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Background: To evaluate serum antidiuretic hormone (ADH), its receptors, and renin levels in cerebral salt wasting (CSW) in tuberculous meningitis (TBM)., Methods: Patients diagnosed with definite (n = 30) or probable TBM (n = 47) who developed hyponatremia (CSW, SIADH, or miscellaneous causes) were included. Sequential measurement of serum ADH, ADH-R, and renin activity by enzyme-linked immunosorbent assay was done and correlated with serum sodium level, urinary output, and fluid balance., Results: Out of 79 TBM patients, CSW was observed in 36, SIADH in four, and miscellaneous hyponatremia in eight patients. CSW patients had a longer hospital stay (P < 0.001), lower GCS score (P < 0.007), higher MRC grade (P < 0.007), and a lower serum Na (P < 0.001) compared to non-CSW TBM patients. In severe CSW patients, serum ADH and ADH-R were correlated with hyponatremia and returned to baseline on correction; however, serum renin levels remained elevated. Serum ADH was related to hyponatremia but ADH-R and renin were not. ADH-R and renin levels did not significantly differ in CSW and SIADH., Conclusion: CSW is the commonest cause of hyponatremia in TBM and correlates with disease severity. ADH is related to hyponatremia, but ADH receptor and renin are not., (© 2022. Fondazione Società Italiana di Neurologia.)

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 ( n  = 43) or placebo ( n  = 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. Clinical trial registration : ClinicalTrials.gov (Number: NCT02874807).

Competing Interests: Declaration of interests We declare no competing interests.

Objective: Treatment of symptomatic hyponatremia is not well established. The European guidelines recommend bolus-wise administration of 150 mL of 3% hypertonic saline. This recommendation is, however, based on low level of evidence., Design: Observational study., Methods: Sixty-two consecutive hyponatremic patients admitted to the emergency department or intensive care unit of the University Hospital Wuerzburg were divided in subgroups according to treatment (150 mL bolus of 3% hypertonic saline or conventional treatment) and symptom severity. Treatment target was defined as an increase in serum sodium by 5-10 mEq/L within first 24 h and maximum 8 mEq/L during subsequent 24 h., Results: Thirty-three out of sixty-two patients (53%) were presented with moderate symptoms and 29/62 (47%) with severe symptoms. Thirty-six were treated with hypertonic saline and 26 conventionally. In the hypertonic saline group, serum sodium increased from 116 ± 7 to 123 ± 6 (24 h) and 127 ± 6 mEq/L (48 h) and from 121 ± 6 to 126 ± 5 and 129 ± 4 mEq/L in the conventional group, respectively. Overcorrection at 24 h occurred more frequent in patients with severe symptoms than with moderate symptoms (38% vs 6%, P < 0.05). Diuresis correlated positively with the degree of sodium overcorrection at 24 h (r = 0.6, P < 0.01). Conventional therapies exposed patients to higher degrees of sodium fluctuations and an increased risk for insufficient sodium correction at 24 h compared to hypertonic saline (RR: 2.8, 95% CI: 1.4-5.5)., Conclusion: Sodium increase was more constant with hypertonic saline, but overcorrection rate was high, especially in severely symptomatic patients. Reducing bolus-volume and reevaluation before repeating bolus infusion might prevent overcorrection. Symptoms caused by hypovolemia can be misinterpreted as severely symptomatic hyponatremia and diuresis should be monitored.

Background: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hypotonic hyponatremia. In our previous work, we have derived a novel model (Voets equation) that can be used by clinicians to predict the effect of crystalloid intravenous fluid therapy on the plasma sodium concentration in SIADH., Methods: In this retrospective chart review, the predictive accuracy of the Voets equation and the Adrogue-Madias equation for the plasma sodium response to crystalloid infusate was compared for fifteen plasma sodium response measurements (n = 15) in twelve SIADH patients. The medical records of these patients were accessed anonymously and none of the authors were their treating physicians. The Pearson correlation coefficient r and corresponding p-value were calculated for the predictions by the Voets model compared to the measured plasma sodium response and for the predictions by the Adrogue-Madias model compared to the measured plasma sodium response., Results and Conclusion: The presented results show that the Voets model (r = 0.94, p < 0.001) predicted the aforementioned plasma sodium response significantly more accurately than the Adrogue-Madias model (r = 0.49, p = 0.07) in SIADH patients and could therefore be a clinically useful addition to the existing prediction models., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Cyclophosphamide (CY) is an alkylating agent used widely to treat cancer and autoimmune diseases. Hyponatremia is a common adverse effect of high-dose and moderate-dose of intravenous CY, but is rare in patients treated with low-dose (<15 mg/kg)., Patient Concerns: A 52-year-old woman with new-onset systemic lupus erythematosus (SLE) was treated with low-dose cyclophosphamide (8 mg/kg, CY), but showed sudden headaches, disorientation and weakness. Laboratory examinations revealed severe isovolumic hyponatremia along with low-serum osmolality and high urine osmolality., Diagnosis: The acute hyponatremia was consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and was an adverse event of low-dose CY, with no evidence of endocrine, cancer, pulmonary, or cerebral abnormalities relevant to the SIADH., Intervention: The hyponatremia was resolved after the supplementation of NaCl solution., Outcomes: The hyponatremia was resolved without any complications., Lessons: Hyponatremia induced by low-dose CY should be recognized as an underlying life-threatening complication in clinical practice.

