Publications by authors named "Mirjam Christ-Crain"

260 Publications

Hyponatremia Intervention Trial (HIT): Study Protocol of a Randomized, Controlled, Parallel-Group Trial With Blinded Outcome Assessment.

Front Med (Lausanne) 2021 6;8:729545. Epub 2021 Sep 6.

Departments of Endocrinology, Diabetology and Metabolism University Hospital Basel, Basel, Switzerland.

Hyponatremia is the most common electrolyte disorder with a prevalence of up to 30% in hospitalized patients. In contrast to acute hyponatremia where the need for immediate treatment is well-recognized, chronic hyponatremia is often considered not clinically relevant. This is illustrated by reports showing that appropriate laboratory tests are ordered in <50% of patients and that up to 75% are still hyponatremic at discharge. At the same time, emerging evidence suggests an association between hyponatremia and adverse events including increased risk of mortality and rehospitalization. This is a randomized (1:1 ratio) controlled, superiority, parallel-group international multi-center trial with blinded outcome assessment. In total 2,278 participants will be enrolled. Participants will be randomly assigned to undergo either targeted correction of plasma sodium levels or standard of care during hospitalization. The primary outcome is the combined risk of death or re-hospitalization within 30 days. All data on hyponatremia and mortality are derived from observational studies and often lack methodologic robustness. Consequently, the direct impact of hyponatremia on mortality and rehospitalization risk is still debated, resulting in a clinical equipoise whether in-hospital chronic hyponatremia should be treated or not. Therefore, a randomized controlled trial is required to study whether targeted plasma sodium correction reduces the risk of mortality and rehospitalization associated with hyponatremia. www.ClinicalTrials.gov, identifier: NCT03557957.
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http://dx.doi.org/10.3389/fmed.2021.729545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450416PMC
September 2021

Impact of Sodium Levels on Functional Outcomes in Patients with Stroke - A Swiss Stroke Registry Analysis.

J Clin Endocrinol Metab 2021 Sep 4. Epub 2021 Sep 4.

Departments of Endocrinology, Diabetology and Metabolism, University of Basel, Basel Hospital, Basel, Switzerland.

Context: Correction of hyponatremia might represent an additional treatment for improving stroke patients' clinical outcomes.

Objective: Admission hyponatremia is associated with worse clinical outcome in stroke patients, but whether normalization of hyponatremia improves outcome is unknown. We investigated whether normalization of hyponatremia affects patients' disability, mortality, and stroke recurrence within three months; length of hospitalization, and discharge destination.

Design: This was a registry-based analysis of data collected between January 2016 and December 2018. We linked data from Swiss Stroke Registry(SSR) with electronic patients' records for extracting sodium values.

Setting: We analyzed data of hospitalized patients treated at University Hospital of Basel.

Patients: Stroke patients whose data and informed consent were available.

Main Outcome Measure: Modified Rankin Scale(mRS) score at three months. The tested hypothesis was formulated after SSR data collection but before linkage with electronic patients' records.

Results: Out of 1995 patients, 144(7.2%) had hyponatremia on admission; 102(70.8%) reached normonatremia, and 42(29.2%) remained hyponatremic at discharge. An increase of initial sodium was associated with better functional outcome at three months (OR 0.94, 95%CI[0.90-0.99], for a shift to higher mRS per 1 mmol/L sodium increase). Compared to normonatremic patients, patients who remained hyponatremic at discharge had a worse functional outcome at three months (OR 2.46, 95%CI[1.20-5.03] for a shift to higher mRS). No effect was found on mortality, recurrence or length of hospitalization.

Conclusions: In hospitalized acute stroke patients, persistent hyponatremia is associated with worse functional outcome. Whether active correction of hyponatremia improves outcome remains to be determined in prospective studies.
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http://dx.doi.org/10.1210/clinem/dgab650DOI Listing
September 2021

A randomized controlled trial of GLP-1 receptor agonist dulaglutide in primary polydipsia.

J Clin Invest 2021 Sep 2. Epub 2021 Sep 2.

Department of Endocrinology, University Hospital Basel, Basel, Switzerland.

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. 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. Treatment effects were estimated using linear mixed-effects models. In a subset of 15 patients and additional 15 matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI.

Findings: Patients on dulaglutide reduced fluid intake by 490ml [95%-CI -780, -199], p=0.002, from 2950ml [95% CI 2435, 3465] on placebo to 2460ml [95% CI 1946, 2475] on dulaglutide (model estimates), corresponding to a relative reduction of 17%. 24-hour urinary output was reduced by -943ml [95%-CI -1473, -413], p=0.001. Thirst perception in response to beverage pictures was higher in patients with primary polydipsia versus controls and lower on dulaglutide versus placebo, but functional activity was similar between groups and treatments.

Interpretation: GLP-1 receptor agonists reduce fluid intake and thirst perception in patients with primary polydipsia and could therefore be a treatment option for these patients.
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http://dx.doi.org/10.1172/JCI151800DOI Listing
September 2021

Can treatment response to SGLT2-inhibitors in syndrome of inappropriate antidiuresis be predicted by copeptin, natriuretic peptides and inflammatory markers?

Biomarkers 2021 Aug 30:1-9. Epub 2021 Aug 30.

Departments of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.

Purpose: The syndrome of inappropriate antidiuresis (SIAD) is the main cause of hyponatremia and the SGLT2-inhibitor empagliflozin is a promising new treatment option. A biomarker predicting treatment response could optimize treatment success.

Materials And Methods: Secondary analysis of a trial including 84 hospitalized patients with SIAD-induced hyponatremia. Patients were randomized to four days of treatment with empagliflozin 25 mg/d ( = 43) or placebo ( = 41) with both groups receiving fluid restriction <1000 ml/d. Baseline levels of copeptin, the natriuretic peptides MR-proANP and NT-proBNP and C-reactive protein (CRP) were evaluated as predictors for treatment response defined as absolute sodium change, using linear regression models. Additionally, urinary sodium was assessed as predictor for non-response to fluid restriction alone by constructing the receiver-operating characteristic (ROC) curve.

