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Sökning: WFRF:(Follin Cecilia)

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  • 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.
  • 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.
  • 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.
  • Follin, Cecilia, et al. (författare)
  • Associations between Metabolic Risk Factors and the Hypothalamic Volume in Childhood Leukemia Survivors Treated with Cranial Radiotherapy.
  • 2016
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolic complications are prevalent in individuals treated with cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia (ALL). The hypothalamus is a master regulator of endocrine and metabolic control. The aim of this study was to investigate whether the hypothalamic volume would be associated to metabolic parameters in ALL survivors. Thirty-eight (21 women) survivors participated in this study 34 years after diagnosis and with a median age of 38 (27-46) years. All were treated with a median CRT dose of 24 Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 31 matched controls. We performed analyses of fat mass, fat free mass, plasma (p)-glucose, p-insulin, Homa-Index (a measure of insulin resistance), serum (s)-leptin, s-ghrelin and of the hypothalamic volume in scans obtained by magnetic resonance imaging (MRI) at 3 Tesla. Serum leptin/kg fat mass (r = -0.4, P = 0.04) and fat mass (r = -0.4, P = 0.01) were negatively correlated with the HT volume among ALL survivors, but not among controls. We also detected significantly higher BMI, waist, fat mass, p-insulin, Homa-Index, leptin/kg fat mass and s-ghrelin and significantly lower fat free mass specifically among female ALL survivors (all P<0.01). Interestingly, s-ghrelin levels increased with time since diagnosis and with low age at diagnosis for childhood ALL. Our results showed that leptin/kg fat mass and fat mass were associated with a reduced HT volume 34 years after ALL diagnosis and that women treated with CRT after ALL are at high risk of metabolic abnormalities. Taken together our data suggest that the hypothalamus is involved in the metabolic consequences after CRT in ALL survivors.
  • Follin, Cecilia, et al. (författare)
  • Attitudes and preferences in patients with acromegaly on long-term treatment with somatostatin analogues
  • 2016
  • Ingår i: Endocrine Connections. - BioScientifica. - 2049-3614. ; 5:4, s. 167-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Patients with acromegaly can be treated with surgery, medical therapy and/or radiation therapy. For the patients not being cured with surgery, treatment with somatostatin analogues (SSAs) is the primary therapy. SSA can be taken by self- or partner-administered injections in addition to being given by a nurse at a clinic. The aim was to assess if patients with acromegaly prefer self-injections and to investigate their attitudes towards long-term medical therapy. Method: All patients in the southern medical region of Sweden with a diagnosis of acromegaly and treated with SSA were eligible for the study (n = 24). The study is based on a questionnaire asking about the patients’ attitudes and preferences for injections with SSA, including their attitudes towards self-injection with SSA. Results: The patients’ (23 included) median age was 68.5 years and the patients had been treated with SSA for 13 (1–38) years. One patient was currently self-injecting. All of the other patients were receiving injections from a nurse at a clinic. Three patients preferred self-injections, one preferred partner injections and 19. patients did not prefer self- or partner injections. The most frequent arguments to not preferring self-injections were ‘feeling more secure with an educated nurse’ and ‘preferring regular contact with a specialised nurse’. Conclusion: Patients with acromegaly prefer regular contact with the endocrine team to the independence offered by self-injections. These findings might mirror the patients’ desires for continuity and safety. We need to address patients’ concerns regarding injections with SSA and support them in their choices.
