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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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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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Abstract
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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The GH Axis in Relation to Accepting an Early Macronutrient Deficit and Outcome of Critically Ill Patients.
Van Dyck, L, Derese, I, Vander Perre, S, Wouters, PJ, Casaer, MP, Hermans, G, Van den Berghe, G, Vanhorebeek, I
The Journal of clinical endocrinology and metabolism. 2019;(11):5507-5518
Abstract
CONTEXT Changes in the GH axis during critical illness resemble fasting in healthy adults and contribute to hypercatabolism, which potentially affects outcome. Accepting macronutrient deficits by withholding parenteral nutrition (PN) during the first week in the intensive care unit (ICU; late PN) reduced complications and accelerated recovery as compared with early use of PN (early PN). OBJECTIVE To investigate how late PN affects the GH axis in relation to its clinical outcome benefits. DESIGN Preplanned subanalysis of the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients randomized controlled trial. PARTICIPANTS A total of 1128 patients for time-course study, 20 patients investigated for nocturnal GH pulsatility, and 600 patients investigated for muscle weakness, with early PN and late PN patients having comparable baseline characteristics. INTERVENTION Withholding PN during the first ICU week (late PN) vs early PN. MAIN OUTCOME MEASURES Changes in serum GH, IGF-I, IGF-binding protein (IGFBP) 3, and IGFBP1 concentrations from ICU admission to day 4 or last ICU day for patients with a shorter ICU stay (d4/LD) and association in multivariable analyses with likelihood of earlier live ICU discharge, risk of new infection, and muscle weakness. RESULTS Late PN attenuated a rise in serum GH and IGF-I (P < 0.0001), did not affect IGFBP3, and attenuated a decrease in IGFBP1 concentrations from admission to d4/LD (P < 0.0001) as compared with early PN. Late PN decreased nonpulsatile (P = 0.005), but not pulsatile, GH secretion. Adjusting the multivariable models for the observed GH axis alterations increased the independent benefit of late PN for all outcomes. GH axis alterations induced by late PN were independently associated with adverse outcomes (P ≤ 0.03). CONCLUSION Accepting macronutrient deficits early during critical illness further suppressed the GH axis, which statistically attenuated its clinical outcome benefits.
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Outcomes after multiple courses of granulocyte colony-stimulating factor and growth hormone in decompensated cirrhosis: A randomized trial.
Verma, N, Kaur, A, Sharma, R, Bhalla, A, Sharma, N, De, A, Singh, V
Hepatology (Baltimore, Md.). 2018;(4):1559-1573
Abstract
UNLABELLED Decompensated cirrhosis (DC) carries a high mortality. Liver transplantation (LT) is the treatment of choice; however, the limited availability of donor organs has resulted in high waitlist mortality. The present study investigated the impact of multiple courses of granulocyte-colony stimulating factor (G-CSF) with or without growth hormone (GH) in these patients. Sixty-five patients with DC were randomized to standard medical therapy (SMT) plus G-CSF 3 monthly plus GH daily (group A; n = 23) or SMT plus G-CSF (group B; n = 21) or SMT alone (group C; n = 21). The primary outcome was transplant-free survival (TFS) at 12 months. Secondary outcomes were mobilization of CD34+ cells at day 6 and improvement in clinical scores, liver stiffness, nutrition, episodes of infection, and quality of life (QOL) at 12 months. There was significantly better 12-month TFS in groups A and B than in group C (P = 0.001). At day 6 of therapy, CD34+ cells increased in groups A and B compared to baseline (P < 0.001). There was a significant decrease in clinical scores, improvement in nutrition, better control of ascites, reduction in liver stiffness, lesser infection episodes, and improvement in QOL scores in groups A and B at 12 months as compared to baseline (P < 0.05). The therapies were well tolerated. CONCLUSION Multiple courses of G-CSF improved 12-month TFS, mobilized hematopoietic stem cells, improved disease severity scores, nutrition, fibrosis, QOL scores, ascites control, reduced infections, and the need for LT in patients with DC. However, the use of GH was not found to have any additional benefit. (Hepatology 2017).
