Your search history is empty.

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Clinical Endocrinology, Wiley, Vol. 97, No. 4 ( 2022-10), p. 448-459
    Abstract: Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours with malignant potential and a hereditary basis in almost 40% of patients. Germline genetic testing has transformed the management of PPGL enabling stratification of surveillance approaches, earlier diagnosis and predictive testing of at‐risk family members. Recent studies have identified somatic mutations in a further subset of patients, indicating that molecular drivers at either a germline or tumour level can be identified in up to 80% of PPGL cases. The aim of this study was to investigate the clinical utility of somatic sequencing in a large cohort of patients with PPGL in the United Kingdom. Design and Patients Prospectively collected matched germline and tumour samples (development cohort) and retrospectively collected tumour samples (validation cohort) of patients with PPGL were investigated. Measurements Clinical characteristics of patients were assessed and tumour and germline DNA was analysed using a next‐generation sequencing strategy. A screen for variants within ‘mutation hotspots’ in 68 human cancer genes was performed. Results Of 141 included patients, 45 (32%) had a germline mutation. In 37 (26%) patients one or more driver somatic variants were identified including 26 likely pathogenic or pathogenic variants and 19 variants of uncertain significance. Pathogenic somatic variants, observed in 25 (18%) patients, were most commonly identified in the VHL, NF1, HRAS and RET genes. Pathogenic somatic variants were almost exclusively identified in patients without a germline mutation (all but one), suggesting that somatic sequencing is likely to be most informative for those patients with negative germline genetic test results. Conclusions Somatic sequencing may further stratify surveillance approaches for patients without a germline genetic driver and may also inform targeted therapeutic strategies for patients with metastatic disease.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2004597-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Clinical Endocrinology, Wiley
    Abstract: Primary polydipsia is characterized by excessive fluid intake which may suppress vasopressin levels. It is speculated that suppressed vasopressin levels lead to a dysregulated hypothalamic–pituitary–adrenal (HPA) axis as vasopressin co‐modulates the HPA axis. However, data are contradictory. The aim of this study was to investigate markers of the HPA axis in patients with primary polydipsia compared to healthy controls. Design Exploratory analysis combining data from two different prospective observational studies. Patients We included 34 patients with primary polydipsia (68% females, median aged 29.5 years (interquartile range, IQR: 26.0, 38.8) and 20 healthy controls (55% females, median age 24.0 years [IQR: 22.0, 27.2]). Measurements The main outcome was difference in HPA axis activity assessed using circadian serum and salivary cortisol, 24‐h urinary free cortisol and cortisol levels before and after adrenocorticotropic hormone (ACTH) stimulation; vasopressin suppression was assessed measuring fasting copeptin levels between patients with primary polydipsia and healthy controls using Wilcoxon rank‐sum test. Results No difference was seen in circadian serum cortisol levels ( p  = .9), urinary free cortisol levels ( p  = .17) and serum cortisol in response to ACTH stimulation ( p  = .77) between groups. Circadian salivary cortisol levels were significantly lower in patients with primary polydipsia compared to healthy controls with an estimated difference of −3.7 nmol/L (95% CI: −5.5, −1.8 nmol/L, p   〈  .001). Fasting copeptin levels were significantly lower in patients with primary polydipsia compared to healthy volunteers ( p   〈  0.01). Conclusion Our results suggest no difference in HPA axis activity between patients with primary polydipsia and healthy controls. The observed difference in salivary cortisol levels may be linked to a dilution effect in saliva rather than an altered stress axis considering the other findings.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2004597-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: BMJ Medicine, BMJ, Vol. 2, No. 1 ( 2023-09), p. e000330-
