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The effect of exercise on intramyocellular acetylcarnitine (AcCtn) concentration in adult growth hormone deficiency (GHD).
Meienberg, F, Loher, H, Bucher, J, Jenni, S, Krüsi, M, Kreis, R, Boesch, C, Betz, MJ, Christ, E
Scientific reports. 2019;(1):19431
Abstract
To cover increasing energy demands during exercise, tricarboxylic cycle (TCA) flux in skeletal muscle is markedly increased, resulting in the increased formation of intramyocellular acetylcarnitine (AcCtn). We hypothesized that reduced substrate availability within the exercising muscle, reflected by a diminished increase of intramyocellular AcCtn concentration during exercise, might be an underlying mechanism for the impaired exercise performance observed in adult patients with growth hormone deficiency (GHD). We aimed at assessing the effect of 2 hours of moderately intense exercise on intramyocellular AcCtn concentrations, measured by proton magnetic resonance spectroscopy (1H-MRS), in seven adults with GHD compared to seven matched control subjects (CS). Compared to baseline levels AcCtn concentrations significantly increased after 2 hours of exercise, and significantly decreased over the following 24 hours (ANOVA p for effect of time = 0.0023 for all study participants; p = 0.067 for GHD only, p = 0.045 for CS only). AcCtn concentrations at baseline, as well as changes in AcCtn concentrations over time were similar between GHD patients and CS (ANOVA p for group effect = 0.45). There was no interaction between group and time (p = 0.53). Our study suggests that during moderately intense exercise the availability of energy substrate within the exercising muscle is not significantly different in GHD patients compared to CS.
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Growth Hormone Treatment Increases Plasma Irisin Concentration in Patients with Turner Syndrome.
Wikiera, B, Zawadzka, K, Łaczmański, Ł, Słoka, N, Bolanowski, M, Basiak, A, Noczyńska, A, Daroszewski, J
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2017;(2):122-128
Abstract
Irisin (Ir) deficiency may be a contributing factor in metabolic disease. This study aimed to investigate the effect of supraphysiological doses of recombinant human growth hormone (rhGH) on Ir plasma concentration in relation to metabolic disorders, including obesity and other components of metabolic syndrome. We studied 36 girls with Turner syndrome (mean age 8.2 years) treated with rhGH (0.05 mg/kg/day). Anthropometric data and fasting blood levels [e. g., Ir, insulin, glucose, glycated hemoglobin (HbA1c), IGF-1, IGFBP-3, cholesterol, insulin resistance (HOMA-IR), and β-cell function (HOMA-β)] were analyzed prior to and following rhGH therapy [mean (SD) follow-up of 1.47 (0.89) years]. Insulin sensitivity (Matsuda index) was calculated before and after the glucose load. Following rhGH therapy, an increase in IGF-1 [mean (SD) of 119.40 (62.47) ng/ml to 439.08 (209.91) ng/ml, p=0.000], Ir [2.10 (1.03) μg/ml to 2.48 (0.78) μg/ml, p=0.036], HOMA-IR [median (IQR) of 0.64 (0.45-1.30) to 0.92 (0.67-2.36), p=0.0206], and HOMA-β values [45.00 (27.69-72.00) to 81.53 (51.43-132.00), p=0.0447] were observed. Multiple regression analysis yielded no associations between Ir and metabolic and hormonal parameters before rhGH treatment; however, on rhGH, the model (R2=0.56, adjusted R2=0.45) showed positive associations between Ir and IGF-1 standard deviation score and HbA1c, and negative associations between Ir and fasting blood glucose, HDL-cholesterol, and triglycerides. Despite manifestation of insulin resistance, rhGH application had a positive effect on Ir regulation, and restored physiological conditions of lipid and glucose metabolism.
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Does Vitamin D Status Correlate with Cardiometabolic Risk Factors in Adults with Growth Hormone Deficiency?
