| 11. |
- Bengtsson, Daniel, et al.
(författare)
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Psychotropic Drugs in Patients with Cushing's Disease Before Diagnosis and at Long-Term Follow-Up: A Nationwide Study
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:6, s. 1750-1760
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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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| 12. |
- Bergthorsdottir, R, et al.
(författare)
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Health-Related Quality of Life In Patients With Adrenal Insufficiency Receiving Plenadren Compared With Immediate-Release Hydrocortisone
- 2015
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Ingår i: Value in Health. - : Elsevier. - 1098-3015 .- 1524-4733. ; 18:7
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrevious studies in patients with primary adrenal insufficiency (PAI) on conventional replacement therapy suggest decreased health-related quality of life (HRQoL), and that patients report more frequently fatigue, increased anxiety and inability to work compared to background population.ObjectivesTo study self-reported health status with EQ-5D in patients with PAI. Patients treated with Plenadren (modified-release hydrocortisone) were compared with patients treated with immediate release hydrocortisone (IRHC) replacement therapy.MethodsThis was a cross-sectional, multi-centre, non-interventional survey of patients with PAI receiving Plenadren or immediate release hydrocortisone (IRHC) replacement.SubjectsOne hundred thirty-four adult patients with PAI of whom 36 (19 females [53%]) were treated with Plenadren and 98 (77 females [79%]) were treated with IRHC, were included.MAIN OUTCOME MEASUREHRQoL described by the EQ-5D, a generic preference-based measure of health.RESULTSPatients on Plenadren and on IRHC had a mean ± SD age of 53.1 ± 12.7 years and 48.0 ± 13.1 years, respectively (P=0.043). The majority of the patients were diagnosed more than 5 years ago (69%). The mean ± SD daily Plenadren and IRHC doses were 27.0 ± 6.8 mg and 26.6 ± 10.9 mg, respectively (P=0.807). 47% of the Plenadren patients had been receiving Plenadren and 82% of the IRHC patients had been receiving IRHC for more than 3 years. Patients receiving Plenadren had better HRQoL measured by the EQ-5D questionnaire compared to patients replaced with IRHC (0.76 ± 0.18 vs 0.68 ± 0.18, respectively [P=0.040]).CONCLUSIONSReplacement therapy with Plenadren in patients with PAI confers measurable benefit on HRQoL relative to IRHC as estimated by the EQ-5D questionnaire, and may therefore be advantageous when compared to IRHC substitution.
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| 13. |
- Blomgren, J, et al.
(författare)
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Non-physiological levels of circulating cortisol in growth hormone-treated hypopituitary adults after conventional cortisone substitution
- 2004
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 64:2, s. 132-139
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the usefulness of measuring plasma cortisol profiles in growth hormone-treated hypopituitary adults and to compare these with cortisol levels in healthy controls. Methods: Eleven ACTH-deficient adult patients received 12.5 mg cortisone-acetate orally at 16.00 h and 25 mg at 07.00 h. The patients arrived in the ward at 12.00 h. After tablet intake at 16.00 h, samples for serum cortisol were taken at hourly intervals for the next 24 h, except between 07.00 and 12.00 h when samples were drawn every half hour, 24-h urinary free cortisol (24-h-UFC) excretion was collected simultaneously. For comparison, 8 healthy controls were investigated. Results: The patients had circulating cortisol levels with very low plasma cortisol at 07.00 h before their morning dose of cortisone acetate. At the same time period, controls had their highest plasma cortisol levels. After tablet intake the patients had a rapid initial absorption of cortisol, but a marked variability in the morning peak levels (Cmax), and the Cmax was in general higher and occurred 90 min later than the Cmax in the controls. The 24-h-UFC excretion and 24-h area under the curve (24-h-AUC) did not differ between patients and controls. The female patients had higher 24-h-AUC for plasma cortisol (p=0.032) and tended to have higher plasma cortisol peaks in the morning, but had levels of 24-h-UFC similar to those of the male patients. Conclusions: Conventional cortisone substitution with a twice-daily replacement regimen in hypopituitary adults results in abnormal circulating cortisol profiles with low or non-measurable morning values and variable individual peaks. This suggests that the present dosing schemes have to be improved and that cortisone substitution should be individualized.
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| 14. |
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| 15. |
- Burman, Pia, et al.
(författare)
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Limited value of cabergoline in Cushing's disease : a prospective study of a 6-week treatment in 20 patients
- 2016
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 174:1, s. 17-24
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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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| 16. |
- Casar Borota, Olivera, et al.
(författare)
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Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:4, s. 1183-1194
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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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| 17. |
- Davidson, Lee Ti, et al.
(författare)
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Admission of patients with chest pain and/or breathlessness from the emergency department in relation to risk assessment and copeptin levels - an observational study
- 2022
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Ingår i: Upsala Journal of Medical Sciences. - : UPSALA MED SOC. - 0300-9734 .- 2000-1967. ; 127:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the most critical decisions that emergency department (ED) physicians make is the discharge versus admission of patients. We aimed to study the association of the decision in the ED to admit patients with chest pain and/or breathlessness to a ward with risk assessment using the Rapid Emergency Triage and Treatment System (RETTS), the National Early Warning Score (NEWS), and plasma levels of the biomarkers copeptin, midregional proadrenomedulin (MR-proADM), and midregional proatrial natriuretic peptide (MR-proANP). Methods: Patients presenting at the ED with chest pain and/or breathlessness with less than one week onset were enrolled. Patients were triaged according to RETTS. NEWS was calculated from the vital signs retrospectively. Results: Three hundred and thirty-four patients (167 males), mean age 63.8 +/- 16.8 years, were included. Of which, 210 (62.8%) patients complained of chest pain, 65 (19.5%) of breathlessness, and 59 (17.7%) of both. Of these, 176 (52.7%) patients were admitted to a ward, and 158 (47.3%) patients were discharged from the ED. In binary logistic models, age, gender, vital signs (O-2 saturation and heart rate), NEWS class, and copeptin were associated with admission to a ward from the ED. In receiver-operating-characteristics (ROC) analysis, copeptin had an incremental predictive value compared to NEWS alone (P = 0.002). Conclusions: Emergency physicians decisions to admit patients with chest pain and/or breathlessness from the ED to a ward are related to age, O-2 saturation, heart rate, NEWS category, and copeptin. As an independent predictive marker for admission, early analysis of copeptin might be beneficial when improving patient pathways at the ED.
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| 18. |
- Ekman, Agneta, et al.
(författare)
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Fusk hotar tilliten till blivande läkares professionalitet
- 2018
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; :115
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Det är med stor sorg vi noterat att några studenter valt att fuska sig till en plats på läkarutbildningarna. Vi förväntar oss nu att Universitets- och högskolerådet skärper säkerheten vid högskoleprovet för att förhindra att fusket fortsätter och att utredningen om vilka som fuskat sig in på utbildningarna drivs vidare.
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| 19. |
- Ekman, Bertil, et al.
(författare)
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A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults
- 2002
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 147:1, s. 49-57
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I.DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects.RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study.CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.
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| 20. |
- Ekman, Bertil, et al.
(författare)
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A randomised double blind crossover study comparing two and four dose hydrocortisone regimen with regard to quality for life, cortisol and ACTH profiles in patients with primary adrenal insufficiency
- 2012
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Ingår i: Clinical Endocrinology. - : Wiley-Blackwell. - 0300-0664 .- 1365-2265. ; 77:1, s. 18-25
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Tidskriftsartikel (refereegranskat)abstract
- ContextCurrent guidelines on how to divide the daily cortisol substitution dose in patients with primary adrenal insufficiency (PAI) are controversial and mainly based on empirical data.ObjectiveTo assess how an equal dose of hydrocortisone given either four times daily or twice daily influence diurnal profiles of cortisol and ACTH, patient preferences and health related quality of life (HRQoL).DesignDouble blind, crossover.MethodsFifteen patients with PAI (6 women) were included. Capsules of hydrocortisone or placebo were given at 07:00, 12:00, 16:00 and 22:00 h in 4-week treatment periods: either one period with four doses (10+10+5+5 mg) or one period with two doses (20+0+10+0 mg). Diurnal profiles of cortisol and ACTH were collected and area under the curve (AUC) was calculated. Questionnaires were used to evaluate patient preferences and HRQoL.ResultsThe four-dose regimen gave a higher serum cortisol before tablet intake in the morning (P = 0.027) and a higher 24-h-cortisolAUC (P < 0.0001) compared with the two-dose period. In contrast a lower median plasma ACTH in the morning before tablet intake (P = 0.003) and a lower 24-h-ln(ACTHAUC) were found during the four-dose period. The patients preferred the four-dose regimen (P = 0.03), and the HRQoL scores tended to be higher (high score indicates better HRQoL) for the four-dose period.In summary a four-dose regimen gives increased availability of cortisol and an enhanced effect with a less elevated ACTH in the morning in comparison with a two-dose regimen but the effect on HRQoL remains inconclusive.
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