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1.
Medicine (Baltimore) ; 99(40): e22432, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019423

RESUMO

Nesfatin-1 was identified as a satiety factor involved in the regulation of metabolism. Altered levels of circulating nesfatin-1 had been observed in a variety of diseases characterized by energy imbalance. However, there was no published data about nesfatin-1 levels in acromegaly.We evaluated serum nesfatin-1 levels in 13 patients with acromegaly at baseline and postoperatively, and in 21 age- and body mass index (BMI)-matched healthy subjects.Compared with the healthy subjects, patients with acromegaly had significantly increased levels of serum insulin, high-density lipoprotein cholesterol, triglyceride, and growth hormone (GH). Moreover, the acromegaly group had nesfatin-1 levels higher than controls (1.96 ±â€Š0.56 ng/mL vs 0.61 ±â€Š0.10 ng/mL, P = .004). There was a positive correlation of serum nesfatin-1 levels with diastolic blood pressure (r = 0.579, P = .038) and homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.598, P = .031) in patients with acromegaly. While a successful surgery decreased serum GH levels, the serum nesfatin-1 levels did not change in acromegaly (P = .965). At last, we compared serum GH/nesfatin-1 levels with predictive markers for aggressive behaviors in pituitary adenomas. There was no relationship between serum nesfatin-1 levels and tumor's size, Ki-67 index, mutant p53, or MGMT proteins. However, increased serum GH levels were positively correlated with tumors' size (P = .023) and mutant p53 proteins expression (P = .028).Circulating nesfatin-1 was increased in acromegaly, which was involved in metabolism regulation.


Assuntos
Acromegalia/sangue , Nucleobindinas/sangue , Adenoma/sangue , Adenoma/patologia , Adenoma/cirurgia , Adulto , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Curva ROC
2.
Eur J Endocrinol ; 183(6): 581-595, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33055295

RESUMO

Objective: Copy number variation (CNV) has been associated with idiopathic short stature, small for gestational age and Silver-Russell syndrome (SRS). It has not been extensively investigated in growth hormone insensitivity (GHI; short stature, IGF-1 deficiency and normal/high GH) or previously in IGF-1 insensitivity (short stature, high/normal GH and IGF-1). Design and methods: Array comparative genomic hybridisation was performed with ~60 000 probe oligonucleotide array in GHI (n = 53) and IGF-1 insensitivity (n = 10) subjects. Published literature, mouse models, DECIPHER CNV tracks, growth associated GWAS loci and pathway enrichment analyses were used to identify key biological pathways/novel candidate growth genes within the CNV regions. Results: Both cohorts were enriched for class 3-5 CNVs (7/53 (13%) GHI and 3/10 (30%) IGF-1 insensitivity patients). Interestingly, 6/10 (60%) CNV subjects had diagnostic/associated clinical features of SRS. 5/10 subjects (50%) had CNVs previously reported in suspected SRS: 1q21 (n = 2), 12q14 (n = 1) deletions and Xp22 (n = 1), Xq26 (n = 1) duplications. A novel 15q11 deletion, previously associated with growth failure but not SRS/GHI was identified. Bioinformatic analysis identified 45 novel candidate growth genes, 15 being associated with growth in GWAS. The WNT canonical pathway was enriched in the GHI cohort and CLOCK was identified as an upstream regulator in the IGF-1 insensitivity cohorts. Conclusions: Our cohort was enriched for low frequency CNVs. Our study emphasises the importance of CNV testing in GHI and IGF-1 insensitivity patients, particularly GHI subjects with SRS features. Functional experimental evidence is now required to validate the novel candidate growth genes, interactions and biological pathways identified.