Uzunova, I, Kirilov, G, Zacharieva, S, Zlatareva, N, Kalinov, K
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2017;(7):499-506
Abstract
Apart from being individually associated with cardiometabolic health, 25(OH)D and IGF-1 interplay with a positive correlation between them, which raises questions about the role of vitamin D for the adverse cardiovascular (CV) risk profile in hyposomatotropism. Thus, we aimed to investigate vitamin D status in GH deficiency (GHD) and the association between 25(OH)D and metabolic syndrome (MetS), its components, and other surrogate markers of CV risk. A total of 129 GHD adults (childhood-onset GHD, 41.9%) underwent blood testing (glucose, insulin, lipid profile, uric acid); blood pressure, anthropometric and bioelectrical-impedance measurements. Other CV risk markers were examined in a subsample of the initial population - hsCRP, adiponectin, and asymmetric dimethylarginine (n=88); carotid intima-media thickness (n=44). Total serum 25(OH)D, measured by electro-chemiluminescence binding assay, was used for vitamin D status assessment (adequate,≥30 ng/ml; insufficient, 20-29.9 ng/ml; deficient,<20 ng/ml). Data demonstrated high prevalence of hypovitaminosis D in GHD (deficiency 79.1%; insufficiency 14.7%), with lower 25(OH)D among adult-onset GHD subjects (14.0±7.2 vs. 16.8±8.0 ng/ml, p=0.039) and patients with MetS (11.8±4.5 vs. 16.3±8.1 ng/ml, p<0.0001). 25(OH)D correlated negatively and weakly with BMI, waist circumference, percent body fat, visceral fat area, and systolic BP. Regardless of whether vitamin D is a cause or a consequence of these metabolic abnormalities, 25(OH)D testing in hyposomatotropism is advisable. Normalization of vitamin D status is not proven to improve CV outcomes in general population, but it might have favorable effects in GHD, as its benefits might be restricted to patients with both low 25(OH)D and certain risk factors.
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FNDC5 relates to skeletal muscle IGF-I and mitochondrial function and gene expression in obese men with reduced growth hormone.
Srinivasa, S, Suresh, C, Mottla, J, Hamarneh, SR, Irazoqui, JE, Frontera, W, Torriani, M, Stanley, T, Makimura, H
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2016;:36-41
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Abstract
OBJECTIVE To investigate the relationship of skeletal muscle FNDC5 mRNA expression and circulating irisin to the GH/IGF-I axis and to skeletal muscle mitochondrial function and mitochondria-related gene expression in obese men. DESIGN Fifteen abdominally obese men with reduced growth hormone received 12weeks of recombinant human GH (rhGH). Before and after treatment, they underwent (31)P-magnetic resonance spectroscopy to evaluate phosphocreatine (PCr) recovery as a measure of mitochondrial function and skeletal muscle biopsy to assess expression of mitochondrial-related genes. Serum irisin and IGF-I and skeletal muscle FNDC5 and IGF-I mRNA were measured. RESULTS At baseline, skeletal muscle FNDC5 mRNA was significantly and positively associated with IGF-I mRNA (ρ=0.81, P=0.005) and rate of PCr recovery (ρ=0.79, P=0.006). Similar relationships of circulating irisin to IGF-I mRNA (ρ=0.63, P=0.05) and rate of PCr recovery (ρ=0.48, P=0.08) were demonstrated, but were not as robust as those with muscle FNDC5 expression. Both serum irisin and skeletal muscle FNDC5 mRNA were significantly associated with PPARγ (ρ=0.73, P=0.02 and ρ=0.85, P=0.002), respectively. In addition, FNDC5 mRNA was correlated with skeletal muscle PGC-1α (ρ=0.68, P=0.03), NRF1 (ρ=0.66, P=0.04) and TFAM (ρ=0.79, P=0.007) mRNA. Neither serum irisin nor muscle mRNA expression of FNDC5 changed with rhGH treatment. CONCLUSION These novel data in skeletal muscle demonstrate that local expression of FNDC5 is associated with mRNA expression of IGF-I and mitochondrial function and mitochondria-related gene expression in obese subjects with reduced growth hormone and suggest a potential role for FNDC5 acting locally in muscle in a low GH state. Further studies are needed to clarify the relationship between the GH/IGF-I axis and irisin.
