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Sökning: WFRF:(Edén Engström Britt) > Tidskriftsartikel

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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.
  • Zetterling, Maria, 1966-, et al. (författare)
  • Cortisol and ACTH dynamics in the acute phase of subarachnoid haemorrhage
  • Ingår i: British Journal of Neurosurgery. - 0268-8697 .- 1360-046X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimizing care in the acute phase of SAH. Patients: 55 patients with spontaneous SAH were evaluated regarding morning levels of S-Cortisol and P-ACTH seven days after the bleeding. In a subgroup of 20 patients the diurnal changes of S-Cortisol and P-ACTH levels were studied and U-Cortisol measured. The relations of hormone levels to clinical and radiological parameters and to outcome were assessed. Results: S-Cortisol and P-ACTH were elevated the day of SAH. S-Cortisol levels below reference range were uncommon. Early global cerebral oedema was associated with higher S-Cortisol concentrations at admission and a worse WFNS and RLS85 grade. Patients in better WFNS grade had higher U-Cortisol levels. All patients showed diurnal variations of S-Cortisol and P-ACTH. A reversed diurnal variation of S-Cortisol was more frequently seen in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-Cortisol peaks occurred especially in periods of secondary brain ischemia. Conclusion: There is a HPA response acutely after SAH with an increase of P-ACTH and S-Cortisol levels. Higher U-Cortisol levels in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-Cortisol levels at admission and may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischemia, indicating a possibly connection between brain ischemia and ACTH suppression. These two novel findings should be evaluated in further studies.
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3.
  • Zetterling, Maria, et al. (författare)
  • Cortisol and adrenocorticotropic hormone dynamics in the acute phase of subarachnoid haemorrhage
  • 2011
  • Ingår i: British Journal of Neurosurgery. - : Informa UK Limited. - 0268-8697 .- 1360-046X. ; 25:6, s. 684-692
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimising care in the acute phase of SAH. Patients. Fifty-five patients with spontaneous SAH were evaluated regarding morning concentrations of serum (S)-cortisol and P-adrenocorticotropic hormone (ACTH) 7 days after the bleeding. In a subgroup of 20 patients, the diurnal changes of S-cortisol and P-ACTH were studied and urine (U)-cortisol was measured. The relationships of hormone concentrations to clinical and radiological parameters and to outcome were assessed. Results. S-cortisol and P-ACTH were elevated the day of SAH. S-cortisol concentrations below reference range were uncommon. Early global cerebral oedema was associated with higher S-cortisol concentrations at admission and a worse World Federation of Neurological Surgeons (WFNS) and Reaction Level Scale 85 grade. Global cerebral oedema was shown to be a predictor of S-cortisol at admittance. Patients in better WFNS grade displayed higher U-cortisol. All patients showed diurnal variations of S-cortisol and P-ACTH. A reversed diurnal variation of S-cortisol was more frequently found in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-cortisol peaks occurred especially in periods of secondary brain ischaemia. Conclusion. There was an HPA response acutely after SAH with an increase in P-ACTH and S-cortisol. Higher U-cortisol in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-cortisol at admission and was a predictor of S-cortisol concentrations. Global cerebral oedema may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischaemia, indicating a possible connection between brain ischaemia and ACTH suppression.
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4.
  • Zetterling, Maria, et al. (författare)
  • Somatotropic and thyroid hormones in the acute phase of subarachnoid haemorrhage
  • 2013
  • Ingår i: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 155:11, s. 2053-2062
  • Tidskriftsartikel (refereegranskat)abstract
    • Somatotropic and thyroid hormones are probably important for the recovery after acute brain injury. Still, the dynamics of these hormones after spontaneous subarachnoid haemorrhage (SAH) is not well described. The purpose of this study was to investigate the relation between somatotropic and thyroid hormones and clinical factors after SAH. Twenty patients with spontaneous SAH were included prospectively. Serum concentrations of TSH, fT4, T3, IGF-1 and GH were measured once a day for 7 days after SAH. Hormone patterns and serum concentrations were compared to the severity of SAH, neurological condition at admission, clinical course and outcome of the patients. During the first week after SAH, all patients showed increased GH and IGF-1 concentrations. In the whole group, concentrations of TSH increased, whereas T3 and fT4 decreased. There were no relations of serum concentrations of IGF-1 or GH to clinical condition at admission, clinical course or outcome of the patients. Half of the patients showed low T3 serum concentrations. A complicated course was associated with a deeper fall in TSH and T3 concentrations. There were negative correlations for mean concentrations of TSH and T3 versus WFNS grade and a positive correlation for T3 versus GOS after 6 months, indicating that low concentrations of TSH and T3 were connected to worse SAH grade and poor outcome. All patients showed increased GH and IGF-1 concentrations irrespective of the grade of SAH or clinical course. Patients with a complicated clinical course showed a more pronounced fall in TSH and T3 concentrations and low serum T3 concentrations were related to a more serious SAH and poor patient outcome. These results need to be studied further and they may contribute to the accumulated knowledge needed to understand the complex mechanisms influencing the unpredictable clinical course after SAH.
