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Sökning: WFRF:(Erfurth EM)

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1.
  • Follin, Cecilia, et al. (författare)
  • Impaired brain metabolism and neurocognitive function in childhood leukemia survivors despite complete hormone supplementation in adulthood
  • 2016
  • Ingår i: Psychoneuroendocrinology. - Elsevier. - 0306-4530. ; 73, s. 157-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27–46) years. All were treated with a CRT dose of 24 Gy and 11 years (3–13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance in neuropsychological tests. ALL survivors scored lower than controls in vocabulary (p < 0.001), memory (p < 0.001), learning capacity (p < 0.001), spatial ability (p < 0.001), executive functions and attention (p < 0.001) 34 years after ALL treatment. Compared to controls ALL survivors had reduced white matter (WM) (492 vs 536 cm3, p < 0.001) and grey matter (GM) volumes (525 vs 555 cm3, p = 0.001). ALL survivors had lower levels of WM N-acetyl aspartate/creatin (NAA/Cr) (1.48 vs 1.63, p = 0.004), WM NAA + NAAG (N-acetylaspartylglutamate)/Cr (1.61 vs 1.85, p < 0.001) and lower levels of GM NAA/Cr (1.18 vs 1.30, p = 0.001) and GM NAA + NAAG/Cr (1.28 vs 1.34, p = 0.01) compared to controls. ALL survivors had higher levels in WM MI (Myoinositol)/NAA (0.65 vs 0.56, p = 0.01) concentrations compared to controls. There was a significantly negative correlation of years since ALL diagnosis to WM NAA + NAAG/Cr (r = −0.4, p = 0.04) in ALL survivors. The present study shows impaired brain metabolism detected by MRS, reduced brain volumes and neurocognitive impairment in childhood ALL survivors treated with cranial radiotherapy and chemotherapy, despite complete hormone substitution. We also report an impairment of metabolites correlated to time since treatment and a progressive impairment in sustained attention, suggesting an accelerated aging in the irradiated brain. Following these survivors many decades, or throughout life, after treatment with cranial radiotherapy and chemotherapy is highly warranted for a broader understanding of long-term outcome in this patient group.
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2.
  • Geffner, M, et al. (författare)
  • Changes in height, weight, and body mass index in children with craniopharyngioma after three years of growth hormone therapy: Analysis of KIGS (Pfizer International Growth Database)
  • 2004
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Oxford University Press. - 1945-7197. ; 89:11, s. 5435-5440
  • Tidskriftsartikel (refereegranskat)abstract
    • Extreme degrees of obesity may occur in association with hypothalamic tumors, usually after surgical intervention. This phenomenon has been reported to occur in as many as 25-75% of children undergoing extensive surgical extirpation of craniopharyngiomas (Cranio). Because less is known about the auxology of children with Cranio with milder alterations in growth, we undertook a 3-yr longitudinal analysis, using the KIGS database ( Pfizer International Growth Database), to study their growth patterns and evolution of weight. We compared the effect of GH therapy on height, weight, and body mass index (BMI) in 199 prepubertal children with diagnosed Cranio treated by surgery and/or radiotherapy to two other groups of children with other causes of organic GH deficiency (OGHD): one with postsurgical and/or postirradiated OGHD (OGHD + S/I; n = 92) and the other with OGHD not due to Cranio and not having undergone either surgery or irradiation (OGHD - S/I; n = 85). At the start of GH therapy, 1) mean chronological (P < 0.0001) and bone (P = 0.0002) ages were youngest in OGHD - S/I and oldest inOGHD - S/I; 2) the mean height SD score (SDS) was lowest in OGHD - S/I and comparably higher in the other two groups (P < 0.0001); 3) mean weight and BMI SDS were greatest in Cranio and least in OGHD - S/I (both P < 0.0001); and 4) the mean initial GH dose prescribed was highest in OGHD - S/I and comparable in the other two groups ( P < 0.0001). After 3 yr of GH therapy, 1) mean bone age remained youngest in OGHD - S/I and oldest in OGHD + S/I (P < 0.0001); 2) mean height SDS was highest in Cranio and comparably lower in the other two groups (P = 0.0159); 3) mean weight and BMI SDS remained greatest in Cranio and least in OGHD - S/I (P < 0.0001 and P = 0.0003, respectively); and 4) the mean GH dose remained highest in the OGHD - S/I group and least in the Cranio group (P = 0.0082). There were statistically significant increases within each group between the start of treatment and after 3 yr of GH therapy in height and weight, but not in BMI SDS. Lastly, after 3 yr of GH treatment, children in the Cranio group continued to have disproportionately heavier weight and higher BMI ( with the greatest values in those with lower stimulated peak GH concentrations) compared with members of the other two groups, with no salutary effect of GH treatment on weight SDS and a mild improvement in BMI SDS. After S/I treatment, children with Cranio are disproportionately prone to varying degrees of weight gain compared with children with other forms of OGHD. In the present cohort of prepubertal children with Cranio, GH therapy induced excellent linear growth, but failed to have an ameliorative effect on weight gain and had only a slight beneficial effect on BMI gain. Because affected children may have resultant significant long-term medical morbidity and diminished quality of life, it is critical that the mechanism of this phenomenon be determined to devise helpful preventive or therapeutic interventions.
3.
  • Holmer, Helene, et al. (författare)
  • Fracture incidence in GH-deficient patients on complete hormone replacement including GH
  • 2007
  • Ingår i: Journal of Bone and Mineral Research. - AMBMR. - 1523-4681. ; 22:12, s. 1842-1850
  • Tidskriftsartikel (refereegranskat)abstract
    • Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential Confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95 % CI 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% C1, 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
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4.
  • Holmer, Helene, et al. (författare)
  • Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone
  • 2007
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Oxford University Press. - 1945-7197. ; 92:9, s. 3560-3567
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus ( T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
5.
  • Holmer, Helene, et al. (författare)
  • Psychosocial health and levels of employment in 851 hypopituitary Swedish patients on long-term GH therapy.
  • 2013
  • Ingår i: Psychoneuroendocrinology. - Elsevier. - 1873-3360. ; 38:6, s. 842-852
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: The psychosocial health and working capacity in hypopituitary patients receiving long-term growth hormone (GH) therapy are unknown. OBJECTIVE: Psychosocial health and levels of employment were compared between GH deficient (GHD) patients on long-term replacement and the general population. DESIGN AND PARTICIPANTS: In a Swedish nationwide study, 851 GHD patients [101 childhood onset (CO) and 750 adult onset (AO)] and 2622 population controls answered a questionnaire regarding current living, employment and educational level, alcohol consumption and smoking habits. The median time on GH therapy for both men and women with CO GHD was 9 years and for AO GHD 6 years, respectively. RESULTS: As compared to the controls, the GHD patients were less often working full time, more often on sick leave/disability pension, and to a larger extent alcohol abstainers and never smokers (all; P<0.05). Predominantly CO GHD women and men, but to some extent also AO GHD women and men, lived less frequently with a partner and more often with their parents. Particularly AO GHD craniopharyngioma women used more antidepressants, while AO GHD men with a craniopharyngioma used more analgesics. CONCLUSIONS: A working capacity to the level of the general population was not achieved among hypopituitary patients, although receiving long-term GH therapy. Patients were less likely to use alcohol and tobacco. The CO GHD population lived a less independent life.
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6.
  • Ragnarsson, Oskar, 1971-, et al. (författare)
  • Overall and disease-specific mortality in patients with Cushing's disease: a Swedish nationwide study.
  • 2019
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 104:6
  • Tidskriftsartikel (refereegranskat)abstract
    • It is still a matter of debate whether patients with Cushing's disease (CD) in remission have increased mortality.To study overall and disease-specific mortality, and predictive factors, in an unselected nationwide cohort of patients with CD.A retrospective study on patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardised mortality ratios (SMRs) with 95% confidence intervals (CI) were calculated and Cox regression models were used to identify predictors of mortality.Five-hundred-and-two patients [387 women (77%)] with CD were identified, of whom 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 years (SD 16) and median follow-up time was 13 years (IQR 6-23). The observed number of deaths was 133 versus 54 expected, resulting in an overall SMR of 2.5 (95% CI 2.1-2.9). The commonest cause of death was cardiovascular diseases [SMR 3.3 (95% CI 2.6 -4.3)]. Excess mortality was also found due to infections and suicides. SMR in patients in remission was 1.9 (95% CI 1.5-2.3), where bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality whereas growth hormone replacement was associated with improved outcome.This large nationwide study shows that patients with CD have an excess mortality. The findings illustrate the importance of obtaining remission and continued active surveillance, along with adequate hormone replacement, and evaluation of cardiovascular risk and mental health.
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7.
  • Ragnarsson, Oskar, 1971-, et al. (författare)
  • The incidence of Cushing’s disease : : a nationwide Swedish study
  • 2019
  • Ingår i: Pituitary. - Springer. - 1386-341X. ; 22:2, s. 179-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden. Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data. Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05). Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
8.
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9.
  • Hagmar, L, et al. (författare)
  • Plasma levels of persistent organohalogens and hormone levels in adult male humans
  • 2001
  • Ingår i: Archives of Environmental Health. - Heldref Publications. - 0003-9896. ; 56:2, s. 138-143
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study the authors assessed the possible relationship between high dietary exposure to persistent organohalogens (OHS) through fatty fish from the Baltic Sea and hormone levels in adult men. Blood samples were drawn from 110 men who consumed varying amounts of fish (i.e., 0-32 meals per month) for analysis of plasma levels of 18 polychlorinated biphenyl (PCB) congeners, 5 hydroxy-PCBs, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)-ethane (p,p'-DDT), 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethene (p,p'-DDE), hexachlorobenzene, and 2,2',4,4'-tetrabromodiphenyl ether. In addition, plasma levels of follicle-stimulating hormone, luteinizing hormone, prolactin, plasma thyrotropin, free and total T3, free and total T4, and free testosterone were analyzed. The authors adjusted for age, and the only significant associations that remained were negative correlations between 2,2',4,4'-tetrabromodiphenyl ether and plasma thyrotropin (p < .001), and between pentachlorophenol and follicle-stimulating hormone (p = .04). The authors expected that there would be some significant correlations that resulted from pure chance. High consumption of organohalogen-polluted fish did not appear to affect plasma concentrations of pituitary, thyroid, or testosterone hormone levels in male adults.
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10.
  • Malmberg, Birgitta, et al. (författare)
  • Physiological restitution after night-call duty in anaesthesiologists: impact on metabolic factors.
  • 2007
  • Ingår i: Acta Anaesthesiologica Scandinavica. - Wiley-Blackwell Publishing Ltd. - 0001-5172. ; 51, s. 823-830
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Several studies have shown impaired mental well-being and performance in physicians work on call, but knowledge of the physiological effects is scarce. The aims of the present study were to investigate if there was a metabolic stress response in the restitutional phase after night-call duty, indicating potential negative health effects, and determine whether there were differences between physician specialities. Methods: Anaesthesiologists (n = 19) were compared with paediatricians/ear, nose and throat (ENT) surgeons (n = 18). On an ordinary workday, 1 and 3 days after work on night call, blood samples were taken for analysis of glucose, thyroid-stimulating hormone (TSH), free thyroxine, testosterone, insulin growth factor-1 (IGF-1), high- and low-density lipoprotein cholesterol (HDL and LDL), triglycerids (TG) and insulin. Saliva cortisol was sampled on an ordinary working day, a day including 16-h night call, the third day following, and for anaesthesiologists also on a day off work. Results: TSH differed significantly between days in both groups, with a 26% lower level 1 day after on-call duty (P < 0.001). A 48% cortisol rise in the morning preceding night duty was found for paediatricians/ENT surgeons (P < 0.01). Conclusion: The significant dip in TSH level 24 h after night-call duty indicates a metabolic effect of working on night call and should be studied further. However, the levels were within the normal range and the overall results do not imply any serious metabolic changes and only minor differences were seen between specialist groups.
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