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Adding Glucagon-Stimulated GH Testing to the Diagnostic Fast Increases the Detection of GH-Sufficient Children.
Hawkes, CP, Grimberg, A, Dzata, VE, De Leon, DD
Hormone research in paediatrics. 2016;(4):265-72
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Abstract
BACKGROUND/AIMS: The evaluation of children with unexplained hypoglycemia may include a diagnostic fast. However, low growth hormone (GH) concentration during hypoglycemia is not specific to GH deficiency (GHD). The aim of this study was to determine if serial GH measurement following glucagon administration, in the setting of a diagnostic fast, would increase the number of children identified as not having GHD. METHODS We conducted a retrospective chart review of children who had serial GH measurements performed after glucagon administration at the end of a diagnostic fast. Glucagon was administered at the end of the fasting study, and GH was measured every 30 min for 210 min. RESULTS Of the 29 children in this series, only 3 (10%) had GH concentrations >7 ng/ml at the end of the fast, which increased by 16 (55%) after serial GH testing. The percentages of samples with GH concentrations >7 ng/ml were: 10% at baseline, and 25, 39, 41, 41, 33, 43, and 0% every 30 min thereafter. CONCLUSION Additional GH measurements after glucagon administration following a diagnostic fast can improve the identification of children without GHD and thereby save them unnecessary GH stimulation testing and potential GH treatment.
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Effect of oral glucose administration on rebound growth hormone release in normal and obese women: the role of adiposity, insulin sensitivity and ghrelin.
Pena-Bello, L, Pertega-Diaz, S, Outeiriño-Blanco, E, Garcia-Buela, J, Tovar, S, Sangiao-Alvarellos, S, Dieguez, C, Cordido, F
PloS one. 2015;(3):e0121087
Abstract
CONTEXT Metabolic substrates and nutritional status play a major role in growth hormone (GH) secretion. Uncovering the mechanisms involved in GH secretion following oral glucose (OG) administration in normal and obese patients is a pending issue. OBJECTIVE The aim of this study was to investigate GH after OG in relation with adiposity, insulin secretion and action, and ghrelin secretion in obese and healthy women, to further elucidate the mechanism of GH secretion after OG and the altered GH secretion in obesity. PARTICIPANTS AND METHODS We included 64 healthy and obese women. After an overnight fast, 75 g of OG were administered; GH, glucose, insulin and ghrelin were obtained during 300 minutes. Insulin secretion and action indices and the area under the curve (AUC) were calculated for GH, glucose, insulin and ghrelin. Univariate and multivariate linear regression analyses were employed. RESULTS The AUC of GH (μg/L•min) was lower in obese (249.8±41.8) than in healthy women (490.4±74.6), P=0.001. The AUC of total ghrelin (pg/mL•min) was lower in obese (240995.5±11094.2) than in healthy women (340797.5±37757.5), P=0.042. There were significant correlations between GH secretion and the different adiposity, insulin secretion and action, and ghrelin secretion indices. After multivariate analysis only ghrelin AUC remained a significant predictor for fasting and peak GH.
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Individual risk factors of the metabolic syndrome in adult patients with growth hormone deficiency--a cross-sectional case-control study.