Assuntos
Variações do Número de Cópias de DNA/genética , Testes Genéticos/métodos , Hormônio do Crescimento Humano/genética , Fator de Crescimento Insulin-Like I/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Lactente , Fator de Crescimento Insulin-Like I/metabolismo , Masculino
4.
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
5.
Metabolism ; 107: 154219, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32240726

RESUMO

BACKGROUND: An adequate metabolic and hormonal response to the switch from rest to exercise is critical for the health benefits of exercise interventions. Previous work suggests that this response is impaired with overweight/obesity but the specific differences between overweight/obese and lean individuals remain unclear. METHODS: We compared glucose and non-esterified fatty acid (NEFA) regulation and the changes of key homeostatic hormones during 45 min of moderate exercise between 17 overweight/obese and 28 lean premenopausal women. For this comparison, we implemented an exercise protocol at 60% of individual peak oxygen uptake, with frequent blood sampling and under fasting conditions. RESULTS: We found that at the same exercise intensity in the overweight/obese and the lean group of women, the metabolic and hormonal response differed. In contrast to the lean group, the overweight/obese group portrayed an activation in the stress axis (adrenocorticotropic hormone (ACTH)/cortisol) and a lower growth hormone (hGH) response and exercise-increase of plasma NEFA. Both groups, however, displayed increased insulin sensitivity during exercise that was accompanied by a normalization of the elevated fasting glucose in the overweight/obese group after 15-20 min. CONCLUSION: We conclude that the response to exercise in overweight/obese subjects indeed differs from that in lean individuals. Additionally, we demonstrate that exercise can elicit beneficial (improved glucose regulation) and unwanted effects (stress axis activation) in overweight/obese subjects at the same time. This second finding suggests that exercise interventions for overweight/obese subjects need careful consideration of intensity and dose in order to achieve the intended results and avoid acute, undesired reactions.


Assuntos
Terapia por Exercício , Exercício Físico , Hormônios/sangue , Obesidade/metabolismo , Obesidade/terapia , Sobrepeso/metabolismo , Sobrepeso/terapia , Hormônio Adrenocorticotrópico/sangue , Adulto , Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Teste de Esforço , Ácidos Graxos não Esterificados/sangue , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Insulina/metabolismo , Pré-Menopausa
6.
BMC Cardiovasc Disord ; 20(1): 190, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321428

RESUMO

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology. METHODS: We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction. RESULTS: POTS patients were younger (26 vs. 31 years; p < 0.001) and had lower BMI than controls. The discovery algorithm identified growth hormone (GH) and myoglobin (MB) as the most specific biomarker fingerprint for POTS. Plasma level of GH was higher (9.37 vs 8.37 of normalised protein expression units (NPX); p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS. CONCLUSIONS: Cardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.


Assuntos
Hormônio do Crescimento Humano/sangue , Mioglobina/sangue , Síndrome da Taquicardia Postural Ortostática/sangue , Proteômica , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome da Taquicardia Postural Ortostática/diagnóstico , Valor Preditivo dos Testes , Fatores Sexuais , Adulto Jovem
7.
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
8.
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
9.
Sci Rep ; 10(1): 5495, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32218464

RESUMO

Metabolic syndrome (MetS) is a multi-factorial disorder including central obesity (CO), insulin resistance, hyperglycemia, dyslipidemia and hypertension which increases the risk of diabetes mellitus and cardiovascular diseases. CO is considered as an essential component of MetS according to International Diabetes Federation (IDF), which may further modulate distinct signalling pathways compared with the other four MetS risk factors. Given that ghrelin signalling and the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis regulates energy balance and metabolic homeostasis, this study examined the changes in various ghrelin products and circulating hormones in response to the interaction between CO and other MetS components including blood pressure, fasting blood glucose, triglycerides, and high-density lipoprotein cholesterol in 133 Hong Kong Chinese adults. Circulating obestatin and GH were increased and reduced, respectively, by either CO or the other 4-risk factor cluster. These changes were further augmented by the presence of all MetS risk factors. However, changes of ghrelin levels were not mediated by CO but the other MetS risk factors. Our findings suggest that CO does not predict all the dysregulation of signalling pathways in individuals with MetS. Although CO and other MetS may share common signalling targets (i.e., obestatin and GH), CO does not contribute to the perturbation of ghrelin signalling.


Assuntos
Grelina/sangue , Hormônio do Crescimento Humano/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Obesidade Abdominal/sangue , Obesidade Abdominal/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , HDL-Colesterol/sangue , Feminino , Hong Kong , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Nucleobindinas/sangue , Fatores de Risco , Transdução de Sinais , Triglicerídeos/sangue , Adulto Jovem
10.
J Neurol ; 267(3): 855-859, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32034477

RESUMO

INTRODUCTION: Despite the consensus criteria for multiple system atrophy (MSA), the diagnosis of MSA of cerebellar type (MSA-C) may be difficult in the early stage of the disease. There are several differential diagnoses including idiopathic late-onset cerebellar ataxias (ILOCA) and it is often necessary to wait for clinical worsening so that the criteria can be met. Our aim was to assess the efficacy of clonidine growth hormone test (CGH test) to distinguish MSA-C from ILOCA in the early stage of the disease. METHODS: Within our cohort of late-onset sporadic, progressive cerebellar ataxia, the group of patients meeting the criteria for possible or probable MSA was compared to the ILOCA group. Clinical and paraclinical examination including CGH test were repeated during the prospective follow-up. RESULTS: Eighty-six patients were recruited, including 42 patients in the MSA group and 44 ILOCA patients with a mean follow-up of 33 months. At the inclusion visit, CHG test was pathological for 31% MSA of patients and 18.2% of ILOCA patients (p = 0.35). During the follow-up, 52.4% of MSA-C had a pathological CGH test, while only 20.5% of ILOCA (p < 0.01). CGH test had a sensitivity of 69.1% and a specificity of 68.2%, (p < 0.001) for MSA-C patients; CGH test allows in three quarters of cases, if negative, to rule out a probable MSA-C (negative predictive value of 75%, p = 0.0014). CONCLUSION: This prospective, controlled study showed that CGH test could be helpful in clinical practice to differentiate MSA-C from ILOCA in the early stage of the disease.


Assuntos
Diagnóstico Precoce , Hormônio do Crescimento Humano/sangue , Atrofia de Múltiplos Sistemas/diagnóstico , Degenerações Espinocerebelares/diagnóstico , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Idoso , Clonidina/farmacologia , Diagnóstico Diferencial , Feminino , Hormônio do Crescimento Humano/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
11.
Arch. endocrinol. metab. (Online) ; 64(1): 82-88, Jan.-Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1088767

RESUMO

ABSTRACT 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
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fator de Crescimento Insulin-Like I/análise , Hidrocortisona/sangue , Hormônio do Crescimento Humano/sangue , Teste de Tolerância a Glucose/métodos , Hipoglicemia/sangue , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Sistema Hipófise-Suprarrenal/metabolismo , Automonitorização da Glicemia , Estudos Retrospectivos , Teste de Tolerância a Glucose/efeitos adversos , Hipoglicemia/diagnóstico , Hipoglicemia/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo
12.
Eur J Endocrinol ; 182(3): 319-331, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31958318

RESUMO

Objective: Acromegaly has a negative influence on health-related quality of life (HRQoL). Previous studies provide limited information on the course of HRQoL during treatment. This study aims to assess the effect of treatment on the course of HRQoL at six predefined time points. Design: This prospective study examines HRQoL in treatment-naive patients before and during the first 2.5 years of acromegaly treatment. Methods: Therapy-naive acromegaly patients completed three validated questionnaires (RAND-36, AcroQoL, and the Appearance Self-Esteem (ASE)) at six predetermined time points before, during, and after treatment. Outcomes were correlated to IGF1 levels and disease control status. Results: Twenty-seven acromegaly patients completed the questionnaires at all time points. After treatment, all patients had controlled acromegaly. Scores of RAND-36 domains General health, Vitality and Health change, and all AcroQoL dimensions (except for Relations) improved during treatment (P ≤ 0.003); the largest changes were detected during the first year. Gender influenced HRQoL scores, since AcroQoL scores significantly improved in males but not in females. Over time, IGF1 levels were negatively correlated with HRQoL. After 2.5 years of follow-up, HRQoL of controlled patients was still lower than in the general population. Conclusion: HRQoL of acromegaly patients was considerably reduced at diagnosis. Disease control was associated with an improvement of HRQoL scores. Males showed a more pronounced improvement than females. The largest changes were detected in the first year of treatment. However, HRQoL during and after treatment remained impaired in acromegaly patients, emphasizing the need of additional support.


Assuntos
Acromegalia/psicologia , Acromegalia/terapia , Qualidade de Vida/psicologia , Adulto , Idoso , Feminino , Nível de Saúde , Hormônios/deficiência , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/psicologia , Estudos Prospectivos , Autoimagem , Fatores Sexuais , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
13.
Medicine (Baltimore) ; 99(2): e18440, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914017

RESUMO

To investigate the relationship amongst human growth hormone (HGH), sex, and age groups.A cross-sectional study was conducted on a health check-up population from Wannan area of China from 2014 to 2016. The study involved 6843 individuals aged 23 to 85 years. Logistic regression analysis and smooth curve were applied to determine the relationship amongst age, sex, and HGH.The average level of HGH in the population was 0.37 ±â€Š0.59 ng/mL. There were significant differences in sex, age, body mass index (BMI), triglycerides (TG), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), and glucose (GLU) amongst different quartiles of HGH (P < .001). A U-shape relationship was established between HGH and age. After sex stratification, the results showed that the thresholds of age were 60 years in women, and 50 years in men, after adjusting for body mass index, triglycerides, total cholesterol, blood pressure, and blood glucose. Logistic regression showed that HGH level decreased in women aged <60 years (OR = 1.472, P < .001) and increased in men aged >50 years (OR = 0.711, P < .001). So the distributive characteristics of HGH concentration vary with sex and age group.


Assuntos
Pressão Sanguínea/fisiologia , Hormônio do Crescimento Humano/sangue , Triglicerídeos/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
14.
Ann Endocrinol (Paris) ; 81(1): 11-17, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31982107

RESUMO

OBJECTIVE: The aim of this study was to describe endocrinological outcome in patients operated on for acromegaly. METHODS: A retrospective study included 167 patients. Patients were assessed in the early postoperative period (EPP), at 3 months (M3), at 1 year (Y1), and then annually. They were classified as grade I (IGF-1 level normal-for-age and positive GH response on oral glucose tolerance test [nadir <0.4ng/L]); grade II (discordant); or grade III or IV (acromegaly, controlled or uncontrolled under medical therapy, respectively). RESULTS: Taking all patients with all grades, 35% changed grades between EPP and M3, 26% between M3 and Y1 and 9% after Y1. In grade I, respectively 22%, 15% and 2% of patients changed grades between EPP and M3, between M3 and Y1, and after Y1, compared to 31%, 6% and 6% in grade IV. Respectively 57%, 67%, and 47% of grade II patients changed grades between EPP and M3, between M3 and Y1, and after Y1; between EPP or M3 and last follow-up (>1 year), respectively 74% and 75% of grade II patients changed grades. Knosp category, resection quality and abnormal GH response (vs. abnormal IGF-1) significantly impacted grade II patients' outcome. CONCLUSIONS: Whereas outcome in grades I and III-IV seems to be determined by 1 year, grade II discordant patients' outcome remains uncertain even after 1 year.


Assuntos
Acromegalia/metabolismo , Acromegalia/cirurgia , Hormônio do Crescimento Humano/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/diagnóstico , Acromegalia/patologia , Adenoma/diagnóstico , Adenoma/metabolismo , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Teste de Tolerância a Glucose , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Hormônio do Crescimento Humano/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Recidiva , Estudos Retrospectivos , Via Secretória/fisiologia , Resultado do Tratamento
15.
J Endocrinol Invest ; 43(2): 163-171, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31392573

RESUMO

PURPOSE: Acromegaly is a cause of secondary osteoporosis and is associated with increased risk of vertebral fractures (VFs). The influence of exon 3-deleted isoform of growth hormone receptor (d3-GHR) on bone microarchitecture has not been studied in acromegaly. AIM: The aim of this study was to analyze the associations between d3-GHR isoform and bone mineral density (BMD), bone microarchitecture, and VFs in acromegaly patients. METHODS: Consecutive acromegaly patients treated at a single reference center were included. BMD was analyzed using dual-energy X-ray absorptiometry (DXA) and bone microarchitecture was analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT). The presence of moderate to severe VFs was assessed by thoracic and lumbar X-ray. GHR genotyping was analyzed by PCR, and full-length isoform of GHR (fl-GHR) was represented by a 935-bp fragment and d3-GHR by a 532-bp fragment. RESULTS: Eighty-nine patients were included [56 females; median age at diagnosis: 43 years (17-78)]. Disease was uncontrolled in 63% of patients. At least one d3-GHR allele was present in 60% of patients. Frequency of active disease (p = 0.276) and hypogonadism (p = 1.000) was not different between patients with fl-GHR and those with at least one d3-GHR. There was no difference in any DXA or HR-pQCT parameters between patients with fl-GHR and those with d3-GHR. Significant VFs were observed in 14% of patients, but there was no difference in frequency between patients with fl-GHR and those with at least one d3-GHR allele (p = 0.578). CONCLUSIONS: Presence of d3-GHR was not associated with worse BMD or bone microarchitecture or with higher frequency of significant VFs.


Assuntos
Acromegalia/diagnóstico por imagem , Acromegalia/genética , Densidade Óssea/genética , Éxons/genética , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/genética , Receptores da Somatotropina/genética , Absorciometria de Fóton/métodos , Acromegalia/sangue , Adolescente , Adulto , Idoso , Feminino , Fraturas Ósseas/sangue , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/sangue , Receptores da Somatotropina/sangue , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
16.
J Endocrinol Invest ; 43(3): 389-393, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31473983

RESUMO

PURPOSE: Incretin-based therapies have been introduced in clinical practice for type 2 diabetes mellitus (T2DM) treatment in the last few years. Current available medications of this class include glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. In addition to GLP-1, DPP-4 is able to inactivate many others peptides as hypothalamic growth hormone-releasing hormone (GHRH). The aim of this exploratory study was to evaluate, on adult diabetic patients, the impact of therapy with incretins, particularly DPP-4 inhibitors on GH/IGF-I axis. METHODS: 60 patients with T2DM were included in the study and they were divided into three groups (age and sex comparable) on the basis of their hypoglycemic drugs in the last 4 months: group 1 (17 patients, exenatide or liraglutide + metformin), group 2 (18 patients, sitagliptin or vildagliptin + metformin), group 3 (25 patients, metformin). Anthropometric data, glycemia, glycosylated hemoglobin (HbA1c), IGF-I and acid-labile subunit (ALS) were collected in all patients. RESULTS: Weight, waist circumference and BMI of group 1 were significantly higher (P < 0.05) compared to the other groups. Fasting plasma glucose and HbA1c of the group 1 were similar compared to those of group 3 (P ns) and higher compared to those of group 2 (P < 0.05). IGF-I absolute values, IGF-I SDS were not significantly different in the three groups. CONCLUSIONS: Our data evidence that DPP-4 inhibition does not influence significantly GH/IGF-I system, confirming what was observed in animal models. Further studies are needed to better characterize the properties of these molecules on endocrine system.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hormônio do Crescimento Humano/sangue , Hipoglicemiantes/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Exenatida/uso terapêutico , Feminino , Humanos , Liraglutida/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade
17.
J Strength Cond Res ; 34(2): 313-322, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31490429

RESUMO

Rissanen, JA, Häkkinen, A, Laukkanen, J, Kraemer, WJ, and Häkkinen, K. Acute neuromuscular and hormonal responses to different exercise loadings followed by a sauna. J Strength Cond Res 34(2): 313-322, 2020-The purpose of this study was to investigate acute responses of endurance (E + SA), strength (S + SA), and combined endurance and strength exercise (C + SA) followed by a traditional sauna bath (70° C, 18% relative humidity) on neuromuscular performance and serum hormone concentrations. Twenty-seven recreationally physically active men who were experienced with taking a sauna participated in the study. All the subjects performed a sauna bath only (SA) first as a control measurement followed by S + SA and E + SA (paired matched randomization) and C + SA. Subjects were measured PRE (before exercise), MID (immediately after exercise and before sauna), POST (after sauna), POST30min (30 minutes after sauna), and POST24h (24 hours after PRE). Maximal isometric leg press (ILPFmax) and bench press (IBPFmax) forces, maximal rate of force development (RFD) and countermovement vertical jump (CMVJ), serum testosterone (TES), cortisol (COR), and 22-kD growth hormone (GH22kD) concentrations were measured. All exercise loadings followed by a sauna decreased ILPFmax (-9 to -15%) and RFD (-20 to -26%) in POST. ILPFmax, RFD, and CMVJ remained at significantly (p ≤ 0.05) lowered levels after S + SA in POST24h. IBPFmax decreased in POST in S + SA and C + SA and remained lowered in POST24h. SA decreased ILPFmax and IBPFmax in POST and POST30min and remained lowered in ILPFmax (-4.1%) at POST24h. GH22kD, TES, and COR elevated significantly in all loadings measured in the afternoon in MID. SA only led to an elevation (15%) in TES in POST. The strength exercise followed by a sauna was the most fatiguing protocol for the neuromuscular performance. Traditional sauna bathing itself seems to be strenuous loading, and it may not be recommended 24 hours before the next training session. A sauna bath after the loadings did not further change the hormonal responses recorded after the exercise loadings.


Assuntos
Exercício Físico/fisiologia , Esforço Físico/fisiologia , Banho a Vapor , Adulto , Temperatura Corporal/fisiologia , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Ácido Láctico/sangue , Masculino , Distribuição Aleatória , Testosterona/sangue , Adulto Jovem
18.
J Diet Suppl ; 17(2): 211-226, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30285503

RESUMO

Multi-ingredient preworkout supplements (MIPS) are marketed as a means to increase exercise performance. The purpose of this study was to determine the effect of a single serving of Bang Pre-Workout Master Blaster (BMB) on upper- and lower-body power output and local muscular endurance. Ten resistance-trained males participated in two exercise testing sessions consisting of the vertical jump (VJ), seated medicine ball throw (SMBT), and local muscular endurance tests for the bench press (BP) and leg extension (LE) exercises at 70% of one-repetition maximum. Participants consumed placebo (PLA) or BMB 30 minutes prior to each exercise session. No difference between trials was observed for SMBT distance or BP repetitions. Vertical jump (p = .006) and LE repetitions (p = .014) were greater for the BMB trial compared with placebo. A significant interaction between trial and time was observed for insulin-like growth factor-1 (IGF-1; p = .044). Serum IGF-1 was significantly increased at both 30 PS (p = .004) and 30PX (p = .038) compared with BL for the BMB trial only. In conclusion, acute ingestion of BMB increased lower-body power and endurance as measured by the VJ and LE repetition tests, respectively, without altering hemodynamics. Furthermore, serum IGF-1 increased in response to acute exercise with BMB supplementation, but not with PLA. No differences in human growth hormone (HGH) or serum cortisol responses were observed between trials.


Assuntos
Suplementos Nutricionais , Teste de Esforço , Resistência Física/efeitos dos fármacos , Desempenho Físico Funcional , Fenômenos Fisiológicos da Nutrição Esportiva/efeitos dos fármacos , Administração Oral , Estudos Cross-Over , Método Duplo-Cego , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Adulto Jovem
19.
Eur J Endocrinol ; 182(1): 123-130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31705796

RESUMO

Objective: Primary SMSa treatment can be associated with hormonal control and tumor shrinkage in patients with GH-secreting pituitary adenomas. The aim of this study was to evaluate whether regular MRI follow-up was necessary in patients with acromegaly-treated and responsive to first-generation long-acting SMSa. Patients and methods: In this retrospective monocentric study we included patients with GH/IGF-1 hypersecretion and pituitary adenomas with normal visual field, primarily treated with first-generation long-acting SMSa between 1995 and 2015 and regularly monitored (clinical evaluation, GH/IGF-1 levels and pituitary MRI) for at least 3 years. Results: We included 83 patients (32 men and 51 women, mean age at diagnosis 50 ± 12 years) with mean GH = 19.3 ± 25.6 ng/mL, IGF-1 = 284 ± 110% ULN and pituitary adenoma height = 12.9 ± 4.7 mm. Mean follow-up was 8.9 ± 4.9 years in 36 controlled patients and 2.0 ± 1.6 years in 47 partial responders to SMSa alone. No significant increase in pituitary adenoma height was observed. Pituitary adenoma height decreased significantly in controlled patients (diagnosis: 11.9 ± 4.8 mm, SMSa: 9.6 ± 3.3 mm, P < 0.001), and in partially responders (diagnosis: 13.6 ± 4.5 mm, SMSa: 11.5 ± 4.5 mm, P < 0.001). Conclusion: During SMSa treatment, no significant increase in GH-secreting adenoma size was observed. Primary SMSa treatment was associated with a significantly decrease in adenoma height in our population. Our cohort data suggest that regular MRI follow-up does not seem relevant in patients with acromegaly who are responsive to SMSa treatment.


Assuntos
Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Imagem por Ressonância Magnética/métodos , Adulto , Feminino , Seguimentos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
20.
Am J Physiol Endocrinol Metab ; 318(2): E297-E309, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31770013

RESUMO

As a model of extreme conditions, eight healthy women, part of a 40-member Nepal mountain-climbing expedition, were monitored for dynamic endocrine adaptations. Endocrine measurements were made at frequent intervals over a 6-10-h period at four altitudes: 450 m, 4,800 m (base camp), 6,050 m, and again at 4,800 m (on descent) after an acclimatization (A) period (4,800 mA). Quantified hormones were growth hormone (GH), prolactin (PROL), cortisol (Cort), thyroid-stimulating hormone (TSH), and free thyroxine. These hormones are important to the anabolic/catabolic balance of the body, and are vital to growth, homeostasis, hypothalamic inhibition, regulation of stress, and metabolism. A key secondary question was the degree to which acclimatization can stabilize hormonal disruption. On the basis of statistical false discovery rates, the present analyses unveil marked adaptive changes in the thyroid axis at the level of pulsatile secretion of the pituitary hormone TSH and its downstream product, free thyroxine; strong effects on the mass of GH, TSH, Cort, and PROL secretion per burst; and prominent pulsatile frequency disruption and recovery for PROL and Cort. Because pulsatility changes reflect de facto perturbations in hypothalamo-pituitary control mechanisms, the present data introduce the concept of both frequency- and amplitude-dependent adaptive control of brain-pituitary neuroendocrine signals under conditions of extreme altitude exertion and exposure.


Assuntos
Altitude , Sistema Endócrino/fisiologia , Aclimatação , Adaptação Fisiológica , Adulto , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Hipóxia/metabolismo , Montanhismo , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiologia , Prolactina/sangue , Hormônios Tireóideos/sangue
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