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The consumption of new selective serotonin reuptake inhibitors (SSRIs) is raising dramatically especially in European countries. It contributes to occurrence of clinically important drug side effects. One of which can be hyponatremia. We present two case reports of 85-year-old and 84-year-old women who developed hyponatremia after escitalopram administration. We hypothesize that in both cases hyponatremia was connected with antidepressants administration. However, due to multiple comorbidities and polypharmacy it is often impossible to establish the exact mechanism of hyponatremia. Moreover, it is crucial to distinguish subtypes of drug-induced syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), such as SSRI-induced SIADH, reset osmostat SIADH, thiazide-associated hyponatremia, thiazide-induced hyponatremia, mineralocorticoid responsive hyponatremia of older adults, in order to properly diagnose and treat geriatric patients. Administration of antidepressants or thiazides should be followed by a regular monitoring of serum sodium level.

BACKGROUND Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is relatively common in several cancers, such as small cell lung cancer. However, nedaplatin-induced SIADH is rare. We describe a case of SIADH mediated by nedaplatin. CASE SUMMARY A 54-year-old female with nasopharyngeal carcinoma was treated with nedaplatin and developed severe hyponatremia due to SIADH. The side effects were successfully treated by fluid restriction and sodium supplementation. CONCLUSION This case report highlights the importance of cautiously treating life-threatening hyponatremia in patients treated with nedaplatin.

We report a 72-year-old woman with Miller-Fisher syndrome (MFS) with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). She developed diplopia and unsteady gait a week after an upper respiratory infection. Neurologic examination revealed ophthalmoplegia, ataxia, symmetrical weakness, numbness, and areflexia. She underwent intravenous immunoglobulin therapy. Her serum sodium concentration decreased to 119 mEq/L on day 12. She had low plasma osmolarity (254 mosm/kg), high urine osmolarity (457 mosm/kg), and high urine sodium level (73 mEq/L), while the blood level of antidiuretic hormone was normal. Anti-GD1b immunoglobulin G (IgG), -GQ1b IgG, -GT1a IgG, and -Gal-C IgM antibodies were positive. We diagnosed her with MFS overlapping with SIADH. Four weeks after onset, her symptoms recovered. The elevation of anti-GD1b, -GQ1b, and -GT1a antibodies that recognize disialosyl residue may be pathologically related to SIADH.

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.

Cerebral salt wasting (CSW) is an uncommon cause of hyponatremia characterized by extracellular volume depletion, high urine sodium concentration and osmolality, and low serum uric acid concentration in association with central nervous system (CNS) disease. Distinguishing CSW from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), a much more common form of hyponatremia in this setting, can be challenging because both present with identical laboratory features. However, treatment of CSW and SIADH differs, making a correct diagnosis important. Here we present a case of CSW in a 75-year-old man in whom severe hyponatremia and volume depletion were discovered in the setting of traumatic head injury and Dandy-Walker malformation of the brain, a rare congenital brain malformation. Treatment with intravenous normal saline and later oral salt supplementation and fludrocortisone was successful.

Purpose The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a well-known complication of transsphenoidal pituitary surgery, related to inappropriate secretion of arginine vasopressin (AVP). Its diagnosis is based on hyponatremia, with a peak of occurrence around day 7 after surgery and, to date, no early marker has been reported. In particular, copeptin levels are not predictive of hyponatremia in this case. Oxytocin (OXT) is secreted into the peripheral blood by axon terminals adjacent to those of AVP neurons in the posterior pituitary. Besides its role in childbirth and lactation, recent evidences suggested a role for OXT in sodium balance. The contribution of this hormone in the dysnatremias observed after pituitary surgery has however never been investigated. Methods We analyzed the urinary output of OXT in patients subjected to transsphenoidal pituitary surgery. Results While OXT excretion remained stable in patients who presented a normonatremic postoperative course, patients who were later diagnosed with SIADH-related hyponatremia presented with a significantly increased urinary secretion of OXT 4 days after surgery. Conclusion Taken together, these results show for the first time that urinary OXT output remains normally stable after transsphenoidal pituitary surgery. OXT excretion however becomes abnormally high on or around 4 days after surgery in patients later developing hyponatremia, suggesting that this abnormal dynamics of OXT secretion might serve as an early marker for transsphenoidal surgery-related hyponatremia attributed to SIADH.