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Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women.
Fantini, C, Sgrò, P, Pittaluga, M, de Perini, A, Dimauro, I, Sartorio, A, Caporossi, D, Di Luigi, L
Journal of endocrinological investigation. 2017;(6):645-652
Abstract
PURPOSE While a good safety for recombinant human growth hormone (rhGH) therapy at replacement doses is recognized, a possible link between high concentration of the GH-IGF-I axis hormones and side negative effect has been reported. The aim of this pilot study was to assess whether a short-term exposure to supra-physiological doses of rhGH may affect DNA integrity in human lymphocytes (PBL). METHODS Eighteen healthy Caucasian female (24.2 ± 3.5 years) were randomly included in a Control (n = 9) and rhGH administration group (n = 9, 3-week treatment). DNA damage (comet assay), chromosomal breaks, and mitotic index in phytohemagglutinin-stimulated PBL were evaluated before (PRE), immediately (POST), and 30 days (POST30) after the last rhGH administration (0.029 mg kg- 1 BW; 6 days/week), together with serum IGF-1 and IGFBP-3 concentrations. RESULTS rhGH administration increased IGF-I, without evidence of persisting IGF-I and IGFBP-3 changes 30 days after withdrawal. Total DNA breakage (% DNA in tails) was not significantly different in subjects treated with rhGH in comparison with controls, although the rhGH-treated subjects showed an higher percentage of heavily damaged nuclei immediately after the treatment (POST30 vs. PRE: p = 0.003), with a lower mitogenic potential of lymphocytes, detectable up to the POST30 (PRE vs. POST p = 0.02; PRE vs. POST30: p = 0.007). CONCLUSIONS This pilot study showed that 3 weeks of short-term supra-physiological rhGH administration in healthy women induce a transient DNA damage and mitogenic impairment in PBL. The analysis of DNA damage should be explored as useful tool in monitoring the mid to long-term effects of high rhGH treatment or abuse.
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GH administration decreases subcutaneous abdominal adipocyte size in men with abdominal obesity.
Bredella, MA, Karastergiou, K, Bos, SA, Gerweck, AV, Torriani, M, Fried, SK, Miller, KK
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2017;:17-20
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OBJECTIVE To investigate the effects of short-term GH administration on abdominal subcutaneous adipocyte size and CT attenuation in men with abdominal obesity. DESIGN 6-week, randomized, double-blind, placebo-controlled study of GH (starting dose 2μg/kg/d) vs placebo of 15 abdominally obese men (mean age: 34±6years; mean BMI: 37.7±6.1kg/m2, mean IGF-1 SDS: -1.9±0.5) who underwent abdominal subcutaneous adipose tissue (SAT) aspirations to determine adipocyte size, CTs for body composition and measures of glucose tolerance at baseline and 6weeks. GH dosing was titrated to target IGF-1 levels in the upper normal age-appropriate range. RESULTS GH administration decreased subcutaneous abdominal adipocyte size compared to placebo. Adipocyte size was positively associated with 120-min glucose and HOMA-IR and inversely associated with peak-stimulated GH and CT attenuation. CT attenuation of SAT was inversely associated with 120-min glucose and HOMA-IR and increased following GH administration. CONCLUSION In men with abdominal obesity, subcutaneous abdominal adipocyte size is positively associated with measures of impaired glucose tolerance and administration of GH at doses that raise IGF-1 levels within the normal range, decreases abdominal subcutaneous adipocyte size, suggesting that GH administration improves the health of adipose tissue. Clinical trials number: NCT00131378.
