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  • 1
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    OR20-06 Diagnosing Central Diabetes Insipidus Using Copeptin Upon Hypertonic Saline Versus Arginine Stimulation
    The Endocrine Society ; 2023
    In:  Journal of the Endocrine Society Vol. 7, No. Supplement_1 ( 2023-10-05)
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: J. Refardt: None. C. Atila: None. I.O. Chifu: None. E. Ferrante: None. Z. Erlic: None. J.B. Drummond: None. B. Mantovani: None. R. Drexhage: None. C.O. Sailer: None. A. Widmer: None. S. Felder: None. A.S. Powlson: None. N. Hutter: None. D. Vogt: None. M. Gurnell: None. B. Rocha: None. J. Hofland: None. F. Beuschlein: None. M. Fassnacht: None. B.F. Winzeler: None. M. Christ-Crain: None. Background: The main challenge in the diagnosis of central diabetes insipidus (cDI) is its distinction against primary polydipsia (PP). Hypertonic saline stimulated copeptin has a high diagnostic accuracy of 97%, but comprises discomfort for patients and requires close sodium monitoring. Arginine stimulated copeptin showed similar diagnostic accuracy of 93% with better tolerability, but a head-to-head comparison is lacking. We hypothesized that arginine stimulated copeptin is non-inferior (non-inferiority margin 10%) to hypertonic saline stimulated copeptin for the diagnosis of cDI. Methods: In this prospective randomized multicentre study conducted between 2018-2022 in seven tertiary medical centres, consecutive patients with cDI and PP underwent diagnostic evaluation with hypertonic saline and arginine stimulation. Serum copeptin levels were measured at sodium-level of & gt;149 mmol/L after hypertonic saline and 60 minutes after arginine infusion, respectively. The final diagnosis was made after treatment response assessment at three-month follow-up blinded to copeptin levels. The main outcome measure was the overall diagnostic accuracy using the pre-defined copeptin cut-off of 4.9 pmol/L for hypertonic saline and 3.8 pmol/L for arginine stimulation. Results: 158 patients underwent both tests, of which 69 (44%) were diagnosed with cDI and 89 (56%) with PP. Forty-one (59%) patients had a complete and 28 (41%) patients had partial cDI. The diagnostic accuracy [95% CI] to differentiate patients with cDI from patients with PP was 95.6% [91.1,97.8] for hypertonic saline stimulated copeptin compared to 74.4% [67.0, 80.6] for arginine stimulated copeptin. Accordingly, arginine stimulation was inferior to hypertonic saline stimulation (estimated difference [95% CI] -21.2% [-28.7, -14.3] ). Side effects were less frequent and less severe under arginine stimulation, resulting in a clear 72% of patients preferring the arginine stimulation over hypertonic saline stimulation. In addition, arginine stimulated copeptin of 3.0 pmol/L diagnosed cDI with a specificity of 90.9% (sensitivity of 59.5%), while a cut-off of 5.2 pmol/L diagnosed PP with a specificity of 91.4% (sensitivity of 56.4%). Conclusion: In the diagnostic evaluation of cDI, copeptin upon hypertonic saline stimulation was superior to arginine stimulation. Arginine stimulation can be used as a first well-tolerated test diagnosing & gt;50% of patients with high accuracy, but hypertonic saline stimulation remains the test with the highest diagnostic accuracy. Presentation: Saturday, June 17, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvad114.1315
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2881023-5
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  • 2
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    THU122 Effects Of A GLP-1 Agonist On Consumption Of Alcohol In Patients Treated For Smoking Cessation
    The Endocrine Society ; 2023
    In:  Journal of the Endocrine Society Vol. 7, No. Supplement_1 ( 2023-10-05)
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: L.S. Probst: None. S. Monnerat: None. S. Lengsfeld: None. C. Bathelt: None. A. Meienberg: None. T. Burkard: None. M. Christ-crain: None. B.F. Winzeler: None. Introduction: Alcohol use disorder causes high socio-economic costs and has a detrimental impact on health globally, being considered a key factor contributing to non-communicable diseases. In Switzerland four substances are currently approved for treatment of alcohol use disorder with only limited to moderate effects. Thus, the need for new treatment options in alcohol and substance use disorder is evident. Recent research has shed light on a new potential target for treatment of addiction: a body of preclinical studies provide evidence for the attenuating effects of GLP-1 agonists on addictive behavior in rodents and non-human primates. A few studies have shown a link between GLP-1 receptors and reward related processes in humans, and a trial from denmark examined the effect of exenatide in patients treated for alcohol use disorder, however clinical data are scarce and results remain inconclusive. Methods: This is a secondary analysis of the SKIP study, a double-blind, randomized, placebo-controlled trial to evaluate treatment with the GLP-1 agonist dulaglutide (Trulicy®) as a new therapy for smoking cessation. In the present analysis, the primary objective was to assess differences in alcohol consumption after 12 weeks of treatment with dulaglutide compared to placebo in alcohol-consuming smokers willing to quit smoking. We selected patients out of the cohort (n=255) who consumed alcohol at baseline and completed 12 weeks of treatment (n= 151). The independent effect of dulaglutide on alcohol consumption was analysed by fitting a multivariate generalized linear regression model with quasipoisson distribution and adjustment for baseline alcohol consumption. Preliminary Results: One hundred and fifty-one patients (placebo n=75, dulaglutide n=76) were included in the primary analysis. Baseline patient characteristics were well balanced between groups. The median age was 42 [IQR 33, 53] years with 61% (n=92) females. At baseline, patients in both treatment groups consumed 3 [IQR 2, 7] standard glasses of alcohol per week on average. At week 12, patients in the dulaglutide group drank an estimated 29% (IRR = 0.71; 95% CI 0.52, 0.97; p=0.04) less compared to the placebo group. For each additional glass consumed at baseline, alcohol consumption at week 12 increased by 6% (95% CI 5, 7; p & lt;0.001). Conclusion: These preliminary findings suggest that in patients who drink, alcohol intake tends to increase during smoking cessation. In the present analysis we were able to show that this increase was attenuated by the addition of a 12-week treatment with dulaglutide to standard smoking cessation therapy. Presentation: Thursday, June 15, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvad114.1200
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
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  • 3
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    THU113 Psychopathological Characteristics In Patients With Arginine Vasopressin Deficiency (Central Diabetes Insipidus) And Primary Polydipsia
    The Endocrine Society ; 2023
    In:  Journal of the Endocrine Society Vol. 7, No. Supplement_1 ( 2023-10-05)
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: J. Beck: None. C. Atila: None. J. Refardt: None. Z. Erlic: None. J.B. Drummond: None. B.S. Soares: None. F. Beuschlein: None. B.F. Winzeler: None. M. Christ-Crain: None. Introduction The differential diagnosis between arginine vasopressin deficiency (AVP-D), formally known as central diabetes insipidus, and primary polydipsia (PP) is challenging. In clinical routine, psychopathologic findings are often used as a hallmark for diagnosing PP; thus, it is often referred to as psychogenic polydipsia. Yet, psychopathologic characteristics are barely assessed in patients with AVP-D, and to date, no data exist comparing AVP-D and PP with regard to these features. Therefore, in this study, we aimed to compare levels of anxiety, depression, alexithymia, and overall mental health in patients with AVP-D and PP. Methods This study combined data from two diagnostic studies conducted at three tertiary medical centers. In total, 82 participants (n=39 with AVP-D, n=28 with PP, and n=15 healthy controls [HC]) underwent a psychological evaluation with standardized questionnaires at study inclusion. Anxiety levels were assessed using the State-Trait Anxiety Inventory, mood using the Beck’s Depression Inventory, alexithymia using the Toronto Alexithymia Scale, and overall physical and mental health using the Short Form 36 Health Survey (SF-36). Higher STAI, BDI, and TAS scores indicate higher anxiety, depression, and alexithymia levels. Higher SF-36 scores indicate better health and less disability. Results Compared with HC, patients with AVP-D and PP showed increased levels of anxiety (HC 28 points [24, 31] vs. AVP-D 36 points [31, 45], p & lt;0.01; vs. PP 38 points [33, 46], p & lt;0.01), depression (HC one point [0, 2] vs. AVP-D 7 points [4, 14] , p & lt;0.01; vs. PP 7 points [3, 13], p & lt;0.01), and alexithymia (HC 30 points [29, 37] vs. AVP-D 43 points [35, 54] , p & lt;0.01; vs. PP 46 points [37, 55], p & lt;0.01). Levels of anxiety, depression, and alexithymia showed no difference between patients with AVP-D and PP (p=0.58, p=0.90, p=0.50). Compared with HC, patients with AVP-D and PP reported comparable reduced self-reported mental health scores (HC 84 [68, 88] vs. AVP-D 60 [52, 80] , p=0.05; vs PP 60 [47, 74], p & lt;0.01). Conclusion This is the first study demonstrating comparable increased levels of anxiety, depression, alexithymia, and overall reduced mental health in patients with AVP-D and PP. Based on these data, psychopathological findings should not be used as a hallmark to differentiate between both conditions. Presentation: Thursday, June 15, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvad114.1191
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
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  • 4
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    FRI068 Gender Differences In Smoking Cessation? Results Of A Randomized Controlled Trial Of Dulaglutide-assisted Smoking Cessation
    The Endocrine Society ; 2023
    In:  Journal of the Endocrine Society Vol. 7, No. Supplement_1 ( 2023-10-05)
    Details
    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
    URL: Article
    DOI: 10.1210/jendso/bvad114.078
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
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  • 5
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    Oxytocin Levels in Response to Pituitary Provocation Tests in Healthy Volunteers
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A631-A631
    Details
    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
    URL: Article
    DOI: 10.1210/jendso/bvab048.1286
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 6
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    GLP1 Receptor Agonists Reduce Fluid Intake in Primary Polydipsia
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A514-A515
    Details
    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
    URL: Article
    DOI: 10.1210/jendso/bvab048.1052
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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