IntroductionDiabetes insipidus (DI) is characterized by the excretion of large volumes of hypotonic urine and thirst due to an impaired ability to concentrate urine, leading to uncontrolled diuresis, which may cause life-threatening dehydration and electrolyte imbalances. Central DI is caused by the deficient secretion of the posterior pituitary antidiuretic hormone arginine vasopressin (AVP). Desmopressin (Deamino-8-D-AVP, the synthetic analogue of AVP, Minirinmelt®) is generally used to treat central DI. Desmopressin orally disintegrating tablets are recently administered to male patients with nocturia. We herein attempted to select male patients with an elevated nocturnal urinary frequency possibly due to a shortage of AVP. These patients may be good candidates for low-dose oral desmopressin administration.Patients and methodsSerum and spot urine osmolality, electrolytes, serum creatinine, casual blood glucose, plasma brain natriuretic polypeptide (BNP), and plasma AVP were measured at the same time in 97 elderly male patients with urinary symptoms under free water drinking. The International Prostate Symptom Score, Overactive Bladder Symptom Score, and frequency-volume charts at least twice were also evaluated.ResultsA binary plot of plasma AVP and serum osmolality indicated a region at which patients had relatively lower AVP considering higher serum osmolality. It was tentatively named the Desmopressin region. Twenty out of 97 (20.6 %) patients were in the Desmopressin region.No significant differences were observed in the frequency of administered urinary drugs or existing co-morbidities between patients in the Desmopressin and non-Desmopressin regions. Daily urine output did not exceed 3 L in any patient. Plasma AVP was lower, while serum osmolality and serum sodium were higher in patients in the Desmopressin region than in those in non-Desmopressin region. Furthermore, urine osmolality was slightly lower in patients in the Desmopressin region. No significant differences were observed in urine volume, urinary frequency, or urination questionnaire scores between both groups.ConclusionAVP-shortage patients may be selected for treatment with oral desmopressin based on measurements of serum osmolality and plasma AVP. After the exclusion of patients with marked hyperglycemia, decreased cardiac, or renal function, low-dose oral desmopressin may be administered to patients with an increased urine output, nocturia, elevated plasma osmolality, and relatively low plasma AVP.

Background Hypochloremia associated with congestive heart failure (CHF) in dogs is likely multifactorial. Loop diuretics cause 1:2 sodium [Na+]:chloride [Cl−] loss, whereas water retention causes a 1:1 [Na+]:[Cl−] dilution. Mathematical [Cl−] correction separates these effects on [Cl−]. Hypothesis We hypothesized that corrected [Cl−] (c[Cl−]) would not differ from measured [Cl−] (m[Cl−]) in dogs with controlled CHF because of loop diuretics, and dogs with refractory CHF would have higher c[Cl−] than m[Cl−], indicating relative water excess. Animals Seventy‐one client‐owned dogs with acquired heart disease, without CHF (NO‐CHF), 76 with Stage C CHF and 24 with Stage D CHF. Methods Clinicopathological data from a previous study were retrospectively analyzed. Corrected [Cl−], m[Cl−], and differences were compared among NO‐CHF, Stage C CHF, and Stage D CHF, using the formula: c[Cl−] = (mid‐reference range [Na+]/measured [Na+]) × m[Cl−]. Results Corrected [Cl−] and m[Cl−] were lower in Stage D vs Stage C and NO‐CHF (all P 2 mmol/L. Conclusions and Clinical Importance Serum [Cl−] increased after mathematical correction in Stage D CHF dogs but not in Stage C and NO‐CHF dogs. Although c[Cl−] was higher than m[Cl−] in Stage D dogs supportive of relative water excess, hypochloremia persisted, consistent with concurrent loop diuretic effects on electrolytes. Future study correlating c[Cl−] to antidiuretic hormone concentrations is warranted.

