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Sökning: WFRF:(Edén Engström Britt) > Ekman Bertil

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1.
  • Casar Borota, Olivera, et al. (författare)
  • Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations
  • 2021
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 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.
  • Al-Shamkhi, Nasrin, 1985-, et al. (författare)
  • Pituitary function before and after surgery for nonfunctioning pituitary adenomas-data from the Swedish Pituitary Register.
  • 2023
  • Ingår i: European journal of endocrinology. - : Bioscientifica. - 1479-683X .- 0804-4643. ; 189:2, s. 217-224
  • Tidskriftsartikel (refereegranskat)abstract
    • Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA).Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded.Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm3. Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively.Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.
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3.
  • Arnardottir, Steinunn, et al. (författare)
  • Long-term outcomes of patients with acromegaly: a report from the Swedish Pituitary Register
  • 2022
  • Ingår i: European Journal of Endocrinology. - : European Society of Endocrinology. - 1479-683X .- 0804-4643. ; 186:3, s. 329-339
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To describe the treatment and long-term outcomes of patients with acromegaly from all healthcare regions in Sweden. Design and methods: Analysis of prospectively reported data from the Swedish Pituitary Register of 698 patients (51% females) with acromegaly diagnosed from 1991 to 2011. The latest clinical follow-up date was December 2012, while mortality data were collected for 28.5 years until June 2019. Results: The annual incidence was 3.7/million; 71% of patients had a macroadenoma, 18% had visual field defects, and 25% had at least one pituitary hormone deficiency. Eighty-two percent had pituitary surgery, 10% radiotherapy, and 39% medical treatment. At the 5- and 10-year follow-ups, insulin-like growth factor 1 levels were within the reference range in 69 and 78% of patients, respectively. In linear regression, the proportion of patients with biochemical control including adjuvant therapy at 10 years follow-up increased over time by 1.23% per year. The standardized mortality ratio (SMR) (95% CI) for all patients was 1.29 (1.11-1.49). For patients with biochemical control at the latest follow-up, SMR was not increased, neither among patients diagnosed between 1991 and 2000, SMR: 1.06 (0.85-1.33) nor between 2001 and2011, SMR: 0.87 (0.61-1.24). In contrast, non-controlled patients at the latest follow-up from both decades had elevated SMR, 1.90 (1.33-2.72) and 1.98 (1.24-3.14), respectively. Conclusions: The proportion of patients with biochemical control increased over time. Patients with biochemically controlled acromegaly have normal life expectancy, while non-controlled patients still have increased mortality. The high rate of macroadenomas and unchanged age at diagnosis illustrates the need for improvements in the management of patients with acromegaly.
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4.
  • Bengtsson, Daniel, 1975-, et al. (författare)
  • Increased Mortality Persists after Treatment of Cushing's Disease: A Matched Nationwide Cohort Study
  • 2022
  • Ingår i: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 6:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Whether biochemical remission normalizes life expectancy in Cushing's disease (CD) patients remains unclear. Previous studies evaluating mortality in CD are limited by using the expected number of deaths in the background population instead of the actual number in matched controls. Objective and setting: To study mortality by time-to-event analysis in an unselected nationwide CD patient cohort. Design and participants: Longitudinal data from the Swedish Pituitary Register of 371 patients diagnosed with CD from 1991 to 2018 and information from the Swedish Cause of Death Register were evaluated. Four controls per patient (n = 1484) matched at the diagnosis date by age, sex, and residential area were included. Main outcome measures: Mortality and causes of death. Results: The median diagnosis age was 44 years (interquartile range 32-56), and the median follow-up was 10.6 years (5.7-18.0). At the 1-, 5-, 10-, 15-, and 20-year follow-ups, the remission rates were 80%, 92%, 96%, 91%, and 97%, respectively. Overall mortality was increased in CD patients compared with matched controls [hazard ratio (HR) 2.1 (95% CI 1.5-2.8)1. The HRs were 1.5 (1.02-2.2) for patients in remission at the last follow-up In = 303), 1.7 (1.03-2.8) for those in remission after a single pituitary surgery In = 177), and 5.6 (2.7-11.6) for those not in remission (n = 31). Cardiovascular diseases (32/66) and infections (12/66) were overrepresented causes of death. Conclusions: Mortality was increased in CD patients despite biochemical remission compared to matched controls. The study highlights the importance of careful comorbidity monitoring, regardless of remission status.
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5.
  • Bengtsson, Daniel, et al. (författare)
  • Psychotropic Drugs in Patients with Cushing's Disease Before Diagnosis and at Long-Term Follow-Up: A Nationwide Study
  • 2021
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:6, s. 1750-1760
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Psychiatric symptoms are common in Cushing's disease (CD) and seem only partly reversible following treatment. Objective: To investigate drug dispenses associated to psychiatric morbidity in CD patients before treatment and during long-term follow-up. Design: Nationwide longitudinal register-based study. Setting: University Hospitals in Sweden. Subjects: CD patients diagnosed between 1990 and 2018 (N = 372) were identified in the Swedish Pituitary Register. Longitudinal data was collected from 5 years before, at diagnosis, and during follow-up. Four matched controls per patient were included. Cross-sectional subgroup analysis of 76 patients in sustained remission was also performed. Main outcome measures: Data from the Swedish Prescribed Drug Register and the Patient Register. Results: In the 5-year period before and at diagnosis, use of antidepressants (odds ratio [OR] 2.2 [95% confidence interval (CI) 1.3-3.7]) and 2.3 [1.6-3.5]), anxiolytics [2.9 (1.6-5.3) and 3.9 (2.3-6.6)], and sleeping pills [2.1 (1.2-3.7) and 3.8 (2.4-5.9)] was more common in CD than controls. ORs remained elevated at 5-year follow-up for antidepressants [2.4 (1.53.9)] and sleeping pills [3.1 (1.9-5.3)]. Proportions of CD patients using antidepressants (26%) and sleeping pills (22%) were unchanged at diagnosis and 5-year follow-up, whereas drugs for hypertension and diabetes decreased. Patients in sustained remission for median 9.3 years (interquartile range 8.1-10.4) had higher use of antidepressants [OR 2.0 (1.1-3.8)] and sleeping pills [2.4 (1.3-4.7)], but not of drugs for hypertension. Conclusions: Increased use of psychotropic drugs in CD was observed before diagnosis and remained elevated regardless of remission status, suggesting persisting negative effects on mental health. The study highlights the importance of early diagnosis of CD, and the need for long-term monitoring of mental health.
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6.
  • Burman, Pia, 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. - : The 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 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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7.
  • Burman, Pia, et al. (författare)
  • Limited value of cabergoline in Cushing's disease : a prospective study of a 6-week treatment in 20 patients
  • 2016
  • Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 174:1, s. 17-24
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT AND OBJECTIVE: The role of cabergoline in Cushing's disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after ≥1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD.DESIGN: Twenty patients (19 naïve and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5-5 mg/week over 6 weeks.METHODS: Urinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end.RESULTS: At study end, the median cabergoline dose was 5 mg, range 2.5-5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a >50% decrease of UFC, three had a >50% rise of UFC. Salivary cortisol at 2300 h showed a congruent >50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study.CONCLUSIONS: Cabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.
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8.
  • Espiard, Stéphanie, et al. (författare)
  • Improved Urinary Cortisol Metabolome in Addison's disease: a Prospective Trial of Dual-Release Hydrocortisone.
  • 2021
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:3, s. 814-825
  • Tidskriftsartikel (refereegranskat)abstract
    • Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism.To study cortisol metabolism during DR-HC and TID-HC.Randomized, 12-week, crossover study.DC-HC and same daily dose of TID-HC in patients with primary adrenal insufficiency (n=50) versus healthy subjects (n=124) as control.Urinary corticosteroid metabolites measured by gas chromatography/mass spectrometry on 24-hour urinary collections.Total cortisol metabolites decreased during DR-HC compared to TID-HC (P < 0.001) and reached control values (P = 0.089). During DR-HC, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity measured by tetrahydrocortisol+5α-tetrahydrocortisol/tetrahydrocortisone ratio was reduced compared to TID-HC (P < 0.05), but remained increased versus controls (P < 0.001). 11β-HSD2 activity measured by urinary free cortisone/free cortisol ratio was decreased with TID-HC versus controls (P < 0.01) but normalized with DR-HC (P = 0.358). 5α- and 5β-reduced metabolites were decreased with DR-HC compared to TID-HC. Tetrahydrocortisol/5α-tetrahydrocortisol ratio was increased during both treatments, suggesting increased 5β-reductase activity.The urinary cortisol metabolome shows striking abnormalities in patients receiving conventional TID-HC replacement therapy with increased 11β-HSD1 activity that may account for the unfavorable metabolic phenotype in primary adrenal insufficiency. Its change towards normalization with DR-HC may mediate beneficial metabolic effects. The urinary cortisol metabolome may serve as a tool to assess optimal cortisol replacement therapy.
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9.
  • Himonakos, Christos, et al. (författare)
  • Long-term Follow-up of 84 Patients With Giant Prolactinomas-A Swedish Nationwide Study.
  • 2023
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : Oxford University Press. - 1945-7197 .- 0021-972X. ; 108:12, s. e1506-e1514
  • Tidskriftsartikel (refereegranskat)abstract
    • To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas.Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 µg/L, tumor diameter ≥40 mm] identified in the Swedish Pituitary Register 1991-2018.Eighty-four patients [mean age 47 (SD ±16) years, 89% men] were included in the study. At diagnosis, the median PRL was 6305 µg/L (range 1450-253 000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received 1 or more additional therapies, including surgery (n = 19), radiotherapy (n = 6), other medical treatments (n = 4), and chemotherapy (n = 2). Ki-67 was ≥10% in 4/14 tumors. At the last follow-up [median 9 years (interquartile range (IQR) 4-15)], the median PRL was 12 µg/L (IQR 4-126), and the median tumor diameter was 22 mm (IQR 3-40). Normalized PRL was achieved in 55%, significant tumor reduction in 69%, and combined response (normalized PRL and significant tumor reduction) in 43%. In the primary DA-treated patients (n = 79), the reduction in PRL or tumor size after the first year predicted the combined response at the last follow-up (P < .001 and P = .012, respectively).DAs effectively reduced PRL and tumor size, but approximately 1 patient out of 4 needed multimodal treatment. Our results suggest that the response to DA after 1 year is useful for identifying patients who need more careful monitoring and, in some cases, additional treatment.
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10.
  • 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. - : Wiley. - 0884-0431 .- 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 wilh 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% CI 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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