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Recombinant Human Growth Hormone Ameliorates Cognitive Impairment in Stroke Patients.
Feng, X, Li, G, Wu, W, Xu, Y, Lin, H, Fan, J
Journal of computer assisted tomography. 2020;(2):255-261
Abstract
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.
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Effects of nutrition and hormones on functional appliance treatment outcome in patients with skeletal Class II malocclusion.
Zhang, X, Yi, J, Li, Y
Journal of the World federation of orthodontists. 2020;(1):9-12
Abstract
BACKGROUND Functional appliances has been used for treatment of skeletal Class II malocclusion for a long time; however, the real skeletal effects, mandibular growth particularly, remain insufficient. Several auxiliary approaches have been attempted with the hope of enhancing treatment effects. In this review, we summarize and discuss the use of additional nutrition and hormones to assist the functional appliance treatment on patients with skeletal Class II malocclusion. METHODS Relevant articles were identified by electronic research in MEDLINE Ovid using keywords such as "nutrition," "hormone," "functional appliance," "orthodontics," "maxillofacial development," and "maxillofacial abnormalities." References of related articles were assessed for relevant studies to identify additional published references. RESULTS The literature search yielded 239 studies. According to the current literature, use of additional nutrition and hormones, including growth hormones, sex hormones, insulin, and insulin-like growth factor I, seem to improve the effects of functional appliance treatment on patients with skeletal Class II malocclusion. CONCLUSIONS The current evidence indicates that additional nutrition or hormones might improve the treatment effects on mandibular hypoplasia compared with the functional appliance alone, which is a promising approach and calls for further studies.
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Ten years with biosimilar rhGH in clinical practice in Sweden - experience from the prospective PATRO children and adult studies.
Lundberg, E, Kriström, B, Zouater, H, Deleskog, A, Höybye, C
BMC endocrine disorders. 2020;(1):55
Abstract
BACKGROUND In 2007, Omnitrope® was the first biosimilar recombinant human growth hormone (rhGH) to be approved in Sweden for treatment in adults and children. Over 10 years' safety and effectiveness data for biosimilar rhGH can now be presented. METHODS PATRO Children and PATRO Adults are multicenter, longitudinal, observational, post-marketing surveillance studies. Eligible patients include children 0-18 years and adults receiving biosimilar rhGH treatment. Adverse events (AEs) are monitored for safety evaluation. Growth variables in children and metabolic data in adults are recorded for effectiveness evaluation. RESULTS As of January 2019, data from 136 children (48% male) were reported from Swedish centers. Mean age in rhGH treatment-naïve patients at study entry (n = 114) was 7.5 years, with mean 3.6 years treatment duration. No severe AEs of diabetes, impaired glucose tolerance, or malignancy were reported. The most frequently reported AE was nasopharyngitis (n = 16 patients). No clinically relevant anti-hGH or neutralizing antibodies were observed. The mean change from baseline in height standard deviation score (SDS) in naïve prepubertal GH deficiency patients was + 0.79 at 1 year, + 1.27 at 2 years, and + 1.55 at 3 years. Data from 293 adults (44% rhGH-naïve, 51% male) were included. Fatigue was the most frequently reported AE (n = 26 patients). The incidence of new neoplasms or existing neoplasm progression was 23.8 patients per 1000 patient-years. Type 2 diabetes mellitus was reported in four patients. At baseline in rhGH-naïve adults, mean (SD) body mass index (BMI) was 29.1 (5.6) kg/m2 and mean (SD) insulin-like growth factor (IGF)-I SDS was - 3.0 (1.4). Mean daily dose increased from 0.1 mg at baseline to 0.3 mg after 4 years. IGF-I SDS normalized during the first year of treatment. Mean BMI and glucose were unchanged over 4 years, while low-/high-density lipoprotein cholesterol ratio decreased. CONCLUSIONS For the first time, Swedish data from the PATRO Children and Adults studies are presented. The 10-year data suggest that biosimilar rhGH is well tolerated across pediatric and adult indications. Safety and effectiveness were similar to previous reports for other rhGH preparations. These results need to be confirmed in larger cohorts, highlighting the importance of long-term post-marketing studies.
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Growth hormone ameliorates high glucose-induced steatosis on in vitro cultured human HepG2 hepatocytes by inhibiting de novo lipogenesis via ChREBP and FAS suppression.