Background. Following acute traumatic brain injury, cerebral salt wasting (CSW) syndrome is considered as an important cause of hyponatremia apart from syndrome of inappropriate antidiuretic hormone. Differentiation between the two syndromes is crucial for the initiation of an adequate treatment. Case Presentation. We report a 15-year-old female adolescent, admitted to intensive care for acute severe traumatic brain injury. During his hospitalization, she developed a hyponatremia with an increase of urine output and hypovolemia. So, the most probable diagnosis was CSW. Initially, she was treated by hypertonic saline and volume expansion. However, his sodium level continued to fall despite infusion of hypertonic saline. That is why fludrocortisone was introduced initially at 50 μg/day then increased to 150 μg/day. Fludrocortisone was continued for the next months. Serum sodium level was 138 mmol/L after one month of treatment. Conclusion. Hyponatremia may occur after severe traumatic brain injury that is why an adequate treatment initiated on time is necessary in order to reduce morbidity and mortality.

We report two patients with Multisystem Inflammatory Syndrome in Children (MIS-C) with evidence of hyponatremia on admission. Despite fluid resuscitation and resolution of dehydration, the hyponatremia worsened. Serum and urine studies were evaluated and demonstrated evidence of syndrome of inappropriate antidiuretic hormone (SIADH). Fluid restriction and anti-inflammatory therapy were initiated with resolution of hyponatremia.

Background The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is the most frequent cause of hyponatremia in patients with cerebrovascular disease, and is often treated with oral salt tablets. However, we have shown that osmolality-dependent variations in gastrointestinal (GI) fluid volume can alter the concentration of a poorly permeable drug in the GI tract, potentially affecting its absorption. Here, we examined the effect of ingestion of hyperosmotic solution (10% NaCl) on drug concentration and absorption in the GI tract. Methods The effects of osmolality on luminal fluid volume and drug absorption in rat intestine (jejunum, ileum and colon) were examined by means of an in situ closed loop method using fluorescein isothiocyanate-dextran 4000 (FD-4) and atenolol. In vivo absorption in rats was determined by measuring the plasma concentration after oral administration of the test compounds dissolved in purified water or hyperosmotic solution (10% NaCl). Results Administration of hyperosmotic solution directly into the GI tract significantly increased the GI fluid volume, owing to secretion of water into the lumen. After administration in hyperosmotic solution, the luminal concentration of non-permeable FD-4 was significantly lower than the initial dosing concentration, whereas after administration in purified water, the luminal concentration exceeded the initial concentration. The fraction absorbed of atenolol was markedly lower after administration in hyperosmotic solution than after administration in purified water. An in vivo pharmacokinetic study in rats was consistent with these findings. Conclusions Administration of hyperosmotic NaCl solution increased GI fluid volume and reduced the plasma level of orally administered atenolol. This may imply that oral salt tablets used to treat hyponatremia in SIADH patients could decrease the intestinal absorption of concomitantly administered drugs, resulting in lower plasma exposure.

Rhodnius prolixus (the kissing bug and a major vector of Chagas disease) is an obligate blood feeder that in the case of the fifth instar consumes up to 10 times its unfed body weight in a single 20-minute feed. A post-prandial diuresis is initiated, within minutes of the start of gorging, in order to lower the mass and concentrate the nutrients of the meal. Thus, R. prolixus rapidly excretes a fluid that is high in NaCl content and hypo-osmotic to the hemolymph, thereby eliminating 50% of the volume of the blood meal within 3 hours of gorging. In R. prolixus, as with other insects, the Malpighian tubules play a critical role in diuresis. Malpighian tubules are not innervated, and their fine control comes under the influence of the neuroendocrine system that releases amines and neuropeptides as diuretic or antidiuretic hormones. These hormones act upon the Malpighian tubules via a variety of G protein-coupled receptors linked to second messenger systems that influence ion transporters and aquaporins; thereby regulating fluid secretion. Much has been discovered about the control of diuresis in R. prolixus, and other model insects, using classical endocrinological studies. The post-genomic era, however, has brought new insights, identifying novel diuretic and antidiuretic hormone-signaling pathways whilst also validating many of the classical discoveries. This paper will focus on recent discoveries into the neuroendocrine control of the rapid post-prandial diuresis in R. prolixus, in order to emphasize new insights from a transcriptome analysis of Malpighian tubules taken from unfed and fed bugs.

