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Prof. Dr. med. Mirjam Christ-Crain

Department of Clinical Research
Profiles & Affiliations

Relevant scientific achievements

In my initial work (2001-2009), I explored the hormone procalcitonin. I could show that the concentration of this hormone is increased in the circulation during bacterial infection, but remained low in the presence of a viral infection. The differentiation between bacterial and viral respiratory tract infections has important clinical implications, allowing reducing the use of antibiotics (Lancet 2004; AJRCCM 2006; JAMA 2009).


Since 2009, I have made pioneering contribution in the development of new diagnostic and therapeutic options in the difficult area of vasopressin-dependent fluid disorders, i.e. Diabetes insipidus and the syndrome of inappropriate antidiuresis (SIAD). In the field of Diabetes insipidus, I directed several multicenter international studies to evaluate the use of copeptin which mirrors the activity of vasopressin. I showed that copeptin improves differential diagnosis of Diabetes insipidus, be it in patients with polyuria polydipsia syndrome (JCEM 2015) or in patients undergoing pituitary surgery (JCEM 2015). I conducted the largest prospective study in patients with Diabetes insipidus including >150 patients in 11 centers worldwide, comparing the water deprivation test with osmoticallystimulated copeptin levels. I showed that the diagnostic accuracy for the water deprivation test versus osmotically-stimulated copeptin to discriminate primary polydipsia from Diabetes insipidus was 76.6% versus 96.5% (New England Journal of Medicine 2018). In another large study, I showed that arginine stimulates copeptin and that this novel test had a similar accuracy than the hypertonic-saline test to differentiate Diabetes insipidus from primary polydipsia, but with a better tolerability (Lancet 2019). Based on these data measurement of copeptin has been recommended to become the new diagnostic reference-standard for patients with Diabetes insipidus.


Concerning treatment, I recently showed in a randomized, double-blind, placebo-controlled trial that GLP-1- receptor-agonists control thirst and compulsive drinking behavior in primary polydipsia indicating a novel treatment option in patients where currently no medical treatment options exist (JCI 2021). In a recent paper, I showed that patients with Diabetes insipidus suffer from many psychological comorbidities and have reduced quality of life (Lancet E & D 2022). Based on this finding, I now investigate whether patients with Diabetes insipidus have Oxytocin deficiency, and whether treatment with Oxytocin improves their quality of life and psychological comorbidities. A multicenter placebo-controlled randomized trial is in preparation. Another important area in fluid disorders is hyponatremia and the syndrome of inappropriate antidiuresis (SIAD) in particular where improvements in diagnosis and treatment are needed. I performed several studies evaluating new diagnostic markers for hyponatremia. Concerning treatment, I showed in two randomized placebo-controlled trials that SGLT-2 inhibitors are a novel treatment option in patients with SIAD increasing 5 osmotic diuresis and consecutively sodium levels (JASN 2020). Most recently, I received a large grant to compare the effect of standard care versus intensive correction of hyponatremia on mortality in hospitalized hyponatremic patients.


Most Important Awards and Honors (selection)

• Taft Lecturer at the Endocrine Society of Australia’s Annual Scientific Meeting, November 2021

• Trust visiting professor, British Endocrine Society, Nov 2022, postponed (COVID) to June 2022

• Award of the European Society of Endocrinology for young investigators (below 45 years of age) 2019, Annual European Endocrine Conference in Lyon, May 2019

• Bebbi Award 2012 of the city of Basel

• National Latsis Award 2009

• SULM (Swiss Union for Laboratory Medicine) presidential Award 2008

• Amerbach Award 2007 for best habilitation of medical faculty (University of Basel) • Servier Award Clinical Endocrinology 2007

• Swiss Society of Internal Medicine (SGIM) Award 2007

• Viollier Award 2005

• Pfizer Award 2005 for best clinical research paper in infectious diseases

• Matura-Preis (Bachelor’s Award) Humanistisches Gymnasium Basel 1993

Selected Publications

Huynh, Tony, Signal, Dana, & Christ-Crain, Mirjam. (2024). Paediatric perspectives in the diagnosis of polyuria-polydipsia syndrome. Clinical Endocrinology, null. https://doi.org/10.1111/cen.15011