Normal physiologic changes in pregnancy include mild hyponatremia. In some cases of preeclampsia, more significant hyponatremia has been associated with syndrome of inappropriate antidiuretic hormone secretion and hypervolemic hyponatremia. A 45-year-old gravida 2, para 0010 with a dichorionic twin gestation was diagnosed with preeclampsia at 30 weeks 6 days and noted to have concomitant hyponatremia of 125 mEq/L at our institution. Her hyponatremia was initially managed with furosemide and water restriction. She was delivered at 33 weeks 5 days due to worsening preeclampsia and continued significant hyponatremia despite treatment. Her hyponatremia resolved within 48 h after delivery. Our objectives were to discuss trends, treatment, and outcomes of cases with hyponatremia in preeclampsia. We performed a systematic review of the literature using Ovid Medline (1963-2017), Scopus (1962-2017), and PubMed (1963-2017, including Cochrane database). Relevant articles describing any case report of hyponatremia in preeclampsia were identified from the above databases without any time, language, or study limitations. Studies were deemed eligible for inclusion if they described a case of hyponatremia in the setting of preeclampsia. 18 manuscripts detailing 55 cases were identified. Pertinent demographic data and laboratory values were extracted. Maternal management strategy, diagnosis, delivery, and neonatal outcome data were also collected. Mean, range, standard deviation, and percentage calculations were used as applicable. Advanced maternal age (46 %), nulliparity (79 %), and multifetal gestation (34 %) were noted in patients with preeclampsia and low sodium. Hyponatremia was detected on average at 34 weeks gestation. 64 % were diagnosed with preeclampsia with severe features. When reported, diagnoses related to hyponatremia were syndrome of inappropriate antidiuretic hormone secretion (41 %) or hypervolemic hyponatremia (59 %). Indications for delivery included severe hyponatremia unresponsive to conservative measures in addition to other known obstetric or preeclamptic indications. Hyponatremia resolved within 48 h on average in cases where postpartum resolution was reported. It may be prudent to screen women with preeclampsia for electrolyte disturbances as part of their evaluation, especially in the setting of severe features. Initially, hyponatremia may be treated with medical management. In addition to established obstetric or preeclamptic indications, delivery may be considered if severe hyponatremia no longer responds to conservative measures., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: In this study, the risk factors associated with sodium overcorrection were investigated with an optimal cutoff for baseline serum sodium for use in daily clinical practice., Methods: Electronic medical records of patients who received tolvaptan for non-hypovolemic hyponatremia were reviewed. Demographic and clinical data including age, sex, weight, height, comorbidity, cause of hyponatremia, hypertonic saline use, and comedication were collected. Baseline laboratory parameters measured included serum sodium, serum potassium, serum creatinine, blood urea nitrogen, serum tonicity, ALT, AST, and urine osmolality. The primary outcome was the overcorrection of serum sodium, which was defined as an increase in serum sodium by more than 10 mmol/L in 24 h., Results: From a total of 77 patients included in the analysis, 24 (31.2%) showed sodium overcorrection (> 10 mmol/L/24 h); 2 (2.6%) in heart failure cohort, 17 (22.1%) in SIADH cohort, and 5 (6.5%) in unknown cause cohort. More than half of patients (51.9%) were administered hypertonic saline prior to tolvaptan. Hypertension, cancer, diuretics, baseline serum sodium, and SIADH were associated with the risk of overcorrection in the univariable analysis. Significant factors for the overcorrection from multivariable analysis were lower body mass index, presence of cancer (adjusted odds ratio, 10.87; 95% CI, 1.23-96.44), and lower serum sodium at baseline (adjusted odds ratio, 0.76 for every 1 mEq/L increase; 95% CI, 0.61-0.94)., Conclusion: The overcorrection of hyponatremia in non-hypovolemic patients treated with tolvaptan was significantly associated with lower body mass index, presence of cancer, and lower serum sodium at baseline. In subgroup analysis using SIADH patients, baseline sodium and cancer were found to be significant factors of overcorrection.

Small cell carcinoma (SCC) of the bladder is a rare malignancy, representing less than 1% of bladder cancers diagnosed annually in the USA. In contrast to SCC of the lung, paraneoplastic syndromes are rarely documented in cases of extrapulmonary SCCs, particularly those of genitourinary origin. We present a case of SCC of the bladder presenting with paraneoplastic syndrome of inappropriate antidiuretic hormone, which resolved after treatment with sequential chemoradiation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Tolvaptan, an oral vasopressin V2 receptor antagonist, is a new approach for the treatment of adult patients with the syndrome of inappropriate antidiuresis (SIADH). However, dose-dependent side effect including rapid increase in serum sodium levels and liver injury, and the expensive price limit the long-term use of tolvaptan. We report a case of SIADH patient treated with intermittent lower dose of tolvaptan combined with fluid restriction., Patient Concerns: A 60-year-old woman presented of nausea and vomiting, dizzy and amaurosis, and transient disturbance, after a week of persistent diarrhea., Diagnosis: Diagnosis of SIADH was based on severe persistent hyponatremia, decreased plasma osmolality, raised urinary sodium excretion, and the absence of other causes., Interventions: She was given the treatment of tolvaptan 15 mg once daily, and experienced tolvaptan-related side effects including thirst and dry mouth, polyuria, and dizziness. Then, single dose of tolvaptan was reduced from 15 to 7.5 mg, and the interval between medication was gradually prolonged from 24 to 72 hours. Meanwhile, serum sodium was negatively correlated with the amount of daily water intake in interval days, so daily water intake of the patient was restricted to 1500 mL in interval days., Outcomes: Serum sodium was maintained within the normal range, 137 to 141 mmol/L without liver damage., Lessons: For patients with chronic SIADH, the tolvaptan dose should be individualized, and the regimen of intermittent lower dose of tolvaptan combined with fluid restriction maybe an effective choice.

Background: A wide range of interesting mathematical models has been derived to predict the effect of intravenous fluid therapy on the serum sodium concentration (most notably the Adrogué-Madias equation), but unfortunately, these models cannot be applied to patients with disorders characterized by aberrant antidiuretic hormone (ADH) release, such as the syndrome of inappropriate ADH secretion (SIADH). The use of intravenous fluids in these patients should prompt caution, as the inability of the kidneys to properly dilute the urine can easily result in deterioration of hyponatremia., Methods: In this report, a transparent and clinically applicable equation is derived that can be used to calculate the estimated effect of different types and volumes of crystalloid infusate on the serum sodium concentration in SIADH patients. As a "proof of concept", we discuss five SIADH patient cases from our clinic. Alternatively, our mathematical model can be used to determine the infusate volume that is required to produce a certain desired change in the serum sodium concentration in SIADH patients., Conclusion: The presented model facilitates rational intravenous fluid therapy in SIADH patients, and provides a valuable addition to existing prediction models.

Aims: We attempted to classify 115 consecutive nonedematous hyponatremic patients according to their history and saline responsiveness. We hereby describe 6 out of them presenting a transient renal salt wasting (TRSW) state of unknown origin., Materials and Methods: Six patients with an initial SNa of 126 ± 3 mEq/L were included in the study. They were treated with 2 L isotonic saline infusion over 24 hours. The evolution of the biochemical data of 5 patients were compared to 6 patients with syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH), 6 hyponatremias following the use of thiazides, and to 5 salt-depleted hyponatremic patients of similar age and body weight, treated in the same way., Results: The mean values of FEurea and FEuric acid in the 6 described patients, together with a clearly inappropriate natriuresis suggested SIADH. However, the high mean fractional potassium excretion (FEK = 34 ± 15%) was not observed in SIADH (13 ± 3%) (p < 0.01). Plasma sodium levels improved quickly after saline infusion in most of these patients, while fractional solute excretions and diuresis decreased. Calciuria is increased in patients with renal salt waisting (RSW), while low calciuria values are observed in the thiazide group. Four of the 6 hyponatremic patients were admitted for syncopal malaise or fall., Conclusion: We observed in 6 out of 115 consecutive hyponatremic patients a TRSW. RSW as a diagnosis has to be considered when in hyponatremia with excessive natriuresis, high FEK and an intake of diuretics is ruled out. This hyponatremia is saline-responsive, but relapse can be frequently observed.