  • Follin, Cecilia, et al. (författare)
  • Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy
  • 2011
  • Ingår i: European Journal of Endocrinology. - Society of the European Journal of Endocrinology. - 1479-683X. ; 164:5, s. 695-703
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Bone mineral density (BMD) in survivors of acute lymphoblastic leukaemia (ALL) seems to vary with time, type of treatments and GH status. We aimed to evaluate BMD in ALL patients with growth hormone deficiency (GHD), with and without GH therapy. DESIGN: Case-control study. METHODS: 44 (21 women) GHD patients (median 25 years), treated with cranial radiotherapy (18-24 Gy) and chemotherapy and matched population controls were examined for BMD with DXA (Dual-energy X-ray absorptiometry). Two subgroups; with (0.5 mg/day) (n=16) and without GH therapy (n=13), and matched controls, were followed for 5 and 8 years, respectively. RESULTS: At baseline, no significant differences in BMD or Z-scores at femoral neck and L2-L4 were recorded (all P > 0.3). After another 8 years with GHD, Z-scores at femoral neck had decreased significantly compared to baseline (0.0 to -0.5; P<0.03), and became lower at femoral neck (P=0.05), and at L2-L4 (P<0.03), compared to controls. After 5 years of GH therapy only female ALL patients had a significantly lower femoral neck Z-scores (P=0.03). The female ALL patients reached an IGF-I level of -0.7 SD and in men the level was +0.05 SD. CONCLUSIONS: On average 25 years since diagnosis GH deficient ALL patients experienced a significant decrease in Z-scores at femoral neck and if Z-scores continuous to decrease there is a premature risk for osteoporosis. GH therapy was not shown to have a clear beneficial effect on BMD. Whether higher GH doses, particularly in women, will improve Z-scores needs further investigation.
  • Follin, Cecilia, et al. (författare)
  • Cardiovascular Risk, Cardiac Function, Physical Activity, and Quality of Life with and without Long-Term Growth Hormone Therapy in Adult Survivors of Childhood Acute Lymphoblastic Leukemia.
  • 2010
  • Ingår i: The Journal of clinical endocrinology and metabolism. - Oxford University Press. - 1945-7197. ; 95, s. 3726-3735
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Long-term data are missing in GH-treated acute lymphoblastic leukemia (ALL) patients. GH therapy may result in poorer outcome regarding cardiovascular (CV) and particularly cardiac effects than in patients with hypothalamic-pituitary disease. Objective: Our objective was to evaluate GH therapy on CV risk, cardiac function, physical activity, and quality of life in ALL patients treated with cranial radiotherapy (18-24 Gy) and chemotherapy (anthracycline dose 120 mg/m(2)). Design and Setting: We conducted a 5- and 8-yr open nonrandomized prospective study in a university hospital clinic. Study Participants: Two groups of GH-deficient ALL patients (aged 25 yr; range 19-32 yr) and matched population controls participated. Interventions: One ALL group (n = 16) received GH for 5 yr, and the other ALL group (n = 13) did not receive GH therapy. Main Outcome Measures: We evaluated the prevalence of CV risk factors and metabolic syndrome (International Diabetes Federation consensus), cardiac function (echocardiography), and quality of life and physical activity questionnaires. Results: In comparison with 8 yr without, 5 yr with GH therapy resulted in significant positive changes in plasma glucose (-0.5 vs. 0.6 mmol/liter, P = 0.002), apolipoprotein B/apolipoprotein A1 ratio (-0.1 vs. 0.0, P = 0.03), and high-density lipoprotein-cholesterol (0.20 vs.-0.01 mmol/liter, P = 0.008) and a significant reduction in the prevalence of metabolic syndrome (P = 0.008). No significant difference in the left-ventricular systolic function or in physical activity and quality of life was recorded before and after 5 or 8 yr, respectively (all P > 0.3). Conclusion: GH therapy reduced the CV risk in this young ALL population but resulted in no clear benefit or deterioration in cardiac function.
  • Follin, Cecilia, et al. (författare)
  • Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome after 2 years of GH treatment in GH deficient adult survivors of childhood acute lymphoblastic leukaemia.
