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Sökning: WFRF:(Berinder Katarina)

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11.
  • Bengtsson, Daniel, 1975-, 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 and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197.
  • 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 (OR 2.2[95%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[1.5-3.9]) 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 (IQR 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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12.
  • Berinder, Katarina (författare)
  • Patients with hyperprolactinemia clinical and epidemiological perspectives
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Hyperprolactinemia (HPL) is the most common endocrine disorder of the hypothalamicpituitary axis and prolactinomas the most frequent pituitary tumour. A majority of the patients are women in reproductive age seeking health care for menstrual disorders or infertility. Because a majority of the patients are relatively young at diagnosis and the medical treatment often life-long, it is essential to study the efficacy of treatment and longterm results in these patients. Data are lacking in women with HPL concerning parity and there is still a void of studies evaluating cancer risk and whether the metabolic state is altered in patients with elevated prolactin (PRL) levels. This thesis, which contains four studies addressing these issues, is aimed to improve our knowledge and the quality of clinical management in patients with HPL. Long-term outcome of treatment: A total of 271 women with HPL were retrospectively evaluated. At diagnosis, 87% of the women presented with menstrual disturbances and 47% had galactorrhea. The outcome after up to 29 years of clinical follow-up (median 9.3 years) showed a good treatment result with restoration of menses and galactorrhea in 94% of the women. Medical therapy with dopamine (DA) agonists normalised PRL levels in 71% of the patients and 80% had a total or partial degree of tumour reduction. Fifty-three per cent (9 of 17) of the surgically treated patients and one third (three of nine) of the patients treated with radiotherapy exhibited long-term normalisation of PRL levels without medical treatment. Parity and pregnancy outcome: In this matched cohort study (271 women with HPL and 1084 comparison subjects) a reduced parity was found in HPL patients, mainly because there were more nulliparous women and fewer women with more than two children. Parity was inversely associated with HPL status (P for trend =0.0009). No increased risk of pregnancy or delivery complications was found. In addition, outcomes of the newborns did not differ between patients and controls. Cancer risk: A small, though significant, increased risk of overall cancer was found in 969 patients with HPL (668 women and 301 men) as compared with matched comparison subjects (hazard ratio [HR] 1.31; 95% CI 1.02-1.68) which was mainly due to increased risk of upper gastrointestinal cancer in all patients and hematopoietic cancer in females. Risk of breast cancer did not differ between patients and controls. Furthermore, a reduced risk of prostate cancer by 60% was found in HPL men (HR 0.40; 95% CI 0.16-0.99). Metabolic assessment: Evaluation of 14 consecutive patients with prolactinomas (eight women and six men) before and after normalisation of PRL levels by DA agonist therapy revealed that HPL men had an unfavourable metabolic profile at diagnosis. After therapy, a significant decrease of body weight, waist circumference and body fat% was found in the men. A positive correlation between PRL levels and low-density lipoprotein (LDL) cholesterol at diagnosis was seen and LDL cholesterol decreased after 2 months of DA agonist treatment. Furthermore, peripheral insulin sensitivity evaluated with a euglycemic hyperinsulinemic clamp tended to improve after therapy. This improvement was associated with a reduction in PRL levels. In conclusion, the results of this thesis show that HPL patients can be effectively treated with DA agonists in the long-term perspective and emphasise its role as first-line therapy. Women treated for HPL have a reduced parity, but there are no increased risks during pregnancy or for their offspring. The small increased risk of cancer that was found in HPL patients and the possible negative effect of elevated PRL levels on metabolic state need to be further evaluated; however, it implies the need for an active treatment approach and close follow-up of patients with HPL.
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13.
  • Bäcklund, Nils, et al. (författare)
  • Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushings syndrome
  • 2020
  • Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 182:6, s. 569-582
  • Tidskriftsartikel (refereegranskat)abstract
    • The challenge of diagnosing Cushings syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST).
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14.
  • Casar Borota, Olivera, et al. (författare)
  • Corticotroph aggressive pituitary tumours and carcinomas frequently harbour ATRX mutations
  • 2021
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - 0021-972X .- 1945-7197. ; 106:4, s. 1183-1194
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Aggressive pituitary tumours (APTs) are characterised by unusually rapid growth and lack of response to standard treatment. About 1-2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumours are overrepresented amongst APTs and PCs. Mutations in the ATRX gene, regulating chromatin remodelling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumours.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 tumours lacking ATRX immunolabeling, mutational status of the ATRX gene was explored.RESULTS: Nine of the 48 tumours (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 tumours, 7/22 (32%), vs 2/24 (8%) in the tumours of the Pit-1 lineage. Loss-of-function ATRX mutations were found in all the nine ATRX immuno-negative cases: nonsense mutations (n=4), frameshift deletions (n=4) and large deletions affecting 22-28 of the 36 exons (n=3). More than one ATRX gene defect was identified in two PCs.CONCLUSION: ATRX mutations occur in a subset of aggressive pituitary tumours and are more common in corticotroph tumours. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumours.
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15.
  • Papakokkinou, Eleni, et al. (författare)
  • Excess Morbidity Persists in Patients with Cushing's Disease during Long-term Remission - A Swedish Nationwide Study.
  • 2020
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 105:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.To investigate comorbidities in patients with CD.A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (a) during the 3 years before diagnosis, (b) from diagnosis to 1 year after remission, and (c) during long-term remission.We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range, 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4, 1.2 to 11.4), fractures (4.9, 2.7 to 8.3), and deep vein thrombosis (13.8, 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs were increased for thromboembolism (18.3, 7.9 to 36.0), stroke (4.9, 1.3 to 12.5), and sepsis (13.6, 3.7 to 34.8). SIRs for thromboembolism (4.9, 2.6 to 8.4), stroke (3.1, 1.8 to 4.9), and sepsis (6.0, 3.1 to 10.6) remained increased during long-term remission.Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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16.
  • Papakokkinou, Eleni, et al. (författare)
  • Excess Morbidity Persists in Patients With Cushings Disease During Long-term Remission: A Swedish Nationwide Study
  • 2020
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 105:8, s. 2616-2624
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Whether multisystem morbidity in Cushings disease (CD) remains elevated during long-term remission is still undetermined. Objective: To investigate comorbidities in patients with CD. Design, Setting, and Patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status. Main Outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (Os) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission. Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission. Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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17.
  • Papakokkinou, Eleni, et al. (författare)
  • Prevalence of Nelsons syndrome after bilateral adrenalectomy in patients with cushings disease : a systematic review and meta-analysis
  • 2021
  • Ingår i: Pituitary. - : Springer. - 1386-341X .- 1573-7403.
  • Forskningsöversikt (refereegranskat)abstract
    • Purpose Bilateral adrenalectomy (BA) still plays an important role in the management of Cushings disease (CD). Nelsons 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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18.
  • 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 (I2 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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19.
  • 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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20.
  • Ragnarsson, Oskar, et al. (författare)
  • The incidence of Cushings disease: a nationwide Swedish study
  • 2019
  • Ingår i: Pituitary. - : SPRINGER. - 1386-341X .- 1573-7403. ; 22:2, s. 179-186
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundStudies on the incidence of Cushings 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.MethodsPatients registered with a diagnostic code for Cushings 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.ResultsOf 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 (Pamp;lt;0.05).ConclusionThe 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.
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