El Sindrome de Takotsubo es una disfuncion ventricular aguda reversible en ausencia de obstruccion coronaria. Una mujer de 85 anos de edad con antecedentes de reemplazo valvular aortico transcateter, ingreso por dos semanas de dolor severo por una cadera desplazada por osteosintesis fallida. Mientras se programaba para cirugia, se documento hiponatremia severa secundaria a secrecion inapropiada de hormona antidiuretica. Subitamente desarrollo edema agudo pulmonar. El ecocardiograma confirmo una valvula protesica funcional y aquinesia medial y apical de las paredes del ventriculo izquierdo. Recibio tratamiento con ventilacion mecanica no invasiva, restriccion de liquidos y diureticos. La hiponatremia y la cardiomiopatia resolvieron. Takotsubo syndrome is a form of acute reversible left ventricular dysfunction in the absence of coronary obstruction. An 85-year-old lady with a medical history of transcatheter aortic valve replacement was readmitted complaining of 2 weeks of severe pain by a displaced hip and failed osteosynthesis. While she was scheduled for hip surgery, severe hyponatremia secondary to inappropriate antidiuretic hormone secretion was documented, and sudden-onset pulmonary edema ensued. Echocardiography confirmed normally functioning aortic prosthetic valve and classical features of Takotsubo. She was treated with non-invasive mechanical ventilation, water restriction, and diuretics. Hyponatremia and the cardiomyopathy resolved and the patient recovered completely.

Objective This study aimed to investigate the role that antidiuretic hormone (ADH) may play in the activation of glucose production during high intensity aerobic exercise. Materials/methods This study was part of larger study based on a repeated measures cross-over study design and involved ten adult participants who exercised in the morning at 80 % V̇O2peak for up to 40 min or until exhaustion. During and after exercise, the participants were subjected to a morning euglycaemic/euinsulinaemic clamp while [6,6-2H2]glucose was infused and blood sampled to measure the endogenous rate of glucose appearance (Ra) and ADH levels. Results The levels of plasma ADH were 1.8 ± 0.2 pmol/L (mean ± SEM) at rest and increased to 10.5 ± 2.1 pmol/L at the end of exercise (mean ± SEM), which lasted 8.5–40 min. In response to exercise, glucose Ra also rose significantly (p, Highlights • Intense aerobic exercise in T1D causes a significant increase in plasma ADH level and endogenous glucose production rate. • This study raises the possibility of a causal relationship between these variables during intense exercise in humans. • The role of ADH in activation of endogenous glucose production during intense exercise warrants further investigations.

Objective: Ephedrine hydrochloride (EH) is a major component from Ephedra sinica STAPF, which is used as a traditional Chinese herbal medicine. This study was designed to investigate the effect of EH on water metabolism and further explore the relevant signaling pathway of body fluid regulation in “lung governing regulation of water passage” using a rabbit model of mechanical ventilation. The molecular mechanism of the EH effect in the kidney was also investigated. Methods: Rabbits were randomly divided into a control group, model group, EH group, and dexmedetomidine hydrochloride (DH) group. Urine volume was measured by the intubation method and pathologic changes in lung and renal tissue were measured by hematoxylin and eosin staining. Nitric oxide (NO) production in lung, serum, and kidney were analyzed using chemical methods. An ELISA was used to analyze angiotensin II (Ang II), antidiuretic hormone (ADH), prostaglandin E2 (PGE2), atrial natriuretic peptide (ANP), and endothelin-1 (ET-1) levels in the lung, serum, and kidney. Aquaporin-1 (AQP1) and aquaporin-2 (AQP2) mRNA and protein expression in the kidney was determined using qRT-PCR and immunohistochemistry. Results: EH significantly inhibited the decrease in the total urine volume in the third and fourth stages, and displayed significant regulatory effects on NO, Ang II, ADH, PGE2, ANP, and ET-1 in serum, lung, and renal tissues compared with the model group. In the kidney, AQP1 and AQP2 mRNA and protein expression in the EH group were remarkably down-regulated compared with the model group. Conclusion: EH exerted a regulatory effect on water metabolism by diffusing the lung and increased urine volume in the rabbit model, which was consistent with the decrease in kidney AQP1 and AQP2 expression levels that led to an increase in urine volume. EH could assist with DH to exert a protective effect on the clinical application of mechanical ventilation. Keywords: Mechanical ventilation, Ephedrine hydrochloride, Dexmedetomidine hydrochloride, Humoral regulation

Nephrogenic diabetes insipidus (NDI) is characterized by impaired urinary concentrating ability, despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). NDI can be inherited or acquired. NDI can result from genetic abnormalities, such as mutations in the vasopressin V2 receptor (AVPR2) or the aquaporin-2 (AQP2) water channel, or acquired causes, such as chronic lithium therapy. Congenital NDI is a rare condition. Mutations in AVPR2 are responsible for approximately 90% of patients with congenital NDI, and they have an X-linked pattern of inheritance. In approximately 10% of patients, congenital NDI has an autosomal recessive or dominant pattern of inheritance with mutations in the AQP2 gene. In 2% of cases, the genetic cause is unknown. The main symptoms at presentation include growth retardation, vomiting or feeding concerns, polyuria plus polydipsia, and dehydration. Without treatment, most patients fail to grow normally, and present with associated constipation, urological complication, megacystis, trabeculated bladder, hydroureter, hydronephrosis, and mental retardation. Treatment of NDI consist of sufficient water intake, low-sodium diet, diuretic thiazide, sometimes in combination with a cyclooxygenase (COX) inhibitor (indomethacin) or nonsteroidal anti-inflammatory drugs (NSAIDs), or hydrochlorothiazide in combination with amiloride. Some authors note a generally favorable long-term outcome and an apparent loss of efficacy of medical treatment during school age.

Structures of the AVP-V2R-Gs protein complex provide molecular insights into the function of this clinically relevant target., The antidiuretic hormone arginine-vasopressin (AVP) forms a signaling complex with the V2 receptor (V2R) and the Gs protein, promoting kidney water reabsorption. Molecular mechanisms underlying activation of this critical G protein–coupled receptor (GPCR) signaling system are still unknown. To fill this gap of knowledge, we report here the cryo–electron microscopy structure of the AVP-V2R-Gs complex. Single-particle analysis revealed the presence of three different states. The two best maps were combined with computational and nuclear magnetic resonance spectroscopy constraints to reconstruct two structures of the ternary complex. These structures differ in AVP and Gs binding modes. They reveal an original receptor-Gs interface in which the Gαs subunit penetrates deep into the active V2R. The structures help to explain how V2R R137H or R137L/C variants can lead to two severe genetic diseases. Our study provides important structural insights into the function of this clinically relevant GPCR signaling complex.

The autosomal dominant familial form of neurohypophyseal diabetes insipidus (adFNDI) is a rare inherited endocrine disorder characterized by hypotonic polyuria, severe thirst and polydipsia, which results from a deficient neurosecretion of the antidiuretic hormone, also known as arginine vasopressin (AVP). To date, adFNDI has been linked to more than 70 different heterozygous point mutations of the 2.5 kb AVP gene, encoding the composite precursor protein of AVP. A minority of disease-causing mutations, such as the common c.55G>A variant, are predicted to affect amino acid residues close to the signal peptide (SP) cleavage site, and result in abnormal post-translational processing and intracellular trafficking of AVP precursors exerting neurotoxic activity on vasopressinergic magnocellular neurons. Generally, SP variants cause a gradual decline in the neurohypophyseal secretion of AVP in small children, although a wide variability in clinical onset and severity of manifestations has been reported. For the first time, we describe a kindred from Calabria (Southern Italy) with adFNDI and document a partial clinical phenotype in one female young adult member of the family. Methods: A young adult woman was subjected to clinical, neuroradiological and genetic assessments for a mild, adolescent-onset, polyuric state at our Endocrinology Unit. Her family medical history revealed an early-onset (A transition, predicting a p.Ala19Thr replacement in the C-terminal region of SP, was the cause of adFNDI in the investigated kindred. Conclusions: The identification of the genetic cause of aFNDI in this Calabrian kindred provides further information and confirms the wide variability of disease onset and severity of manifestations related to SP variants of the AVP gene, supporting the need for genetic testing in all patients with familial occurrence of polyuria, regardless of their clinical and radiological phenotype. Even though sexual differences in the antidiuretic responses are documented, it is unclear whether female gender would attenuate clinical disease progression in the presence of a pathogenic c.55G>A mutation.

Syndrome of inappropriate antidiuretic hormone release (SIADH) can sometimes be caused by an adverse effect of certain psychotropic drugs. However, suvorexant has never been reported to cause SIADH. A 77-year-old man with type 2 diabetes was admitted to the Jichi Medical University Hospital for the treatment of major depression. During the treatment, he was prescribed suvorexant for insomnia. Twelve days after the initiation of suvorexant, he developed hyponatremia, which met the diagnostic criteria of SIADH. We suspected the hyponatremia to be an adverse drug effect of suvorexant because no other cause for SIADH was detected. Accordingly, suvorexant was discontinued 15 days after the onset of SIADH, and hyponatremia improved in 6 days. Although suvorexant has fewer adverse drug reactions and is considered relatively safe, clinicians should be aware of the possibility of SIADH induced by suvorexant. CITATION: Takano M, Okada T, Kobayashi T, Suda S. Syndrome of inappropriate antidiuretic hormone secretion induced by suvorexant: a case report. J Clin Sleep Med. 2021;17(3):593–594.

This narrative review synthesizes current evidence on the medical management of nocturnal polyuria, including antidiuretic replacement therapy as well as other emerging modalities, with particular emphasis on areas of active investigation and future research directions. Relative to earlier formulations, the pharmacological profiles of novel desmopressin acetate nasal spray and orally disintegrating tablet formulations appear favorable in optimizing the balance between efficacy and safety. Additionally, several highly selective small-molecule arginine vasopressin 2 receptor agonists are under active development, while appropriately timed short-acting diuretics, pharmacotherapy for hypertension, nonsteroidal anti-inflammatory drugs, and sex hormone replacement therapy are also a focal point of extensive ongoing nocturnal polyuria research. Emerging laboratory technologies now make feasible a sub-stratification of nocturnal polyuria patients into substrate-based phenotypes for individualized treatment. An increasingly refined understanding of the pathogenesis of nocturnal polyuria, and arginine vasopressin dysregulation in particular, has also introduced new opportunities for point-of-care testing in patients with nocturnal polyuria.

The adverse effects of vasopressin (AVP) in diverse forms of chronic kidney disease have been well described. They depend on the antidiuretic action of AVP mediated by V2 receptors (V2R). Tolvaptan, a selective V2R antagonist, is now largely used for the treatment of patients with autosomal dominant polycystic kidney disease. Another way to reduce the adverse effects of AVP is to reduce endogenous AVP secretion by a voluntary increase in fluid intake. These two approaches differ in several ways, including the level of thirst and AVP. With voluntary increased drinking, plasma osmolality will decline and so will AVP secretion. Thus, not only will V2R-mediated effects be reduced, but also those mediated by V1a and V1b receptors (V1aR and V1bR). In contrast, selective V2R antagonism will induce a loss of fluid that will stimulate AVP secretion and thus increase AVP's influence on V1a and V1b receptors. V1aR is expressed in the luminal side of the collecting duct (CD) and in inner medullary interstitial cells, and their activation induces the production of prostaglandins, mostly prostaglandin E2 (PGE2). Intrarenal PGE2 has been shown to reduce sodium and water reabsorption in the CD and increase blood flow in the renal medulla, both effects contributing to increase sodium and water excretion and reduce urine-concentrating activity. Conversely, non-steroidal anti-inflammatory drugs have been shown to induce significant water and sodium retention and potentiate the antidiuretic effects of AVP. Thus, during V2R antagonism, V1aR-mediated actions may be responsible for part of the diuresis observed with this drug. These V1aR-dependent effects do not take place with a voluntary increase in fluid intake. In summary, while both strategies may have beneficial effects, the information reviewed here leads us to assume that pharmacological V2R antagonism, with resulting stimulation of V1aR and increased PGE2 production, may provide greater benefit than voluntary high water intake. The influence of tolvaptan on the PGE2 excretion rate and the possibility to use somewhat lower tolvaptan doses than presently prescribed remain to be evaluated.

