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Sökning: WFRF:(Engstrom BE)

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1.
  • Casar-Borota, O., et al. (författare)
  • Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations
  • 2021
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 106:4, s. 1183-1194
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.
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2.
  • 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. - 0306-4530 .- 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. less thanbrgreater than less thanbrgreater thanObjective: Psychosocial health and levels of employment were compared between GH deficient (GHD) patients on long-term replacement and the general population. less thanbrgreater than less thanbrgreater thanDesign 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. less thanbrgreater than less thanbrgreater thanResults: 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 andlt; 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. less thanbrgreater than less thanbrgreater thanConclusions: 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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3.
  • Vouzouneraki, K., et al. (författare)
  • Temporal relationship of sleep apnea and acromegaly: a nationwide study
  • 2018
  • Ingår i: Endocrine. - : Springer. - 1355-008X .- 1559-0100. ; 62:2, s. 456-463
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposePatients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis.MethodsCross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients' follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea investigations.ResultsOf the 259 participants, 75 (29%) were diagnosed with sleep apnea before the study start. In 43 (57%) of these patients, sleep apnea had been diagnosed before the diagnosis of acromegaly. After clinical assessment and sleep studies, sleep apnea was diagnosed in an additional 20 patients, yielding a total sleep apnea prevalence of 37%. Higher sleep apnea risk was associated with higher BMI, waist circumference, and index finger circumference. Sleep apnea was more frequent among patients with S-IGF-1 levels in the highest quartile.ConclusionSleep apnea is common among patients with acromegaly, and is often diagnosed prior to their acromegaly diagnosis. These results support early screening for sleep apnea in patients with acromegaly and awareness for acromegaly in patients with sleep apnea.
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4.
  • Burman, P., et al. (författare)
  • Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality
  • 2013
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 98:4, s. 1466-1475
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for Objective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism Design and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with Main Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for Results: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence Conclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response
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5.
  • Burman, P, et al. (författare)
  • Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality
  • 2013
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 98:4, s. 1466-1475
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. less thanbrgreater than less thanbrgreater thanObjective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. less thanbrgreater than less thanbrgreater thanDesign and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. less thanbrgreater than less thanbrgreater thanMain Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. less thanbrgreater than less thanbrgreater thanResults: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. less thanbrgreater than less thanbrgreater thanConclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease. (J Clin Endocrinol Metab 98: 1466-1475, 2013)
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6.
  • Elinder, Göran, et al. (författare)
  • Traumatic shaking : the role of the triad in medical investigations of suspected traumatic shaking
  • 2018
  • Ingår i: Acta Paediatrica. - Hoboken : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 107, s. 3-23
  • Forskningsöversikt (refereegranskat)abstract
    • The Swedish Agency for Health Technology Assessment and Assesment of Social Services (SBU) is an independent national authority, tasked by the government with assessing methods used in health, medical and dental services and social service interventions from a broad perspective, covering medical, economic, ethical and social aspects. The language in SBU's reports are adjusted to a wide audience. SBU's Board of Directors has approved the conclusions in this report. The systematic review showed the following graded results:There is limited scientific evidence that the triad (Three components of a whole. The triad associated with SBS usually comprises subdural haematoma, retinal haemorrhages and encephalopathy.) and therefore, its components can be associated with traumatic shaking (low-quality evidence).There is insufficient scientific evidence on which to assess the diagnostic accuracy of the triad in identifying traumatic shaking (very low-quality evidence).Limited scientific evidence (low-quality evidence) represents a combined assessment of studies of high or moderate quality which disclose factors that markedly weaken the evidence. It is important to note that limited scientific evidence for the reliability of a method or an effect does not imply complete lack of scientific support. Insufficient scientific evidence (very low-quality evidence) represents either a lack of studies or situations when available studies are of low quality or show contradictory results. Evaluation of the evidence was not based on formal grading of the evidence according to GRADE but on an evaluation of the total scientific basis.
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7.
  • 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 .- 0021-972X. ; 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.
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8.
  • Onnestam, Lisa, et al. (författare)
  • National Incidence and Prevalence of TSH-Secreting Pituitary Adenomas in Sweden.
  • 2013
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 1945-7197 .- 0021-972X. ; 98:2, s. 626-635
  • Tidskriftsartikel (refereegranskat)abstract
    • Context:TSH-secreting pituitary adenomas (TSHomas) are rare. Epidemiological data are scant and there are no reports on national incidence.Objective:The objective of the study was to estimate the national Swedish incidence and prevalence of TSHomas.Design:This was an observational study.Setting:The study was conducted at tertiary referral centers.Patients:The Swedish Pituitary Registry and World Health Organization International Statistical Classification of Diseases and Related Health Problems coding at all university hospitals were used to identify patients diagnosed with TSHomas 1990-2010. The identified patients' medical records were studied until the latest follow-up [median 5.0 years (range < 1-20 years)].Main Outcome Measurements:Incidence, prevalence, demographics, tumor characteristics, treatment outcome, and thyroid hormone level at diagnosis were measured.Results:The age-standardized national incidence of 28 TSHoma patients was 0.15 per 1 million inhabitants per year, with an increasing incidence over time (0.05 per 1 million per year in 1990-1994 to 0.26 per 1 million per year in 2005-2009). The national prevalence in 2010 was 2.8 per 1 million inhabitants, in which 0.85 per 1 million had active disease. Most patients (n = 22) underwent pituitary surgery, 5 had radiotherapy, and 6 had somatostatin analogues. Eighteen patients were considered cured at the latest follow-up; 25% remained uncontrolled. Subjects treated for putative primary hyperthyroidism prior to diagnosis had TSH levels more than double those with intact thyroid at diagnosis (P = .013). The median time to diagnosis was longer for women than men (4 vs < 1 year, P = .026). More women than men were treated surgically (94.1% vs 54.5%, P = .022).Conclusion:This is the first estimate of a national incidence of TSHoma. Additional epidemiological studies are needed to compare these results with other geographical areas. This study suggests an increased incidence of TSHomas, in agreement with reports on other pituitary adenomas.
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9.
  • Papakokkinou, Eleni, et al. (författare)
  • Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis
  • 2021
  • Ingår i: Pituitary. - : Springer. - 1386-341X .- 1573-7403.
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. Data sources Systematic literature search in four databases. Study Selection Observational studies reporting the prevalence of NS after BA in adult patients with CD. Data extraction Data extraction and risk of bias assessment were performed by three independent investigators. Data synthesis Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I-2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. Conclusions Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
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10.
  • Schill, Fredrika, et al. (författare)
  • Pituitary Metastases: a Nationwide Study on Current Characteristics with Special Reference to Breast Cancer.
  • 2019
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : ENDOCRINE SOC. - 1945-7197 .- 0021-972X. ; 104:8, s. 3379-88
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the contemporary presentation of pituitary metastases.Thirty-eight patients diagnosed with pituitary metastases 1996 to 2018 in Sweden.Pituitary metastases were confirmed by histopathology (n = 27) or considered highly likely due to radiological findings, including rapid tumor progression (n = 11). Medical charts were reviewed and sellar images re-examined centrally.Breast and lung cancer were the most common primary tumors, 45% and 21% of the patients. The pituitary was the only metastatic site in 9 patients. 67% of the breast cancers overexpressed HER2. 53% of the pituitary metastases from breast cancers appeared ≥10 years after diagnosis of the primary tumor. At presentation, 71% appeared to have ACTH deficiency, 65% had TSH deficiency, and 26% had diabetes insipidus. 47% of patients with morning cortisol <100 nmol/L vs 23% with cortisol ≥200 nmol/L reported fatigue, nausea/vomiting, loss of appetite, weight loss, myalgia and/or arthralgia. Sixteen patients had visual field defects, eight had diplopia. Intra- and suprasellar tumor growth was the most frequent finding. Initially, a pituitary adenoma was considered to be the etiology in 18% of the patients. Radiotherapy, pituitary surgery, and chemotherapy were used in 68%, 68% and 11% of the patients. One and 2 years after diagnosis of PM, 50% and 26% of the patients were alive.Pituitary metastases may be mistaken for pituitary adenomas and can appear late, especially in breast cancer. Breast cancers overexpressing HER2 seem prone to metastasize to the pituitary. Hypocortisolism, may be misdiagnosed as cancer-related malaise. An increased awareness of PM and undiagnosed pituitary failure can improve the management in these patients.
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