Objective: Hyponatraemia is common in community-acquired pneumonia (CAP) and is associated with increased mortality. The mechanism of hyponatraemia in CAP is not completely understood and treatment is therefore ill-defined. We aimed to define the causation of hyponatraemia in CAP., Design: Prospective, single-centre, observational study of all patients with CAP and hyponatraemia (≤ 130 mmol/L) during a 9-month period., Patients: The prevalence of each subtype of hyponatraemia, and the associated mortality, was determined in 143 admissions with CAP (Study 1). A sub-cohort of patients with SIAD (n = 10) was prospectively followed, to document the natural history of SIAD associated with CAP (Study 2)., Measurements: In Study 2, blood and urine were collected on day 1, 3, 5 and 7 following admission for measurement of plasma vasopressin, sodium, osmolality and urine osmolality., Results: In study 1, 143/1723(8.3%) of CAP patients had hyponatraemia (≤130 mmol/L). About 66 had SIAD (46%), 60(42%) had hypovolaemic hyponatraemia (HON), 13(9%) had hypervolaemic hyponatraemia (HEN) and 4(3%) patients had hyponatraemia due to glucocorticoid hormone deficiency. Mortality was higher in the HEN than in the HON, SIAD or normonatraemic groups (P < 0.01). In Study 2, plasma sodium concentration normalized in 8/10 (80%) by day 7. Two patients with persistent hyponatraemia were discovered to have underlying bronchiectasis., Conclusions: Hyponatraemia in CAP is most commonly secondary to SIAD or hypovolaemia. HEN is less common, but has worse prognosis. Prospective observation demonstrates that in SIAD, plasma AVP and sodium concentrations normalize with antimicrobials; failure of reversal of suggests underlying lung disease, such as bronchiectasis., (© 2019 John Wiley & Sons Ltd.)

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD), first described in 2005, is a rare genetic X-linked disease, presenting with hyponatremia, hyposmolarity, euvolemia, inappropriately concentrated urine, increased natriuresis, and undetectable or very low arginine-vasopressine (AVP) circulating levels. It can occur in neonates, infants, or later in life. NSIAD must be early recognized and treated to prevent severe hyponatremia, which can show a dangerous impact on neonatal outcome. In fact, it potentially leads to death or, in case of survival, neurologic sequelae. This review is an update of NSIAD 12 years after the first description, focusing on reported cases of neonatal and infantile onset. The different molecular patterns affecting the AVP receptor 2 (V2R) and determining its gain of function are reported in detail; moreover, we also provide a comparison between the different triggers involved in the development of hyponatremia, the evolution of the symptoms, and modality and efficacy of the different treatments available.

CME: Paraneoplastic Endocrine Syndromes Abstract. Paraneoplastic endocrine syndromes are caused by ectopic hormone production by malignant tumor cells. Knowledge of paraneoplastic endocrine syndromes may allow a timely diagnosis of the underlying cancer at a treatable stage and, on the other hand, appropriate treatment of the endocrine manifestations reduces morbidity and mortality of the affected patients. The most common endocrine syndromes are paraneoplastic hypercalcaemia, caused by the secretion of PTHrP, and hyponatremia, caused by the inadequate secretion of ADH. Although there may be clinical symptoms like fatigue, nausea/vomiting and renal insufficiency for hypercalcaemia and gait disturbances and mental alterations for hyponatremia, the diagnosis must be confirmed by laboratory testing and prompt the search for associated tumors.

Background: The approach to hyponatremia is in a state of flux, especially in differentiating syndrome of inappropriate antidiuretic hormone secretion (SIADH) from cerebral-renal salt wasting (RSW) because of diametrically opposite therapeutic goals. Considering RSW can occur without cerebral disease, we determined the prevalence of RSW in the general hospital wards., Methods: To differentiate SIADH from RSW, we used an algorithm based on fractional excretion (FE) of urate and nonresponse to saline infusions in SIADH as compared to excretion of dilute urines and prompt increase in serum sodium in RSW., Results: Of 62 hyponatremic patients, (A) 17 patients (27%) had SIADH, 11 were nonresponsive to isotonic saline, and 5 normalized a previously high FEurate after correction of hyponatremia; (B) 19 patients (31%) had a reset osmostat based on normal FEurates and spontaneously excreted dilute urines; (C) 24 patients (38%) had RSW, 21 had no clinical evidence of cerebral disease, 19 had saline-induced dilute urines; 2 had undetectable plasma ADH levels when urine was dilute, 10 required 5% dextrose in water to prevent rapid increase in serum sodium, 11 had persistently increased FEurate after correction of hyponatremia and 10 had baseline urinary sodium < 20 mEq/L; (D) 1 patient had Addison disease with a low FEurate and (E) 1 patient (1.6%) had hyponatremia due to hydrochlorothiazide., Conclusions: Of the 24 patients with RSW, 21 had no cerebral disease, supporting our proposal to change cerebral-renal salt wasting to renal salt wasting. Application of established pathophysiological standards and a new algorithm based on determination of FEurate were superior to the volume approach for determination of urinary sodium when identifying the cause of hyponatremia., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Introduction: Hypercalcemia is a common pathological condition in clinical practice. The two most common causes are primary hyperparathyroidism and cancer. SIADH is often encountered in cancer cases and is the most common cause of hyponatremia. The aim of this study is to evaluate serum sodium levels in a cohort of patients with hypercalcemia and consider its predictive value in determining the origin of this hypercalcemia., Materials and Methods: We performed a retrospective study on a series of 15.284 blood tests among adult patients with hypercalcemia. After selection, the study population had 151 patients. We studied mainly serum sodium and etiology of hypercalcemia in our population., Results: We observed a statistically significant association between the presence of hyponatremia and the neoplastic etiology of hypercalcemia. This association persisted after exclusion of patients under treatment with loop diuretics. Conversely, there was no association between hypernatremia and cancer-related hypercalcemia. Among 151 patients with hypercalcemia, 16 presented hyponatremia and 7 with hypernatremia. SIADH was the main cause of hyponatremia. We performed univariate and multivariate logistic regression showing the association between the presence of cancer and the presence of hyponatremia., Conclusion: Our study shows that there is an association between the presence of hyponatremia and neoplastic origin of hypercalcemia. Besides, the association described between hyponatremia and cancer is not faulted by the presence of hypercalcemia, a potential cause of acquired nephrogenic diabetes insipidus.

