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Recombinant Human GH (recombinant + human_gh)
Selected AbstractsGH administration and discontinuation in healthy elderly men: effects on body composition, GH-related serum markers, resting heart rate and resting oxygen uptakeCLINICAL ENDOCRINOLOGY, Issue 1 2001Kai Henrik Wiborg Lange BACKGROUND AND OBJECTIVES GH administration results in increased lean body mass (LBM), decreased fat mass (FM) and increased energy expenditure (EE). GH therapy may therefore have potential benefits, especially in the elderly, who are known to have decreased function of the GH/IGF-I axis. Several studies have focused on effects of GH administration in the elderly in the last decade. However, very limited information is available regarding changes in body composition and EE upon GH discontinuation in the elderly. The present study therefore investigated the effects of 12 weeks of GH administration and subsequent discontinuation on body composition, resting oxygen uptake (VO2), resting heart rate (HR) and GH related serum markers in healthy elderly men. SUBJECTS AND METHODS Sixteen healthy men [age 74 ± 1 years (mean ± SEM), height 174·2 ± 1·6 cm, body weight 80·7 ± 2·6 kg, body fat 27·5 ± 1·1%] completed the study protocol. Recombinant human GH (1·80 ± 0·24 IU/day) was administered for 12 weeks in a single-blinded, placebo-controlled design. Body composition (dual energy X-ray absorptiometry), resting VO2 (indirect calorimetry), resting HR (telemetry) and serum IGF-I, IGF-II, IGFBP-3 and acid labile subunit (ALS) were measured at baseline, after 12 weeks of GH administration and, additionally in the GH group, 1, 2, 3, 4, 5 and 9 days after GH discontinuation. RESULTS Body weight was unchanged from baseline to 12 weeks in both groups. However, GH administration caused a decrease in FM (3·4 ± 1·0 kg, P < 0·012), paralleled by a similar increase in LBM (3·2 ± 0·4 kg, P < 0·0002). Resting VO2 and resting HR increased by 31 ± 3·6% and 7·3 ± 1·9 per minute, respectively, in the GH-group, where significant increases in serum IGF-I, IGFBP-3 and ALS also were noted. None of the above parameters changed in the placebo group. Within 2,3 days after GH discontinuation, the GH related serum markers and resting HR returned to baseline levels, whereas resting VO2 remained elevated even 9 days after GH discontinuation. In addition, GH discontinuation caused a significant decrease in body weight (1·86 ± 0·35 kg), derived exclusively from a decrease in LBM (1·63 ± 0·43 kg), while the decreased FM was maintained (12 weeks: 17·93 ± 1·65 kg, +9 days: 17·74 ± 1·62 kg). CONCLUSIONS The increases in serum IGF-I, IGFBP-3, ALS and resting heart rate induced by 12 weeks of GH administration in elderly men returned to baseline levels within 2,3 days after GH discontinuation. However, resting VO2 remained elevated for a longer period. GH administration reduced fat mass but maintained body weight by increasing lean body mass. In contrast, 9 days of GH discontinuation reduced body weight exclusively by reducing lean body mass. [source] Growth hormone and changes in energy balance in growth hormone deficient adultsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2008D. Deepak ABSTRACT Background, Adults with growth hormone deficiency (AGHD) have an adverse body composition with an increased prevalence of obesity. It is not known whether growth hormone replacement (GHR) results in alterations in energy intake (EI) and/or energy expenditure (EE). The aim of the study was to investigate the effects of GHR on EI and EE. Materials and methods, Nineteen hypopituitary adults (14 males, 5 females, mean age 46·2 years) with severe GHD (peak GH response to glucagon , 9 mU L,1) were studied. All patients self-injected recombinant human GH starting with 0·3 mg s.c. daily. The following were measured before and following 6 months of stable maintenance of GHR: food intake during a test meal, appetite ratings, resting EE (indirect calorimetry) and voluntary physical activity (accelerometry). Results, GHR nearly doubled voluntary physical activity (mean activity units 3319 vs. 1881, P = 0·007) and improved quality of life score (mean score 9·1 vs. 16·5, P < 0·0001). Subjects reported higher fasting hunger ratings (mean 64·8 vs. 49·6, P = 0·02) but ad libitum energy intake remained unchanged. Eating behavioural traits were favourably altered with lower disinhibition (mean 6·0 vs. 7·2, P = 0·02) and lower susceptibility to hunger ratings (4·6 vs. 6·8, P = 0·001) after GHR. Additionally, GHR did not result in significant changes in resting EE, body weight and body mass index. Conclusions, GHR in AGHD significantly improves voluntary physical activity and quality of life. Following GHR, subjects experience greater ,state' (physiological) hunger, reductions in eating disinhibition and hunger susceptibility, but no effects on calorie intake or macronutrient choice were detected. [source] GH responsiveness in a large multinational cohort of SGA children with short stature (NESTEGG) is related to the exon 3 GHR polymorphismCLINICAL ENDOCRINOLOGY, Issue 3 2007M. Tauber Summary Objective, The polymorphic deletion of exon 3 of the GH receptor (d3-GHR) has recently been linked to the magnitude of growth response to recombinant human GH (rhGH) therapy in short children with or without GH deficiency. We investigated this association in a large multinational cohort from the Network of European Studies of Genes in Growth (NESTEGG), comprising short children born small for gestational age (SGA). Design, The study included short prepubertal SGA children treated with rhGH for 1 or 2 years. Population, Two hundred and forty white Caucasian SGA children (138 male, 102 female) aged 6·6 ± 2·3 years with a height at ,3·0 ± 0·7 SDS at start of rhGH treatment; 