Urea transporter UT-A1 as a novel drug target for hyponatremia.

Hyponatremia is the most common disorder of electrolyte imbalances. It is necessary to develop new type of diuretics to treat hyponatremia without losing electrolytes. Urea transporters (UT) play an important role in the urine concentrating process and have been proved as a novel diuretic target. In this study, rat and mouse syndromes of inappropriate antidiuretic hormone secretion (SIADH) models were constructed and analyzed to determine if UTs are a promising drug target for treating hyponatremia. Experimental results showed that 100 mg/kg UT inhibitor 25a significantly increased serum osmolality (from 249.83 ± 5.95 to 294.33 ± 3.90 mOsm/kg) and serum sodium (from 114 ± 2.07 to 136.67 ± 3.82 mmol/L) respectively in hyponatremia rats by diuresis. Serum chemical examination showed that 25a neither caused another electrolyte imbalance nor influenced the lipid metabolism. Using UT-A1 and UT-B knockout mouse SIADH model, it was found that serum osmolality and serum sodium were lowered much less in UT-A1 knockout mice than in UT-B knockout mice, which suggest UT-A1 is a better therapeutic target than UT-B to treat hyponatremia. This study provides a proof of concept that UT-A1 is a diuretic target for SIADH-induced hyponatremia and UT-A1 inhibitors might be developed into new diuretics to treat hyponatremia.

Urea to Treat Hyponatremia Due to Syndrome of Inappropriate Antidiuretic Hormone Secretion: A Systematic Review and Meta-Analysis.

RATIONALE & OBJECTIVE: The use of urea to treat hyponatremia related to the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) has not been universally adopted due to questions about effectiveness, safety, and tolerability. This systematic review and meta-analysis of observational studies aimed to address these questions. STUDY DESIGN: This PRISMA-guided study examined published research across four electronic databases. STUDY POPULATIONS: Patients with SIADH-related hyponatremia. SELECTION CRITERIA: Clinical trials and observational studies reporting at least one outcome related to serum sodium concentration, symptom resolution, or adverse effects after oral or nasogastric urea administration. DATA EXTRACTION: Data extraction was performed independently by two reviewers using a standardized form recording study characteristics, participant demographics, intervention details, and treatment outcomes. ANALYTICAL APPROACH: A meta-analysis was conducted using the restricted maximum likelihood method for the random-effects model to assess the effect of urea treatment on serum sodium and serum urea compared to other treatment modalities. Subgroup analyses were conducted based on treatment duration and SIADH severity. RESULTS: Urea treatment significantly increased serum sodium [mean difference (MD) = 9.08 (95%CI 7.64-10.52), p < 0.01] and urea [MD = 31.66 (95%CI 16.05-47.26), p < 0.01] in patients with SIADH albeit with significantly high heterogeneity. Subgroup analysis based on the treatment duration showed a significant rise in the serum sodium level after 24 hours, two, five, seven, and fourteen days, as well as after one year of treatment. Greater increases in serum sodium levels after treatment with urea occurred in patients with severe (<120 mEq/L) [MD = 18.04 (95%CI 13.68-22.39)] than with moderate (120-129 mEq/L [MD = 7.86 (95%CI 6.78-8.94)] or mild (130-135 mEq/L) [MD = 8.00 (95%CI 7.31-8.69)] SIADH induced hyponatremia. Urea treatment was comparable to fluid restriction [MD = 0.81 (95%CI: -0.93-2.55), p = 0.36) and vaptans [MD = -1.96 (95%CI: -4.59-0.66, p = 0.14) but superior to no treatment [MD = 7.99 (95%CI 6.25-9.72), p < 0.01]. Urea was associated with minor adverse events, with poor palatability being most common. LIMITATIONS: As no RCTs investigating urea as a treatment for hyponatremia were identified for inclusion, these analyses were based on observational studies. CONCLUSIONS: Urea is safe and effective for managing SIADH-induced hyponatremia. These finding suggest that urea may be a useful treatment modality in resource-limited settings or when other treatments are contraindicated or poorly tolerated.

Tolvaptan and urea in paediatric hyponatraemia.

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.

Hyponatremia in Guillain-Barre Syndrome: A Review of Its Pathophysiology and Management.

Guillain-Barre syndrome (GBS) is the commonest cause of acute polyradiculoneuropathy that requires hospitalization. Many of these patients experience systemic and disease-related complications during its course. Notable among them is hyponatremia. Though recognized for decades, the precise incidence, prevalence, and mechanism of hyponatremia in GBS are not well known. Hyponatremia in GBS patients is associated with more severe in-hospital disease course, prolonged hospitalization, higher mortality, increased costs, and a greater number of other complications in the hospital and worse functional status at 6 months and at 1 year. Though there are several reports of low sodium associated with GBS, many have not included the exact temporal relationship of sodium or its serial values during GBS thereby underestimating the exact incidence, prevalence, and magnitude of the problem. Early detection, close monitoring, and better understanding of the pathophysiology of hyponatremia have therapeutic implications. We review the complexities of the relationship between hyponatremia and GBS with regard to its pathophysiology and treatment.

Fructose: A New Variable to Consider in SIADH and the Hyponatremia Associated With Long-Distance Running?

Fructose has recently been proposed to stimulate vasopressin secretion in humans. Fructose-induced vasopressin secretion is not only postulated to result from ingestion of fructose-containing drinks but may also occur from endogenous fructose production via activation of the polyol pathway. This raises the question of whether fructose might be involved in some cases of vasopressin-induced hyponatremia, especially in situations where the cause is not fully known such as in the syndrome of inappropriate secretion of diuretic hormone (SIADH) and exercise-associated hyponatremia, which has been observed in marathon runners. Here we discuss the new science of fructose and vasopressin, and how it may play a role in some of these conditions, as well as in the complications associated with rapid treatment (such as the osmotic demyelination syndrome). Studies to test the role of fructose could provide new pathophysiologic insights as well as novel potential treatment strategies for these common conditions.

Presentation of severe brucellosis in 5-year-old boy - challenges and results.

Brucellosis is highly contagious zoonotic bacterial disease caused by gram-negative genus. It has a wide spectrum of clinical manifestations and due to variety and nonspecificity of clinical signs the diagnostics can be very complicated. We present a clinical case of severe chronic brucellosis in a 5-years old boy with long-term course of disease and multiorgan involvement. A different complication of brucellosis including severe syndrome of inappropriate ADH secretion (SIADH) are discussed. Despite severe course of disease patient achieved significant clinical improvement due to multidisciplinary approach and optimal etiotropic and pathogenetic treatment.

Time-dependent association between omeprazole and esomeprazole and hospitalization due to hyponatremia.

PURPOSE: The aim of this study was to explore the time-course of hospitalization due to hyponatremia associated with omeprazole and esomeprazole. METHODS: In this register-based case-control study, we compared patients hospitalized with a main diagnosis of hyponatremia (n = 11,213) to matched controls (n = 44,801). We used multiple regression to investigate time-related associations between omeprazole and esomeprazole and hospitalization because of hyponatremia. RESULTS: The overall adjusted OR (aOR) between proton pump inhibitor (PPI) exposure, regardless of treatment duration and hospitalization with a main diagnosis of hyponatremia, was 1.23 (95% confidence interval CI 1.15-1.32). Exposure to PPIs was associated with a prompt increase in risk of hospitalization for hyponatremia from the first week (aOR 6.87; 95% CI 4.83-9.86). The risk then gradually declined, reaching an aOR of 1.64 (0.96-2.75) the fifth week. The aOR of ongoing PPI treatment was 1.10 (1.03-1.18). CONCLUSION: The present study shows a marked association between omeprazole and esomeprazole and hyponatremia related to recently initiated treatment. Consequently, newly initiated PPIs should be considered a potential culprit in any patient suffering from hyponatremia. However, if the patient has had this treatment for a longer time, the PPI should be considered a less likely cause.

Hyponatraemia caused by transient syndrome of inappropriate antidiuresis to urinary retention.

Hyponatraemia is frequently seen in the emergency department, possibly caused by the syndrome of inappropriate antidiuresis (SIAD). We report three cases in which we believe urinary retention with bladder distention caused hyponatraemia. Laboratory findings fulfilled the criteria for SIAD, for which no cause was found. Possibly pain or sympathetic nerve system activation leads to SIAD. Brisk diuresis occurred after placement of an indwelling urinary catheter with overly correction of sodium for which treatment was necessary. Clinicians should be aware that placement of an indwelling urinary catheter may prompt brisk water diuresis and a tendency to overcorrection.

Case report: Hyponatremia is an initial presentation of Neuromyelitis optica spectrum disorder.

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSD) is often misdiagnosed or delayed because of the complex and diverse clinical manifestations, especially the atypical initial presentation. Hyponatremia can be an infrequently isolated initial presentation of NMOSD and is associated with hypothalamus involvement. Awareness of this mechanism will help clinicians to identify NMOSD early, treat it in time and improve the prognosis. METHODS: We describe a 36-year-old woman who developed repeated hyponatremia and then experienced diplopia. Serum AQP4, MOG, MBP and GFAP antibody were detected, and NMOSD was finally diagnosed. RESULTS: She responded well to high-dose glucocorticoids. Sequential treatment with mycophenolate mofetil (MMF) was prescribed. Two-month follow-up revealed full recovery. So far, after 10 months, the patient still has no recurrence. CONCLUSION: For young patients, repeated hyponatremia, with or without slight fever, and no evidence of obvious infection, brain magnetic resonance imaging (MRI) and serum AQP4/MOG antibody detection may be useful to determine whether there is a possibility of NMOSD.

Determinants of hyponatremia following a traumatic brain injury.

BACKGROUND: Hyponatremia is common in patients with central nervous system disease. It may prolong hospitalization and increase morbidity and mortality. However, the incidence and risks factors remain largely unknown in traumatic brain injury (TBI). The objectives of this study are to characterize hyponatremia in TBI patients and find its main risk factors. METHODS: All patients admitted with a diagnosis of acute TBI over a 1-year period were included, except patients with known chronic hyponatremia, those who died within 72 h, and those receiving hyperosmolar therapy to treat their intracranial hypertension. Sodium levels throughout hospitalization were collected. Post-traumatic hyponatremia was defined as follows: borderline (1-2 points below normal and 1-2 days duration) and significant (more than 2 points below normal and/or more than 2 days duration). Demographic data, GCS, mechanism of injury, and CT findings were collected. These factors were correlated to the incidence of hyponatremia. RESULTS: Hyponatremia was found in 29% of the 283 included patients and was significant in 2/3 of the cases. Significant hyponatremia had a narrower peak, between 7 and 11 days, while borderline hyponatremia started earlier and was more distributed in time. Factors associated with hyponatremia were greater age (p = 0.004), worse ISS (p = 0.017), worse Marshall Grade on CT (p = 0.007), and a diffuse pattern of injury on CT (p < 0.001). Significant hyponatremia was associated with: a diffuse pattern of injury on CT (p = 0.032), the presence of intracerebral hemorrhage (p = 0.027), and multiple lesions on CT (p = 0.043). CONCLUSIONS: Post-traumatic hyponatremia is common and can lead to serious consequences in TBI patients. Adequate monitoring and treatment are therefore important. Older patients and those with more significant injury on CT are more at risk.

Ketamine-precipitated syndrome of inappropriate antidiuretic hormone secretion in a patient with persistent lumbar pain: a case report.

PURPOSE: To report on an unusual case of ketamine-precipitated syndrome of inappropriate antidiuretic hormone secretion (SIADH) in an individual managed by an outpatient pain specialty team. CLINICAL FEATURES: A 78-yr-old male presented to the emergency department with lethargy, malaise, nausea, and abdominal bloating three days following intravenous ketamine infusion for intractable postsurgical lumbar radicular pain with neuropathic features. The patient had a history of resected prostate cancer, hyperlipidemia, chronic kidney disease, and spinal stenosis and the cause of his symptoms was investigated. He was found to be hyponatremic and the treating team excluded reversible surgical and medical causes. A Naranjo score of 7 was calculated, suggesting that the correlation between ketamine and hyponatremia was "likely." Hence, a diagnosis of ketamine-precipitated SIADH was made. The patient was treated with fluid restriction and symptoms were controlled with antiemetics. He returned to baseline function with resolution of the hyponatremia within three days of discharge. CONCLUSION: This case is of clinical importance for providers using ketamine in the field of pain management as the effect of this medication reaction can be profound. Clinicians should develop an awareness that ketamine can potentiate adverse effects such as SIADH and they should monitor, detect, and manage as appropriate.

RéSUMé: OBJECTIF: Nous signalons un cas inhabituel de syndrome de sécrétion inappropriée d'hormones antidiurétiques (SIADH - syndrome of inappropriate antidiuretic hormone secretion) précipité par la kétamine chez une personne prise en charge par une équipe spécialisée en douleur en soins ambulatoires. CARACTéRISTIQUES CLINIQUES: Un homme de 78 ans s'est présenté à l'urgence souffrant de léthargie, de malaise, de nausées et de ballonnements abdominaux trois jours après avoir reçu une perfusion intraveineuse de kétamine pour le traitement d'une douleur radiculaire lombaire postopératoire rebelle avec des caractéristiques neuropathiques. Le patient avait des antécédents de résection de cancer de la prostate, d'hyperlipidémie, d'insuffisance rénale chronique et de sténose du canal rachidien, et la cause de ses symptômes a été évaluée. Il s'est avéré hyponatrémique et l'équipe soignante a exclu les causes chirurgicales et médicales réversibles. Un score Naranjo de 7 a été calculé, suggérant que la corrélation entre la kétamine et l'hyponatrémie était « probable ¼. Par conséquent, un diagnostic de SIADH précipité par la kétamine a été posé. Le patient a été traité par restriction hydrique et les symptômes ont été contrôlés par des antiémétiques. Il est revenu à son fonctionnement de référence avec la résolution de l'hyponatrémie dans les trois jours suivant son congé. CONCLUSION: Ce cas est important d'un point de vue clinique pour les praticiens qui utilisent la kétamine pour la prise en charge de la douleur, car l'effet de cette réaction médicamenteuse peut être profond. Les cliniciens devraient prendre conscience que la kétamine peut augmenter des effets indésirables tels que le SIADH et ils devraient monitorer, dépister et prendre en charge le patient, le cas échéant.

Giant cystic hypothalamic hamartoma in an infant associated with persistent syndrome of inappropriate antidiuretic hormone secretion.

BACKGROUND: A giant hypothalamic hamartoma (GHH) is a rare congenital malformation only reported in a few cases in the literature and is often associated with precocious puberty, gelastic seizures, or less commonly, Pallister-Hall syndrome. Persistent syndrome of inappropriate antidiuretic hormone secretion (SIADH) is very rare in infancy, and most patients with GHH do not develop persistent SIADH, usually only transient electrolyte disturbances postoperatively. Previous cases of GHH have not been associated with persistent derangements in antidiuretic hormone levels. CASE DESCRIPTION: A 7-month-old male infant presented to our hospital with a history of an intracranial cystic lesion diagnosed at 23 weeks gestational age (GA), later impressed as a solid-cystic mass at 37 weeks GA by ultrasound prenatally. Postnatal MRI after birth showed a large mass with a dorsal cyst occupying the hypothalamus, causing hydrocephalus and brainstem compression. The patient started to have subtle seizures on the seventh day after birth and eventually developed dacrystic seizures. Hyponatremia with persistent SIADH was observed at 3 months of age before surgery. He received long-term oral sodium supplementation, polytherapy of anti-epileptic medications, ventriculocystostomy for progressive enlargement of the cystic cavity, and later surgical treatment for disconnection and partial resection which confirmed a histological diagnosis of hypothalamic hamartoma. CONCLUSION: In this case study, we present a novel association of GHH with persistent SIADH and a rare presentation of a cystic component at the dorsal part of the tumor. Clinicians should be aware of this potential endocrine derangement and provide emergent treatment.

Severe headache trajectory following aneurysmal subarachnoid hemorrhage: the association with lower sodium levels.

BACKGROUND: A clinical hallmark of aneurysmal SAH (aSAH) is headache. Little is known about post-aSAH headache factors which may point to underlying mechanisms. In this study, we aimed to characterize the severity and trajectory of headaches in relation to clinical features of patients with aSAH. METHODS: This is a retrospective longitudinal study of adult patients admitted to an academic tertiary care center between 2012 and 2019 with aSAH who could verbalize pain scores. Factors recorded included demographics, aneurysm characteristics, analgesia, daily morning serum sodium concentration, and occurrence of vasospasm. Group-based trajectory modeling was used to identify headache pain trajectories, and clinical factors were compared between trajectories. RESULTS: Of 91 patients included in the analysis, mean age was 57 years and 20 (22%) were male. Headache score trajectories clustered into two groups: patients with mild-moderate and moderate-severe pain. Patients in the moderate-severe pain group were younger (P<0.05), received more opioid analgesia (P<0.001), and had lower sodium concentrations (P<0.001) than patients in the mild-moderate pain group. CONCLUSION: We identified two distinct post-aSAH headache pain trajectory cohorts and identified an association with age, analgesia, and sodium levels. Future prospective studies considering sodium homeostasis and volume status under standardized analgesic regimens are warranted.

Differential diagnosis of hyponatremia and hypernatremia.

Dysnatremias are among the most common mineral imbalances encountered in clinical practice. Both hyponatremia and hypernatremia are associated with increased morbiditidy and mortality and represent negative prognostic factors regardless of their cause. Serum osmolality, extracellular fluid volume and sodium urine concentration are important parameters for evaluation the cause and differential diagnosis. The rate of onset of ionic disorder and severity of clinical symptoms are essential. While acute disorders with symptoms are treated immediately, in chronic disorders, thorough diagnostic evaluation and a careful approach to their correction are necessary. Especially with rapid substitution of chronic hyponatremia, there is a risk of osmotic demyelination syndrome. Therefore, a slow correction of the serum sodium level with frequent mineralogram checks is required.

Non-thiazide diuretics and hospitalization due to hyponatraemia: A population-based case-control study.

OBJECTIVE: Diuretics are often implicated in hyponatraemia. While thiazides constitute one of the most common causes of hyponatraemia, data on loop diuretics and potassium-sparing agents are limited and partly conflicting. The objective of this investigation was to study the association between use of different types of non-thiazide diuretics and hospitalization due to hyponatraemia. DESIGN, PATIENTS AND MEASUREMENTS: This was a register-based case-control study on the adult Swedish population. By linking national registers, patients hospitalized with a principal diagnosis of hyponatraemia (n = 11,213) from 1 October 2005 through 31 December 2014 were compared with matched controls (n = 44,801). Multivariable logistic regression, adjusted for multiple confounders, was used to analyse the association between use of diuretics and hyponatraemia. In addition, newly initiated use (≤90 days) and ongoing use were examined separately. RESULTS: Adjusted odds ratios (aORs) (95% CI) were 0.61 (0.57-0.66) for the use of furosemide, 1.69 (1.54-1.86) for the use of amiloride and 1.96 (1.78-2.18) for the use of spironolactone and hospitalization due to hyponatraemia. For newly initiated therapy, aORs ranged from 1.23 (1.04-1.47) for furosemide to 3.55 (2.75-4.61) for spironolactone. The aORs for ongoing use were 0.52 (0.47-0.57) for furosemide, 1.62 (1.47-1.79) for amiloride and 1.75 (1.56-1.98) for spironolactone. CONCLUSIONS: Ongoing use of furosemide was inversely correlated with hospitalization due to hyponatraemia, suggesting a protective effect. Consequently, if treatment with furosemide precedes the development of hyponatraemia by some time, other causes of hyponatraemia should be sought. Spironolactone and amiloride may both contribute to hyponatraemia; this effect is most prominent early in treatment.

Symptomatic sinus bradycardia due to electrolyte imbalances in syndrome of inappropriate antidiuretic hormone (SIADH) related covid-19: a case report.

BACKGROUND: Coronavirus Disease-2019 (COVID-19) has been declared a global pandemic since March 11th, 2020. Despite emerging reports and literature covering a broad spectrum of COVID-19 clinical manifestations, facets of COVID-19 have not been fully elucidated. To the authors' concern, sinus bradycardia as a manifestation of COVID-19-induced syndrome of inappropriate antidiuretic hormone (SIADH) has never been reported before. CASE PRESENTATION: In this paper, we report a case of a 59-year-old male patient with confirmed COVID-19 initially presented with presyncope. Further investigations reveal sinus bradycardia related to COVID-19-induced SIADH. This case highlights the possibility of immuno-neuroendocrino-cardiovascular crosstalk resulting in an atypical manifestation of COVID-19: near syncope due to sinus bradycardia. CONCLUSIONS: Another possible cause of sinus bradycardia in COVID-19 is electrolyte imbalance due to COVID-19-related SIADH.

The syndrome of inappropriate antidiuresis after vaccination against COVID-19: case report.

BACKGROUND: The Syndrome of Inappropriate Antidiuresis (SIADH) has been described to be associated with a multitude of conditions and medications, including the severe acute respiratory syndrome coronavirus 2. We describe the case of a patient with newly diagnosed and symptomatic SIADH after receiving the second COVID-19 vaccination not explained otherwise. CASE PRESENTATION: A 79-year-old male person was admitted to the emergency department due to a worsening of his general health state expressed by weakness, fatigue and anorexia. Vital signs and clinical findings were normal, in particular the patient was considered to be euvolemic. Laboratory investigations revealed a serum sodium of 117 mmol/L, a serum osmolality of 241 mosm/kg and a urea of 1.2 mmol/L with creatinine within normal range. Urine chemistry showed a urine osmolality of 412 mosm/kg and urine sodium of 110 mmol/L. TSH, C-reactive protein, and basal cortisol levels were normal. Under therapy with balanced crystalloid fluids, hyponatremia worsened and in absence of diuretic medications, diagnosis of SIADH was made. Since fluid restriction was not sufficiently effective, oral urea was administered. Under this therapy regimen hyponatremia resolved. CONCLUSIONS: Local as well as systemic reactions have been described for the new mRNA-based vaccines including pain and fever. Therefore, it is imaginable that the vaccine might trigger SIADH in some patients.

Association between lipid-lowering agents and severe hyponatremia: a population-based case-control study.

PURPOSE: Drug-induced hyponatremia is common, with medications from many drug-classes implicated. Lipid-lowering agents are among the most prescribed drugs. Limited evidence suggests an inverse association between statins and hyponatremia, while data on other lipid-lowering agents is absent. The objective of this investigation was to study the association between lipid-lowering drugs and hospitalization due to hyponatremia. METHODS: This was a register-based case-control study of the general Swedish population. Those hospitalized with a main diagnosis of hyponatremia (n = 11,213) were compared with matched controls (n = 44,801). Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations, and socioeconomic factors was used to explore the association between severe hyponatremia and the use of lipid-lowering drugs. RESULTS: Unadjusted ORs (95% CI) for hospitalization due to hyponatremia were 1.28 (1.22-1.35) for statins, 1.09 (0.79-1.47) for ezetimibe, 1.38 (0.88-2.12) for fibrates, and 2.12 (1.31-3.35) for resins. After adjustment for confounding factors the adjusted odds ratios (95% CI) compared with controls were 0.69 (0.64-0.74) for statins, 0.60 (0.41-0.86) for ezetimibe, 0.87 (0.51-1.42) for fibrates, and 1.21 (0.69-2.06) for resins. CONCLUSIONS: Use of statins and ezetimibe was inversely correlated with severe hyponatremia. Consequently, these drugs are unlikely culprits in patients with hyponatremia, and they appear safe to initiate in hyponatremic patients. A potential protective effect warrants further studies on how statins and other lipid-lowering drugs are linked to dysnatremias.

In-Hospital Endocrinology Consultation After Transsphenoidal Surgery: Is It Always Necessary?

BACKGROUND: Patients with sellar masses undergoing transsphenoidal surgery (TSS) frequently develop endocrine dysfunction; therefore, in-hospital endocrinology consultation (IHEC) is recommended. However, we wondered whether routine endocrinology assessment of all TSS patients is always necessary. METHODS: We developed an IHEC Physician's Guide to identify patients who would require peri-operative IHEC. An analysis of all patients undergoing TSS for a sellar mass over a 4-year period was conducted to assess the predictive value of the IHEC Physician's Guide in identifying patients who required IHEC. RESULTS: A total of 116 patients underwent TSS; 24 required IHEC. As expected, the risk of endocrine complications requiring peri-operative endocrine management was significantly higher in the IHEC group versus no-IHEC group (96% vs. 1%; p < 0.001). The negative predictive value of the IHEC Physician's Guide in identifying patients who did not require IHEC was 0.99 (95% CI 0.9409-0.9997); Fisher's exact test, p < 0.001), meaning that the IHEC Physician's Guide successfully identified all but one patient who truly required IHEC. CONCLUSION: Results from our study show that most patients do not need IHEC after TSS and that those patients requiring IHEC can be reliably predicted at surgery by using a simple IHEC Physician's Guide.

Diabetes insipidus after endoscopic transsphenoidal surgery: multicenter experience and development of the SALT score.

OBJECTIVE: To identify risk factors for the development of postoperative diabetes insipidus (DI) in a modern cohort of endoscopic endonasal transsphenoidal surgery. METHODS: Analysis of prospectively collected data of 449 consecutive patients operated on for anterior skull base pathology. DI was defined as a polyuria (> 250 ml/h for ≥ 2 consecutive hours) polydipsia syndrome associated with hypotonic urine with or without hypernatraemia. Multivariate logistic regression was used to identify predictors of postoperative DI. A simple scoring system was then created. RESULTS: Postoperative DI occurred in 46 (10.2%) patients. The development of DI did not affect quality of life. Predictors of DI on multivariate analysis included suprasellar extension (OR 2.2; p = 0.04), age < 50 years (OR 2.8; p = 0.003), craniopharyngioma histology (OR 6.7; p = 0.002), and Kelly grade 3 intraoperative CSF leak (OR 2.1; p = 0.04). The SALT score was created based on these characteristics, with one point awarded for each feature present, and predicted DI with fair to good predictive value in our cohort (AUROC 0.735 (95%CI 0.65-0.82)). The rates of postoperative DI were 4.0%, 6.5%, 15.0%. 36.8% and 85.7% for SALT scores of zero, one, two, three, and four, respectively. CONCLUSIONS: The SALT score predicts postoperative DI with fair to good accuracy, and now requires prospective external validation. Improved prediction of DI could optimize resource allocation and facilitate individualised preoperative patient counselling. We also provide our algorithm for diagnosis and treatment of DI.