Purpose: Tolvaptan (TLV) is indicated to treat hyponatremia due to syndrome of inappropriate diuretic hormone (SIADH) in Europe. Treatment is to be initiated at 15 mg QD but post-approval reporting indicates increasing use of 7.5 mg as the starting dose. Physicians believe 7.5 mg is effective and has a lower incidence of overly rapid correction of serum sodium., Methods: Single TLV doses of 3.75, 7.5, and 15 mg were administered to 14 healthy adults in a crossover design and to 29 subjects ≥18 years with SIADH and serum sodium between 120 and 133 mmol/L in a parallel-group design. Pharmacodynamics and TLV plasma concentrations were assessed for 24 h post-dose., Results: In SIADH subjects, corrections of serum sodium (Δ of ≥8 mmol/L in the first 8 h or ≥12 mmol/L in the first 24 h) were observed in one, one, and two subjects in the 3.75-, 7.5-, and 15-mg dose groups. Fluid balance (FB) for 0-6 h post-dose was correlated (r 2  = 0.37) with maximum increases in serum sodium; subjects with large corrections had large (~1 L) negative FB. Compared to healthy adults, subjects with SIADH did not drink in response to their negative FB and had larger increases in serum sodium at 24 h. Median time of maximum increase in healthy adults was 6 h, with no rapid corrections, and FB was near 0 mL by 24 h., Conclusion: Starting titration with 7.5 mg TLV will not eliminate the risk of rapid corrections in serum sodium. Monitoring FB may indicate that a subject is at risk for over correction.

Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic. Its clinical efficacy is in principle due to impaired vasopressin-regulated water reabsorption via aquaporin-2 (AQP2). Nevertheless, no direct in vitro evidence that tolvaptan prevents AQP2-mediated water transport, nor that this pathway is targeted in vivo in patients with syndrome of inappropriate antidiuresis (SIAD) has been provided. The effects of tolvaptan on the vasopressin-cAMP/PKA signalling cascade were investigated in MDCK cells expressing endogenous V2R and in mouse kidney. In MDCK, tolvaptan prevented dDAVP-induced increase in ser256-AQP2 and osmotic water permeability. A similar effect on ser256-AQP2 was found in V1aR -/- mice, thus confirming the V2R selectively. Of note, calcium calibration in MDCK showed that tolvaptan per se caused calcium mobilization from the endoplasmic reticulum resulting in a significant increase in basal intracellular calcium. This effect was only observed in cells expressing the V2R, indicating that it requires the tolvaptan-V2R interaction. Consistent with this finding, tolvaptan partially reduced the increase in ser256-AQP2 and the water permeability in response to forskolin, a direct activator of adenylyl cyclase (AC), suggesting that the increase in intracellular calcium is associated with an inhibition of the calcium-inhibitable AC type VI. Furthermore, tolvaptan treatment reduced AQP2 excretion in two SIAD patients and normalized plasma sodium concentration. These data represent the first detailed demonstration of the central role of AQP2 blockade in the aquaretic effect of tolvaptan and underscore a novel effect in raising intracellular calcium that can be of significant clinical relevance., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Hyponatremia is the most frequent electrolyte disorder with the syndrome of inappropriate antidiuresis (SIADH) being its predominant cause. Physiological studies in patients with SIADH are difficult to interpret due to usually several comorbidities and polymedication. Therefore, a SIADH model in healthy volunteers would be very helpful to allow insight in this complex disease and to test new therapeutic approaches. The aim of the study was to create a SIADH model with evaluation of subsequent physiological changes.The prospective interventional study on 14 healthy volunteers was carried out at the University Hospital Basel. The intervention was done by induction of hypotonic hyponatremia through hydration and administration of desmopressin. Clinical and laboratory parameters in a SIADH model were the main outcome of the measure.14 participants (64% males), BMI 23.1 kg/m 2 (±2.4), aged 28.6 years (±9), completed the study. Through the intervention, serum sodium level decreased from 140 mmol/l (±1.3) to 132 mmol/l (±2.0) and serum osmolality from 286 mmol/kg (±4.7) to 267 mmol/kg (±3.5). Simultaneously urine osmolality increased to 879 mmol/kg (±97.7) and urine sodium to 213 mmol/l (±51.5) verifying the artificial SIADH model. A significant decrease of copeptin (5 pmol/l (±1.9) to 2.6 pmol/l (±0.5), p 0.002), aldosterone (314.7 pmol/l (±154.1) to 86.7 pmol/l (±23.6), p 0.019), and renin (21.2 ng/l (±26.7) to 3.6 ng/l (3.2), p 0.035) were noted, while NT-proBNP and MR-proANP significantly increased (31.7 ng/l (±18.6) to 50.5 ng/l (±33.0), p 0.001; 48.4 pmol/l (±16.8) to 56.8 pmol/l (±9.0), p 0.003).In conclusion, we were able to induce an artificial SIADH in healthy volunteers and study the changes of various hormonal biomarkers involved. This SIADH model could be helpful in evaluating diagnostic and therapeutic approaches., Competing Interests: Conflicts of interest: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aims: The aims of the current study were to determine the distribution of aetiologies for the drug-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) in hospitalized patients, and to characterize them according to the different drug groups., Methods: A single-centre retrospective study was carried out, including all patients diagnosed with SIADH in a large community hospital and tertiary centre between 1 January 2007 and 1 January 2013 who were treated with drugs known to be associated with SIADH. Two physicians reviewed every patient's medical file for predetermined relevant clinical data., Results: The study cohort included 198 patients who had SIADH and received drugs associated with SIADH. Most patients [146 (73.7%)] were diagnosed with drug-associated SIADH, while 52 (26.3%) were diagnosed with SIADH due to other aetiologies. The Naranjo algorithm differentiated well between the two groups (P < 0.001). Five drug classes (antidepressants, anticonvulsants, antipsychotic agents, cytotoxic agents and pain medications) were implicated in 82.3% of patients diagnosed with drug-associated SIADH. Specific serotonin reuptake inhibitors and carbamazepine were commonly implicated. There were no clinically significant differences in the characteristics or severity of SIADH according to drug class., Conclusions: The clinical characteristics of SIADH caused by different drugs are comparable. Patients with SIADH treated with drugs from five common medication classes will probably be diagnosed with drug-induced SIADH. Physicians should be aware of the significance of these medication classes as SIADH aetiologies., (© 2017 The British Pharmacological Society.)

Background: Fluid restriction is recommended as first line therapy for Syndrome of Inappropriate Antidiuresis (SIAD), despite of lack of good evidence base to support its use, and poor efficacy in clinical practice and in the literature., Aim: We set out to determine how many patients with well-defined SIAD had pre-treatment criteria which would predict failure to fluid restriction., Design and Methods: This was a consecutive, prospective evaluation of 183 patients with a diagnosis of SIAD in two different hospitals. Full ascertainment of the diagnostic criteria for SIAD was obtained in all patients., Results: About 47% of patients had a urine volume <1500 ml in 24 h, 41% had initial urine osmolality > 500 mOsm/kg, 26% a Furst-equation ratio > 1. About 59% had one criterion predicting failure to respond to fluid restriction, 37% two criteria, and 3% three criteria., Conclusions: Our data suggest that up to 60% of patients with SIAD had criteria which recent clinical guidelines suggest would predict nonresponse to fluid restriction. This may explain why the recommended first line therapy for SIAD has been shown to be ineffective., (© The Author 2017. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objective: The aim of the study was to evaluate the usefulness of copeptin for differentiation of hyponatremia in the course of tick-borne encephalitis (TBE) and for being a prognostic marker of the severity of TBE., Materials and Methods: One hundred and fourteen patients with TBE were included in the study. The control group consisted of 62 patients diagnosed with viral meningitis., Results: Copeptin concentration did not differ in patients with hyponatremia and normonatremia. Urinary sodium excretion to plasma copeptin (copeptin/UNa Secretion) ratio was significantly lower in Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion patients than in patients with hyponatremia of other origin. Mean copeptin concentration in TBE patients was higher than in control group (VM) patients. There were no differences between patients with severe and mild course of TBE., Conclusions: Copeptin/UNa ratio may be used as a potential biomarker of SIADH in patients with TBE. Copeptin concentration is significantly higher in patients with TBE than in viral meningitis of other origin, especially in patients aged 18-34 and >49 years old. Copeptin does not differentiate TBE of mild and severe course.

Hyponatremia is a common electrolyte disorder in cancer patients and has been associated with poor prognosis. A frequent cause of cancer-related hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH). This study was a post hoc subgroup analysis of the SALT-1 (Study of Ascending Levels of Tolvaptan in Hyponatremia) and SALT-2 clinical trials. Hyponatremic subjects with SIADH and cancer received the oral selective vasopressin V2-receptor antagonist tolvaptan (n = 12) or matching placebo (n = 16) once-daily for 30 days. The initial tolvaptan dose (15 mg) was titrated over 4 days to 30 or 60 mg per day, as needed, according to serum sodium level and tolerability. Baseline serum sodium levels in the SIADH/cancer cohort of the SALT trials was 130 and 128 mEq/L for tolvaptan and placebo, respectively. Mean change from baseline in average daily serum sodium AUC for tolvaptan relative to placebo was 5.0 versus -0.3 mEq/L (P < 0.0001) at day 4, and 6.9 versus 1.0 mEq/L (P < 0.0001) at day 30; the observed treatment effects were similar to those in the overall SIADH population (i.e., with and without cancer) at both time points. Serum sodium normalization was observed in 6/12 and 0/13 subjects at day 4 and 7/8 and 2/6 subjects at day 30 in the tolvaptan and placebo groups, respectively (P < 0.05 for both). Common treatment-emergent AEs for tolvaptan were consistent with previously reported results. In this post hoc study of the SALT trial population, oral tolvaptan was an effective and safe therapy for the treatment of hyponatremia in subjects with SIADH and cancer., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Electrolyte abnormalities are hallmark metabolic disturbances during the treatment of acute lymphoblastic leukemia (ALL). Hyponatremia is an ominous laboratory sign in the setting of neoplasia. We analyzed the incidence, risk factors, associations, specific interventions and outcomes of severe hyponatremia in a single-center series of children with ALL. The incidence of severe hyponatremia, defined as serum sodium levels below 130 mmol/L on at least 2 of 3 consecutive days, was 11.9%. History of hyponatremia episode is associated with neurologic complications (P=0.023) and the presence of overt central nervous system leukemia (CNS3) at diagnosis (P=0.005). Most observed hyponatremia episodes resolved relatively quickly, rarely requiring specific treatment. All but 1 hyponatremia episodes occurred in the induction or reinduction phases, but none before the administration of cytotoxic drugs, pointing to the role of therapy complications rather than leukemia per se. Most patients received vincristine shortly before hyponatremia onset, and vincristine has been previously strongly implicated in hyponatremia. We also suggest a role for imatinib. Although every patient with severe hyponatremia requires swift and thorough diagnostics a serious sequelae in the setting of pediatric ALL is rare. Hyponatremia association with neurotoxicity likely points to vincristine hypersensitivity in the subgroup of patients with both complications.

The syndrome of inappropriate antidiuretic hormone (SIADH) is reported as the most common cause of hyponatraemia. This retrospective cross-sectional study evaluated the diagnosis of SIADH in 110 hospitalised patients in an Australian tertiary hospital with reference to recently published clinical guidelines. Investigation of SIADH was incomplete in all but 20% of cases. Adrenal insufficiency and hypothyroidism were not excluded in a significant number of cases., (© 2017 Royal Australasian College of Physicians.)

Purpose: The syndrome of inappropriate antidiuresis is often undertreated with most patients discharged with persistent hyponatraemia. This study tested the hypothesis that an endocrine input is superior to routine care in correcting hyponatraemia and can improve patient outcomes., Methods: This single-centre prospective-controlled intervention study included inpatients admitted at a UK teaching hospital, with serum sodium ≤ 127 mmol/l, due to syndrome of inappropriate antidiuresis over a 6-month period. The prospective intervention group (18 subjects with mean serum sodium 120.7 mmol/l) received prompt endocrine input, while the historical control group (23 patients with mean serum sodium 124.1 mmol/l) received routine care. The time needed for serum sodium increase ≥ 5 mmol/l was the primary endpoint., Results: The intervention group achieved serum sodium rise by ≥5 mmol/l in 3.5 vs. 7.1 days in the control group (P = 0.005). In the intervention group, the mean total serum sodium increase was 12 mmol/l with only 5.8 % of patients discharged with serum sodium < 130 vs. 6.3 mmol/l increase (P < 0.001) and 42.1 % of the subjects discharged with serum sodium < 130 mmol/l in the control group (P = 0.012). The mean length of hospital stay in the intervention group (10.9 days) was significantly shorter than in the control group (14.5 days; P = 0.004).The inpatient mortality rate was 5.5 % in intervention arm vs. 17.4 % in control arm, but this difference was not statistically significant., Conclusions: Since the endocrine input improved time for correction of hyponatraemia and shortened length of hospitalisation, widespread provision of endocrine input should be considered., Competing Interests: The authors declare that they have no competing interests. Ethical approval "All procedures performed in studies involving human participants were in accordance with the ethical standards of the institution and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards."

