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Sökning: WFRF:(van der Lely A. J.)

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1.
  • Müller, T D, et al. (författare)
  • Ghrelin.
  • 2015
  • Ingår i: Molecular metabolism. - 2212-8778. ; 4:6, s. 437-60
  • Tidskriftsartikel (refereegranskat)abstract
    • The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.
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2.
  • Trainer, P J, et al. (författare)
  • Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
  • 2000
  • Ingår i: The New England journal of medicine. - 0028-4793. ; 342:16, s. 1171-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
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3.
  • van der Lely, A J, et al. (författare)
  • Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.
  • 2001
  • Ingår i: Lancet (London, England). - 0140-6736. ; 358:9295, s. 1754-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days.Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis.Mean serum IGF-1 concentrations fell by at least 50%: 467 mg/L (SE 24), 526 mg/L (29), and 523 mg/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 mg/L (2.1), 12.5 mg/L (3.0), and 14.2 mg/L (5.7) (p<0.001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8.0 mg/L (2.5) at baseline, rose to 15.2 mg/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mg/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p<0.05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353).Pegvisomant is an effective medical treatment for acromegaly.
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4.
  • Bengtsson, D., et al. (författare)
  • Long-Term Outcome and MGMT as a Predictive Marker in 24 Patients With Atypical Pituitary Adenomas and Pituitary Carcinomas Given Treatment With Temozolomide
  • 2015
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 100:4, s. 1689-1698
  • Tidskriftsartikel (refereegranskat)abstract
    • Context/Objective: Locally aggressive pituitary tumors (LAPT) and pituitary carcinomas respond poorly to conventional therapy and cytotoxic drugs. Temozolomide (TMZ) is an oral alkylating drug with good tolerability, approved for treatment of malignant gliomas. The experience of its use in pituitary tumors is limited. Design and Setting: We report on 24 patients with aggressive pituitary tumors (16 LAPTs, 8 carcinomas) treated with TMZ for a median of 6 months (range 1-23). Follow-up ranged from 4 to 91 months with a median of 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4, GH 4, GH/PRL 2). Ki-67 was 2-50% in LAPTs, and 5-80% in carcinomas. Main Outcome: Response to TMZ and the association with tumor expression of O6-methylguanine DNA methyltransferase (MGMT), MLH1, MSH2, and MSH6, examined by immunohistochemistry. Results: Complete tumor regression occurred in two carcinomas and persisted at follow-up after 48 and 91 months, respectively. Partial regress of tumor mass ranging from 35% to 80% occurred in 5 LAPTs and 2 carcinomas. Another patient with LAPT had a 71% decrease in prolactin levels without change in tumor volume. Three LAPTs could not be evaluated. Median MGMT staining was 9% (5-20%) in responders vs 93% (50-100%) in nonresponders. Loss of MSH2 and MSH 6 was observed in a single patient who had a rapid development of resistance to TMZ. Conclusions: This study shows that TMZ is a valuable treatment option for patients with uncontrolled pituitary tumors. The data suggest that tumoral MGMT staining below 50% is associated with a high likelihood of treatment response.
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5.
  • Wijnen, M, et al. (författare)
  • Efficacy and safety of bariatric surgery for craniopharyngioma-related hypothalamic obesity: a matched case-control study with 2 years of follow-up.
  • 2017
  • Ingår i: International journal of obesity (2005). - 1476-5497. ; 41
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypothalamic obesity is a devastating consequence of craniopharyngioma. Bariatric surgery could be a promising therapeutic option. However, its efficacy and safety in patients with craniopharyngioma-related hypothalamic obesity remain largely unknown.We investigated the efficacy of bariatric surgery for inducing weight loss in patients with craniopharyngioma-related hypothalamic obesity. In addition, we studied the safety of bariatric surgery regarding its effects on hormone replacement therapy for pituitary insufficiency.In this retrospective matched case-control study, we compared weight loss after bariatric surgery (that is, Roux-en-Y gastric bypass and sleeve gastrectomy) between eight patients with craniopharyngioma-related hypothalamic obesity and 75 controls with 'common' obesity during 2 years of follow-up. We validated our results at 1 year of follow-up in a meta-analysis. In addition, we studied alterations in hormone replacement therapy after bariatric surgery in patients with craniopharyngioma.Mean weight loss after bariatric surgery was 19% vs 25% (difference -6%, 95% confidence of interval (CI) -14.1 to 4.6; P=0.091) at 2 years of follow-up in patients with craniopharyngioma-related hypothalamic obesity compared with control subjects with 'common' obesity. Mean weight loss was 25% vs 29% (difference -4%, 95% CI -11.6 to 8.1; P=0.419) after Roux-en-Y gastric bypass and 10% vs 20% (difference -10%, 95% CI -14.1 to -6.2; P=0.003) after sleeve gastrectomy at 2 years of follow-up in patients with craniopharyngioma-related hypothalamic obesity vs control subjects with 'common' obesity. Our meta-analysis demonstrated significant weight loss 1 year after Roux-en-Y gastric bypass, but not after sleeve gastrectomy. Seven patients with craniopharyngioma suffered from pituitary insufficiency; three of them required minor adjustments in hormone replacement therapy after bariatric surgery.Weight loss after Roux-en-Y gastric bypass, but not sleeve gastrectomy, was comparable between patients with craniopharyngioma-related hypothalamic obesity and control subjects with 'common' obesity at 2 years of follow-up. Bariatric surgery seems safe regarding its effects on hormone replacement therapy.International Journal of Obesity advance online publication, 22 November 2016; doi:10.1038/ijo.2016.195.
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6.
  • van Santen, Selveta Sanne, et al. (författare)
  • Diagnosing Metabolic Syndrome in Craniopharyngioma Patients: Body Composition versus BMI.
  • 2019
  • Ingår i: European journal of endocrinology. - 1479-683X. ; 181:2, s. 173-183
  • Tidskriftsartikel (refereegranskat)abstract
    • Craniopharyngioma patients often have poor metabolic profiles due to hypothalamic-pituitary damage. Previously, using body mass index (BMI) as obesity marker, the occurrence of the metabolic syndrome in these patients was estimated at 46%. Our aim was to determine if Dual X-ray Absorptiometry (DXA-) scan in evaluation of obesity and metabolic syndrome would be superior.Retrospective study of craniopharyngioma patients for whom DXA-scan results were available.BMI, fat percentage and fat mass index were used to evaluate obesity and as components for obesity in metabolic syndrome.Ninety-five craniopharyngioma patients were included (51% female, 49% childhood-onset disease). Metabolic syndrome occurred in 34-53 (45-51%) subjects (depending on the definition of obesity, although all definitions occurred in higher frequency than in the general population). Metabolic syndrome frequency was higher if obesity was defined by fat percentage (52% vs. 42%) or fat mass index (51% vs. 43%) compared to BMI. Misclassification appeared in 9% (fat percentage vs. BMI) and 7% (fat mass index vs. BMI) for metabolic syndrome and 29% and 13% for obesity itself, respectively. For metabolic syndrome, almost perfect agreement was found for BMI compared with fat percentage or fat mass index. For obesity, agreement was fair to moderate (BMI vs. fat percentage).Using BMI to evaluate obesity underestimates the true prevalence of metabolic syndrome in patients with craniopharyngioma. Furthermore, fat percentage contributes to a better evaluation of obesity than BMI. The contribution of DXA-scan might be limited for identification of the metabolic syndrome.
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7.
  • van Santen, Selveta S, et al. (författare)
  • Body composition and bone mineral density in craniopharyngioma patients: a longitudinal study over 10 years.
  • 2020
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197.
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with craniopharyngioma suffer from obesity and impaired bone health. Little is known about longitudinal changes in body composition and bone mineral density (BMD).To describe body composition and BMD (change).Retrospective longitudinal study.Two Dutch/Swedish referral centers.Patients with craniopharyngioma (n=112) with a DXA-scan available [two DXA-scans, n=86; median Δtime 9.6 years (range 0.4-23.3)] at age ≥18 years [58 (52%) male, 50 (44%) childhood-onset].Longitudinal changes of body composition and BMD, and associated factors of ΔZ-score (sex and age standardized).BMI (from 28.8±4.9 to 31.2±5.2 kg/m 2, P<0.001), fat mass index (FMI) (from 10.5±3.6 to 11.9±3.8 kg/m 2, P=0.001) and fat free mass index (FFMI) (from 18.3±3.2 to 19.1±3.2 kg/m 2, P<0.001) were high at baseline and increased. Fat percentage and Z-scores of body composition did not increase, except for FFMI Z-scores (from 0.26±1.62 to 1.06±2.22, P<0.001). Z-scores of total body, L2-L4, femur neck increased (mean difference 0.66±1.00, P<0.001; 0.78±1.63, P<0.001; 0.51±1.85, P=0.02). Linear regression models for ΔZ-score were positively associated with growth hormone replacement therapy (GHRT) [femur neck: beta 1.45 (95% CI 0.51-2.39)]; and negatively with radiotherapy [femur neck: beta -0.79 (-1.49--0.09)], glucocorticoid dose [total body: beta -0.06 (-0.09--0.02)]) and medication to improve BMD [L2-L4: beta -1.06 (-1.84--0.28)]).Z-scores of BMI, fat percentage and FMI remained stable in patients with craniopharyngioma over time, while Z-scores of FFMI and BMD increased. Higher glucocorticoid dose and radiotherapy were associated with BMD loss and GHRT with increase.
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8.
  • Wijnen, Mark, et al. (författare)
  • Excess morbidity and mortality in patients with craniopharyngioma: a hospital-based retrospective cohort study.
  • 2018
  • Ingår i: European journal of endocrinology. - 1479-683X. ; 178:1, s. 95-104
  • Tidskriftsartikel (refereegranskat)abstract
    • Most studies in patients with craniopharyngioma did not investigate morbidity and mortality relative to the general population nor evaluated risk factors for excess morbidity and mortality. Therefore, the objective of this study was to examine excess morbidity and mortality, as well as their determinants in patients with craniopharyngioma.Hospital-based retrospective cohort study conducted between 1987 and 2014.We included 144 Dutch and 80 Swedish patients with craniopharyngioma identified by a computer-based search in the medical records (105 females (47%), 112 patients with childhood-onset craniopharyngioma (50%), 3153 person-years of follow-up). Excess morbidity and mortality were analysed using standardized incidence and mortality ratios (SIRs and SMRs). Risk factors were evaluated univariably by comparing SIRs and SMRs between non-overlapping subgroups.Patients with craniopharyngioma experienced excess morbidity due to type 2 diabetes mellitus (T2DM) (SIR: 4.4, 95% confidence interval (CI): 2.8-6.8) and cerebral infarction (SIR: 4.9, 95% CI: 3.1-8.0) compared to the general population. Risks for malignant neoplasms, myocardial infarctions and fractures were not increased. Patients with craniopharyngioma also had excessive total mortality (SMR: 2.7, 95% CI: 2.0-3.8), and mortality due to circulatory (SMR: 2.3, 95% CI: 1.1-4.5) and respiratory (SMR: 6.0, 95% CI: 2.5-14.5) diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence were identified as risk factors for excess T2DM, cerebral infarction and total mortality.Patients with craniopharyngioma are at an increased risk for T2DM, cerebral infarction, total mortality and mortality due to circulatory and respiratory diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence are important risk factors.
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9.
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10.
  • van Santen, S. S., et al. (författare)
  • Fractures, Bone Mineral Density, and Final Height in Craniopharyngioma Patients with a Follow-up of 16 Years
  • 2020
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - 0021-972X. ; 105:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Pituitary hormonal deficiencies in patients with craniopharyngioma may impair their bone health. Objective: To investigate bone health in patients with craniopharyngioma. Design: Retrospective cross-sectional study. Setting: Dutch and Swedish referral centers. Patients: Patients with craniopharyngioma (n = 177) with available data on bone health after a median follow-up of 16 years (range, 1-62) were included (106 [60%] Dutch, 93 [53%] male, 84 [48%] childhood-onset disease). Main outcome measures: Fractures, dual X-ray absorptiometry-derived bone mineral density (BMD), and final height were evaluated. Low BMD was defined as T- or Z-score <=-1 and very low BMD as <=-2.5 or <=-2.0, respectively. Results: Fractures occurred in 31 patients (18%) and were more frequent in men than in women (26% vs. 8%, P = .002). Mean BMD was normal (Z-score total body 0.1 [range, -4.1 to 3.5]) but T- or Z-score <=-1 occurred in 47 (50%) patients and T-score <=-2.5 or Z-score <=-2.0 in 22 (24%) patients. Men received less often treatment for low BMD than women (7% vs. 18%, P = .02). Female sex (OR 0.3, P = .004) and surgery (odds ratio [OR], 0.2; P = .01) were both independent protective factors for fractures, whereas antiepileptic medication was a risk factor (OR, 3.6; P = .03), whereas T-score <=-2.5 or Z-score <=-2.0 was not (OR, 2.1; P = .21). Mean final height was normal and did not differ between men and women, or adulthood and childhood-onset patients. Conclusions: Men with craniopharyngioma are at higher risk than women for fractures. In patients with craniopharyngioma, a very low BMD (T-score <=-2.5 or Z-score <=-2.0) seems not to be a good predictor for fracture risk.
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