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Comparison of low-normal and high-normal IGF-1 target levels during growth hormone replacement therapy: A randomized clinical trial in adult growth hormone deficiency.
van Bunderen, CC, Lips, P, Kramer, MH, Drent, ML
European journal of internal medicine. 2016;:88-93
Abstract
BACKGROUND Current guidelines state that the goals of growth hormone (GH) therapy in adults should be an appropriate clinical response, avoidance of side effects, and an IGF-1 value within the age-adjusted reference range. There are no published studies on the target level for IGF-1 that offer specific guidance in this regard. OBJECTIVES To compare low-normal and high-normal target levels of IGF-1 on efficacy and safety of GH treatment. METHODS A randomized, open-label, clinical trial including thirty-two adults from one university hospital receiving GH therapy for at least one year with a stable IGF-1 concentration between -1 and 1 SD score (SDS). Subjects were randomized to receive either a decrease (IGF-1 target level of -2 to -1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24weeks. The effect on cardiovascular risk factors and physical performance, next to tolerability, was compared. RESULTS Thirty subjects (65.6% men, mean age 46.6 (SD 9.9) years) could be analyzed. In subjects with a high-normal IGF-1 target level, waist circumference decreased (p=0.05), and overall they felt better (p=0.04), compared to subjects with a low-normal IGF-1 target level. However, increasing IGF-1 levels led to more myalgia, and decreasing IGF-1 levels to more fatigue. There was a gender-dependent difference in effect on HDL cholesterol. CONCLUSION Although increasing GH dose to IGF-1 levels between 1 and 2 SDS improved waist circumference and well-being, safety was not guaranteed with the demonstrated effect on HDL cholesterol in men, and reported myalgia.
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Low myocardial glucose uptake in Turner syndrome is unaffected by growth hormone: a randomized, placebo-controlled FDG-PET study.
Trolle, C, Hjerrild, B, Mortensen, KH, Knorr, S, Søndergaard, HM, Christiansen, JS, Gravholt, CH
Clinical endocrinology. 2015;(1):133-40
Abstract
BACKGROUND An unfavourable cardiovascular and metabolic phenotype causes threefold excess mortality in Turner syndrome (TS), and perturbed cardiac substrate metabolism is increasingly recognized as a common component of cardiovascular and metabolic diseases. We therefore hypothesized that myocardial glucose uptake (MGU) is reduced in TS and that growth hormone (GH) treatment improves MGU. To this end, this controlled trial elucidates MGU in TS and the impact of 6 months of growth hormone treatment on MGU. METHODS AND RESULTS Women with TS (n = 9) were examined at baseline, sequentially treated with either Norditropin(®) SimpleXx or placebo and re-examined after 6 months. MGU and myocardial blood flow (MBF) were measured using 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) during a hyperinsulinaemic euglycaemic clamp (at baseline and 6 months). Blood pressure measurement, blood sampling, echocardiography and dual energy X-ray absorptiometry scan were also performed. Age-matched female controls (n = 9) were examined once. Baseline MGU was reduced in TS (0.24 ± 0.08 vs. 0.36 ± 0.13 μmol/g/min in controls; P = 0.036) despite similar insulin sensitivity (whole body glucose uptake (M-value): 9.69 ± 1.86 vs. 9.86 ± 2.58 mg/(min*kg) in controls; P = 0.9). Six months of GH carried no impact on MGU (0.25 ± 0.08 vs. 0.26 ± 0.12 μmol/g/min in the placebo group; P = 0.8). Plasma glucose, low-density cholesterol and triglycerides increased, while M-value and exercise capacity decreased during 6 months of GH treatment. CONCLUSION MGU is reduced in TS despite normal insulin sensitivity. GH treatment does not alter MGU despite decreased whole body insulin sensitivity. A perturbed cardiac glucose uptake appears to be a feature of TS.
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Effect of Zinc Supplementation on GH, IGF1, IGFBP3, OCN, and ALP in Non-Zinc-Deficient Children.
Rocha, ÉD, de Brito, NJ, Dantas, MM, Silva, Ade A, Almeida, Md, Brandão-Neto, J
Journal of the American College of Nutrition. 2015;(4):290-9
Abstract
OBJECTIVE Because most publications on growth and development deal with children with zinc deficiency, we decided to study the effects of this micronutrient on the secretion of growth hormone (GH), insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), osteocalcin (OCN), and alkaline phosphatase (ALP) in healthy and eutrophic children. This study is original because the methodology was unique. METHODS Forty schoolchildren participated in the study, 17 females and 23 males, aged 8 and 9 years. The study was carried out during a 3-month period. It was characterized as a triple-blind randomized controlled trial. The children were divided in a control group (20 schoolchildren using 10% sorbitol) and experimental group (20 schoolchildren using zinc). All were submitted to oral zinc supplementation (10 mg Zn/day) and venous zinc administration (0.06537 mg Zn/kg of body weight). Blood samples were collected at 0, 60, 120, 180, and 210 min. All schoolchildren were also submitted to anthropometric, clinical, and dietetic assessments as well as biochemistry analyses. RESULTS Oral zinc supplementation in the experimental group (1) stimulated an increase in the consumption of protein and fat (p = 0.0007, p < 0.0001, p < 0.0001, respectively), (2) increased basal serum zinc (p < 0.0001), (3) increased plasma ALP (p = 0.0270), and (4) showed a positive correlation for IGF1, IGFBP3, and OCN, comparing before and after oral zinc supplementation (p = 0.0011, p < 0.0001, p < 0.0446, respectively). During zinc administration, plasma IGF1 and IGFBP3 increased significantly in the experimental group (p = 0.0468, p < 0.0001, respectively). Plasma GH increased in the experimental group but without statistical difference comparing before and after oral zinc supplementation. CONCLUSIONS Zinc supplementation stimulated an increase in the consumption of some macronutrients and basal serum zinc and improved plasma alkaline phosphatase levels. Zinc administration increased hormones of the GH-IGF1 system.
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A critical evaluation of bioimpedance spectroscopy analysis in estimating body composition during GH treatment: comparison with bromide dilution and dual X-ray absorptiometry.
Birzniece, V, Khaw, CH, Nelson, AE, Meinhardt, U, Ho, KK
European journal of endocrinology. 2015;(1):21-8
Abstract
OBJECTIVE To compare estimates by bioimpedance spectroscopy analysis (BIS) of extracellular water (ECW), fat mass (FM), and fat-free mass (FFM) against standard techniques of bromide dilution and dual energy X-ray absorptiometry (DXA) during intervention that causes significant changes in water compartments and body composition. METHODS Body composition analysis using BIS, bromide dilution, and DXA was performed in 71 healthy recreational athletes (43 men, 28 women; aged 18-40 years; BMI 24 ± 0.4 kg/m(2)) who participated in a double-blinded, randomized, placebo-controlled study of GH and testosterone treatment. The comparison of BIS with bromide dilution and DXA was analyzed using linear regression and the Bland-Altman method. RESULTS At baseline, there was a significant correlation between BIS and bromide dilution-derived estimates for ECW, and DXA for FM and FFM (P<0.001). ECW by BIS was 3.5 ± 8.1% lower compared with bromide dilution, while FM was 22.4 ± 26.8% lower and FFM 13.7 ± 7.5% higher compared with DXA (P<0.01). During treatment, the change in ECW was similar between BIS and bromide dilution, whereas BIS gave a significantly greater reduction in FM (19.4 ± 44.8%) and a greater increase in FFM (5.6 ± 3.0%) compared with DXA (P<0.01). Significant differences in body composition estimates between the BIS and DXA were observed only in men, particularly during the treatment that caused greatest change in water compartments and body composition. CONCLUSION In healthy adults, bioimpedance spectroscopy is an acceptable tool for measuring ECW; however, BIS overestimates FFM and substantially underestimates FM compared with DXA.