Results: No clinically relevant predictive value for treatment response to empagliflozin could be found for copeptin, MR-proANP, NT-proBNP or CRP. A urinary sodium cut-off of >76 mmol/l led to a specificity of 91.7% [95% confidence interval (CI): 75%, 100%] and sensitivity of 51.9% [33.3%, 70.4%] to predict non-response to fluid restriction alone.

Conclusions: Based on our data, no biomarker could be identified as predictor for treatment response to empagliflozin. Urinary sodium was confirmed as a good marker for non-response to fluid restriction in SIAD patients. : ClinicalTrials.gov (Number: NCT02874807).
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http://dx.doi.org/10.1080/1354750X.2021.1970808DOI Listing
August 2021

ENDOCRINOLOGY IN THE TIME OF COVID-19-2021 UPDATES: The management of diabetes insipidus and hyponatraemia.

Eur J Endocrinol 2021 Aug 27;185(4):G35-G42. Epub 2021 Aug 27.

Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counselling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of postoperative SIAD. They should know hyponatraemia symptoms. Hyponatraemia in COVID-19 is common with a prevalence of 20-30% and is mostly due to SIAD or hypovolaemia. It mirrors disease severity and is an early predictor of mortality. Hypernatraemia may also develop in COVID-19 patients, with a prevalence of 3-5%, especially in ICU, and derives from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.
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http://dx.doi.org/10.1530/EJE-21-0596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428073PMC
August 2021

Pituitary Society Delphi Survey: An international perspective on endocrine management of patients undergoing transsphenoidal surgery for pituitary adenomas.

Pituitary 2021 Jul 20. Epub 2021 Jul 20.

Oregon Health & Science University, Portland, OR, USA.

Purpose: In adults and children, transsphenoidal surgery (TSS) represents the cornerstone of management for most large or functioning sellar lesions with the exception of prolactinomas. Endocrine evaluation and management are an essential part of perioperative care. However, the details of endocrine assessment and care are not universally agreed upon.

Methods: To build consensus on the endocrine evaluation and management of adults undergoing TSS, a Delphi process was used. Thirty-five statements were developed by the Pituitary Society's Education Committee. Fifty-five pituitary endocrinologists, all members of the Pituitary Society, were invited to participate in two Delphi rounds and rate their extent of agreement with statements pertaining to perioperative endocrine evaluation and management, using a Likert-type scale. Anonymized data on the proportion of panelists' agreeing with each item were summarized. A list of items that achieved consensus, based on predefined criteria, was tabulated.

Results: Strong consensus (≥ 80% of panelists rating their agreement as 6-7 on a scale from 1 to 7) was achieved for 68.6% (24/35) items. If less strict agreement criteria were applied (ratings 5-7 on the Likert-type scale), consensus was achieved for 88% (31/35) items.

Conclusions: We achieved consensus on a large majority of items pertaining to perioperative endocrine evaluation and management using a Delphi process. This provides an international real-world clinical perspective from an expert group and facilitates a framework for future guideline development. Some of the items for which consensus was not reached, including the assessment of immediate postoperative remission in acromegaly or Cushing's disease, represent areas where further research is needed.
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http://dx.doi.org/10.1007/s11102-021-01170-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294287PMC
July 2021

Oxytocin levels in response to pituitary provocation tests in healthy volunteers.

Eur J Endocrinol 2021 Aug 3;185(3):355-364. Epub 2021 Aug 3.

Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.

Objective: Oxytocin, secreted into 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. The aim of this study was to investigate known pituitary provocation tests to stimulate plasma oxytocin.

Design: Sixty-five healthy volunteers underwent either the hypertonic saline or arginine infusion test, known to stimulate copeptin, or the oral macimorelin test, known to stimulate growth hormone. Plasma oxytocin was measured before and once plasma sodium level ≥ 150 mmol/L for the hypertonic saline, after 60 min for the arginine infusion, and after 45 min for the oral macimorelin test (expected peak of copeptin and growth hormone levels, respectively). Primary outcome was a change from basal to stimulated oxytocin levels using paired t-tests.

Results: As expected, copeptin increased in response to hypertonic saline and arginine infusion (P < 0.001), and growth hormone increased to oral macimorelin (P < 0.001). Oxytocin increased in response to hypertonic saline infusion from 0.4 (0.2) to 0.6 pg/mL (0.3) (P = 0.003) but with a high variance. There was no change to arginine infusion (P = 0.4), and a trend to lower stimulated levels to oral macimorelin (P = 0.05).

Conclusion: Neither the arginine infusion nor the oral macimorelin test stimulates plasma oxytocin levels, whereas there was an increase with high variance upon hypertonic saline infusion. As a predictable rise in most participants is required for a reliable pituitary provocation test, none of the investigated pituitary provocation tests can be recommended diagnostically to identify patients with an oxytocin deficiency.
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http://dx.doi.org/10.1530/EJE-21-0346DOI Listing
August 2021

Selective resection of cushing microadenoma guided by preoperative hybrid 18-fluoroethyl-L-tyrosine and 11-C-methionine PET/MRI.

Pituitary 2021 Jun 21. Epub 2021 Jun 21.

Department of Nuclear Medicine, St. Claraspital, Basel, CH, Switzerland.

Purpose: 11-C-methionine (MET)-positron emission tomography (PET) as an adjunct to magnetic resonance imaging (MRI) has been proposed as a suitable molecular imaging modality for localizing pituitary adenomas in Cushing's disease. 18-F-Fluoroethyl-L-tyrosine (FET)-PET, which is more widely available has not yet been reported in this context.

Methods: Retrospective double-center cohort study on 15 patients who underwent transsphenoidal surgery for biochemically proven Cushing's disease between 2011 and 2019. Preoperative MET-PET/MRI and/or FET-PET/MRI were compared with intraoperative and histopathological examinations using the Mann Whitney U test and the Fisher's Exact test, along with positive predictive value calculations.