  • 2006
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Oxford University Press. - 1945-7197. ; 91:5, s. 1872-1875
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Survivors of childhood- onset ( CO) acute lymphoblastic leukemia ( ALL) treated with prophylactic cranial radiotherapy often exhibit GH deficiency ( GHD), which is associated with increased prevalence of cardiovascular risk factors and cardiac dysfunction. Objective: The objective of the study was to evaluate the effect of GH replacement on cardiovascular risk factors and cardiac function in former CO ALL patients. Design: Eighteen former CO ALL patients ( aged 19 - 32 yr) treated with cranial radiotherapy ( 18 - 24 Gy) and chemotherapy and with confirmed GHD were studied at baseline and after 12 ( n = 18) and 24 months ( n = 13) of GH treatment ( median 0.5 mg/ d). A group of 18 age- and sex- matched subjects served as controls. Results: After 12 months of GH treatment, a significant decrease in serum leptin ( P = 0.002), leptin per kilogram fat mass ( FM) ( P = 0.01),plasma glucose ( P = 0.004), FM ( P = 0.002), and hip ( P = 0.04) and waist ( P = 0.02) circumference and increased muscle mass ( P = 0.004) were recorded in the patients. Before GH treatment six patients had a metabolic syndrome, but after 12 months only one had it and after 24 months none. After 24 months of GH treatment, an increase in left ventricular mass index ( P = 0.06) and significant improvements in cardiac systolic function, measured as fractional shortening ( P = 0.03) and ejection fraction ( P = 0.03), were recorded. Conclusions: Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome were recorded after 2 yr of GH replacement in former CO ALL patients with GHD. Long- term follow-up is highly warranted.
  • Follin, Cecilia (författare)
  • Late complications of childhood acute lymphoblastic leukaemia (ALL), with special reference to hormone secretion, cardiovascular risk and bone health
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • An increased prevalence of cardiovascular (CV) risk factors and cardiac abnormalities has been shown among adult GH deficient ALL survivors subjected to cranial irradiation. The ALL treatment includes many known risk factors for low bone mineral density (BMD), but little is known about pituitary insufficiencies, except for GH deficiency. In study I we evaluated the impact of 2 years GH therapy on CV risk and cardiac function and in study II, 5 years of GH therapy and 8 years without. In study III, BMD was evaluated 20 years after diagnosis, and also after another 5 years with GH therapy and 8 years without. In study IV we evaluated the prevalence of PRL and thyroid hormone insufficiency and the effect of GH therapy on these levels. We have shown that GH therapy in ALL survivors, both of short - and long term duration decreases the prevalence of metabolic syndrome and of CV risk factors. An improvement in cardiac systolic function was recorded after 2 years of GH therapy, but after 5 years, this improvement was not sustained. Twenty years after diagnosis, BMD was normal among ALL patients compared to matched controls, but during follow up BMD Z-score had decreased, irrespective of a low dose of GH therapy. ALL survivors were PRL insufficient 20 years after diagnosis, with a further decline in PRL levels after another 5 and 8 years, irrespective of GH therapy, indicating a progressive radiation effect. In contrast, normal thyroid hormone function was recorded.
  • Follin, Cecilia, et al. (författare)
  • Long-Term Effect of Cranial Radiotherapy on Pituitary-Hypothalamus Area in Childhood Acute Lymphoblastic Leukemia Survivors
  • 2016
  • Ingår i: Current Treatment Options in Oncology. - Springer. - 1527-2729. ; 17:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. There is evidence that the hypothalamus is more radiosensitive than the pituitary and is damaged by lower doses of CRT. With doses of CRT 50 Gy) may produce direct anterior pituitary damage, which contributes to multiple pituitary deficiencies. The large group of ALL survivors treated with CRT in the 70–80-ties has now reached adulthood, and these survivors were treated mainly with 24 Gy, and the vast majority of these patients suffer from GHD. Further, after long-term follow-up, insufficiencies in prolactin (PRL) and thyroid stimulating hormone (TSH) have also been reported and a proportion of these patients were also adrenocoticotrophic hormone (ACTH) deficient. CRT to the hypothalamus causes neuroendocrine dysfunction, which means that the choice of GH test is crucial for the diagnosis of GHD.
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