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- Barbosa, Edna J L, 1961, et al.
(författare)
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Influence of the Exon 3-deleted/full-length Growth Hormone Receptor Polymorphism on the Response to Growth Hormone Replacement Therapy in Adults with Severe Growth Hormone Deficiency. : d3-GHR isoform in GHD adults
- 2009
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:2, s. 639-644
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Tidskriftsartikel (refereegranskat)abstract
- Context: There is considerable individual variation in the clinical response to growth hormone (GH) replacement therapy in GH deficient (GHD) adults. Useful predictors of treatment response are lacking. Objective: To assess the influence of the exon 3-deleted (d3-GHR) and full-length (fl-GHR) GH receptor isoforms on the response to GH replacement therapy in adults with severe GHD. Design, Patients: 124 adult GHD patients (79 men, median age 50 years) were studied before and after 12 months of GH therapy. GHD patients were divided into those bearing fl/fl alleles (Group 1) and those bearing at least one d3-GHR allele (Group 2), and the genotype was related to the effects of GH therapy on IGF-I levels and total body fat (BF). Intervention: GH dose was individually titrated to obtain normal serum IGF-I levels. Main Outcome Measures: GHR genotype was determined by PCR amplification, IGF-I levels by immunoassay, and BF by a four-compartment model. Results: Seventy-two (58%) patients had fl/fl genotype and were classified as Group 1, while 52 (42%) had at least one d3-GHR allele and were classified as Group 2 (40 were heterozygous and 12 were homozygous). At baseline, there were no significant differences in the study groups. Changes in IGF-I and BF after 12 months of GH treatment did not differ significantly between the two genotype groups. Conclusion: The presence of d3-GHR allele did not influence the response to GH replacement therapy in our cohort of adults with severe GHD.
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| 3. |
- Ehrnborg, Christer, 1968, et al.
(författare)
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Increased serum concentration of IGFBP-4 and IGFBP-5 in healthy adults during one month's treatment with supraphysiological doses of growth hormone.
- 2007
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374. ; 17:3, s. 234-41
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the effects on insulin-like growth factor binding proteins (IGFBP)-4 and -5 after one month's treatment with supraphysiological doses of growth hormone (GH) in healthy, active young adults with a normal GH-IGF-I axis. Furthermore, the possible use of IGFBP-4 and IGFBP-5 as markers of GH doping is discussed. DESIGN: Thirty healthy, physically active volunteers (15 men and 15 women), mean age 25.9 years (range 18-35), participated in this randomized, double-blind, placebo-controlled, parallel study with three groups (n=10; 5 men and 5 women in each group). The groups comprised the following: placebo, GH 0.1IU/kg/day [0.033mg/kg/day] and GH 0.2IU/kg/day [0.067mg/kg/day]. RESULTS: Baseline levels of IGFBP-4 were higher (+20%), while IGFBP-5 levels were lower (-37%) in women than in men. IGFBP-5 levels were positively correlated to age, but no significant correlation was found for IGFBP-4. In the pooled group with active GH treatment (n=20), both IGFBP-4 and IGFBP-5 levels were increased vs. the placebo group from day 14 until end of treatment [day 28, IGFBP-4 (+40%, p<0.01) and IGFBP-5 (+61%, p <0.001)]. After inclusion of serum IGF-I as a covariate in the linear regression analysis, the associations between GH treatment and the IGFBP-4 and IGFBP-5 levels were not significant. CONCLUSIONS: This study shows that the levels of IGFBP-4 and IGFBP-5 are affected by supraphysiological GH treatment given to young, healthy, physically active adults of both genders. The present study, including relatively few subjects, does not support that IGFBP-4 and IGFBP-5 can be used as IGF-I independent markers in a forthcoming method for detecting GH doping, although, further studies are needed to investigate the potential use of IGFBP-4 and IGFBP-5 as markers of GH doping.
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| 5. |
- Franco Ramos, Celina, 1956, et al.
(författare)
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Baseline characteristics and effects of growth hormone therapy over two years in younger and elderly adults with adult onset GH deficiency.
- 2006
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:11, s. 4408-14
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effects of GH replacement in elderly GH-deficient (GHD) adults are not well known. OBJECTIVE/DESIGN/PATIENTS: In this prospective, single-center, open-label study, baseline characteristics and the effects of 2-yr GH replacement were determined in 24 GHD adults above 65 yr of age and in 24 younger GHD patients (mean age, 37 yr; range, 27-46 yr). All patients had adult onset disease, and both groups were comparable in terms of the number of pituitary hormonal deficiencies, gender, body mass index, and waist/hip ratio. Duration of hypopituitarism was, however, longer in the elderly patients. RESULTS: The mean maintenance dose of GH was 0.31 (sem, 0.03) mg/d in the elderly GHD patients and 0.44 (0.04) mg/d in the younger patients. The less marked response in IGF-I sd score, total body fat, and extracellular water in the elderly patients lost significance when the dose of GH was accounted for in the statistical analyses. Despite the lower dose in the elderly GHD group, these patients had a more marked reduction in waist/hip ratio and serum low-density lipoprotein-cholesterol level, and these differences remained also after correction for duration of hypopituitarism. There was no difference at baseline or in responsiveness in lean mass, bone mineral density, and glucose homeostasis. CONCLUSIONS: This study identifies elderly GHD adults as a GH-sensitive group in whom a low dose of GH can improve body composition and serum lipid profile without any significant impairment of glucose metabolism. GH replacement should therefore be considered in elderly GHD adults.
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| 6. |
- Franco Ramos, Celina, 1956, et al.
(författare)
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Growth hormone reduces inflammation in postmenopausal women with abdominal obesity: a 12-month, randomized, placebo-controlled trial.
- 2007
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:7, s. 2644-7
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Abdominal obesity is associated with low GH secretion, elevated circulating markers of inflammation, and increased risk of cardiovascular disease. OBJECTIVE: The objective was to study the effect of GH treatment on inflammatory markers and vascular adhesion molecules in postmenopausal women with abdominal obesity. DESIGN: Forty women aged 51-63 yr received GH (0.67 mg/d) in a randomized, double-blind, placebo-controlled, 12-month trial. Measurements of inflammatory markers [highly sensitive C-reactive protein (CRP), IL-6, and amyloid polypeptideA] and markers of endothelial dysfunction (soluble E-selectin, vascular adhesion molecule-1, intercellular molecule-1, and matrix metalloproteinase-9) were performed at baseline and after 6 and 12 months of treatment. RESULTS: After 12 months, the mean IGF sd score was 0.9 +/- 1.5 and -0.8 +/- 0.6 in the GH and placebo groups, respectively. GH treatment reduced CRP and IL-6 levels compared with placebo (P = 0.03 and P = 0.05, respectively), whereas the markers of endothelial dysfunction were unaffected. Within the GH-treated group, a reduction was shown in CRP (4.3 +/- 4 to 3.0 +/- 3 mg/liter; P < 0.05) and in IL-6 (4.4 +/- 2 to 3.3 +/- 2 ng/liter; P < 0.01). In the GH-treated group, the decrease in CRP and IL-6 correlated with a reduction in visceral adipose tissue (r = 0.7, P < 0.001 and r = 0.5, P < 0.05, respectively). CONCLUSION: GH treatment in postmenopausal women with abdominal obesity reduced serum markers of systemic inflammation. Circulating markers of endothelial dysfunction were unaffected by treatment.
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| 7. |
- Franco Ramos, Celina, 1956, et al.
(författare)
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Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebo-controlled trial.
- 2005
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 90:3, s. 1466-74
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal obesity is associated with blunted GH secretion and a cluster of cardiovascular risk factors that characterize the metabolic syndrome. GH treatment in abdominally obese men reduces visceral adipose tissue and has beneficial effects on the metabolic profile. There are no long-term data on the effects of GH treatment on postmenopausal women with abdominal obesity. Forty postmenopausal women with abdominal obesity participated in a randomized, double-blind, placebo-controlled, 12-month trial with GH (0.67 mg/d). The primary aim was to study the effect of GH treatment on insulin sensitivity. Measurements of glucose disposal rate (GDR) using a euglycemic, hyperinsulinemic glucose clamp; abdominal fat, hepatic fat content, and thigh muscle area using computed tomography; and total body fat and fat-free mass derived from (40)K measurements were performed at baseline and at 6 and 12 months. GH treatment reduced visceral fat mass, increased thigh muscle area, and reduced total and low-density lipoprotein cholesterol compared with placebo. Insulin sensitivity was increased at 12 months compared with baseline values in the GH-treated group. In the GH-treated group only, a low baseline GDR was correlated with a more marked improvement in insulin sensitivity (r = -0.68; P < 0.001). A positive correlation was found between changes in GDR and liver attenuation as a measure of hepatic fat content between baseline and 12 months (r = 0.7; P < 0.001) in the GH-treated group. In postmenopausal women with abdominal obesity, 1 yr of GH treatment improved insulin sensitivity and reduced abdominal visceral fat and total and low-density lipoprotein cholesterol concentrations. The improvement in insulin sensitivity was associated with reduced hepatic fat content.
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| 8. |
- Franco Ramos, Celina, 1956, et al.
(författare)
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The GH/IGF-1 Axis in Obesity: Physiological and Pathological Aspects.