Uzunova, I, Kirilov, G, Zacharieva, S, Shinkov, A, Borissova, AM, Kalinov, K
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2015;(1):39-43
Abstract
OBJECTIVE Growth hormone deficiency in adults (GHDA) is considered to be associated with increased cardiovascular risk, most commonly reflected by the prevalence of the metabolic syndrome (MS). However, there are still a limited number of studies comparing directly the MS prevalence in GHD patients to that in general population. The aim of this study was to investigate the individual risk factors of the MS in a cohort of GHD patients and to compare its prevalence with an age- and sex-matched control group. DESIGN A cross-sectional case-control study. METHODS In total, 54 adult patients with GHD (childhood onset GHD (COGHD): n=19, adult onset GHD (AOGHD): n=35) and 2 153 control subjects were studied. GHD was diagnosed according to the Endocrine Society Clinical Practice Guideline recommendations from 2011 and MS was scored by the NCEP-ATP III definition. RESULTS The main metabolic abnormalities in GHD group were increased waist circumference (50.0%), low HDL-cholesterol (42.6%) and hypertriglyceridemia (40.7%) and their prevalence was significantly higher (p=0.013, p=0.019 and p=0.010, respectively) than in control group, where increased blood pressure prevailed (64.2%, p<0.0001). However, the difference in the MS prevalence between the 2 groups (29.6% vs. 24.9% in controls) failed to reach statistical significance (p=0.429). Patients with MS from both groups did not differ significantly in their metabolic profile (except for increased blood pressure), mean age and gender distribution. CONCLUSIONS Although GHDA was associated with the development of visceral obesity and dyslipidemia, these adverse cardiovascular risk factors did not determine a higher prevalence of the MS in Bulgarian GHD patients compared to control subjects. Furthermore, the individual risk factors of the MS did not significantly differ between patients with MS from both groups.
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Homoarginine (hArg) and asymmetric dimethylarginine (ADMA) in short stature children without and with growth hormone deficiency: hArg and ADMA are involved differently in growth in the childhood.
Langen, J, Kayacelebi, AA, Beckmann, B, Weigt-Usinger, K, Carmann, C, Hörster, I, Lilienthal, E, Richter-Unruh, A, Tsikas, D, Lücke, T
Amino acids. 2015;(9):1875-83
Abstract
Adult subjects with growth hormone (GH) deficiency (GHD) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events. In adults, these events are associated with elevated circulating concentrations of asymmetric dimethylarginine (ADMA) which is an endogenous inhibitor of L-arginine (Arg)-derived nitric oxide (NO). Low circulating concentrations of homoarginine (hArg) emerged as a cardiovascular risk factor. In adults, hArg seems to antagonize ADMA. In the present work, we tested the hypothesis that children with short stature without or with GHD have altered Arg/NO pathway as compared to children with normal growth. We studied 66 short stature children (38 boys, 28 girls) aged 3.5-17.3 years, who underwent the routine L-Arginine Test to diagnose presence of GHD. GHD was confirmed in 47 children (GHD group; 30 boys, 17 girls) and was absent in the remaining 19 children (non-GHD group; 8 boys, 11 girls). In addition, we investigated 24 healthy age- and gender-matched children (10 boys, 14 girls) with normal growth. In EDTA plasma samples of all children, we determined by mass spectrometry-based methods the concentrations of Arg, hArg and ADMA, and calculated the Arg/ADMA and hArg/ADMA molar ratios. With respect to these biochemical parameters, we did not find statistically significant differences between the GHD and non-GHD groups. Comparing short with normal stature children, we found small differences regarding plasma hArg concentrations [mean ± SD; median (25th-75th percentile)]: 2.06 ± 0.52 µM; 2.12 (1.74-2.36) µM vs. 1.7 ± 0.5 µM; 1.6 (1.4-1.8) µM, P < 0.001. Compared to normal stature children, short stature children had considerably higher plasma concentrations of ADMA [0.77 ± 0.15 µM; 0.77 (0.66-0.85) µM vs. 0.57 ± 0.09 µM; 0.58 (0.50-0.63) µM, P < 0.001], but not of Arg [83.3 ± 19.2 µM; 82.2 (71.9-90.3) µM vs. 86.5 ± 17.8 µM; 84.8 (77.2-94.8) µM, P = 0.336], or the hArg/ADMA ratio [2.74 ± 0.76; 2.7 (2.2-3.1) vs. 3.1 ± 1.2; 2.85 (2.42-3.66), P = 0.161. hArg in the GHD group (r = 0.41, P = 0.004) and the hArg/ADMA ratio in both groups (r = 0.44, P = 0.002 in GHD; r = 0.55, P = 0.01 in non-GHD)], but not ADMA were positively correlated with insulin-like growth factor-1 (IGF-1). hArg and hArg/ADMA differed between girls and boys in the GHD and non-GHD groups but in the normal growth group. The hArg/ADMA ratio increased with age in all groups. Our study suggests that hArg and ADMA are involved in growth in the childhood, presumably in an antagonistic manner, with ADMA slowing and hArg accelerating growth.
