| 1. |
- Barbosa, Edna J L, 1961, et al.
(författare)
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Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.
- 2012
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 167:3, s. 353-62
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Tidskriftsartikel (refereegranskat)abstract
- bjective: GH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults. Design and methods: In 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations. Results: At baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations; CETP SNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C; APOE SNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, and CETP SNP rs1800775 with higher LDL-C; and APOE/C1/C4/C2 cluster SNP rs35136575 with lower serum TG. After treatment, APOB SNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C and PPARG SNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI. Conclusions: In GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in the APOB and PPARG genes.
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| 2. |
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| 3. |
- Elbornsson, Mariam, et al.
(författare)
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Effects of 3-year growth hormone (GH) replacement therapy on bonemineral density in younger and elderly adults with adult onset GH deficiency.
- 2011
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Little is known of the effects of long-term GH replacement on bone mineral content (BMC) and bone mineral density (BMD) in elderly GH deficient (GHD) adults.Design/Patients/Methods: In this prospective, single-centre, open-label study, the effects of 3-year GH replacement were determined in 45 GHD patients above 65 years of age and in 45 younger control GHD patients with a mean age of 39.5 (SEM 1.1) years. All patients had adult onset disease and both groups were comparable in terms of number of anterior pituitary hormonal deficiencies, gender, body mass index (BMI), and waist:hip ratio.Results: The mean maintenance dose of GH was 0.24 (0.02) mg/day in the elderly patients and 0.33 (0.02) mg/day in the younger GHD patients (p<0.01). The three years of GH replacement induced a marginal effect on total body BMC and BMD whereas femur neck and lumbar (L2-L4) spine BMC and BMD increased in both the elderly and the younger patients. The treatment response in femur neck BMC was less marked in the elderly patients (p<0.05 vs. younger group). However, this difference disappeared after correction for the lower dose of GH in the elderly patients using an analysis of covariance. There were no between-group differences in responsiveness in BMC or BMD at other skeletal locations.Conclusions: This study shows that GH replacement increases lumbar (L2-L4) spine and femur neck BMD and BMC in younger as well as elderly GHD patients. This supports that long-term GH replacement is useful also in elderly GHD patients.
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| 4. |
- Elbornsson, Mariam, et al.
(författare)
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Fifteen years of GH replacement improves body composition and cardiovascular risk factors
- 2013
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 168:5, s. 745-753
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Few studies have determined the effects of more than 5-10 years of GH replacement in adults on body composition and cardiovascular risk factors. Design/patients: In this prospective, single-center, open-label study, the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults (93 men) with adult-onset GH deficiency (GHD). Mean age was 50.5 (range 22-74) years at study start. Body composition was measured using dual-energy X-ray absorptiometry. Results: The mean initial GH dose of 0.55 (S. E. M. 0.03) mg/day was gradually lowered to 0.40 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.53 (0.10) at baseline to 0.74 (0.13) at study end (P<0.001 vs baseline). Lean soft tissue (LST) increased to 3% above the baseline level at study end (P<0.001). After a 9% decrease during the first year of treatment (P<0.001 vs baseline), body fat (BF) started to increase and had returned to the baseline level after 15 years. Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased. Fasting plasma glucose increased from 4.4 (0.1) at baseline to 4.8 (0.1) mmol/l at study end (P<0.001). However, blood HbA1c decreased from 5.0 (0.1) to 4.6 (0.1) % (P<0.001). Conclusions: Fifteen-year GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile. Fasting plasma glucose increased whereas blood HbA1c was reduced. European Journal of Endocrinology 168 745-753
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| 5. |
- Elbornsson, Mariam, et al.
(författare)
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Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency
- 2012
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 166:5, s. 787-795
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Few studies have determined the effects of more than 5-10 years of GH replacement in adults on bone mineral content (BMC) and bone mineral density (BMD). Design/patients: In this prospective, single-centre, open-label study, the effects of 15 years of GH replacement on BMC and BMD, measured using dual-energy X-ray absorptiometry, were determined in 126 hypopituitary adults (72 men) with adult-onset GH deficiency (GHD). Mean age was 49.4 (range 22-74) years at the initiation of the study. Results: The mean initial GH dose of 0.63 (S.E.M. 0.03) mg/day was gradually lowered to 0.41 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.69 (0.11) at baseline to 0.63 (0.16) at the study end (P < 0.001 vs baseline). The 15 years of GH replacement induced a sustained increase in total body BMC (+5%, P < 0.001) and BMD (+2%, P < 0.001). Lumbar (L2-L4) spine BMC increased by 9% (P < 0.001) and BMD by 5% (P < 0.001). In femur neck, a peak increase in BMC and BMD of 7 and 3%, respectively, was observed after 7 years (both P < 0.001). After 15 years, femur neck BMC was 5% above the baseline value (P < 0.01), whereas femur neck BMD had returned to the baseline level. In most variables, men had a more marked response to GH replacement than women. Conclusions: Fifteen-year GH replacement in GHD adults induced a sustained increase in total body and lumbar (L2-L4) spine BMC and BMD. In femur neck, BMC and BMD peaked at 7 years and then decreased towards baseline values.
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| 6. |
- Elbornsson, Mariam, et al.
(författare)
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Seven years of growth hormone (GH) replacement improves quality of life in hypopituitary patients with adult-onset GH deficiency.
- 2017
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Ingår i: European journal of endocrinology. - 1479-683X. ; 176:2, s. 99-109
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Tidskriftsartikel (refereegranskat)abstract
- Few studies have determined the effects of long-term growth hormone (GH) replacement on quality of life (QoL). This study investigated the effects of 7 years of GH replacement on QoL.A prospective, single-center, open-label study of 95 adults (mean age 52.8 years; 46 men) with adult-onset GH deficiency (GHD).QoL was measured using Quality of Life-Assessment for Growth Hormone Deficiency in Adults (QoL-AGHDA) and Psychological General Well-Being (PGWB) scores.The GH dose was gradually increased from 0.13 mg/day to 0.42 mg/day. IGF-I SD score increased from -1.49 at baseline to 0.35 at study end. The GH replacement induced sustained improvements in total QoL-AGHDA and PGWB scores. GHD women had a more marked improvement in total QoL-AGHDA score than GHD men after 5 and 7 years. Most of the improvement in QoL was seen during the first year, but there was a small further improvement also after one year as measured using QoL-AGHDA. All QoL-AGHDA dimensions improved, but the improvement in memory and concentration as well as tenseness occurred later than that of other dimensions. Correlation analysis demonstrated that the patients with the lowest baseline QoL had the greatest improvement in QoL.Seven years of GH replacement improved QoL with the most marked improvements in GHD women and in patients with low baseline QoL. Most, but not all, of the improvement in QoL was seen during the first year. Some QoL-AGHDA dimensions (memory and concentration, tenseness) responded at a slower rate than other dimensions.
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| 7. |
- 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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| 8. |
- Götherström, Galina, 1962, et al.
(författare)
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A prospective study of 5 years of GH replacement therapy in GH-deficient adults: sustained effects on body composition, bone mass, and metabolic indices.
- 2001
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 86:10, s. 4657-65
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Tidskriftsartikel (refereegranskat)abstract
- GH replacement therapy has proved its efficacy and safety in short-term trials and in a few long-term trials with limited number of subjects. In this 1-center study, including 118 consecutive adults (70 men and 48 women; mean age, 49.3 yr; range, 22-74 yr) with adult-onset GH deficiency, the effects of 5 yr of GH replacement on body composition, bone mass, and metabolic indices were determined. The mean initial GH dose was 0.98 mg/d. The dose was gradually lowered, and after 5 yr the mean dose was 0.48 mg/d. The mean IGF-I SD score increased from -1.73 at baseline to 1.66 at study end. A sustained increase in lean body mass and a decrease in body fat were observed. The GH treatment increased total body bone mineral content as well as lumbar (L2-L4) and femur neck bone mineral contents. BMD in lumbar spine (L2-L4) and femur neck were increased and normalized at study end. Total cholesterol and low density lipoprotein cholesterol decreased, and high density lipoprotein cholesterol increased. At 5 yr, serum concentrations of triglycerides and hemoglobin A(1c) were reduced compared with baseline values. The treatment responses in IGF-I SD score, body fat as estimated by four- and five-compartment body composition models, total body protein and nitrogen, and lumbar bone mineral content and BMD were more marked in men than in women. One patient died during the period, four patients discontinued the study due to adverse events, and one dropped out due to lack of compliance. Four patients were lost to follow-up. However, all patients were retained in the statistical analysis according to the intention to treat approach used. In conclusion, 5 yr of GH substitution in GH-deficient adults is safe and well tolerated. The effects on body composition, bone mass, and metabolic indices were sustained. The effects on body composition and low density lipoprotein cholesterol were seen after 1 yr, whereas the effects on bone mass, triglycerides, and hemoglobin A(1c) were first observed after years of treatment.
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| 9. |
- Götherström, Galina, 1962, et al.
(författare)
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Effects of 18 months of GH replacement on cardiovascular risk factors and quality of life in GH deficient adults; a randomized controlled trial using a fixed very low and a standard dose of GH
- 2022
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1096-6374. ; 67
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Little is known of the effects of a fixed very low dose of growth hormone (GH) replacement on car-diovascular risk factors, bone mass, muscle strength and quality of life (QoL) in hypopituitary patients.Design/patients/methods: This was an open-label randomized study performed at a single center. Consecutive hypopituitary patients with adult onset GH deficiency (GHD) and BMI >= 27 kg/m2 were randomized to receive a very low fixed dose of GH (LG, n = 9) or a standard dose of GH (SG, n = 9). Body composition, glucose and lipid metabolism, bone mineral content (BMC) and density (BMD), muscle strength, and QoL were measured at baseline and after 6, 12 and 18 months. Results: The fixed GH dose in LG was 0.1 mg/day. In SG, the mean baseline GH dose of 0.13 mg/day was gradually increased to 0.31 mg/day at study end. Lean body mass (LBM) as measured using DEXA as well as total body water (TBW) and extracellular water (ECW) were increased only in SG (P < 0.01, P < 0.05, and P < 0.01 vs. LG, respectively). There were no between-groups differences in BMD, BMC, insulin sensitivity, lipids, or muscle strength. Finally, although not significant compared with SG, a sustained improvement in QoL was seen in LG according to the QoL-AGHDA questionnaire. Conclusion: In this pilot study, a fixed very low GH dose improved QoL in GHD adults without any induction of fluid retention. Other effects were comparable to those produced by the standard GH dose. Replacement with a very low GH dose could therefore be a treatment option in hypopituitary patients, especially in patients who do not tolerate higher GH dosage.Trial registrationThis study is registered at ClinicalTrials.gov, EU-nr 2009-016783-37.
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| 10. |
- Götherström, Galina, 1962, et al.
(författare)
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Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement.
- 2010
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 163:2, s. 207-15
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Only few studies have investigated the effects of GH replacement on muscle strength in elderly patients with GH deficiency (GHD). OBJECTIVE, DESIGN, AND PATIENTS: In this prospective open-labeled study, the effects of 10 years of GH replacement on muscle strength and neuromuscular function were followed in 24 elderly GHD adults (mean age of 65.2 years; range 61-74 years). Muscle strength was compared with reference values obtained from the background population. RESULTS: The mean initial GH dose of 0.72 mg/day was lowered to 0.37 mg/day. The mean IGF1 SDS increased from -1.10 at baseline to 1.17 at study end. GH replacement induced a sustained increase in lean body mass and a transient increase in isometric knee flexor strength. Isometric knee extensor strength was reduced after 10 years. However, after correction for age and gender, using observed/predicted value ratios, there was sustained and even progressive increase in most variables reflecting muscle strength. Measurements of neuromuscular function showed unchanged voluntary motor unit activation after 10 years. CONCLUSIONS: Ten years of GH replacement therapy in elderly GHD adults resulted in a transient increase in isometric knee flexor strength, and provided protection from most of the normal age-related decline in muscle performance and neuromuscular function.
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