Background: Hyponatremia is a frequent and potentially life-threatening adverse side effect of thiazide diuretics. This sub-analysis of the Hyponatremia Registry database focuses on current management practices of thiazide-associated hyponatremia (TAH) and compares differences between TAH and syndrome of inappropriate antidiuretic hormone secretion (SIADH)., Methods: We analyzed 477 patients from 225 US and EU sites with euvolemic hyponatremia ([Na+] ≤130 mEq/L) who were receiving a thiazide diuretic. Of these, 118 met criteria for true thiazide-induced hyponatremia (TIH)., Results: Thiazide was withdrawn immediately after hyponatremia was diagnosed only in 57% of TAH; in these patients, the median rate of [Na+] change (Δdaily[Na+]) was significantly higher than those with continued thiazide treatment (3.8 [interquartile range: 4.0] vs. 1.7 [3.8] mEq/L/day). The most frequently employed therapies were isotonic saline (29.6%), fluid restriction (19.9%), the combination of these two (8.2%), and hypertonic saline (5.2%). Hypertonic saline produced the greatest Δdaily[Na+] (8.0[6.4] mEq/L/day) followed by a combination of fluid restriction and normal saline (4.5 [3.8] mEq/L/day) and normal saline alone (3.6 [3.5] mEq/L/day). Fluid restriction was markedly less effective (2.7 [2.7] mEq/L/day). Overly rapid correction of hyponatremia occurred in 3.1% overall, but in up to 21.4% given hypertonic saline. Although there are highly significant differences in the biochemical profiles between TIH and SIADH, no predictive diagnostic test could be derived., Conclusions: Despite its high incidence and potential risks, the management of TAH is often poor. Immediate withdrawal of the thiazide is crucial for treatment success. Hypertonic saline is most effective in correcting hyponatremia but associated with a high rate of overly rapid correction. We could not establish a diagnostic laboratory-based test to differentiate TIH from SIADH., (© 2017 The Author(s) Published by S. Karger AG, Basel.)

Hyponatremia due to isolated adrenocorticotropic hormone (ACTH) deficiency is difficult to diagnose as it is usually indistinguishable from non-endocrine syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present a case secondary to empty sella. Most patients with empty sella remain asymptomatic throughout life and require no treatment; however, in cases involving the development of isolated ACTH deficiency, corticosteroid treatment should be enforced to avoid fatal consequences.

Background: There is controversy over the prevalence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral or renal salt wasting (RSW), 2 syndromes with identical common clinical and laboratory parameters but different therapies. The traditional approach to the hyponatremic patient relies on volume assessment, but there are limitations to this method., Methods: We used an algorithm that relies on fractional excretion of urate (FEurate) to evaluate patients with hyponatremia and present 4 illustrative cases., Results: Overall, 2 patients had increased FEurate [normal: 4-11%], as is seen in SIADH and RSW. A diagnosis of SIADH was made in 1 patient by correcting the hyponatremia with 1.5% saline and observing a characteristic normalization of an elevated FEurate that is characteristic of SIADH as compared to FEurate being persistently increased in RSW. A patient with T-cell lymphoma had symmetrical leg edema due to lymphomatous obstruction of the inferior vena cava, postural hypotension, pleural effusion, ascites, decreased cardiac output and urine sodium level of 10mmol/L. Saline-induced excretion of dilute urines and undetectable plasma antidiuretic hormone were consistent with RSW. Furosemide, given for presumed heart failure, induced a profound diuresis that required large volumes of fluid resuscitation. A normal FEurate identified a reset osmostat in a transplant patient with a slowly developing pneumocystis carinii pneumonia. A volume-depleted hyponatremic patient with Addison׳s disease had a low FEurate of 1.4%., Conclusions: These illustrative cases suggest that an approach to hyponatremia using FEurate may be a useful alternative to traditional volume-based approaches., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

BACKGROUND Our study aimed to demonstrate the frequency of the syndrome of inappropriate ADH secretion (SIADH) and associated factors during the course of brucellosis in children and adolescents. MATERIAL AND METHODS The study included children and adolescents aged 0-18 years old diagnosed with brucellosis between 2012 and 2014. The data were collected from patient charts. The diagnosis of brucellosis was made based on titrations >1:160 in standard Wright tube agglutination tests and/or positive culture tests. SIADH diagnosis was made based on the following criteria: euvolemic hyponatremia, serum Na+ <135 mmol/L, presence of serum hypoosmolarity (serum osmolarity <275 mOsm/L), increased urinary sodium (>25 mmol/L with normal dietary salt intake), low uric acid (<2 mg/dL), absence of kidney, thyroid or adrenal disease, and any anti-diuretic use. RESULTS The study included 160 children and adolescents with mean age of 9.58±3.95 years (range: 2-18 years) including 70 girls (43.8%) and 90 boys (56.2%). When the patients were stratified based on SIADH, it was found that SIADH was present in 35 patients (21.9%). SIADH was associated with elevated glucose (p<0.001), ALT (p<0.05), AST (p<0.05), LDH (p<0.001), CRP (p<0.001), and MPV (p<0.001); and decreased potassium (p<0.05), chloride (p<0.001), albumin (p<0.001), total protein (p<0.05), and hemoglobin (p<0.05) levels. CONCLUSIONS Our study reports on the frequency, clinical characteristics, predisposing factors, and management of SIADH that can develop in children and adolescents diagnosed with brucellosis.

Purpose: To determine the distribution of etiologies for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in hospitalized patients with active malignancies and to characterize them according to the different etiologies., Methods: A single center retrospective study including all patients with active malignancies diagnosed with SIADH in a large community hospital and tertiary center between 1 January 2007 and 1 January 2013. Two physicians reviewed every patient's medical file for predetermined relevant clinical data., Results: The study cohort included 204 patients. 74.4% of those with solid tumors had metastatic disease. Most patients (149, 73%) had malignancy associated SIADH, while 55 (27%) had SIADH due to other etiologies. All of the major malignancy types were implicated in SIADH. Patients with breast cancer without lung or brain involvement were significantly less likely to be diagnosed with malignancy associated SIADH compared with other malignancies [Odds ratio (OR) 0.031, 95% CI 0.003-0.25, p < 0.001]. Patients with malignancy associated SIADH had lower serum sodium concentrations on short-term follow-up (p = 0.024) and significantly shorter median survival (58 vs. 910 days, p < 0.001). Short-term hyponatremia correction was associated with better survival., Conclusions: SIADH is associated with most malignancy types. Physicians caring for patients with breast cancer without lung or brain involvement diagnosed with SIADH without an obvious etiology should consider obtaining lung and brain imaging to rule out undiagnosed metastatic spread. Patients with malignancy associated SIADH have considerably worse outcomes compared to cancer patient with SIADH due to other etiologies. Short-term sodium concentration can be used as a prognostic marker for these patients.

Background: To investigate and differentiate the causes of hyponatremia in an 8-y old boy., Methods: An 8-y boy presented with headache, vomiting, and diplopia. Magnetic resonance imaging of the brain confirmed a mass in the pineal region. Pathology report demonstrated a mixed germ cell tumor with a yolk sac component. A multi-agent chemotherapy and radiation regimen was initiated. He developed hyponatremia, with sodium concentrations varying from 116 to 133 mEq/l., Results: Serum levels of sodium, chloride, phosphorous, uric acid, and osmolality were low. Serum α-fetoprotein, β-HCG, and lactate dehydrogenase were highly elevated. Urine sodium and osmolality were increased., Conclusions: These presentations suggest that the patient has cerebral salt-wasting syndrome caused by intracranial germ cell tumor. Recognition and differentiation of cerebral salt-wasting syndrome from other disorders are essential., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aim: The aim of the study was the evaluation of frequency and origin of hyponatremia in tick borne encephalitis (TBE) in comparison to non-TBE viral meningitis and bacterial meningitis., Methods: A total of 124 patients aged 18-80 years, with TBE were included to the study. The mild form of TBE was diagnosed in 59 patients, while the severe form was diagnosed in 65 patients. The first control group (VMG) consisted of 72 patients with viral meningitis, but excluded TBE. The second control group (BMG) consisted of 16 patients diagnosed with bacterial meningitis., Results: Hyponatremia was diagnosed in 55 (44.4%) patients with TBE. In 12 (9.7%) patients (mean age 56.6 ± 19.9 years; 9 men, 3 women) syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was diagnosed. In VMG hyponatremia was diagnosed in 7 (9.7%) patients. In the age group <35 years and in the age group of 50-64 years the frequency of hyponatremia and SIADH was higher in TBE than in VMG (p < 0.05). In BMG hyponatremia was diagnosed in 6 (37.5%) patients. No statistically significant differences in frequency of hyponatremia between BMG and TBE groups were observed., Conclusions: (1) Hyponatremia is a common disorder in TBE and is more frequent than in other viral types of meningitis, especially in young patients (< 35 years). (2) The most common cause of hyponatremia in TBE patients is dehydration and fluid supplementation should be a treatment of choice. (3) Overall, 16.9% of the patients with the severe form of TBE develop SIADH syndrome and they required treatment based on fluid restriction and hypertonic saline infusion.

Background: Haptoglobin (Hp) genotype has been shown to be a predictor of clinical outcomes in subarachnoid hemorrhage. Cerebral salt wasting (CSW) has been suggested to precede the development of symptomatic vasospasm., Objective: To determine if Hp genotype was associated with CSW and subsequent vasospasm after aneurysmal subarachnoid hemorrhage., Methods: Hp genotypic determination was done for patients admitted with a diagnosis of subarachnoid hemorrhage. Outcome measures included CSW, delayed cerebral infarction, and Glasgow Outcome Score of 4 to 5 at 30 days. Criteria for CSW included hyponatremia <135 mEq/L, and urine output >4 L in 12 hours with urine sodium >40 mEq/L., Results: A total of 133 patients were included in the study. The 3 Hp subgroups did not differ in terms of baseline characteristics. CSW occurred in 1 patient (3.4%) with Hp 1-1, 8 (14.0%) patients with Hp 2-1, and 15 (31.9%) patients with Hp 2-2 (P = .004). In the multivariate regression model, Hp 2-2 was associated with CSW (odds ratio [OR]: 4.94; CI: 1.78-17.43; P = .01), but Hp 2-1 was not (OR: 2.92; CI: 0.56-4.95; P = .15) compared with Hp 1-1. There were no associations between Hp genotypes and functional outcome or delayed cerebral infarction. CSW was associated with delayed cerebral infarction (OR: 7.46; 95% CI: 2.54-21.9; P < .001)., Conclusion: Hp 2-2 genotype was an independent predictor of CSW after subarachnoid hemorrhage. Because CSW is strongly associated with delayed cerebral infarction, the use of Hp genotype testing requires more investigation, and larger prospective confirmation is warranted. Additionally, a more objective definition of CSW needs to be delineated.

The syndrome of inappropriate secretion of antidiuretic hormone is a disorder of impaired water excretion caused by the inability to suppress secretion of antidiuretic hormone. It has been commonly associated with small cell carcinoma. The association of this syndrome with squamous cell lung carcinoma has rarely been reported, with only 4 cases over the past two decades in the English literature. We describe the case of a 75-year-old Caucasian male who developed the syndrome after a right pneumonectomy for down-staged squamous cell lung cancer previously treated with neoadjuvant platinum-based chemotherapy and radiotherapy., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

We present a case of rapidly progressing Addison's disease in adrenal crisis with severe hyponatraemia and absence of hyperkalaemia in a 10-year-old girl. She presented with 2 weeks of vomiting, fatigue and weight loss. Her serum electrolytes obtained 1 week prior to presentation were normal, except for mild hyponatraemia at 131 mmol/L, which dropped to 112 mmol/L on admission. She had normal serum potassium, low-serum osmolality, with elevated urine sodium and osmolality, indistinguishable from syndrome of inappropriate antidiuretic hormone (SIADH). Subsequently, Addison's disease was diagnosed on the basis of gingival hyperpigmentation and undetectable cortisol on adrenocorticotropic hormone stimulation test. She rapidly responded to stress dose hydrocortisone, followed by hydrocortisone and fludrocortisone replacement therapy. The absence of hyperkalaemia in the presence of severe hyponatraemia cannot rule out Addison's disease in children. The mechanism of hypo-osmolar hyponatraemia in primary adrenal insufficiency and clinical clues to differentiate it from SIADH are discussed., (2015 BMJ Publishing Group Ltd.)

Hyponatremia is the most frequent electrolyte disorder in hospitalized patients but also a well known poor prognostic factor in cancer patients. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is often misdiagnosed by oncologist because of difficulties in the interpretation of laboratory tests. Etiology is heterogeneous but the predominant cause is represented by the unbalance between excessive presence of water and serum sodium deficiency. Ectopic production of arginine vasopressin (AVP) develops more frequently in small cell lung cancer but it is not so rare in other malignancies. Neurological impairment may range from subclinical to life-threating symptoms depending by the rate of serum sodium deficiency. Appropriate diagnosis is essential to set a proper therapy. When hyponatremia is caused by SIADH, hypertonic saline infusion is indicated for acute presentation whereas fluid restriction is preferred in case of chronic asymptomatic evolution. Other options include vaptans, vasopressin receptor antagonists, targeted specifically for the correction of euvolemic hyponatremia. The aim of this brief report is to provide concise and specific informations for the management of SIADH in oncology clinical practice.

Introduction: The small cell lung cancer (SCLC) is a rapidly progressive malignancy with a poor prognosis. Its chemosensitivity mandates prompt treatment. Hyponatremia occurs frequently in patients with small cell lung cancer due to the syndrome of inappropriate antidiuretic hormone (SIADH). We report a case of severe hyponatremia induced by chemotherapy that required management in intensive care., Observation: A 68-year-old patient was undergoing treatment for small cell cancer, invading the right lung. On the second day of the first cycle of treatment (cisplatine-vepeside), the patient became comatose and required transfer to an intensive care unit. The coma was due to severe hyponatremia (107 mmol/L) and improved with specific treatment. The patient had similar episodes on the second day of each chemotherapy treatment but with less and less severe clinical manifestations. Hyponatremia due to chemotherapy in SCLC is not commonly known; a relation between hyponatremia intensity and the tumor size is suspected., Conclusion: This clinical case highlights the possibility of severe hyponatremia during small cell lung cancer chemotherapy. Hyponatremia may be related to the reduction in tumor size. Monitoring of electrolytes on day 2 of chemotherapy is advised., (Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

To study the effect of tolvaptan on non-acute, non-hypovolemic hyponatremia in inappropriate secretion of antidiuretic hormone (SIADH) syndrome in Chinese patients. Hyponatremic SIADH patients received placebo (N = 18) or tolvaptan (N = 19) at an initial dose of 15 mg/day with further titration to 30 mg/day and 60 mg/day based on serum sodium concentrations. Randomized, double-blind, placebo-controlled trial. Primary endpoint was the change of the serum sodium from baseline to days 4 and 7. Analysis of covariance (ANCOVA) was used for statistical analysis. At day 4, average daily changes in serum sodium levels from baseline was 1.9 ± 2.9 mmol/L (1.9 ± 2.9 mEq/L) in the placebo group and 8.1 ± 3.6 mmol/L (8.1 ± 3.6 mEq/L) in the tolvaptan group; at day 7, the values were 2.5 ± 3.9 mmol/L (2.5 ± 3.9 mEq/L) and 8.6 ± 3.9 mmol/L (8.6 ± 3.9 mmEq/L) for the placebo and tolvaptan groups (ANCOVA, P < 0.001). At days 4 and 7, daily urine output and proportions of patients with normalized serum sodium were significantly superior in the tolvaptan group. The most common adverse events occurring in the tolvaptan group were dry mouth and thirst. Tolvaptan demonstrated superiority to placebo in the treatment of Chinese SIADH patients with hyponatremia by elevating serum sodium concentration with acceptable safety profile., (© 2014, The American College of Clinical Pharmacology.)

Hyponatremia, the most frequent electrolyte disorder, is caused predominantly by the syndrome of inappropriate antidiuresis (SIAD). A comprehensive characterization of SIAD subtypes, defined by type of osmotic dysregulation, is lacking, but may aid in predicting therapeutic success. Here, we analyzed serial measurements of serum osmolality and serum sodium, plasma arginine vasopressin (AVP), and plasma copeptin concentrations from 50 patients with hyponatremia who underwent hypertonic saline infusion. A close correlation between copeptin concentrations and serum osmolality existed in 68 healthy controls, with a mean osmotic threshold±SD of 282±4 mOsM/kg H2O. Furthermore, saline-induced changes in copeptin concentrations correlated with changes in AVP concentrations in controls and patients. With use of copeptin concentration as a surrogate measure of AVP concentration, patients with SIAD could be grouped according to osmoregulatory defect: Ten percent of patients had grossly elevated copeptin concentrations independent of serum osmolality (type A); 14% had copeptin concentrations that increased linearly with rising serum osmolality but had abnormally low osmotic thresholds (type B); 44% had normal copeptin concentrations independent of osmolality (type C), and 12% had suppressed copeptin concentrations independent of osmolality (type D). A novel SIAD subtype discovered in 20% of patients was characterized by a linear decrease in copeptin concentrations with increasing serum osmolality (type E or "barostat reset"). In conclusion, a partial or complete loss of AVP osmoregulation occurs in patients with SIAD. Although the mechanisms underlying osmoregulatory defects in individual patients are presumably diverse, we hypothesize that treatment responses and patient outcomes will vary according to SIAD subtype., (Copyright © 2014 by the American Society of Nephrology.)

Colonoscopic screening has been reported to reduce deaths from colorectal cancer. Adequate bowel preparation is essential for this and safety is an important issue in choosing the methods. Polyethylene glycol (PEG) is regarded as a safe method for cleansing, especially compared with oral sodium phosphate. Here, we present a case of hyponatremia caused by the syndrome of inappropriate antidiuretic hormone (ADH) syndrome after PEG precolonoscopic cleansing resulting in generalized tonic-clonic seizures. A 62-year-old women had ingested PEG for precolonoscopic bowel cleansing. While waiting for the colonoscopy, she developed a stuporous mentality and generalized tonic-clonic seizures, which did not correlate with brain magnetic resonance imaging. Her serum sodium level was 113 mEq per liter and laboratory analyses were consistent with inappropriate ADH syndrome. Her thyroid and adrenal functions were normal. There were no malignancies, infections, respiratory disorders or central nervous disorders and she had no history of taking either diuretics or other medications, which might have caused inappropriate ADH syndrome. She was treated with 3% hypertonic saline and showed a complete neurological recovery as her sodium levels recovered. Follow-up visits showed the patient to have a normal sodium level without neurologic deficits. This case shows that inappropriate ADH syndrome can be caused by PEG preparation, which implies that physicians have to be aware of the possible side effects of this colonic cleansing approach and mindful of the possible ensuing symptoms.