Results: Fifteen patients were included, with a mean age of 47.2 (18-69) years. Six patients received either a MET-PET/MRI or a FET-PET/MRI and 3 patients both exams, respectively. 67% of the tumors were detected by MRI (MET-PET-group [56%]; FET-PET-group [78%]). All tumors were microadenomas with a mean adenoma volume of 0.19 cm (0.02-0.78), all of which displayed a circumscribed pathological FET- and/or MET-uptake. FET-PET/MRI results positively correlated with the localization of the tumor confirmed intraoperatively and histopathologically in all cases, resulting in a sensitivity and specificity of FET-PET/MRI for tumor localization of 100% (95% CI 66.37-100%). One MET-PET/MRI suggested a localization contralateral to the expected spot. The sensitivity and specificity of MET-PET for tumor localization hence was 89% (95% CI 51.75-99.72%).

Conclusions: Preoperative hybrid FET-PET/MRI and MET-PET/MRI have a high predictive value in localizing corticotroph adenoma for selective adenomectomy in Cushing's disease.
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http://dx.doi.org/10.1007/s11102-021-01160-5DOI Listing
June 2021

Influence of Prednisone on Inflammatory Biomarkers in Community-Acquired Pneumonia: Secondary Analysis of a Randomized Trial.

J Clin Pharmacol 2021 May 25. Epub 2021 May 25.

Department of General Internal and Emergency Medicine and Department of Endocrinology, Diabetology and Metabolism, Medical University Clinic, Aarau, Switzerland.

Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID-19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous multicenter, randomized, placebo-controlled trial that compared a 7-day treatment course of 50-mg prednisone to placebo in patients hospitalized with community-acquired pneumonia. We compared levels of C-reactive protein (CRP), procalcitonin (PCT), leukocyte and neutrophil count between patients with and without glucocorticoid treatment at baseline and on days 3, 5, and 7 and at discharge by Wilcoxon tests and analysis of variance. A total of 356 patient data sets in the prednisone group and 355 in the placebo group were available for analysis. Compared to placebo, use of prednisone was associated with reductions in levels of CRP on days 3, 5, and 7 (mean difference of 46%, P < .001 for each time point). For PCT, no such difference was observed. Leukocyte and neutrophil count were higher in the prednisone group at all time points (mean difference of 27% for leukocytes and 33% for neutrophils, P <.001 for all time points). We conclude that after administration of glucocorticoids in community-acquired pneumonia, patients had lower CRP levels and increased leukocyte and neutrophil count as compared to the placebo group. PCT levels were not different between treatment groups. PCT levels thus may more appropriately mirror the resolution of infection compared to more traditional inflammatory markers.
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http://dx.doi.org/10.1002/jcph.1914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242868PMC
May 2021

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

Age Ageing 2021 09;50(5):1546-1556

Critical Care and Peri-operative Medicine, Monash Health, Melbourne, Australia.

Background: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients.

Objective And Design: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome.

Subjects And Methods: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay.

Results: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05).

Conclusions: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.
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http://dx.doi.org/10.1093/ageing/afab078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437072PMC
September 2021

Validity of different copeptin assays in the differential diagnosis of the polyuria-polydipsia syndrome.

Sci Rep 2021 05 12;11(1):10104. Epub 2021 May 12.

Departments of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.

The aim of this study was to correlate three commercially available copeptin assays and their diagnostic accuracy in the differential diagnosis of the polyuria-polydipsia syndrome. Analyzed data include repeated copeptin measures of 8 healthy volunteers and 40 patients with polyuria-polydipsia syndrome undergoing osmotic stimulation and of 40 patients hospitalized with pneumonia. Copeptin was measured using the automated Brahms KRYPTOR, the manual Brahms LIA and the manual Cloud Clone ELISA assay. Primary outcome was the interrater correlation coefficient (ICC) and diagnostic accuracy in the polyuria-polydipsia syndrome of the three assays. In healthy volunteers, there was a moderate correlation for the KRYPTOR and LIA (ICC 0.74; 95% CI 0.07 to 0.91), and a poor correlation for the KRYPTOR and ELISA (ICC 0.07; 95% CI - 0.06 to 0.29), as for the LIA and ELISA (ICC 0.04; 95% CI - 0.04 to 0.17). The KRYPTOR had the highest diagnostic accuracy (98% (95% CI 83 to100)), comparable to the LIA (88% (95% CI 74 to 100)), while the ELISA had a poor diagnostic accuracy (55% (95% CI 34 to 68)) in the differential diagnosis of the polyuria-polydipsia syndrome. The KRYPTOR and LIA yield comparable copeptin concentrations and high diagnostic accuracy, while the ELISA correlates poorly with the other two assays and shows a poor diagnostic accuracy for polyuria-polydipsia patients. The current copeptin cut-off is valid for the KRYPTOR and LIA assay. Our results indicate that interpretation with other assays should be performed with caution and separate validation studies are required before their use in differentiating patients with polyuria-polydipsia syndrome.Trial registration: NCT02647736 January 6, 2016/NCT01940614 September 12, 2013/NCT00973154 September 9, 2009.
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http://dx.doi.org/10.1038/s41598-021-89505-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114908PMC
May 2021

Impact of Adrenal Function on Hemostasis/Endothelial Function in Patients Undergoing Surgery.

J Endocr Soc 2021 May 23;5(5):bvab047. Epub 2021 Mar 23.

Division of Endocrinology, Diabetes and Clinical Nutrition, Luzerner Kantonsspital, 6000 Luzern, Switzerland.

Context: Glucocorticoids regulate hemostatic and endothelial function, and they are critical for adaptive functions during surgery. No data regarding the impact of adrenal function on hemostasis and endothelial function in the perioperative setting are available.

Objective: We assessed the association of adrenal response to adrenocorticotropic hormone (ACTH) and markers of endothelial/hemostatic function in surgical patients.

Methods: This prospective observational study, conducted at a tertiary care hospital, included 60 patients (35 male/25 female) undergoing abdominal surgery. Adrenal function was evaluated by low-dose ACTH stimulation test on the day before, during, and the day after surgery. According to their stimulated cortisol level (cutoff ≥ 500 nmol/L), patients were classified as having normal hypothalamic-pituitary-adrenal (HPA)-axis function (nHPA) or deficient HPA-axis function (dHPA). Parameters of endothelial function (soluble vascular cell adhesion molecule-1, thrombomodulin) and hemostasis (fibrinogen, von Willebrand factor antigen, factor VIII [FVIII]) were measured during surgery.

Results: Twenty-one patients had dHPA and 39 had nHPA. Compared with nHPA, patients with dHPA had significantly lower peak cortisol before (median 568 vs 425 nmol/L,  < 0.001) and during (693 vs 544 nmol/L,  < 0.001) surgery and lower postoperative hemoglobin levels (116 g/L vs 105 g/L,  = 0.049). FVIII was significantly reduced in patients with dHPA in uni- and multivariable analyses; other factors displayed no significant differences. Coagulation factors/endothelial markers changed progressively in relation to stimulated cortisol levels and showed a turning point at cortisol levels between 500 and 600 nmol/L.

Conclusions: Patients with dHPA undergoing abdominal surgery demonstrate impaired hemostasis which can translate into excessive blood loss.
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http://dx.doi.org/10.1210/jendso/bvab047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057135PMC
May 2021

Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome.

Sci Rep 2021 Apr 12;11(1):7911. Epub 2021 Apr 12.

Division of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, Basel, Switzerland.

Fibroblast growth factor-21 (FGF21) is elevated in patients with the metabolic syndrome. Although the exact underlying mechanisms remain ill-defined, chronic low-grade inflammation with increased Interleukin-(IL)-1β expression may be responsible. The aim of this study was to investigate effects of two different anti-inflammatory treatments (IL-1 antagonism or high-dose corticosteroids) on FGF21 in patients with the metabolic syndrome. This is a secondary analysis of two interventional studies in patients with obesity and features of the metabolic syndrome. Trial A was an interventional trial (n = 73) investigating short-term effects of the IL-1 antagonist anakinra and of dexamethasone. Trial B was a randomized, placebo-controlled, double-blinded trial (n = 67) investigating longer-term effects of IL-1 antagonism. In total, 140 patients were included in both trials. Median age was 55 years (IQR 44-66), 26% were female and median BMI was 37 kg/m (IQR 34-39). Almost half of the patients were diabetic (45%) and had increased c-reactive protein levels of 3.4 mg/L. FGF21 levels correlated with fasting glucose levels, HOMA-index, C-peptide levels, HbA1c and BMI. Short-term treatment with anakinra led to a reduction of FGF21 levels by - 200 pg/mL (95%CI - 334 to - 66; p = 0.004). No effect was detectable after longer-term treatment (between-group difference: - 8.8 pg/mL (95%CI - 130.9 to 113.3; p = 0.89). Acute treatment with dexamethasone was associated with reductions of FGF21 by -175 pg/mL (95%CI - 236 to - 113; p < 0.001). Anti-inflammatory treatment with both, IL-1 antagonism and corticosteroids reduced FGF21 levels at short-term in individuals with the metabolic syndrome.Trial registration: ClinicalTrials.gov Identifiers NCT02672592 and NCT00757276.
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http://dx.doi.org/10.1038/s41598-021-87207-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041761PMC
April 2021

Incidence of hyperkalemia during hypertonic saline test for the diagnosis of diabetes insipidus.

Endocr Connect 2021 Apr;10(4):401-409

Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.

Objective: Hyperkalemia has been reported upon different hypertonic saline infusion protocols. Since hypertonic saline test has recently been validated for the differential diagnosis of diabetes insipidus (DI), we aimed to investigate the course of plasma potassium during the test.

Design: We analyzed data of 90 healthy volunteers and 141 patients with polyuria-polydipsia syndrome (PPS) from two prospective studies evaluating the hypertonic saline test. Our primary outcome was the incidence rate of hypertonic saline-induced hyperkalemia > 5 mmol/L.

Methods: Participants received a 250 mL bolus of 3% NaCl solution, followed by 0.15 mL/min/kg body weight continuously infused targeting a plasma sodium level of 150 mmol/L. Blood samples and clinical data were collected every 30 min.

Results: Of the 231 participants, 16% (n = 37/231) developed hyperkalemia. The incidence of hyperkalemia was higher in healthy volunteers and in patients with primary polydipsia (25.6% (n = 23/90) and 9.9% (n = 14/141), respectively), and only occurred in 3.4% (n = 2/59) of patients with diabetes insipidus. Hyperkalemia developed mostly at or after 90-min test duration (81.1%, n => 30/37). Predictors of hyperkalemia (OR (95% CI)) were male sex (2.9 (1.2-7.4), P => 0.02), a plasma potassium at baseline > 3.9 mmol/L (5.2 (1.8-17.3), P => 0.004), normonatremia at 30-min test duration (3.2 (1.2-9.5), P => 0.03), and an increase in potassium levels already at 30-min test duration as compared to baseline (4.5 (1.7-12.3), P => 0.003). Hyperkalemia was transient and resolved spontaneously in all cases.

Conclusion: The hypertonic saline test can lead to hyperkalemia, especially in patients with primary polydipsia who experience a longer test duration. Monitoring potassium levels in these patients is recommended.
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http://dx.doi.org/10.1530/EC-20-0531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133371PMC
April 2021

Effects of oral macimorelin on copeptin and anterior pituitary hormones in healthy volunteers.

Pituitary 2021 Aug 22;24(4):555-563. Epub 2021 Feb 22.

Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.

Purpose: The test with the highest diagnostic accuracy for diabetes insipidus is copeptin measurement after hypertonic saline infusion. However, the procedure is cumbersome and unpleasant due to rapid sodium increase. An oral stimulation test would be highly desirable. Macimorelin, an oral ghrelin agonist, is a newly approved diagnostic test for growth hormone (GH) deficiency, but its effects on copeptin/vasopressin are unknown and the effects on other pituitary hormones only scarcely investigated.

Methods: In this prospective, interventional, proof-of-concept study Copeptin and anterior pituitary hormones were measured in 28 healthy volunteers on two test days at baseline, 30, 45, 60, 90 and 120 min after a single dose of macimorelin (first visit: 0.5 mg/kg, second visit: 0.75 mg/kg).

Results: Baseline copeptin levels were 5.26 pmol/L [1.57, 6.81] and did not change after macimorelin intake (0.5 mg/kg: maximal median change 0.40 [- 0.49, 0.65] pmol/L, p = 0.442; 0.75 mg/kg: - 0.13 [- 0.45, 0.17] pmol/L, p = 0.442. Median GH levels increased from 3.67 mU/L with a maximal median change of 94.66 [IQR 56.5; 110.96] mU/L, p < 0.001. No effect was seen on cortisol, ACTH, LH and FSH levels. Prolactin (max. median change 100 [2.5; 146.5] mU/L, p = 0.004) and free thyroxine (fT4) (0.5 [0.2; 0.8] pmol/L, p < 0.001) increased, whereas TSH decreased (- 0.18 [- 0.22, - 0.09] mU/L, p < 0.001).

Conclusion: We confirm an increase of GH upon macimorelin in healthy volunteers. However, macimorelin did not stimulate copeptin and therefore does not provide an oral test alternative for the diagnosis of diabetes insipidus. Additionally, a stimulatory effect was seen for prolactin and fT4, but not for ACTH and gonadotropic hormones.

Registration: The trial was registered on ClinicalTrials.gov (NCT03844217) on February 18, 2019.
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http://dx.doi.org/10.1007/s11102-021-01132-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270818PMC
August 2021

C-Terminal-Pro-Endothelin-1 Adds Incremental Prognostic Value for Risk Stratification After Ischemic Stroke.

Front Neurol 2020 27;11:629151. Epub 2021 Jan 27.

Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.

Endothelins have shown to play a role in the pathophysiology of ischemic stroke. We aimed at evaluating the incremental prognostic value of C-terminal-pro-endothelin-1 (CT-pro-ET-1) in a well-described cohort of acute stroke patients. We performed serial measurements of CT-pro-ET-1 in 361 consecutively enrolled ischemic stroke patients and assessed functional outcome and mortality after 90 days. As we found peak levels of CT-pro-ET-1 and the most prominent association with mortality on day 1 after admission ( = 312), we focused on this time point for further outcome analyses. We calculated logistic regression and cox proportional hazards models to estimate the association of CT-pro-ET-1 with our outcome measures after adjusting for demographic and clinical risk factors. To evaluate the incremental value of CT-pro-ET-1, we calculated the area under the receiver operating characteristics (AUC) curve and the continuous net reclassification index (cNRI) comparing the model with and without the biomarker CT-pro-ET-1. In the univariate analysis CT-pro-ET-1 with a peak on day 1 after admission was associated with unfavorable outcome with an OR of 1.32 (95% CI, 1.16-1.51, < 0.001) and with mortality with a HR of 1.45 (95% CI, 1.29-1.63, < 0.001). After adjusting, CT-pro-ET-1 remained an independent predictor of mortality with an adjusted HR of 1.50 (95% CI, 1.29-1.74, < 0.001), but not for functional outcome. Adding CT-pro-ET-1 to the cox-regression model for mortality, the discriminatory accuracy improved from 0.89 (95% CI, 0.84-0.94) to 0.92 (95% CI, 0.88-0.96) < 0.001, and the cNRI was 0.72 (95% CI, 0.17-1.13). CT-pro-ET-1 with a peak level on day 1 was an independent predictor of mortality adding incremental prognostic value beyond traditional risk factors.
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http://dx.doi.org/10.3389/fneur.2020.629151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873365PMC
January 2021

Prevalence and outcome of dysnatremia in patients with COVID-19 compared to controls.

Eur J Endocrinol 2021 Mar;184(3):409-418

Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.

Objective: The pandemic of coronavirus disease (COVID-19) has rapidly spread globally and infected millions of people. The prevalence and prognostic impact of dysnatremia in COVID-19 is inconclusive. Therefore, we investigated the prevalence and outcome of dysnatremia in COVID-19.

Design: The prospective, observational, cohort study included consecutive patients with clinical suspicion of COVID-19 triaged to a Swiss Emergency Department between March and July 2020.

Methods: Collected data included clinical, laboratory and disease severity scoring parameters on admission. COVID-19 cases were identified based on a positive nasopharyngeal swab test for SARS-CoV-2, patients with a negative swab test served as controls. The primary analysis was to assess the prognostic impact of dysnatremia on 30-day mortality using a cox proportional hazard model.

Results: 172 (17%) cases with COVID-19 and 849 (83%) controls were included. Patients with COVID-19 showed a higher prevalence of hyponatremia compared to controls (28.1% vs 17.5%, P < 0.001); while comparable for hypernatremia (2.9% vs 2.1%, P = 0.34). In COVID-19 but not in controls, hyponatremia was associated with a higher 30-day mortality (HR: 1.4, 95% CI: 1.10-16.62, P = 0.05). In both groups, hypernatremia on admission was associated with higher 30-day mortality (COVID-19 - HR: 11.5, 95% CI: 5.00-26.43, P < 0.001; controls - HR: 5.3, 95% CI: 1.60-17.64, P = 0.006). In both groups, hyponatremia and hypernatremia were significantly associated with adverse outcome, for example, intensive care unit admission, longer hospitalization and mechanical ventilation.

Conclusion: Our results underline the importance of dysnatremia as predictive marker in COVID-19. Treating physicians should be aware of appropriate treatment measures to be taken for patients with COVID-19 and dysnatremia.
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http://dx.doi.org/10.1530/EJE-20-1374DOI Listing
March 2021

Multicenter, Observational Study of Lanreotide Autogel for the Treatment of Patients with Acromegaly in Routine Clinical Practice in Germany, Austria and Switzerland.

Exp Clin Endocrinol Diabetes 2021 Mar 7;129(3):224-233. Epub 2020 Dec 7.

ENDOC Center for Endocrine Tumors, Hamburg.

Background: Evidence from controlled trials has shown that lanreotide autogel is effective in achieving biochemical and symptom control in patients with acromegaly. However, it is important to better understand the real-world patient population receiving lanreotide autogel treatment.

Methods: In this non-interventional study the long-term treatment response to lanreotide autogel in adult patients with acromegaly from office-based centers or clinics in Germany, Austria and Switzerland was studied. Assessments included growth hormone and insulin-like growth factor-I levels, symptoms, quality of life, lanreotide plasma levels and tumor somatostatin receptor subtype expression. The primary endpoint was achievement of full biochemical control, defined as growth hormone ≤2.5 µg/L and insulin-like growth factor I normalization at month 12.

Results: 76 patients were enrolled from 21 sites. 7/51 (13.7%) patients of the efficacy population had full biochemical control at baseline, 15/33 (45.5%) at month 12 and 10/26 (38.5%) at month 24 of treatment. At 12 months of treatment higher rates of biochemical control were observed in the following subgroups: older patients (>53 years [median]), females, treatment-naïve patients, and patients with a time since diagnosis of longer than 1.4 years (median). No clinically relevant differences in acromegaly symptoms or quality of life scores were observed. Median fasting blood glucose and glycated hemoglobin levels remained unchanged throughout the study. No new safety signals were observed. Overall tolerability of treatment with lanreotide autogel was judged by 80.8% of the enrolled patients at month 12 as 'very good' or 'good'.

Conclusion: Treatment with lanreotide autogel in a real-world setting showed long-term effectiveness and good tolerability in patients with acromegaly.
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http://dx.doi.org/10.1055/a-1247-4713DOI Listing
March 2021

Diabetes insipidus - An update in diagnosis and management.

Best Pract Res Clin Endocrinol Metab 2020 09 13;34(5):101470. Epub 2020 Oct 13.

Division of Endocrinology, University Hospital Basel, University of Basel, CH-4031, Basel, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.beem.2020.101470DOI Listing
September 2020

Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment: a patient-level meta-analysis from randomized controlled trials.

Clin Chem Lab Med 2020 09 28;59(2):441-453. Epub 2020 Sep 28.

Medical University Department, Kantonsspital Aarau, Aarau, Switzerland.

Objectives: Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission.

Methods: We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15-89 [CKD 2-4] and GFR<15 [CKD 5]). The main efficacy and safety endpoints were duration of antibiotic treatment and 30-day mortality.

Results: Mean duration of antibiotic treatment was significantly shorter in PCT-guided (n=2,492) compared to control patients (n=2,510) (9.5-7.6 days; adjusted difference in days -2.01 [95% CI, -2.45 to -1.58]). CKD 5 patients had overall longer treatment durations, but a 2.5-day reduction in treatment duration was still found in patients receiving in PCT-guided care (11.3 vs. 8.6 days [95% CI -3.59 to -1.40]). There were 397 deaths in 2,492 PCT-group patients (15.9%) compared to 460 deaths in 2,510 control patients (18.3%) (adjusted odds ratio, 0.88 [95% CI 0.78 to 0.98)]. Effects of PCT-guidance on antibiotic treatment duration and mortality were similar in subgroups stratified by infection type and clinical setting (p interaction >0.05).

Conclusions: This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates.
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http://dx.doi.org/10.1515/cclm-2020-0931DOI Listing
September 2020

Copeptin response to hypoglycemic stress is linked to prolactin activation in children.

Pituitary 2020 Dec;23(6):681-690

Laboratory of Endocrinology, Federal University of Minas Gerais, Av. Alfredo Balena, 190, Belo Horizonte, Minas Gerais, Brazil.

Purpose: The physiological role of arginine vasopressin (AVP) in the acute stress response in humans and especially in children is unclear. The aim of this study was to explore the interaction between copeptin, a well-established surrogate marker of AVP release, and anterior pituitary hormone activation in response to acute hypoglycemic stress in children and adolescents.

Methods: We conducted an exploratory single center study involving 77 children and adolescents undergoing insulin-induced hypoglycemia. Blood levels of copeptin, ACTH, cortisol, GH, prolactin, interleukin-6 (IL-6), adrenaline and noradrenaline were determined at baseline and after insulin-induced hypoglycemia.

Results: Basal plasma levels of copeptin (median: 5.2 pmol/L) increased significantly after hypoglycemia (median 9.7 pmol/L; P < 0.0001). Subjects with insufficient HPA axis response or severe GH deficiency had lower hypoglycemia-induced copeptin increase (median: 2.3 pmol/L) compared with individuals with intact pituitary response (median: 5.2 pmol/L, P = 0.02). Copeptin increase correlated significantly with the maximal increase of ACTH (r = 0.30; P = 0.010), cortisol (r = 0.33; P = 0.003), prolactin (r = 0.25; P = 0.03), IL-6 (r = 0.35; P = 0.008) and with BMI-SDS (r = - 0.28, P = 0.01). In multivariate regression analysis, prolactin increase was the only independent variable associated with copeptin increase (P = 0.0004).

Conclusion: Our data indicate that: (1) hypoglycemic stress elicits a marked copeptin response in children and adolescents, pointing out its role as an acute stress marker in this population; (2) stress-induced AVP/copeptin release is associated with anterior pituitary activation, mainly a prolactin response.
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http://dx.doi.org/10.1007/s11102-020-01076-6DOI Listing
December 2020

Risk of Adverse Clinical Outcomes in Hyponatremic Adult Patients Hospitalized for Acute Medical Conditions: A Population-Based Cohort Study.

J Clin Endocrinol Metab 2020 11;105(11)

Endocrinology, Diabetes, and Metabolism, University Hospital Basel, Basel, Switzerland.

Context: Hyponatremia has been associated with excess long-term morbidity and mortality. However, effects during hospitalization are poorly studied.

Objective: The objective of this work is to examine the association of hyponatremia with the risk of in-hospital mortality, 30-day readmission, and other short-term adverse events among medical inpatients.

Design And Setting: A population-based cohort study was conducted using a Swiss claims database of medical inpatients from January 2012 to December 2017.

Patients: Hyponatremic patients were 1:1 propensity-score matched with normonatremic medical inpatients.

Main Outcome Measure: The primary outcome was a composite of all-cause in-hospital mortality and 30-day hospital readmission. Secondary outcomes were intensive care unit (ICU) admission, intubation rate, length-of-hospital stay (LOS), and patient disposition after discharge.

Results: After matching, 94 352 patients were included in the cohort. Among 47 176 patients with hyponatremia, 8383 (17.8%) reached the primary outcome compared with 7994 (17.0%) in the matched control group (odds ratio [OR] 1.06 [95% CI, 1.02-1.10], P = .001). Hyponatremic patients were more likely to be admitted to the ICU (OR 1.43 [95% CI, 1.37-1.50], P < .001), faced a 56% increase in prolonged LOS (95% CI, 1.52-1.60, P < .001), and were admitted more often to a postacute care facility (OR 1.38 [95% CI 1.34-1.42, P < .001). Of note, patients with the syndrome of inappropriate antidiuresis (SIAD) had lower in-hospital mortality (OR 0.67 [95% CI, 0.56-0.80], P < .001) as compared with matched normonatremic controls.

Conclusion: In this study, hyponatremia was associated with increased risk of short-term adverse events, primarily driven by higher readmission rates, which was consistent among all outcomes except for decreased in-hospital mortality in SIAD patients.
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http://dx.doi.org/10.1210/clinem/dgaa547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500475PMC
November 2020

Excess Mortality Among Hospitalized Patients With Hypopituitarism-A Population-Based, Matched-Cohort Study.

J Clin Endocrinol Metab 2020 11;105(11)

Division of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, Basel, Switzerland.

Context: Patients with hypopituitarism face excess mortality in the long-term outpatient setting. However, associations of pituitary dysfunction with outcomes in acutely hospitalized patients are lacking.

Objective: The objective of this work is to assess clinical outcomes of hospitalized patients with hypopituitarism with or without diabetes insipidus (DI).

Design, Setting, And Patients: In this population-based, matched-cohort study from 2012 to 2017, hospitalized adult patients with a history of hypopituitarism were 1:1 propensity score-matched with a general medical inpatient cohort.

Main Outcome Measures: The primary outcome was in-hospital mortality. Secondary outcomes included all-cause readmission rates within 30 days and 1 year, intensive care unit (ICU) admission rates, and length of hospital stay.

Results: After matching, 6764 cases were included in the study. In total, 3382 patients had hypopituitarism and of those 807 (24%) suffered from DI. All-cause in-hospital mortality occurred in 198 (5.9%) of patients with hypopituitarism and in 164 (4.9%) of matched controls (odds ratio [OR] 1.32, [95% CI, 1.06-1.65], P = .013). Increased mortality was primarily observed in patients with DI (OR 3.69 [95% CI, 2.44-5.58], P < .001). Patients with hypopituitarism had higher ICU admissions (OR 1.50 [95% CI, 1.30-1.74], P < .001), and faced a 2.4-day prolonged length of hospitalization (95% CI, 1.94-2.95, P < .001) compared to matched controls. Risk of 30-day (OR 1.31 [95% CI, 1.13-1.51], P < .001) and 1-year readmission (OR 1.29 [95% CI, 1.17-1.42], P < .001) was higher among patients with hypopituitarism as compared with medical controls.

Conclusions: Patients with hypopituitarism are highly vulnerable once hospitalized for acute medical conditions with increased risk of mortality and adverse clinical outcomes. This was most pronounced among those with DI.
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http://dx.doi.org/10.1210/clinem/dgaa517DOI Listing
November 2020

Diabetes Insipidus: An Update.

Endocrinol Metab Clin North Am 2020 09 15;49(3):517-531. Epub 2020 Jul 15.

Division of Endocrinology, Diabetes and Metabolism, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Endocrinology, University Hospital Basel, University of Basel, Petersgraben 4, Basel 4031, Switzerland. Electronic address:

The differential diagnosis of diabetes insipidus involves the distinction between central or nephrogenic diabetes insipidus and primary polydipsia. Differentiation is important because treatment strategies vary; the wrong treatment can be dangerous. Reliable differentiation is difficult especially in patients with primary polydipsia or partial forms of diabetes insipidus. New diagnostic algorithms are based on the measurement of copeptin after osmotic stimulation by hypertonic saline infusion or after nonosmotic stimulation by arginine and have a higher diagnostic accuracy than the water deprivation test. Treatment involves correcting preexisting water deficits, but is different for central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia.
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http://dx.doi.org/10.1016/j.ecl.2020.05.012DOI Listing
September 2020

The role of IL-1 in the regulation of copeptin in patients with metabolic syndrome.

Endocr Connect 2020 Jul;9(7):715-723

Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.

Arginine vasopressin (AVP) was suggested to contribute to cardiovascular risk and type 2 diabetes in patients with metabolic syndrome. The proinflammatory cytokine interleukin (IL)-1 is able to induce AVP secretion and plays a causal role in cardiovascular mortality and type 2 diabetes. We investigated in two studies whether copeptin levels - the surrogate marker for AVP - are regulated by IL-1-mediated chronic inflammation in patients with metabolic syndrome. Study A was a prospective, interventional, single-arm study (2014-2016). Study B was a randomized, placebo-controlled, double-blind study (2016-2017). n = 73 (Study A) and n = 66 (Study B) adult patients with metabolic syndrome were treated with 100 mg anakinra or placebo (only in study B) twice daily for 1 day (study A) and 28 days (study B). Fasting blood samples were drawn at day 1, 7, and 28 of treatment for measurement of serum copeptin. Patients with chronic low-grade inflammation (C-reactive protein levels ≥2 mg/L) and BMI >35 kg/m2 had higher baseline copeptin levels (7.7 (IQR 4.9-11.9) vs 5.8 (IQR 3.9-9.3) pmol/L, Pinflamm = 0.009; 7.8 (IQR 5.4-11.7) vs 4.9 (IQR 3.7-9.8) pmol/L, PBMI = 0.008). Copeptin levels did not change either in the anakinra or in the placebo group and remained stable throughout the treatment (P = 0.44). Subgroup analyses did not reveal effect modifications. Therefore, we conclude that, although IL-1-mediated inflammation is associated with increased circulating copeptin levels, antagonizing IL-1 does not significantly alter copeptin levels in patients with metabolic syndrome.
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http://dx.doi.org/10.1530/EC-20-0197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424357PMC
July 2020

Hyponatremia at discharge: A solid risk or accidental findings in community acquired pneumonia - Authors' reply.

Eur J Intern Med 2020 08 16;78:137-138. Epub 2020 Jul 16.

Departments of Endocrinology Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland; Department of Clinical Research, University of Basel, Basel, Switzerland.

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http://dx.doi.org/10.1016/j.ejim.2020.07.004DOI Listing
August 2020

Effects of glucagon-like peptide-1 receptor agonists on fluid intake in healthy volunteers.

Endocrine 2020 11 4;70(2):292-298. Epub 2020 Jul 4.

Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.

Purpose: Glucagon-like peptide-1 (GLP-1) receptor agonists (RA) reduce appetite and energy intake. Recent findings from animal studies suggest a role of GLP-1 in drinking and water homeostasis. We aimed to elucidate whether GLP-1 RA reduce fluid intake in healthy volunteers.

Methods: Double-blind, randomized, placebo-controlled, crossover study. 20 healthy volunteers received dulaglutide 1.5 mg and placebo (0,9% sodium chloride) subcutaneously once weekly for 3 weeks. At the end of each treatment period, participants attended an 8-h evaluation visit, during which they were requested to eat two standardized meals and to drink water ad libitum. The primary outcome was the total fluid intake (ml) during the evaluation visit.

Results: Mean [SD] age of participants (60% female) was 27 [9.2] years. All but four participants drank less on dulaglutide versus placebo treatment despite identical food intake. The median [IQR] difference of fluid intake on dulaglutide compared to placebo treatment was -100 ml [-400-0]. Median [IQR] total fluid intake was 1300 ml [888-1600] versus 1600 ml [1000-1720], on dulaglutide and placebo treatment, p = 0.06. Median [IQR] 24-h urine output was reduced in dulaglutide versus placebo-treated participants: 1250 ml [975-2080] versus 1680 ml [1400-2040], p = 0.04. Median serum sodium levels were 140 mmol/L on both visits and no difference in thirst perception was noted.

Conclusions: GLP-1 RA such as dulaglutide seem to modulate fluid balance in humans. This leads us to speculate that GLP-1 RA may be an interesting therapeutic options for patients with excessive drinking behavior e.g., primary polydipsia.
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http://dx.doi.org/10.1007/s12020-020-02394-2DOI Listing
November 2020

Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia.

Clin Endocrinol (Oxf) 2020 10 13;93(4):456-465. Epub 2020 Jul 13.

Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Switzerland.

Objective: Arginine vasopressin (AVP) is released upon osmotic stimulation or hypovolaemia in order to maintain water balance. A recent study showed a role of AVP in haematopoiesis by stimulating red blood cell precursors, suggesting a higher risk of anaemia in patients with AVP deficiency. The objective was to explore the effect of low AVP levels in patients with central diabetes insipidus (cDI) and primary polydipsia (PP) on haemoglobin and the prevalence of anaemia.

Methods: A total of 164 patients with either cDI (70, 43%) or PP (94, 57%) and 30 healthy volunteers from two prospective diagnostic studies performed in Switzerland, Germany and Brazil were studied. A standardized clinical and biochemical (eg copeptin, full blood count) assessment was performed. Haemoglobin and haematocrit levels and prevalence of anaemia (defined as haemoglobin values of <120 g/L in women and <130 g/L in men) were analysed.

Results: Mean copeptin values were 2.63 pmol/L (±1.08) and 3.91 pmol/L (±4.28) in patients with cDI and PP and 24.76 pmol/L (±5.75) in healthy volunteers, P = .02. The prevalence of anaemia was low in all participants with 7.1%, 2.2% and 10% in cDI, PP and in healthy volunteers, P = .15. Mean haemoglobin values were similar in all groups: 139 g/L (±15.85), 140 g/L (±13.16) and 139 g/L (±13.05) in patients with cDI, PP and healthy volunteers, P = .90, as were mean haematocrit values with 41% in all groups (P = .85).

Conclusion: Chronic low AVP levels in patients with cDI and PP do not affect haemoglobin levels and prevalence of anaemia.
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http://dx.doi.org/10.1111/cen.14265DOI Listing
October 2020

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of diabetes insipidus and hyponatraemia.

Eur J Endocrinol 2020 Jul;183(1):G9-G15

Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counseling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of the postoperative syndrome of inappropriate antidiuresis (SIAD). They should know hyponatraemia symptoms. The prevalence of hyponatraemia in patients with pneumonia due to COVID-19 is not yet known, but seems to be low. In contrast, hypernatraemia may develop in COVID-19 patients in ICU, from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.
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http://dx.doi.org/10.1530/EJE-20-0338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938013PMC
July 2020
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