Villanueva-Ortega, E, Méndez-García, LA, Garibay-Nieto, GN, Laresgoiti-Servitje, E, Medina-Bravo, P, Olivos-García, A, Muñoz-Ortega, MH, Ventura-Juárez, J, Escobedo, G
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2020;:101332
Abstract
OBJECTIVE Growth hormone (GH) deficiency has been associated with increased steatosis but the molecular mechanism has not been fully elucidated. We investigated the effect of GH on lipid accumulation of HepG2 cells cultured on an in vitro steatosis model and examined the potential involvement of insulin-like growth factor 1 (IGF-1) as well as lipogenic and lipolytic molecules. METHODS Control and steatosis conditions were induced by culturing HepG2 cells with 5.5 or 25 mmol/l glucose for 24 h, respectively. Afterward, cells were exposed to 0, 5, 10 or 20 ng/ml GH for another 24 h. Lipid content was quantified as well as mRNA and protein levels of IGF-1, carbohydrate responsive element-binding protein (ChREBP), sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyltransferase 1A (CPT1A), and peroxisome proliferator-activated receptor alpha (PPAR-alpha) by qPCR and western blot, respectively. Data were analyzed by one-way ANOVA and the Games-Howell post-hoc test. RESULTS In the steatosis model, HepG2 hepatocytes showed a significant 2-fold increase in lipid amount as compared to control cells. IGF-1 mRNA and protein levels were significantly increased in control cells exposed to 10 ng/ml GH, whereas high glucose abolished this effect. High glucose also significantly increased both mRNA and protein of ChREBP and FAS without having effect on SREBP1c, CPT1A and PPAR-alpha. However, GH inhibited ChREBP and FAS production, even in HepG2 hepatocytes cultured under steatosis conditions. CONCLUSIONS Growth hormone ameliorates high glucose-induced steatosis in HepG2 cells by suppressing de novo lipogenesis via ChREBP and FAS down-regulation.
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Increased Human Growth Hormone After Oral Consumption of an Amino Acid Supplement: Results of a Randomized, Placebo-Controlled, Double-Blind, Crossover Study in Healthy Subjects.
Tam, CS, Johnson, WD, Rood, J, Heaton, AL, Greenway, FL
American journal of therapeutics. 2020;(4):e333-e337
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BACKGROUND Human growth hormone (hGH) is best known for influencing bone and muscle growth, as well as body composition, but the use of recombinant hGH is controversial. Amino acids are a potentially safer alternative; however, preliminary investigations of the effects of oral amino acids on hGH release have been inconclusive. Therefore, we tested the effects of a novel blend of amino acids optimized to increase hGH release. STUDY QUESTION Does an investigational amino acid supplement affect hGH release? STUDY DESIGN This was a randomized, placebo-controlled, double-blind, crossover study that included 16 (12 men, 4 women; age 32 ± 14 years; body mass index 26.4 ± 5.0 kg/m) healthy participants. All participants received both placebo and the amino acid supplement after an overnight fast and completed all study visits. Treatment order was randomized, and each treatment was separated by a 1-week washout period. MEASURES AND OUTCOMES The primary outcomes were the percent change in hGH from baseline to 120 minutes and the area under the curve of hGH over baseline. Serum hGH was measured using enzyme-linked immunosorbent assay at baseline and 15, 30, 60, 90, and 120 minutes. RESULTS At 120 minutes, hGH levels increased by 682% (8-fold) from baseline and were significantly higher than placebo (P = 0.01). In addition, a significantly higher mean area under the curve was observed for the amino acid supplement compared with the placebo [20.4 (95% confidence interval, 19.9-21.0 ng/mL) vs. 19.7 (95% confidence interval, 18.7-20.6 ng/mL); P = 0.04]. CONCLUSIONS These results show that a single dose of the oral amino acid supplement was sufficient to significantly increase hGH levels in healthy adult men and women. CLINICAL TRIAL REGISTRY clinicaltrials.gov NCT01540773.
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Human growth hormone level decreased in women aged <60 years but increased in men aged >50 years.
Wang, X, Wang, S, Wu, H, Jiang, M, Xue, H, Zhu, Y, Wang, C, Zha, X, Wen, Y
Medicine. 2020;(2):e18440
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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 ± 0.59 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.
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Adherence to treatment in children with growth hormone deficiency, small for gestational age and Turner syndrome in Mexico: results of the Easypod™ connect observational study (ECOS).
Blanco-López, A, Antillón-Ferreira, C, Saavedra-Castillo, E, Barrientos-Pérez, M, Rivero-Escalante, H, Flores-Caloca, O, Calzada-León, R, Rosas-Guerra, CC, Koledova, E, Chiquete, E, et al
Journal of endocrinological investigation. 2020;(10):1447-1452
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BACKGROUND Assessing adherence to growth hormone (GH) is challenging. The Easypod™ connect device delivers pre-set doses of recombinant human GH (r-hGH) and stores a digital record of adherence that can be shared with healthcare provider. We assessed adherence to r-hGH delivered with Easypod™ according to the approved pediatric indications for r-hGH: growth hormone deficiency (GHD), born small for gestational age (SGA) who failed to show catch-up growth and Turner syndrome (TS). METHODS ECOS (NCT01555528) was a multicenter (24 countries), 5-year, longitudinal, observational study, which aimed to evaluate country-specific adherence to r-hGH therapy prescribed via the Easypod™ electronic injection device. The primary endpoint was yearly adherence. Secondary endpoints were height velocity, height velocity standard deviation scores (SDS), height, height SDS and IGF-1 concentrations. Clinical and auxological data were obtained from medical records and adherence from Easypod™ logs. RESULTS This study included 147 Easypod™-naïve Mexican children assessed during 3 years (mean age: 9.96 ± 3.41 years, 56.8% boys, mean height SDS at baseline: - 2.17 ± 0.97): 118 with GHD, 24 SGA and 5 with TS. A total of 105 (71.4%) patients were GH naïve. Overall median adherence was > 90% over the first year of treatment and > 80% at 3 years. Adherence was not different by r-hGH indication or between GH-naïve or experienced patients. At 1-year follow-up, mean change in height SDS was 0.57 ± 0.34, whereas mean height velocity SDS was 2.85 ± 2.51. In all, 84.7% patients had normal IGF-1 concentrations at 1-year follow-up. Adherence was associated with change in height SDS (r = 0.239, p = 0.005) and height velocity SDS (r = 0.194, p = 0.027). CONCLUSION Adherence rates with the Easypod™ device are high and maintained over time in GHD, SGA and TS Easypod™-naïve Mexican patients. High adherence is associated with better outcomes. Easypod™ assists physicians in monitoring adherence to r-hGH.
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Growth hormone therapy for people with thalassaemia.
Ngim, CF, Lai, NM, Hong, JY, Tan, SL, Ramadas, A, Muthukumarasamy, P, Thong, MK
The Cochrane database of systematic reviews. 2020;(5):CD012284
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BACKGROUND Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency. This review on the role of growth hormone was originally published in September 2017 and updated in April 2020. OBJECTIVES To assess the benefits and safety of growth hormone therapy in people with thalassaemia. SEARCH METHODS We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of latest search: 14 November 2019. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Date of latest search: 06 January 2020. SELECTION CRITERIA Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity. DATA COLLECTION AND ANALYSIS Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The certainty of the evidence was assessed using GRADE criteria. MAIN RESULTS We included one parallel trial conducted in Turkey. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The certainty of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre-specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) -0.09 (95% confidence interval (CI) -0.33 to 0.15 (moderate-certainty evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate-certainty evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one-year trial period. AUTHORS' CONCLUSIONS A small single trial contributed evidence of moderate certainty that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.
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Short-term evaluation of cardiac morphology, function, metabolism and structure following diagnosis of adult-onset growth hormone deficiency.
De Cobelli, F, Rossini, A, Esposito, A, Canu, T, Manzoni, G, Del Maschio, A, Rubinacci, A, Sirtori, M, Losa, M, Lanzi, R, et al
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2019;:50-54
Abstract
OBJECTIVE The impact of growth hormone (GH) deficiency of the adult on cardiovascular function remains only partially elucidated. Purpose of this study was to test cardiac function in adult GH deficient patients using cardiac magnetic resonance (CMR). DESIGN Cardiac magnetic resonance (CMR) techniques, including cardiac 31P MR spectroscopy and evaluation of gadolinium late-enhancement, were applied to assess simultaneously, in a cross-sectional fashion, morphological, functional, metabolic, and structural parameters of the left (LV) and right ventricle (RV) in 15 patients with adult onset GH deficiency. Fifteen healthy individuals served as controls. RESULTS In GH deficient patients LV systolic function (EF%: 61 ± 1.7 vs 62.1 ± 0.8; p = .44) was not different in spite of a lower LV mass (83.2 ± 5.3 vs 145.3 ± 11.9 g; p = .001), a subclinical impairment of diastolic function (E/A peak ratio: 1.6 ± 0.2 vs 2.1 ± 0.2 p = .05), and a trend for lower PCr/ATP ratio (2.1 ± 0.8 vs 2.3 ± 0.1 p = .07). The RV showed reduced chamber size (end diastolic volume 123.8 ± 9 vs 147.9 ± 7.6 mL; p = .021) with preserved mass. No structural alterations of the LV and RV at late-enhancement were detected in these patients. CONCLUSIONS GH deficient patients represent a unique model of reduced LV myocardial mass in which major structural and metabolic alterations are lacking. Mal-adaptive mechanisms developing in the long term in response to GH deficiency and more severely affecting the LV remain to be elucidated.
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ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly.
Álvarez-Escolá, C, Venegas-Moreno, EM, García-Arnés, JA, Blanco-Carrera, C, Marazuela-Azpiroz, M, Gálvez-Moreno, MÁ, Menéndez-Torre, E, Aller-Pardo, J, Salinas-Vert, I, Resmini, E, et al
Endocrinologia, diabetes y nutricion. 2019;(5):320-329
Abstract
OBJECTIVES The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). METHODS From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. RESULTS Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. CONCLUSIONS Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals.