| 1. |
- Allen, D. B., et al.
(författare)
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GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults
- 2016
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:2
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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| 2. |
- Andela, C. D., et al.
(författare)
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MECHANISMS IN ENDOCRINOLOGY Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies
- 2015
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 173:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cushing's syndrome (CS) is characterized by excessive exposure to cortisol, and is associated with both metabolic and behavioral abnormalities. Symptoms improve substantially after biochemical cure, but may persist during long-term remission. The causes for persistent morbidity are probably multi-factorial, including a profound effect of cortisol excess on the brain, a major target area for glucocorticoids. Objective: To review publications evaluating brain characteristics in patients with CS using magnetic resonance imaging (MRI). Methods: Systematic review of literature published in PubMed, Embase, Web of Knowledge, and Cochrane databases. Results: Nineteen studies using MRI in patients with CS were selected, including studies in patients with active disease, patients in long-term remission, and longitudinal studies, covering a total of 339 unique patients. Patients with active disease showed smaller hippocampal volumes, enlarged ventricles, and cerebral atrophy as well as alterations in neurochemical concentrations and functional activity. After abrogation of cortisol excess, the reversibility of structural and neurochemical alterations was incomplete after long-term remission. MRI findings were related to clinical characteristics (i.e., cortisol levels, duration of exposure to hypercortisolism, current age, age at diagnosis, and triglyceride levels) and behavioral outcome (i.e., cognitive and emotional functioning, mood, and quality of life). Conclusion: Patients with active CS demonstrate brain abnormalities, which only partly recover after biochemical cure, because these still occur even after long-term remission. CS might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.
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| 3. |
- 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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| 4. |
- Boguszewski, M. C. S., et al.
(författare)
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Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement
- 2022
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 186:6
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.
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| 5. |
- Christiansen, J. S., et al.
(författare)
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Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations
- 2016
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Esposito, Daniela, et al.
(författare)
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Decreasing mortality and changes in treatment patterns in patients with acromegaly from a nationwide study
- 2018
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 178:5, s. 459-469
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Tidskriftsartikel (refereegranskat)abstract
- Context: New therapeutic strategies have developed for the management of acromegaly over recent decades. Whether this has improved mortality has not been fully elucidated. Objective: The primary aim was to investigate mortality in a nationwide unselected cohort of patients with acromegaly. Secondary analyses included time trends in mortality and treatment patterns. Design: A total of 1089 patients with acromegaly were identified in Swedish National Health Registries between 1987 and 2013. To analyse time trends, the cohort was divided into three periods (1987–1995, 1996–2004 and 2005–2013) based on the year of diagnosis. Main outcome measures: Using the Swedish population as reference, standardized mortality ratios (SMRs) were calculated with 95% confidence intervals (CIs). Results: Overall SMR was 2.79 (95% CI: 2.43–3.15) with 232 observed and 83 expected deaths. Mortality was mainly related to circulatory diseases (SMR: 2.95, 95% CI: 2.35–3.55), including ischemic heart disease (2.00, 1.35–2.66) and cerebrovascular disease (3.99, 2.42–5.55) and malignancy (1.76, 1.27–2.26). Mortality decreased over time, with an SMR of 3.45 (2.87–4.02) and 1.86 (1.04–2.67) during the first and last time period, respectively (P=.015). During the same time periods, the frequency of pituitary surgery increased from 58% to 72% (P<0.001) and the prevalence of hypopituitarism decreased from 41% to 23% (P<0.001). Conclusions: Excess mortality was found in this nationwide cohort of patients with acromegaly, mainly related to circulatory and malignant diseases. Although still high, mortality significantly declined over time. This could be explained by the more frequent use of pituitary surgery, decreased prevalence of hypopituitarism and the availability of new medical treatment options. © 2018 European Society of Endocrinology Printed in Great Britain.
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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. |
- Fuchtbauer, Laila, et al.
(författare)
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Muscle strength in patients with acromegaly at diagnosis and during long-term follow-up
- 2017
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 177:2, s. 217-226
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Patients with acromegaly have decreased body fat (BF) and increased extracellular water (ECW) and muscle mass. Although there is a lack of systematic studies on muscle function, it is believed that patients with acromegaly may suffer from proximal muscle weakness despite their increased muscle mass. We studied body composition and muscle function in untreated acromegaly and after biochemical remission. Methods: Patients with acromegaly underwent measurements of muscle strength (dynamometers) and body composition (four-compartment model) at diagnosis (n = 48), 1 year after surgery (n = 29) and after long-term follow-up (median 11 years) (n = 24). Results were compared to healthy subjects. Results: Untreated patients had increased body cell mass (113 +/- 9% of predicted) and ECW (110 +/- 20%) and decreased BF (67 +/- 7.6%). At one-year follow-up, serum concentration of IGF-I was reduced and body composition had normalized. At baseline, isometric muscle strength in knee flexors and extensors was normal and concentric strength was modestly increased whereas grip strength and endurance was reduced. After one year, muscle strength was normal in both patients with still active disease and patients in remission. At long-term follow-up, all patients were in remission. Most muscle function tests remained normal, but isometric flexion and the fatigue index were increased to 153 +/- 42% and 139 +/- 28% of predicted values, respectively. Conclusions: Patients with untreated acromegaly had increased body cell mass and normal or modestly increased proximal muscle strength, whereas their grip strength was reduced. After biochemical improvement and remission, body composition was normalized, hand grip strength was increased, whereas proximal muscle fatigue increased.
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