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5.
  • Abdellah, Tebani, et al. (författare)
  • Annotation of pituitary neuroendocrine tumors with genome-wide expression analysis
  • 2021
  • Ingår i: Acta neuropathologica communications. - : BioMed Central (BMC). - 2051-5960. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Pituitary neuroendocrine tumors (PitNETs) are common, generally benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNETs can be classified based on the expression pattern of anterior pituitary hormones and three main transcriptions factors (TF), SF1, PIT1 and TPIT that regulate differentiation of adenohypophysial cells. Here, we have extended this classification based on the global transcriptomics landscape using tumor tissue from a well-defined cohort comprising 51 PitNETs of different clinical and histological types. The molecular profiles were compared with current classification schemes based on immunohistochemistry. Our results identified three main clusters of PitNETs that were aligned with the main pituitary TFs expression patterns. Our analyses enabled further identification of specific genes and expression patterns, including both known and unknown genes, that could distinguish the three different classes of PitNETs. We conclude that the current classification of PitNETs based on the expression of SF1, PIT1 and TPIT reflects three distinct subtypes of PitNETs with different underlying biology and partly independent from the expression of corresponding hormones. The transcriptomic analysis reveals several potentially targetable tumor-driving genes with previously unknown role in pituitary tumorigenesis.
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6.
  • Abrahamsson, Niclas, et al. (författare)
  • Gastric Bypass Surgery Elevates NT-ProBNP Levels
  • 2013
  • Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 23:9, s. 1421-1426
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundBrain natriuretic peptide (BNP) is produced in the heart in response to stretching of the myocardium. BNP levels are negatively correlated to obesity, and in obese subjects, a reduced BNP responsiveness has been described. Diet-induced weight loss has been found to lower or to have no effect on BNP levels, whereas gastric banding and gastric bypass have reported divergent results. We studied obese patients undergoing gastric bypass (GBP) surgery during follow-up of 1 year.MethodsTwenty patients, 18 women, mean 41 (SD 9.5) years old, with a mean preoperative BMI of 44.6 (SD 5.5) kg/m2 were examined. N-terminal pro-brain natriuretic peptide (NT-ProBNP), glucose and insulin were measured preoperatively, at day 6 and months 1, 6 and 12. In 14 of the patients, samples were also taken at days 1, 2 and 4.ResultsThe NT-ProBNP levels showed a marked increase during the postoperative week (from 54 pg/mL preop to 359 pg/mL on day 2 and fell to 155 on day 6). At 1 year, NT-ProBNP was 122 pg/mL (125 % increase, p = 0.01). Glucose, insulin and HOMA indices decreased shortly after surgery without correlation to NT-ProBNP change. Mean BMI was reduced from 44.6 to 30.5 kg/m2 at 1 year and was not related to NT-ProBNP change.ConclusionsThe data indicate that GBP surgery rapidly alters the tone of BNP release, by a mechanism not related to weight loss or to changes in glucometabolic parameters. The GBP-induced conversion of obese subjects, from low to high NT-ProBNP responders, is likely to influence the evaluation of cardiac function in GBP operated individuals.
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7.
  • Abrahamsson, Niclas, et al. (författare)
  • GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery : a potential new indication?
  • 2013
  • Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 169:6, s. 885-889
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia. Design: We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms. Results: Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements. Conclusion: These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.
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8.
  • Abrahamsson, Niclas, et al. (författare)
  • Hypoglycemia in everyday life after gastric bypass and duodenal switch
  • 2015
  • Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 173:1, s. 91-100
  • Tidskriftsartikel (refereegranskat)abstract
    • Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (< 3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P < 0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.
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9.
  • 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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10.
  • 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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