síndrome de Prader-Willi/psicologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Cognição/efeitos dos fármacos , Estudos de Coortes , Feminino , Genótipo , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Lactente , Estudos Longitudinais , Masculino , Países Baixos , Síndrome de Prader-Willi/genética , Estudos Prospectivos , Resultado do Tratamento , Escalas de Wechsler
20.
Eur J Endocrinol ; 182(3): 285-292, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917681

RESUMO

Objective: To examine all-cause mortality rates in patients with acromegaly on pegvisomant and identify pertinent risk factors, including insulin-like growth factor I (IGF-I). Design: Retrospective cohort analysis of data from ACROSTUDY (global surveillance study of patients with acromegaly treated with pegvisomant). Methods: Kaplan-Meier analyses and Cox regression techniques were used to examine survival rates. Standardized mortality ratios (SMR) with reference to general population (WHO GBD 2016) were estimated. Multiplicative multiple Poisson regression models were used to characterize the association between SMR, IGF-I, and other risk factors associated with mortality risk. Results: The study consisted of 2077 subjects who were followed for a median interval of 4.1 years, contributing to 8957 patient-years. Higher on-treatment IGF-I (P = 0.0035), older attained age (P < 0.0001), and longer duration of acromegaly (>10 years) before starting pegvisomant (P = 0.05) were associated with higher mortality rates. In reference to general population rates, higher SMR (1.10, 1.42, and 2.62, at attained age 55 years) were observed with higher serum IGF-I category (SMR trend: 1.44 (44%)/per fold level of IGF-I/ULN (95% CI: 1.10, 1.87), P = 0.0075). SMR increased per year of younger attained age (1.04 (1.02-1.04), P < 0.0001) and were higher for longer disease duration (>10 years) before starting pegvisomant (1.57 (1.02, 2.43), P = 0.042). Serum IGF-I levels within the normal range during pegvisomant therapy were associated with all-cause mortality rates that were indistinguishable from the general population. Conclusions: Higher on-treatment IGF-I, older attained age, and longer duration of acromegaly before starting pegvisomant are associated with higher all-cause mortality rates. Younger patients with uncontrolled acromegaly have higher excess all-cause mortality rates in comparison with older patients.


Assuntos
Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Mortalidade , Receptores da Somatotropina/antagonistas & inibidores , Acromegalia/metabolismo , Adulto , Fatores Etários , Idoso , Causas de Morte , Estudos de Coortes , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tempo para o Tratamento
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