- 2006
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Ingår i: Metabolic syndrome and related disorders. - : Mary Ann Liebert Inc. - 1557-8518 .- 1540-4196. ; 4:1, s. 51-6
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Tidskriftsartikel (refereegranskat)abstract
- The cluster of cardiovascular risk factors-abdominal obesity, dyslipidaemia, insulin resistance and hypertension-has been recognized as the core of the metabolic syndrome. Adults with severe growth hormone (GH) deficiency have, to a large extent, features of the metabolic syndrome, and there is a strong inverse association between visceral fat accumulation and blunted GH secretion in adults. Hyposomatotropism in abdominal obesity has therefore been suggested to be of importance for its metabolic consequences. However, the underlying pathophysiological mechanisms are poorly understood. Prevalence of the metabolic syndrome is steadily increasing worldwide. Overnutrition and sedentary habits are the stigmata of modern society that predispose genetically susceptible individuals to develop central obesity and other features of the metabolic syndrome including glucose intolerance, hypertension and dyslipidemia. Although there are still no unified definitions of the syndrome, it is clear that this condition is associated with an increased risk for development of cardiovascular disease (CVD) and diabetes mellitus (DM). In this review, we discuss current evidence regarding alterations in the GH-IGF- 1 axis in abdominal obesity and its possible impact on other features of the metabolic syndrome.
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| 9. |
- Franco Ramos, Celina, 1956, et al.
(författare)
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Thigh intermuscular fat is inversely associated with spontaneous GH release in post-menopausal women with abdominal obesity.
- 2006
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - : Oxford University Press (OUP). - 0804-4643. ; 155:2, s. 261-8
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The metabolic syndrome is characterized by an increased accumulation of visceral adipose tissue (VAT) and blunted GH secretion. There are, however, no data on the association between GH secretion and other fat depots (in liver and muscle). OBJECTIVE/DESIGN: The aim of this cross-sectional study, which included 20 post-menopausal women with abdominal obesity, was to determine the association between GH secretion and regional adipose tissue (AT) distribution. Twelve-hour GH profiles (2000-0800 h) were performed by blood sampling every 20 min. GH was analyzed using an ultra-sensitive assay followed by approximate entropy (ApEn) and deconvolution analysis. RESULTS: In simple regression analyses, both basal and pulsatile GH secretions correlated negatively with VAT and thigh intermuscular adipose tissue (IMAT), but not with hepatic fat content. There was no correlation between ApEn and the AT depots studied. In multiple regression analysis, pulsatile GH secretion correlated inversely with thigh IMAT (B-coefficient=-0.67; P<0.01), whereas the correlation with VAT became non-significant. Furthermore, in multiple regression analysis, basal GH secretion correlated negatively with VAT (B-coefficient=-0.77; P=0.001), but not significantly with thigh IMAT. CONCLUSION: In post-menopausal women with abdominal obesity, pulsatile GH secretion demonstrated an independent, negative association with thigh IMAT, whereas basal GH secretion showed an independent, negative association with VAT. These findings suggest that the neuroendocrine association between fat mass and somatotropic axis is depot-dependent. We have identified thigh IMAT to be important in this interplay.
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| 10. |
- Götherström, Galina, 1962, et al.
(författare)
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A 10-year, prospective study of the metabolic effects of growth hormone replacement in adults.
- 2007
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:4, s. 1442-5
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Only a few studies have investigated the effects of GH replacement in adults for more than 5 yr. OBJECTIVE/DESIGN/PATIENTS: In a prospective, open-label, single-center study, the effects of 10-yr GH replacement were determined. Eighty-seven consecutive patients (52 men and 35 women), with a mean age of 44.1 (range 22-74) yr with adult-onset GH deficiency (GHD) were included. RESULTS: The initial mean dose of GH (0.98 mg/d) was reduced during the study and at yr 10 was 0.47 mg/d. The mean IGF-I sd score increased from -1.81 at baseline to 1.29 at study end. The absolute reduction in total body fat was transient. However, after correction for age and sex using a four-compartment model, the reduction in body fat was sustained during the 10-yr study period. There was a sustained improvement in serum lipid profile and after 10 yr, and blood glycosylated hemoglobin level was reduced. The treatment responses in IGF-I sd score, serum high-density lipoprotein cholesterol level, and body composition as measured using dual-energy x-ray absorptiometry were more marked in men, whereas women had a more marked reduction in blood glycosylated hemoglobin level. CONCLUSION: The effect on the absolute amount of body fat was seen early and was transient, which could be due to the normal aging of the patients. The effects on metabolic indices were detected later, but they were sustained and even progressive throughout the study period.
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