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Warren AM, Grossmann M, Christ-Crain M, & Russell N. (2023). Syndrome of Inappropriate Antidiuresis: From Pathophysiology to Management. Endocrine Reviews, 44(5), 819–861. https://doi.org/10.1210/endrev/bnad010

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Christ-Crain M. (2020). Diabetes insipidus - An update in diagnosis and management. (Patent No. 5). 34(5), Article 5. https://doi.org/10.1016/j.beem.2020.101470

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Selected Projects & Collaborations

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Targeted correction of plasma sodium levels in hospitalized patients with hyponatremia: a randomized, controlled, parallel-group trial with blinded outcome-assessment - The Hyponatremia Intervention Trial (HIT trial)

Research Project  | 6 Project Members

Hyponatremia is the most common electrolyte disorder with a prevalence of up to 30% in hospitalized patients. It can be caused by the underlying disease, prescribed drugs, or aspecific stimuli such as nausea and pain. Hyponatremia may be life-threatening if it develops acutely and causes cerebral edema with neurological symptoms. The treatment of acute symptomatic hyponatremia is therefore straight forward and implies the administration of hypertonic saline to treat cerebral edema. In contrast, the rationale for treatment of chronic hyponatremia - the most prevalent subtype - is less evident. There are no intervention studies to show that correcting chronic hyponatremia improves outcomes.Importantly, there is increasing data showing an association between chronic hyponatremia and complications such as falls or attention deficit, as well as increased risk of fractures and osteoporosis. It has also been reported that hyponatremia is associated with a poorer prognosis of cardiac, hepatic, kidney and pulmonary diseases as well as the overall outcome of ICU patients resulting in a significant association with an increased mortality and readmission risk. However, it is unclear whether these are merely associations or indicate causality: despite several retrospective analyses showing improvement of readmission and mortality rates, as well as some small uncontrolled studies reporting reduction of adverse events with plasma sodium correction, there is a complete lack of randomized clinical trials investigating whether correction of hyponatremia counteracts the increased risk of readmission and mortality. Thus, there is clinical equipoise on whether chronic hyponatremia should be treated or not. Therefore, the aim of this intervention study is to determine the benefits and harms of a targeted correction of plasma sodium concentration on the combined endpoint 30-day mortality and rehospitalization rate. Patients will be randomly assigned to targeted correction of plasma sodium concentration or standard care alone. Study Design: Pragmatic randomized (1:1 ratio) controlled, superiority, parallel-group international multi-center study with blinded outcome assessment.Patients: Hospitalized patients with chronic hypotonic hyponatremia <130mmol/l. Patients requiring acute treatment with 3% saline infusion due to severe symptomatic hyponatremia, patients on dialysis, patients with acute liver failure, encephalopathic complications of liver failure or hepatorenal syndrome will be excluded. Intervention: Targeted correction of plasma sodium concentrationComparison: Current standard careOutcome measures: The primary objective is to investigate whether targeted correction of hyponatremia compared to standard care alone reduces the combined risk of death or rehospitalization within 30 days. Secondary objectives will include: Short- (30 days) and longterm (1 year) risk of death and rehospitalization; other clinical outcomes (neurocognition, quality of life, falls, fractures, length of hospital stay); Safety of the intervention; Exploratory analysis of biomarkers for hyponatremia. Main statistical hypothesis and sample size calculation:The intervention is superior to standard care by reducing the patients risk of death or re-hospitalization within 30 days from 23% to 18%. 2050 patients are required to detect an effect that is relevant for patients, clinicians and policy makers, i.e. an absolute reduction of 5% of the primary outcome (combined mortality and rehospitalization rate) with a statistical power of 80% (two-sided significance level 5%). With an assumed drop-out rate of 10 %, 2278 patients should be recruited.Importance: This study will influence future hyponatremia management on a national and international level regardless of its outcome:If the intervention results in a significant reduction of mortality and rehospitalization rate, hyponatremia awareness and its consecutive treatment during hospitalization will change substantially.If the intervention shows no effect on mortality and rehospitalization rate, hyponatremia will be recognized more as a marker of severity of the disease and not as its cause. Current treatment guidelines will be adapted.