193 ethnically matched controls. Methods, The GHR polymorphism (fl/fl, fl/d3 or d3/d3) was genotyped by polymerase chain reaction (PCR) multiplex assay. Growth velocity (G/V) in cm/year and changes in GV during the first and second year of rhGH treatment were evaluated. Results, The change in GV was significantly greater in SGA children carrying one or two copies of the d3-GHR allele (P = 0·038 for the first year and P = 0·041 for the second year of GH treatment), but the change in height was not significantly different. Birthweight was significantly lower in SGA children with the d3/d3 genotype than in SGA children with the fl/fl genotype (P = 0·034) and in those with the fl/d3 genotype (P = 0·016). Conclusion, Our data, based on a large cohort, showed that the exon 3 GHR polymorphism is associated with responsiveness to rhGH treatment in SGA children with short stature. [source] Different effects of short- and long-term recombinant hGH administration on ghrelin and adiponectin levels in GH-deficient adultsCLINICAL ENDOCRINOLOGY, Issue 1 2004Claudia Giavoli Summary objective, To evaluate circulating levels of ghrelin and adiponectin (ApN) in GH-deficient (GHD) adults before and after short- and long-term recombinant human GH (rhGH) administration. patients and methods, Twenty-three patients were studied. Seventeen subjects (Group A, 12 men, five women) were evaluated at baseline and after 1 year rhGH therapy (dose mean ± SD: 0·3 ± 0·1 mg/day) with the assessment of serum IGF-I, ghrelin, ApN, leptin, insulin and glucose levels, percentage of body fat (BF%), HOMA-IR and QUICKI. Seventeen age-, sex- and body mass index (BMI)-matched healthy subjects were recruited for comparisons. Six patients (Group B, three men, three women) underwent IGF-I generation test (rhGH 0·025 mg/kg/day for 7 days), blood sampled at baseline and on day 8 for determination of IGF-I, ghrelin and ApN levels. results, Group,A: at baseline GHD patients showed low IGF-I levels and BF% significantly higher than controls (31·4 ± 2·5 vs. 26·4 ± 1·3, P < 0·05). Glucose, insulin, leptin, tryglicerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, as well as HOMA-IR and QUICKI values were similar in the two series, while total cholesterol levels were higher in GHD. In GHD, ghrelin levels were significantly lower than in controls (193·9 ± 27·1 vs. 298·1 ± 32·5 pmol/l, respectively, P = 0·02), while ApN levels were similar (10·2 ± 1·1 and 9 ± 1 mg/l, respectively, P = ns). After 1 year of rhGH therapy, BF%, BMI, serum total and LDL cholesterol significantly decreased, serum leptin levels showed a trend to decrease, while HOMA-IR and QUICKI did not change. Ghrelin and ApN levels significantly increased from 193·9 ± 27·1 to 232·4 ± 26·3 pmol/l (P < 0·01) and from 8·6 ± 0·8 to 10·3 ± 1·1 mg/l (P < 0·05), respectively. In group B, the expected increase in IGF-I levels was associated with a significant decrease in ghrelin levels, while ApN did not change. conclusion, GHD patients showed serum ghrelin lower than controls, probably due to the higher BF%. No difference in ApN was observed. Ghrelin and ApN increments induced by long-term treatment may be related to the significant BMI and BF% reduction that is the predominant metabolic effect of rhGH therapy. Conversely, the decrease in ghrelin levels observed after short-term rhGH administration may be consistent with an inhibitory feedback of GH and/or IGF-I on ghrelin release. [source] Recombinant hGH replacement therapy and the hypothalamus,pituitary,thyroid axis in children with GH deficiency: when should we be concerned about the occurrence of central hypothyroidism?CLINICAL ENDOCRINOLOGY, Issue 6 2003Claudia Giavoli Summary objective, Recombinant hGH treatment may alter thyroid hormone metabolism and we have recently reported that 50% of patients with GH deficiency (GHD) due to organic lesions, previously not treated with thyroxine, developed hypothyroidism during treatment with recombinant human GH (rhGH). These results prompted us to evaluate the impact of rhGH treatment on thyroid function in children with GHD. design, Open study of GH treatment up to 12 months. Investigations were performed at baseline, and after 6 and 12 months of GH therapy. measurement and study subjects, Serum TSH, FT4, FT3, AbTg and AbTPO, IGF-I, height and weight, were evaluated in 20 euthyroid children (group A) with idiopathic isolated GHD and in six children (group B) with multiple pituitary hormone deficiencies (MPHD) due to organic lesions. Among the latter, four already had central hypothyroidism and were on adequate LT4 replacement therapy, while two were euthyroid at the beginning of the study. results, Serum IGF-I levels normalized in all patients. In both groups, a significant reduction in FT4 levels (P < 0·01) occurred during rhGH therapy. No patient in group A had FT4 values into the hypothyroid range, while in four of six patients in group B, fell FT4 levels into the hypothyroid range during rhGH. In particular, the two euthyroid children developed central hypothyroidism during rhGH treatment, and their height velocities did not normalize until the achievement of euthyroidism through appropriate LT4 substitution. No variation in serum FT3 and TSH levels was recorded in either groups. conclusion, Contrary to that observed in patients with MPHD, rhGH replacement therapy does not induce central hypothyroidism in children with idiopathic isolated GHD, further supporting the view that in children with MPHD, as in adults, GHD masks the presence of central hypothyroidism. Slow growth (in spite of adequate rhGH substitution and normal IGF-I levels) is an important clinical marker of central hypothyroidism, therefore a strict monitoring of thyroid function is mandatory in treated children with MPHD. [source] | ||||||||||