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Relationship between GH/IGF-1 axis, graft recovery, and early survival in patients undergoing liver transplantation.
Salso, A, Tisone, G, Tariciotti, L, Lenci, I, Manzia, TM, Baiocchi, L
BioMed research international. 2014;:240873
Abstract
BACKGROUND High levels of IGF-1 have been reported in patients with initial poor function of the graft after liver transplantation (LT). Correlation with other clinical variables or early survival has not been extensively investigated. AIM: To evaluate the GH/IGF-1 profile as a function of liver recovery and patients' early survival after LT. METHODS 30 transplanted patients (23 survivors and 7 nonsurvivors), were retrospectively enrolled in the study. GH and IGF-1 serum levels were assessed at baseline, graft reperfusion, and 1, 7, 15, 30 , 90, and 360 days after LT. Individual biochemical variables were also recorded. RESULTS After grafting, IGF-1 in blood linearly correlated with cholesterol (r = 0.6, P = 0.001). IGF-1 levels from day 15 after surgery were statistically higher in survivors as compared to nonsurvivors. ROC curves analysis identified an IGF-1 cut-off >90 μg/L, from day 15 after surgery, as a good predictor of survival (sensitivity 86%, specificity 95%, and P < 0.001). CONCLUSIONS After LT, GH levels correlate with the extent of cytolysis, while IGF-1 is an indicator of liver synthetic function recovery. IGF-1 levels >90 μg/L (day 15-30) seem to be an indicator of short-term survival.
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Quality of life in children and adolescents with growth hormone deficiency: association with growth hormone treatment.
Geisler, A, Lass, N, Reinsch, N, Uysal, Y, Singer, V, Ravens-Sieberer, U, Reinehr, T
Hormone research in paediatrics. 2012;(2):94-9
Abstract
BACKGROUND Quality of life (QoL) as it is related with growth hormone deficiency (GHD) is a matter of controversy. METHODS We analyzed QoL in 95 children aged 8-18 years with isolated GHD (72% male) treated with growth hormone (GH). These children were compared to 190 age- and gender-matched healthy children with similar height [height <10th percentile; control group 1 (CG1)] and age- and gender-matched 285 healthy children of normal stature (control group 2: CG2). QoL was measured by the KINDL® questionnaire referring to six domains (physical well-being, emotional well-being, self-esteem, family, friends, and school). RESULTS QoL was significantly reduced in CG1 (effect-size 0.21) compared to CG2, while QoL was not significantly altered in children with GHD. In multiple linear regression analyses adjusted to age, gender, BMI, migration background, and socioeconomic status, decreasing height-SDS was associated with poorer QoL (especially emotional well-being), and treatment with GH was related significantly to better self-esteem. Increase of height-SDS in children treated with GH was associated positively with QoL and all its subscales except family and school. CONCLUSIONS These findings suggest psychological consequences of short stature in children and an improvement of QoL in children treated with GH with the focus on self-esteem and emotional well-being.