    Abstract: To evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization, and to test newly proposed cut-off values. Design International, prospective, multicentre cohort study. Setting Six university or cantonal departments in Austria, Germany, and Switzerland, from 1 May 2016 to 31 January 2019. Participants Low risk cohort of 829 participants aged 18-45 years with singleton pregnancies attending first trimester screening and consenting to have an early 75 g OGTT at 12-15 weeks of gestation. Participants and healthcare providers were blinded to the results. Main outcome measures Fasting, one hour, and two hour plasma glucose concentrations after an early 75 g OGTT (12-15 weeks of gestation) and a late 75 g OGTT (24-28 weeks of gestation). Results Of 636 participants, 74 (12%) developed gestational diabetes mellitus, according to World Health Organization 2013 criteria, at 24-28 weeks of gestation. Applying WHO 2013 criteria to the early OGTT with at least one abnormal value gave a low sensitivity of 0.35 (95% confidence interval 0.24 to 0.47), high specificity of 0.96 (0.95 to 0.98), positive predictive value of 0.57 (0.41 to 0.71), negative predictive value of 0.92 (0.89 to 0.94), positive likelihood ratio of 10.46 (6.21 to 17.63), negative likelihood ratio of 0.65 (0.55 to 0.78), and diagnostic odds ratio of 15.98 (8.38 to 30.47). Lowering the postload glucose values (75 g OGTT cut-off values of 5.1, 8.9, and 7.8 mmol/L) improved the detection rate (53%, 95% confidence interval 41% to 64%) and negative predictive value (0.94, 0.91 to 0.95), but decreased the specificity (0.91, 0.88 to 0.93) and positive predictive value (0.42, 0.32 to 0.53) at a false positive rate of 9% (positive likelihood ratio 5.59, 4.0 to 7.81; negative likelihood ratio 0.64, 0.52 to 0.77; and diagnostic odds ratio 10.07, 6.26 to 18.31). Conclusions The results of this prospective low risk cohort study indicated that the 75 g OGTT as a screening tool in early pregnancy is not sensitive enough when applying WHO 2013 criteria. Postload glucose values were higher in early pregnancy complicated by diabetes in pregnancy. Lowering the postload cut-off values identified a high risk group for later development of gestational diabetes mellitus or those who might benefit from earlier treatment. Results from randomised controlled trials showing a beneficial effect of early intervention are unclear. Trial registration ClinicalTrials.gov NCT02035059 .
    Type of Medium: Online Resource
    ISSN: 2754-0413
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 3128592-2
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Trials, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2014-12)
    Type of Medium: Online Resource
    ISSN: 1745-6215
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2014
    detail.hit.zdb_id: 2040523-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A631-A631
    Abstract: Background: Oxytocin, secreted into the circulation through the posterior pituitary, regulates lactation, weight, and socio-behavioral functioning. Oxytocin deficiency has been suggested in patients with hypopituitarism, however, diagnostic testing for oxytocin deficiency has not been developed. Known stimuli used in the diagnosis of pituitary deficiencies - the hypertonic saline and arginine infusion tests stimulating copeptin levels, and the oral macimorelin test stimulating growth hormone levels - have also been shown to stimulate oxytocin secretion in animal models. We hypothesized that these provocation tests would stimulate plasma oxytocin levels in humans. Methods: Basal plasma oxytocin levels were measured for all three tests. Stimulated plasma oxytocin was measured once plasma sodium & gt;150 mmol/l for the hypertonic saline and after 45 minutes for the arginine infusion and the oral macimorelin test, expected peak of copeptin and growth hormone levels, respectively. Primary outcome was change between basal and stimulated oxytocin levels using a paired t-test. Results: Median (IQR) age of all participants was 24 years (22, 28), 51% were female. As expected, copeptin increased in response to hypertonic saline from 4.0 pmol/L [3.3, 6.7] to 34.2 pmol/L [23.2, 45.4] (p-value & lt;0.001) and in response to arginine infusion from 4.6 pmol/L [3.2, 6.2] to 8.3 pmol/L [6.4, 10.8] (p-value & lt;0.001). Growth hormone increased in response to oral macimorelin from 1.6 ng/mL [0.3, 17.2] to 106.0 ng/mL [73.3, 127.2] (p-value & lt;0.001). Oxytocin levels increased in response to hypertonic saline infusion from 0.3 pg/mL [0.3, 0.5] to 0.6 pg/mL [0.4, 0.7] (p-value 0.007), while there was no change in response to arginine infusion (basal 0.4 pg/mL [0.4, 0.6], stimulated 0.4 pg/mL [0.3, 0.6] , p-value 0.6), nor to oral macimorelin (basal 38.7 pg/mL [31.1, 66.9], stimulated 34.2 pg/mL [31.2, 48.2] , p-value 0.3). Conclusion: We found that hypertonic saline infusion results in doubling of oxytocin levels. Further research will be important to determine whether this test could be used diagnostically to identify patients with oxytocin deficiency. In contrast to animal data, arginine and macimorelin did not stimulate oxytocin.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A514-A515
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A514-A515
    Abstract: Background Primary polydipsia, characterized by excessive fluid intake, carries the risk of water intoxication and hyponatremia, but treatment options are scarce. Glucagon-like peptide-1 (GLP-1) reduces appetite and food intake. In experimental models, they also play a role in thirst and drinking behavior in. The aim of this trial was to investigate whether GLP-1 receptor agonists reduce fluid intake in patients with primary polydipsia. Methods: In this randomized, double-blind, placebo-controlled, 3-week crossover-trial, 34 patients with primary polydipsia received weekly dulaglutide (Trulicity®) 1.5mg and placebo (0.9% sodium chloride). During the last treatment week, patients attended an 8-hour evaluation visit with free water access. The primary endpoint was total fluid intake during the evaluation visits. The treatment effect was estimated using a linear mixed-effects model. In a subset of 15 patients and matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI. Results Median [IQR] total fluid intake was 2250ml [1600-2600] on dulaglutide versus 2400ml [1850-3400] on placebo. Patients on dulaglutide reduced fluid intake by 490ml [95%-CI -780, -199] , p=0.002, corresponding to a relative reduction of 17%. 24-hour urinary output was reduced by -943ml [95%-CI -1473, -413]. Thirst perception in response to beverage pictures was higher in patients with primary polydipsia versus controls and lower on dulaglutide versus placebo, but functional neuronal activity was similar between groups and treatments. Conclusion: GLP-1 receptor agonists reduce fluid intake and thirst perception in patients with primary polydipsia and could therefore be a novel treatment option for these patients.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Online Resource
    Online Resource
    The Endocrine Society ; 2022
    In:  Journal of the Endocrine Society Vol. 6, No. Supplement_1 ( 2022-11-01), p. A585-A586
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 6, No. Supplement_1 ( 2022-11-01), p. A585-A586
    Abstract: Differential diagnosis of hyponatremia is challenging, particularly for thiazide associated hyponatremia (TAH), as patients might have either volume depletion in need for fluid substitution or syndrome of inappropriate antidiuresis (SIAD)-like presentation requiring fluid restriction. Urine indices are of little utility, because they are influenced by thiazide therapy. Apparent strong ion difference (aSID) describes the relation between sodium, potassium and chloride in serum and is used in evaluation of acid-base disorders according to Stewart model. aSID could help in the differential diagnosis of TAH because a value & gt;40 identifies patients with contraction alkalosis due to relative hypochloremia, and hypochloremic alkalosis is a well-known possible adverse effect of thiazide diuretics. Material and Methods This was a post-hoc analysis of prospectively collected data of hospitalized patients with hypotonic hyponatremia & lt;125 mmol/l. TAH patients were divided according to treatment response in patients needing intravenous fluid substitution or fluid restriction. Treatment response was defined as a sodium increase of at least 4 mmol/l/die or & gt;130 mmol/l based on chart review. aSID at baseline was calculated with the formula serum sodium plus potassium minus chloride and a value & gt;40 was used to identify volume-depleted TAH patients. Descriptive analysis was carried out to find differences between volume-depleted and SIAD-like TAH patients, and patients with SIAD without thiazide use. Logistic regression and ROC curves were computed to investigate the role of aSID & gt;40 for differential diagnosis of hyponatremia in TAH patients, in addition to known factors for identifying SIAD patients as body mass index (BMI) and fractioned uric acid excretion (FUA) with the previous described cut-off of 12%. Results Out of 303 hyponatremia patients, 131 (43.2%) had a TAH and 75 (24.8%) SIAD without thiazide use. Among TAH patients, 81 (61.8%) were successfully treated with fluid substitution and 31 (23.7%) with fluid restriction. 19 patients (14.5%) were excluded as they received no treatment, or needed to switch treatment during hospitalization. No differences in baseline characteristics were seen between patients with SIAD and SIAD-like TAH patients, except for BMI, lower in SIAD patients (mean(SD) 23.5(5.1) vs 27.0(5.7) kg/m2, p=0.003). A higher BMI and a FUA & lt;12% had a sensitivity of 84% with a specificity of 60% in identifying volume-depleted TAH patients. Adding aSID & gt;40 improved the specificity to 74% maintaining a sensitivity to 82%. Conclusion In hospitalized patients with TAH, calculation of aSID may help differentiating patients with volume depletion in need of fluid substitution from SIAD-like manifestation requiring fluid restriction. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:37 p.m. - 12:42 p.m.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2881023-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: F. Baur: None. D. Coynel: None. C. Atila: None. S. Lengsfeld: None. T. Burkard: None. A. Meienberg: None. C. Bathelt: None. M. Christ-Crain: None. B.F. Winzeler: None. Introduction: Smoking harms women more than men and women seem to be less successful in quitting. Greater concerns about post-cessational weight in women and gender differences in craving and reward processing have been postulated as possible explanations. Our group recently showed that the GLP-1 analogue dulaglutide reduces post-cessational weight gain. We hypothesize that women compared to men might profit more from the weight-lowering effects of dulaglutide in terms of abstinence rates. Methods: This is a predefined secondary analysis of a placebo-controlled, double-blind, single-center randomized trial including 255 daily smokers (155 women, 100 men). Participants received weekly dulaglutide (1.5mg) or placebo (0.9% sodium chloride) subcutaneous injections for 12 weeks in addition to standardized smoking cessation care. Smoking status was self-reported and confirmed by end-expiratory carbon monoxide measurement. We analyzed gender differences after 12 weeks of dulaglutide / placebo treatment in weight change, abstinence rates and craving assessed by a visual analogue scale (VAS, minimum 1, maximum 10). Additionally, fMRI was performed in a subset of participants and craving and neuronal activity in response to smoking cue videos were examined for gender differences. Results: Median [IQR] age at inclusion was 42 [32,53] years in females and 44 [34,53] years in males. Mean (SD) BMI was 26.0 (5.0) kg/m² and 28.9 (4.9) kg/m², respectively. After 12 weeks, 61% of females in the dulaglutide and 65% in the placebo group were abstinent, compared to 66% and 64% of male participants. Among quitters, there were no gender differences in absolute or percentual weight change neither on dulaglutide (difference: 0.2 kg, 95%-CI [-1.2, 1.6] ; p=0.762 / 0.7%, 95%-CI [-0.9, 2.3]; p= 0.382) nor on placebo treatment (difference: 0.0 kg, 95%-CI [-1.0, 1.0] ; p=0.954 / -0.6 %, 95%-CI [-1.8, 0.6]; p=0.340).There is no evidence for either a direct association of gender with change in craving (mean difference females vs. males: 0.05 points, 95%-CI [-1.34, 1.43] , p= 0.947) or that the effect of gender on change in craving might depend on dulaglutide treatment (interaction term: p=0.712). Smoking cessation was directly associated with a decline in craving (mean difference quitters vs. persistent smokers: -3.07 points, 95%-CI [-4.67, -1.47], p & lt;0.001); however, this did not depend on gender (interaction term: p=0.380). Data of the fMRI substudy are currently being analyzed and will be presented at the congress. CONCLUSION: Our data showed similar abstinence rates, post-cessational weight changes and craving intensity in females and males. Presentation: Friday, June 16, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2881023-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: International Journal of Endocrinology, Hindawi Limited, Vol. 2017 ( 2017), p. 1-8
    Abstract: Objective . Syndrome of inappropriate antidiuresis (SIADH) is the predominant cause of hyponatremia, but treatment options are unsatisfying. SGLT2 inhibitors increase urinary glucose excretion with concomitant osmotic diuresis. We therefore hypothesized SGLT2-inhibitors as a novel treatment for SIADH. Design . Double-blind placebo-controlled randomised crossover study in 14 healthy volunteers. Methods . We induced an artificial SIADH model by administration of desmopressin and overhydration. Afterwards, empagliflozin 25 mg or placebo was given in random order. The main outcomes were total urinary excretion, glucosuria, and the area under the curve (AUC) of serum sodium concentration. Outcome measures were obtained 2–8 hours after administration of study drug. Results . 14 participants (64% males), BMI 23 kg/m 2 (±2.4), aged 28.6 years (±9), completed the study. Empagliflozin led to significantly increased total urinary excretion (579.3 ml (±194.8) versus 367.3 ml (±158.8); treatment effect 158 ml (CI 48.29, 267.74), p = 0.017 ) due to glucosuria (74.18 mmol (±22.3) versus 0.12 mmol (±0.04); treatment effect (log scale) 2.85 (CI 2.75, 2.96), p 〈 0.001 ). There was no difference in the AUC of serum sodium concentration (treatment effect 0.2 (CI −7.38, 6.98), p = 0.96 ). Conclusion . In our SIADH model, empagliflozin increased urinary excretion due to osmotic diuresis. Due to the short treatment duration, serum sodium levels remained unchanged. Real-live studies are needed to further examine empagliflozin as a new treatment for SIADH.
    Type of Medium: Online Resource
    ISSN: 1687-8337 , 1687-8345
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2502951-4
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Journal of Perinatal Medicine, Walter de Gruyter GmbH, Vol. 45, No. 3 ( 2017-01-1)
    Abstract: The aim was to evaluate the influence of the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) guidelines for screening of gestational diabetes mellitus (GDM) on GDM prevalence in a cohort from a Swiss tertiary hospital. Methods: This was a retrospective cohort study involving all pregnant women who were screened for GDM between 24 and 28 weeks of gestation. From 2008 until 2010 (period 1), a two-step approach with 1-h 50 g glucose challenge test (GCT) was used, followed by fasting, 1- and 2-h glucose measurements after a 75 g oral glucose tolerance test (OGTT) in case of a positive GCT. From 2010 until 2013 (period 2), all pregnant women were tested with a one-step 75 g OGTT according to new IADPSG guidelines. In both periods, women with risk factors could be screened directly with a 75 g OGTT in early pregnancy. Results: Overall, 647 women were eligible for the study in period 1 and 720 in period 2. The introduction of the IADPSG criteria resulted in an absolute increase of GDM prevalence of 8.5% (3.3% in period 1 to 11.8% in period 2). Conclusions: The adoption of the IADPSG criteria resulted in a considerable increase in GDM diagnosis in our Swiss cohort. Further studies are needed to investigate if the screening is cost effective and if treatment of our additionally diagnosed GDM mothers might improve short-term as well as long-term outcome.
    Type of Medium: Online Resource
    ISSN: 1619-3997 , 0300-5577
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2017
    detail.hit.zdb_id: 1467968-1
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages