Search

Background: Hyponatremia is a common complication following endoscopic endonasal resection (EER) of pituitary adenomas. We report a single-center, multisurgeon study detailing baseline clinical data, outcomes, and factors associated with postoperative hyponatremia., Methods: This was a retrospective cohort study of patients undergoing EER for pituitary adenoma at Tufts Medical Center. Most procedures were performed by the senior author (C.B.H.). Cases were included if at least 1 postoperative sodium value was available and pathology confirmed pituitary adenoma. Hyponatremia was defined as a postoperative sodium level <135 mEq/L., Results: A total of 272 patients underwent 310 EER procedures that met the study inclusion criteria. The mean patient age was 53.3 years, and mean tumor size was 18.8 mm. Postoperative hyponatremia occurred in 12.6% of cases, with 3.6% developing hyponatremia prior to discharge. Lower preoperative sodium level was associated with an increased risk of developing any postoperative hyponatremia. Older age, prolactinoma pathology, and use of selective serotonin reuptake inhibitors were associated with moderate to severe hyponatremia (≤129 mEq/L), and lower preoperative sodium was associated with mild hyponatremia (130-134 mEq/L). Hyponatremia-related readmissions within 30 days occurred in 3.9% of patients. Both African-American race and postoperative hyponatremia were associated with an increased risk of 30-day readmission. The mean nadir sodium for hyponatremic patients was 129.9 mEq/L. Growth hormone-secreting pathology was associated with lower postoperative nadir sodium, whereas higher preoperative sodium was associated with higher postoperative nadir sodium., Conclusions: Hyponatremia is a common postoperative complication of EER for pituitary lesions that can cause significant morbidity, increased readmissions, and increased healthcare costs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sodium imbalance is a common electrolyte disturbance in COVID-19, often linked to disruptions in hormonal regulation. This review explores the relationship between sodium dysregulation and endocrine disturbances, particularly focusing on primary and secondary hypothyroidism, hypocortisolism, and the renin-angiotensin-aldosterone system (RAAS). Hypocortisolism in COVID-19, due to adrenal insufficiency or secondary to pituitary dysfunction, can lead to hyponatremia through inadequate cortisol levels, which impair renal free water excretion and enhance antidiuretic hormone (ADH) secretion. Similarly, hypothyroidism is associated with decreased renal blood flow and the glomerular filtration rate (GFR), which also increases ADH activity, leading to water retention and dilutional hyponatremia. Furthermore, COVID-19 can disrupt RAAS (primarily through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor), diminishing aldosterone secretion and further contributing to sodium loss and hyponatremia. These hormonal disruptions suggest that sodium imbalance in COVID-19 is multifactorial and warrants further investigation into the complex interplay between COVID-19, endocrine function, and sodium homeostasis. Future research should focus on understanding these mechanisms to develop management algorithms that address both sodium imbalance and underlying hormonal disturbances in order to improve prognosis and outcomes in COVID-19 patients.

Background: Hyponatremia (hypoNa) is a potentially serious adverse event of antidepressant treatment. Previous research suggests the risk of drug-induced hyponatremia differs between antidepressants. This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes., Methods: A PRISMA-compliant systematic search of Web of Science and PubMed databases was performed from inception until Jan 5, 2023, for original studies reporting incidences or risks of hypoNa in adults using antidepressants. We modelled random-effects meta-analyses to compute overall event rates and odds ratios of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa event rates. We conducted subgroup analyses for geriatric populations and sodium cut-off value. The study is registered with PROSPERO, CRD42021269801., Results: We included 39 studies (n = 8,175,111). Exposure to antidepressants was associated with significantly increased odds of hypoNa (k = 7 studies, OR = 3.160 (95%CI 1.911-5.225)). The highest event rates were found for SNRIs (7.44%), SSRIs (5.59%), and TCAs (2.66%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). Compared to SSRIs, SNRIs were significantly more likely (k = 10, OR = 1.292 (1.120 - 1.491), p < 0.001) and mirtazapine significantly less likely (k = 9, OR = 0.607 (0.385 - 0.957), p = 0.032) to be associated with hypoNa., Conclusion: Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.

Background: The syndrome of inappropriate antidiuretic hormone (SIADH) is usually treated with fluid restriction. This can be challenging in patients with obligate fluid intake for nutrition or medication. Pharmaceutical treatment with tolvaptan and urea is available but minimal paediatric data are available. We review the efficacy and safety of tolvaptan and urea in paediatric patients with SIADH., Methods: Retrospective review of paediatric inpatients with clinical diagnosis of SIADH. Patients were identified from pharmacy records based on tolvaptan and urea prescriptions. Relevant information was extracted from patient electronic records. The main outcome measures included the number of days to sodium normalisation, the daily change in plasma sodium concentration, and the maximum increase of plasma sodium concentration in 24 h. Reported side effects were captured., Results: Thirteen patients received tolvaptan and six urea. Five patients had both agents (tolvaptan converted to urea). Tolvaptan led to plasma sodium normalisation in 10/13 (77%) within 6 days (median 2.5 days, range [1, 6]), with a median change of sodium concentration of 7 mmol/L (- 1, 14) within the first 24 h of treatment. Three patients experienced a change in plasma sodium > 10 mmol/l/day but had no apparent side effects. Urea led to sodium normalisation in 5/6 (83%) patients. The median number of days to normalisation with urea was 2 (1, 10) with a median change of plasma sodium concentration of 2 mmol/L (- 1, 6) within the first 24 h. All patients tolerated tolvaptan and/or urea without unexpected side effects., Conclusions: Tolvaptan and urea appear to be safe and effective when fluid restriction is challenging in paediatric SIADH. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Hyponatremia is one of the most common electrolyte disorders in emergency departments and hospitalized patients. Serum sodium concentration is controlled by osmoregulation and volume regulation. Both pathways are regulated via the release of antidiuretic hormone (ADH). Syndrome of inappropriate release of ADH (SIADH) may be caused by neoplasms or pneumonia but may also be triggered by drug use or drug abuse. Excessive fluid intake may also result in a decrease in serum sodium concentration. Rapid alteration in serum sodium concentration leads to cell swelling or cell shrinkage, which primarily causes neurological symptoms. The dynamics of development of hyponatremia and its duration are crucial. In addition to blood testing, a clinical examination and urine analysis are essential in the differential diagnosis of hyponatremia., (© 2023. The Author(s).)

Background and Objectives: Antileucine-rich glioma-inactivated 1 (anti-LGI1) autoimmune encephalitis was first described in 2010 and is today the most common type of limbic encephalitis. During the course of the disease, 60%-88% of the patients develop hyponatremia. The etiology of the sodium disorder is unclear, often presumed to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Other electrolyte abnormalities have not been reported in association with anti-LGI1 antibody encephalitis. Due to the presence of hypomagnesemia and hypophosphatemia in our patients, we set out to try to find the expression of LGI1 protein in the kidney as an explanation for these abnormalities., Methods: We reviewed the medical files of all patients diagnosed with anti-LGI1 antibody encephalitis, at the Department of Neurology in the Tel Aviv Medical Center between January 2011 and December 2020, exploring for electrolyte abnormalities. Using tissue staining, Western blot, mass spectrometry, and RNA expression techniques, we tried to demonstrate the expression of LGI1 protein in the human kidney., Results: We identified 15 patients diagnosed with anti-LGI1 antibody encephalitis. Their average age was 65 years (44-80), and 9 were male individuals. Thirteen of the 15 patients (87%) developed varying degrees of hyponatremia. Laboratory studies demonstrated low serum osmolality, low serum blood urea nitrogen, and low uric acid, with a high urinary sodium and inappropriately high urine osmolality, supporting the presumable diagnosis of SIADH. One patient with hyponatremia that was tested, had high levels of copeptin, supporting the diagnosis of SIADH. In addition to hyponatremia, 7 patients (47%) exhibited other electrolyte abnormalities; 5 patients (33%) had overt hypophosphatemia, 4 patients (27%) had overt hypomagnesemia, and 2 other patients (13%) had borderline low magnesium levels. Western blot analysis of human kidney lysate, mass spectrometry, and qRT-PCR failed to demonstrate the expression of LGI1 protein in the kidney., Discussion: Hyponatremia in patients with anti-LGI1 antibody encephalitis is due to SIADH as previously assumed. Other electrolyte abnormalities such as hypomagnesemia and hypophosphatemia occur in at least 40% of patients and may be another clue for the diagnosis of anti-LGI1 antibody encephalitis. Because we failed to demonstrate LGI1 expression in the kidney, the results of our study suggest that renal losses lead to these disturbances, most probably due to SIADH., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Dysnatremia is a common occurrence in patients with COVID-19 and is associated with higher mortality and risk for septic conditions. The pathomechanisms are probably multifaceted, but severe hyponatremia may also occur as a result of underlying SIADH or hypocortisolism. Patients with preexisting AVP dysfunction, like SIADH or diabetes insipidus, are at high risk for severe electrolyte imbalances in the event of a COVID-19 infection.The recently growing use of immune checkpoint inhibitors in oncology is associated with a spectrum of endocrine immune-related adverse events (endocrine irAEs). These AEs usually occur unpredictably and may even manifest after discontinuation of the anticancer therapy. Hyponatremia is a common factor of several endocrine irAEs and may serve as a red flag biomarker for possibly underlying endocrine irAEs such as hypophysitis or adrenalitis. New-onset hyponatremia should always prompt a comprehensive diagnostic workup and exclusion of endocrine irAEs before the diagnosis of SIADH is made.Hyponatremia with severe symptoms should be treated with hypertonic (3 %) saline solution to resolve the cerebral edema and prevent from detrimental neurological sequelae. Both rapid intermittent bolus (RIB) therapy and continuous infusion therapy have now been reported to be safe and equally effective. The RIB therapy limits the risk of overcorrection and requires less often re-lowering treatment than continuous infusion therapy.Fluid restriction has long been considered as first-line treatment of chronic hyponatremia due to SIADH. Additional treatment with Furosemid and/or oral NaCl tablets does not improve efficacy but reduces tolerance to therapy.Copeptin-based dynamic tests show higher diagnostic accuracy in the differential diagnosis of patients with hypotonic polyuria polydipsia syndrome than the indirect water deprivation test., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Adverse events, particularly severe adverse events, after coronavirus disease vaccination are the primary concern for many patients. We present the first report of symptomatic hyponatremia, a potentially life-threatening condition, after administration of the ChAdOx1 nCoV-19 coronavirus disease-19 vaccine. A 24-year-old man developed altered consciousness and high-grade fever a day after receiving this vaccine. Computed tomography of the brain showed diffuse brain swelling with bilateral descending transtentorial brain herniation. His serum sodium level, urine sodium level, and urine osmolarity were 114 mEq/L, 77 mEq/L, and 230 mOsm/kg, respectively. He was diagnosed with symptomatic hyponatremia due to syndrome of inappropriate antidiuretic hormone. His symptoms rapidly improved after treatment with 3% NaCl. Seven days after admission, his serum sodium level was normal, and no further intervention was required. We believe that the vaccine was the trigger for hyponatremia in this case based on temporal relationship of vaccination and hyponatremia, the rapid improvement of the patient, and the transient nature of the hyponatremia. We postulate that cytokine underlies the pathophysiology of hyponatremia in this case. Recognition of adverse events after coronavirus disease-19 vaccination is essential. Symptomatic hyponatremia should be included in the differential diagnosis in altered-consciousness patients after administration of ChAdOx1 nCoV-19 coronavirus disease-19 vaccine.

Introduction: Hyponatremia is a common condition of varying etiology among hospitalized patients and is associated with adverse outcomes. Treatment to normalize serum sodium is advisable. Tolvaptan received European Union marketing authorization for hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Post-marketing pharmacovigilance activities were required to characterize the safety profile of tolvaptan more fully in this population, which is often elderly with a high burden of comorbid illness., Methods: This was a prospective, observational, multinational, post-authorization pharmacovigilance study (NCT01228682) in seven European countries. Hospitalized patients were enrolled who received tolvaptan for hyponatremia associated with SIADH and consented to data collection. Tolvaptan was initiated and assessments performed at physician discretion per local standards of care. To reflect actual clinical practice, no assessments or procedures were required outside the standard of care. Patients who continued to receive long-term tolvaptan following hospital discharge and provided consent received follow-up from their community physicians., Results: A total of 252 patients (mean age 70.6 years) enrolled. Mean tolvaptan treatment duration was 139.4 days, median 18.5 (range 1-1130) days; most frequent dose was 15 mg/day (used in 75% of patients). Serum sodium increased from baseline (mean 123.2 mmol/l) during treatment week 1 and remained stable during follow-up, with little difference across doses of 7.5, 15, and 30 mg/day. Hyponatremia symptoms (e.g., confusion, unsteady gait, lethargy) were present in 122/252 (48.4%) patients at pre-treatment baseline, decreasing to 46/252 (18.3%) during treatment. Sixty-two patients (24.6%; mean baseline serum sodium 120 mmol/l) experienced rapid correction of hyponatremia within 72 h. No osmotic demyelination syndrome occurred., Conclusion: In clinical practice, tolvaptan improved serum sodium and decreased hyponatremia symptoms in hyponatremia secondary to SIADH. Serum sodium should be monitored during treatment to minimize risk of rapid correction., Trial Registration: Clinicaltrials.gov identifier NCT01228682., (© 2021. The Author(s).)

Objective: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common problem during the postoperative course after pituitary surgery. Although treatment of this condition is well characterized, prevention strategies are less studied and reported. The authors sought to characterize outcomes and predictive factors of SIADH after implementation of routine postoperative fluid restriction for patients undergoing endoscopic transsphenoidal surgery for pituitary adenoma., Methods: In March 2018, routine postoperative fluid restriction to 1000 ml/day for 7 days was instituted for all patients who underwent surgery for pituitary adenoma. These patients were compared with patients who underwent surgery for pituitary adenoma between March 2016 and March 2018, prior to implementation of routine fluid restriction. Patients with preoperative history of diabetes insipidus (DI) or concern for postsurgical DI were excluded. Patients were followed by neuroendocrinologists and neurosurgeons, and sodium levels were checked between 7 and 10 days postoperatively. SIADH was defined by a serum sodium level less than 136 mmol/L, with or without symptoms within 10 days after surgery. Thirty-day readmission was recorded and reviewed to determine underlying reasons., Results: In total, 82 patients in the fluid-unrestricted cohort and 135 patients in the fluid-restricted cohort were analyzed. The patients in the fluid-restricted cohort had a significantly lower rate of postoperative SIADH than patients in the fluid-unrestricted cohort (5% vs 15%, adjusted OR [95% CI] 0.1 [0.0-0.6], p = 0.01). Higher BMI was associated with lower rate of postoperative SIADH (adjusted OR [95%] 0.9 [0.9-1.0], p = 0.03), whereas female sex was associated with higher rate of SIADH (adjusted OR [95% CI] 3.1 [1.1-9.8], p = 0.03). There was no difference in the 30-day readmission rates between patients in the fluid-unrestricted and fluid-restricted cohorts (4% vs 7%, adjusted OR [95% CI] 0.5 [0-5.1], p = 0.56). Thirty-day readmission was more likely for patients with history of hypertension (adjusted OR [95% CI] 5.7 [1.3-26.3], p = 0.02) and less likely for White patients (adjusted OR [95% CI] 0.3 [0.1-0.9], p = 0.04)., Conclusions: Routine fluid restriction reduced the rate of SIADH in patients who underwent surgery for pituitary adenoma but was not associated with reduction in 30-day readmission rate.

Along with the arrival of the first vasopressin-receptor V2R inhibitor, the indications for its use have increased. We review here and focus on polycystic kidney disease (PKD) and hyponatremia. Tolvaptan is the first drug available to slow down the progression of PKD in patients with rapid progressing disease. However, the benefits are moderate and the side effects are important, making important to share the decision of treatment together with the patient. Hyponatremia with preserved extra-cellular volume or associated with edema may be reversed by tolvaptan. Patients with SIADH or hyponatremia and edema might benefit from this treatment under strict monitoring. Overall, vaptans are helpful in several conditions, but remain tools that must be used under close control., Competing Interests: Olivier Bonny et Pierre-Yves Martin ont reçu un défraiement pour participations à des advisory boards d’Otsuka-Suisse et sont des investigateurs de l’étude PASS-156-12-299. Toutefois, Otsuka n’a en rien interféré avec le contenu du présent article. Fabien Stucker n’a déclaré aucun conflit d’intérêts en relation avec cet article.

Objective: To analyze the clinical and genetic features, as well as the treatment outcomes of two boys with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by gain-of-function mutations in the V2 vasopressin receptor gene (AVPR2). Methods: The clinical manifestations, genetic testing, therapeutic interventions and the outcomes of two boys with NSIAD hospitalized in the Department of Endocrinology, Beijing Children's Hospital in April 2019 were reported. A literature search with "Nephrogenic syndrome of inappropriate antidiuresis" and "AVPR2 gene" as keywords was conducted at the China national knowledge infrastructure (CNKI), the Wanfang Data Knowledge Service Platform, PubMed and Springer Link up to May 2020. Relevant published articles were reviewed. Results: The two cases presented with chronic and severe hyponatremia with hypo-osmolality, inappropriately elevated urinary osmolality and urinary sodium levels. The onset age was 5.25-years and 2 months respectively. AVPR2 sequencing revealed a previously described hemizygous activating mutation (c.409C>T, p.R137C) in both of boys, each inherited the variant from their mother. Patient 1 limited fluid intake by himself in his daily life, intravenous and oral sodium supplementations showed no significant increase of serum sodium level. Oral furosemide increased the serum sodium level and maintained it within normal range. The serum sodium and potassium levels were in the normal range during the 1-year follow-up period with oral furosemide. The serum sodium level of Patient 2 increased with restricting fluid intake and with salt supplementation. However, after he experienced respiratory infection, the plasma sodium level decreased. Subsequently, oral anti-infection medicine and furosemide were applied. The serum sodium level increased two days later and remained at a normal range afterwards. The boy was 1 year old with normal growth. He stopped taking furosemide after 4 months while taking 1 gram of salt per day, the blood sodium level maintained at normal range. Literature search identified no reports in Chinese journals, whereas 50 publications were found in English journals. A total of 30 NSIAD probands were reported and 16 of those (53%) had childhood onset, most presented with seizures. The majority had a hotspot change at the nucleotide position of 409 in AVPR2. Nine cases had an amino acid change as R137C and five cases as R137L. Fluid restriction and oral urea intake were main treatment options, no report so far was found with oral furosemide treatment. Conclusions: NSIAD presented with hyponatremia without any other specific presentations. Genetic testing for variants in AVPR2 is helpful for early diagnosis and timely treatment. The first two cases of oral furosemide treatment were reported by the article which helped to maintain a normal serum sodium level after limiting fluid intake and supplementing sodium which showed limited effect.

Low molecular weight heparin-induced hyperkalemia is not an uncommon side effect. The development of hyponatremia is well described although it is less common. We report a 72-year-old woman with lumbar metastases who developed hyponatremia and hyperkalemia on the tenth day of hospitalization. Hyponatremia, with limited criteria for syndrome of inappropriate secretion of antidiuretic hormone, did not resolve with vigorous volume restriction. Hyperkalemia without an acid-base disorder or baseline renal failure, did not resolve after losartan was stopped. Enoxaparin-induced hypoaldosteronism was proposed and the drug was discontinued. After four days' persistence of the electrolyte disturbance, dexamethasone was changed to Hydrocortisone, and parameters normalized in 24 hours. The patient remained well until discharge and during outpatient control.

Hyponatremia is a common electrolyte disorder observed in a wide variety of malignancies and is associated with substantial morbidity and mortality. Newer cancer therapies have improved patient outcomes while contributing to new cases of hyponatremia. Patients should be monitored closely for the development of vasopressin- and non-vasopressin-mediated hyponatremia. Acute and symptomatic forms of hyponatremia require urgent intervention, and recent findings support the correction of chronic "asymptomatic" hyponatremia. Optimizing hyponatremia may reduce medical costs, and improve cancer survival likelihood and quality of life. In this article, we review the epidemiology, pathophysiology, etiology, diagnosis, and treatment of hyponatremia in the cancer patient., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Hyponatremia is a common condition affecting hospitalized and ambulatory patients as well. The clinical spectrum of hyponatremia can range from asymptomatic laboratory findings to severely symptomatic conditions such as acute epileptic seizures. Etiologies of hyponatremia include excessive intake of solute-free fluids, side-effects of medication, diseases associated with hypervolemic states such as congestive heart failure, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH).As hyponatremia can be a potentially life-threatening condition, it requires an efficient management with the goal of identifying the etiology and to subsequently provide adequate treatment, while avoiding treatment-related adverse effects such as overcorrection and pontine myelinolysis. This article summarizes the pathophysiology and differential diagnosis, as well as useful diagnostic tests and therapy of hyponatremia in a practice-oriented manner., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of euvolemic hyponatremia, and many disorders have been associated with it. Baroreflex failure is a rare disorder characterized by extreme blood pressure (BP) fluctuations, most frequently caused by neck or head trauma and irradiation. We report a case of a 48-year-old patient referred to our department for asymptomatic hyponatremia and volatile hypertension. His past medical history included nasopharyngeal carcinoma treated with surgery and bilateral neck radiation. Following the diagnostic algorithm for hyponatremia, the diagnosis of SIADH was made. Ambulatory BP monitoring revealed highly variable BP; extensive autonomic nervous system function testing suggested baroreflex-cardiovagal failure. We propose the hypothesis that not only labile hypertension because of baroreflex failure but also hyponatremia can develop as a late consequence of neck trauma and irradiation.

The aim of this continuing medical education (CME) article (part II) is to describe the particular challenge of the treatment of hyponatremia, which occurs in older patients. This part II follows on from part I concerning the diagnosis in the previous volume. A staged approach is necessary. The best treatment is always when the underlying cause can be eliminated. Hyponatremia in older patients is mainly induced by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. The authors use a concept for the first, second and third line strategy: (1) changing or discontinuation of drugs, (2) fluid restriction and (3) tolvaptan medication. The algorithm for treatment should be simple. It also contains recommendations for the correction rate. Caution is also needed in order to avoid the occurrence of an osmotic demyelination syndrome (ODS).

Hyponatremia (sodium <135 mmol/l) is the most common electrolyte disorder. Despite identical serum concentrations, clinical symptomatology can vary greatly from mild to life-threatening. Accordingly, individual patients require immediate active treatment, while the majority of (mostly oligosymptomatic) patients should first undergo differentiated diagnosis. The most important element is the assessment of the clinical situation of the patient and never isolated laboratory chemical constellations: "Treat the patient, not the numbers".

Background: Hyponatremia is the most common electrolyte disorder encountered clinically. While acute and/or severe hyponatremia is commonly associated with significant symptoms, milder and more chronic forms of hyponatremia remain clinically inconspicuous. Recent evidence suggests that even milder forms of hyponatremia are associated with increased morbidity and mortality. Despite this, currently available treatments for chronic hyponatremia lack data on efficacy and/or have important limitations related to patient nonadherence, adverse side effects, and/or significant costs. Consequently, there is a clear need for investigation of alternative treatments for this common condition., Summary: Small case series conducted in Europe since the early 1980s suggest that urea, an oral osmotic diuretic that increases urinary water excretion, is safe and effective for the treatment of chronic hyponatremia. In 2016, a novel formulation of urea became available in the United States. Our group recently reported the first and only study describing the efficacy and safety of this American formulation of oral urea among hospitalized patients with hyponatremia. Key Messages: Oral urea appears to be an effective, safe, and well-tolerated therapeutic strategy in the management of chronic hyponatremia., (© 2019 S. Karger AG, Basel.)

Objective: The study was aimed to investigate the prevalence and causes of hyponatremia in hospitalized patients, and to analyze the relationship between hyponatremia and mortality. Methods: A retrospective analysis was carried out in 525 patients with hyponatremia, who were older than 14 years old and hospitalized in the Zhoushan Hospital from Jan. 2014 to Apr. 2014. Based on the severity of the hyponatremia the patients were divided into three groups: the mild, moderate and severe hyponatremia groups. The underlying causes of hyponatremia were analyzed, and the association between hyponatremia and mortality was explored using logistic regression analyses. Results: (1) The prevalence of hyponatremia was 5.26% in whole hospitalized patients ( n= 9 989) during the study period. It was 6.1% in the elderly population (≥60 years old). (2) Malignant tumors and infectious diseases were the main primary diseases of hyponatremia in all three groups. Among them, lung cancer was the most common malignant tumor, and pneumonia was the most common infectious disease associated with hyponatremia. Cerebral hemorrhage was common in patients with moderate and severe hyponatremia, in which subarachnoid hemorrhage was the major primary disease associated with moderate to severe hyponatremia. In the subgroup of elderly patients, malignant tumor and infectious diseases were the major basic diseases. (3) Among the 525 cases, 13.7% and 3.8% of them were diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt-wasting syndrome (CSWS), respectively. The proportions of SIADH and CSWS increased to 17.4% and 4.2%, respectively, in the elderly hyponatremic patients ( n= 264). (4) More patients were prescribed with sodium-excretion drugs in the moderate and severe hyponatremia groups than those in the mild one(42.2% vs.21.4%, 43.2% vs.21.4%, all P< 0.05). (5) Patients with moderate or severe hyponatremia had a higher mortality compared to those with mild hyponatremia (moderate vs. mild group: OR 6.92, 95 %CI 2.53-18.92, P< 0.001; severe vs. mild group: OR 4.54, 95 %CI 1.05-19.58, P= 0.043). Conclusions: Hyponatremia was common in hospitalized patients. The major primary diseases were malignant tumor (lung cancer), infectious diseases (pneumonia) and cerebral hemorrhage complicated with SIADH and CSWS. Use of sodium-excretion drugs increased the risk of moderate to severe hyponatremia. Patients with moderate to severe hyponatremia had a higher risk of death in hospitals.

Objective To summarize and analyze the causes of hyponatremia in patients with brucellosis and explore the clinical manifestations of syndrome of inappropriate antidiuresis(SIAD)in patients with brucellosis. Methods The clinical data of 111 patients with acute brucellosis who were treated in Peking Union Medical College Hospital from September 2011 to December 2017 were retrospectively reviewed.Hyponatremia was defined by serum sodium level lower than 135 mmol/L.Clinical characteristics including medical histories,vital signs,and laboratory test findings were collected and analyzed. Results Hyponatremia was found in 14(12.6%)of 111 patients with brucellosis,among whom 3 patients were confirmed to be with SIAD,10 were suspected as SIAD,and 1 was diagnosis as hypopituitarism.Hypoalbuminemia,elevation of erythrocyte sedimentation rate,and high sensitivity C reactive protein were found in brucellosis patients with SIAD,along with severe complications such as infective endocarditis,septic shock,and anemia. Conclusion Hyponatremia is not a rare condition in brucellosis patients and may be caused by SIAD.

Objective: Hyponatraemia in hospitalized patients is common and associated with increased mortality. International guidelines give conflicting advice regarding the role of urea in the treatment of SIADH. We hypothesized that urea is a safe, effective treatment for fluid restriction-refractory hyponatraemia., Design: Review of urea for the treatment of hyponatraemia in patients admitted to a tertiary hospital during 2016-2017. Primary end-point: proportion of patients achieving a serum sodium ≥130 mmol/L at 72 hours., Patients: Urea was used on 78 occasions in 69 patients. The median age was 67 (IQR 52-76), 41% were female. Seventy (89.7%) had hyponatraemia due to SIADH-CNS pathology (64.3%) was the most common cause. The duration was acute in 32 (41%), chronic in 35 (44.9%) and unknown in the rest., Results: The median nadir serum sodium was 122 mmol/L (IQR 118-126). Fluid restriction was first-line treatment in 65.4%. Urea was used first line in 21.8% and second line in 78.2%. Fifty treatment episodes (64.1%) resulted in serum sodium ≥130 mmol/L at 72 hours. In 56 patients who received other prior treatment, the mean sodium change at 72 hours (6.9 ± 4.8 mmol/L) was greater than with the preceding treatments (-1.0 ± 4.7 mmol/L; P < 0.001). Seventeen patients (22.7%) had side effects (principally distaste), none were severe. No patients developed hypernatraemia, overcorrection (>10 mmol/L in 24 hours or >18 mmol/L in 48 hours), or died., Conclusions: Urea is safe and effective in fluid restriction-refractory hyponatraemia. We recommend urea with a starting dose of ≥30 g/d, in patients with SIADH and moderate to profound hyponatraemia who are unable to undergo, or have failed fluid restriction., (© 2019 John Wiley & Sons Ltd.)

Background and Objectives: Current therapies for hyponatremia have variable effectiveness and tolerability, and in certain instances, they are very expensive. We examined the effectiveness, safety, and tolerability of urea for the treatment of inpatient hyponatremia., Design, Setting, Participants, & Measurements: We identified all patients hospitalized at the University of Pittsburgh Medical Center between July 2016 and August 2017 with hyponatremia (plasma sodium <135 mEq/L) who received urea, including a subgroup of patients who received urea as the sole drug therapy for hyponatremia (urea-only treated). We matched urea only-treated patients to a group of patients with hyponatremia who did not receive urea (urea untreated) and compared changes in plasma sodium at 24 hours and the end of therapy as well as the proportion of patients who achieved plasma sodium ≥135 mEq/L. We abstracted data on adverse events and reported side effects of urea., Results: Fifty-eight patients received urea (7.5-90 g/d) over a median of 4.5 (interquartile range, 3-8) days and showed an increase in plasma sodium from 124 mEq/L (interquartile range, 122-126) to 131 mEq/L (interquartile range, 127-134; P <0.001). Among 12 urea only-treated patients, plasma sodium increased from 125 mEq/L (interquartile range, 122-127) to 131 mEq/L (interquartile range, 129-136; P =0.001) by the end of urea therapy. There was a larger increase in plasma sodium at 24 hours in urea only-treated patients compared with urea-untreated patients (2.5 mEq/L; interquartile range, 0-4.5 versus -0.5 mEq/L; interquartile range, -2.5 to 1.5; P =0.04), with no difference in change in plasma sodium by the end of therapy (6 mEq/L; interquartile range, 3.5-10 versus 5.5 mEq/L; interquartile range, 3-7.5; P =0.51). A greater proportion of urea only-treated patients achieved normonatremia, but this difference was not statistically significant (33% versus 8%; P =0.08). No patients experienced overly rapid correction of plasma sodium, and no serious adverse events were reported., Conclusions: Urea seems effective and safe for the treatment of inpatient hyponatremia, and it is well tolerated., (Copyright © 2018 by the American Society of Nephrology.)

Competing Interests: There are no conflicts of interest

Background: The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)., Methods: Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 ± 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4., Results: Serum sodium increased significantly from baseline during the first 24 hours (126.8 ± 4.3 vs. 133.7 ± 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 ± 3.8 vs. 135.6 ± 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 ± 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = -0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 ± 4.8 mmol/L) than in moderate (6.4 ± 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 ± 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775-0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500-0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected., Conclusion: TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2018 The Korean Academy of Medical Sciences.)

During the past 50 years the molecular mechanisms of renal reabsorption of sodium and water have been described and molecules specifically interfering with these mechanisms have been developed (diuretics, vasopressin receptor antagonists). Chronic hyponatremia is caused by relative excess of free water, it occurs within a broad spectrum of diseases associated with hypervolemia (heart failure, liver cirrhosis), normovolemia and hypovolemia and it is a negative prognostic factor for patients with chronic heart failure and cirrhotic ascites. Vaptans (vasopressin antagonists, vasopressin V2-receptor inhibitors) reduce reabsorption of water in the distal nephron, they increase free water excretion and normalize serum concentrations of sodium in normovolemic and hypervolemic conditions associated with hyponatremia. Hyponatremia can be corrected (depending on cause, severity and speed of development) through the reduction of fluid intake, administration of a hypertonic solution NaCl, diuretics, oral administration of urea and by vaptans. The role of vaptans in the treatment of hyponatremia should be defined even better, in Europe vaptans can be used to treat the syndrome of inadequate antidiuretic hormone secretion (SIADH).Key words: hyponatremia - liver cirrhosis - heart failure - syndrome of inadequate secretion ADH - tolvaptan - vasopressin.

This present review analyzes the etiology, diagnostics and management of conditions associated with hyponatremia. Excess water and/or sodium wasting lead to the development of hyponatremia in children. There are diverse etiologies associated with hyponatremia, correct diagnosis is based on detailed history, physical examination and basic laboratory tests. Symptomatic hyponatremia can be a life threatening emergency and thus requires fast and vigorous management. Inappropriate treatment may cause fatal consequences.

Hyponatremia (Na ˂ 135 mmol/l) is the most frequent electrolyte disorder in clinical practice, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the commonest cause of hyponatremia in cancer patients. Correcting hyponatremia in these patients can reduce morbidity and mortality, increase the response to anti-cancer agents, and help reduce hospital length of stay and costs. Tolvaptan is an oral medication used to treat SIADH-related hyponatremia patients that needs to be initiated at hospital so patients can have their serum sodium monitored. If tolvaptan could be initiated in hospital day care units (DCUs), performing the same tests, hospitalization could be avoided, quality of life improved, and costs reduced. This is the first publication where a panel of oncologists are sharing their experience and making some recommendations with the use of tolvaptan to treat SIADH-related hyponatremia in DCU after collecting and examining 35 clinical cases with these type of patients. The conclusion from this retrospective observational analysis is that the use of tolvaptan in DCU is safe and effective in the therapeutic management of SIADH-related hyponatremia.

Hyponatremia could be defined as a public health topic: too many patients are concerned in both hospitalized and general populations; hyponatremia induces lots of clinical outcomes and a great economic burden. Its pathophysiology involves thirst regulation (hypotonic water intakes) and losses regulation (through the kidney under vasopressin control). Diagnostic approach should insure that hyponatremia reflects hypo-osmolality and hypotonicity: first, a false hyponatremia should be ruled out, then a non-hypotonic one. Next step is clinic: extracellular status should be evaluated. When increased, any edematous status should be evoked: heart failure, liver cirrhosis or nephrotic syndrome. When decreased, any cause of extracellular dehydration should be evoked: natriuresis could help distinguishing between renal (adrenal insufficiency, diuretics use or salt-losing nephropathy) or extrarenal (digestive mostly) etiologies. When clinically normal, a secretion of inappropriate antidiuretic hormone (SIADH) should be evoked, once hypothyroidism or hypoadrenocorticism have been ruled out. Therapy depends on the severity of the clinical impact. From extracellular rehydration, through fluid restriction, the paraneoplastic and heart failure-induced SIADH benefit from a new class of drug, available among the therapeutic strategies: aquaretics act through antidiuretic hormone receptor antagonism (vaptans). Their long-term benefits still have to be proven but it is a significant step forward in the treatment of hyponatremias., (Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Hyponatremia is frequently seen in heart failure patients and has a high mortality rate. If not treated adequately, acute and chronic hyponatremia may worsen the prognosis of heart failure. Despite its high incidence in heart failure patients, other underlying conditions that possibly lead to the incidence of hyponatremia may be underestimated, thus making its treatment more difficult. In this case study, we describe a rare case of levetiracem-induced and tolvaptan-resistant hyponatremia.

This study assessed the effect of endocrine input on the investigation of hyponatraemia and examined the prevalence of endocrine causes of hyponatraemia. This single-centre, retrospective study included 139 inpatients (median age, 74 years) with serum sodium (Na) levels ≤128 mmol/l during hospitalisation at a UK teaching hospital over a three-month period. In total, 61.9% of patients underwent assessment of volume status and 28.8% had paired serum and urine osmolality, and Na measured. In addition, 14.4% of patients received endocrine input; 80% of these patients underwent full work-up of hyponatraemia compared with 5% of patients not referred to endocrine services (p < 0.001; relative risk, 15.86; 95% confidence interval, 7.17-31.06). The prevalence of adrenal insufficiency was 0.7%, but basal serum cortisol levels were not measured in around two-thirds of patients. Despite 26.7% of patients having abnormal thyroid function tests, no patient was diagnosed with severe hypothyroidism. More widespread provision of expert input should be considered., (© 2015 Royal College of Physicians.)