Suprasellar arachnoid cysts represent a rare occurrence in the pediatric population and usually cause symptoms related to mass effect and can occasionally cause endocrine dysfunctions. The association between SAC and the syndrome of inappropriate antidiuretic hormone (SIADH) in the pediatric population has rarely been described previously. In most cases, SIADH is temporary and resolves by treating the underlying cause. The first-line treatment consists of fluid restriction in asymptomatic children. Oral urea and demeclocycline are other effective treatment options. Vaptans are a new class of medication for the management of SIADH. These agents are a nonpeptide vasopressin V2 receptor antagonist that selectively antagonizes the antidiuretic effect of AVP, resulting in excretion of diluted urine or “aquaresis.” Their efficacy has been shown in adult patients with euvolemic or hypervolemic hyponatremia. However, evidence is lacking in pediatric patients with SIADH. We report the case of a 9-year-old female child with a SAC, who underwent endoscopic fenestration at the age of 2 years. After surgery she developed chronic hyponatremia due to SIADH. Hyponatremia was refractory to treatment with fluid restriction, oral sodium, and urea. In order to normalize serum sodium levels, tolvaptan treatment was started on a compassionate-use basis; 24–48 h later serum sodium levels returned to normal. To date, tolvaptan has been used regularly for 6 years with no side effects occurring during the treatment period. This is the first case of a child with chronic SIADH secondary to SAC successfully treated with tolvaptan. Further studies are needed to demonstrate its usefulness on a broader case series.

Colonoscopy is considered a gold standard tool for the diagnostic evaluation of colorectal diseases. Bowel preparation, a pre-requisite for a colonoscopy, usually involves the ingestion of purgatives for the cleansing of the bowel so that visualization is not obscured during the procedure. Commonly used preparations are sodium phosphate-based solutions, sodium picosulphate, and polyethylene glycol. The use of such preparations is associated with electrolyte disturbances, commonly hyponatremia. Hyponatremia is usually seen with sodium phosphate-based solutions and is rare with polyethylene glycol. Symptomatic hyponatremia, however, is rare following bowel preparation and is attributable to other factors as well, such as the age of the patient, non-osmotic release of anti-diuretic hormone, and the procedure itself. In this report, we discuss a case of severe symptomatic hyponatremia observed in a 71-year-old gentleman who underwent polyethylene glycol-based bowel preparation for colonoscopy.

Therapeutic advances have revolutionised cancer treatment over the last two decades, but despite improved survival and outcomes, adverse effects to anticancer therapy such as dyselectrolytaemias do occur and need to be managed appropriately. This review explores essential aspects of sodium homeostasis in cancer with a focus on alterations arising from anticancer medications. Sodium and water balance are tightly regulated by close interplay of stimuli arising from hypothalamic osmoreceptors, arterial and atrial baroreceptors and the renal juxtaglomerular apparatus. This delicate balance can be disrupted by cancer itself, as well as the medications used to treat it. Some of the conventional chemotherapeutics, such as alkylating agents and platinum-based drugs, can cause hyponatraemia and, on rare occasions, hypernatraemia. Other conventional agents such as vinca alkaloids, as well as newer targeted cancer therapies including small molecule inhibitors and monoclonal antibodies, can cause hyponatraemia, usually as a result of inappropriate antidiuretic hormone secretion. Hyponatraemia can also sometimes occur secondarily to drug-induced hypocortisolism or salt-wasting syndromes. Another atypical but distinct mechanism for hyponatraemia is via pituitary dysfunction induced by immune checkpoint inhibitors. Hypernatraemia is uncommon and occasionally ensues as a result of drug-induced nephrogenic diabetes insipidus. Identification of the aetiology and appropriate management of these conditions, in addition to averting treatment-related problems, can be lifesaving in critical situations.

We report a case of acute severe hyponatremia within 24 hours after a duloxetine overdose. An 82-year-old woman presented to the ED after ingesting duloxetine and diltiazem. She became hemodynamically unstable due to the diltiazem overdose and was appropriately resuscitated. During hospitalization she experienced hyponatremia consistent with syndrome of inappropriate antidiuretic hormone (SIADH). Based on the observations we concluded there was a probable relationship between the hyponatremia and the duloxetine overdose. Clinicians should monitor patients' electrolytes for acute disturbances after an overdose of duloxetine.

There is fast-emerging, cumulative clinical data on coronavirus disease 2019 (COVID-19) in kidney transplant recipients. Although respiratory tract symptoms are often the initial presentation among kidney transplant recipients who contract COVID-19, other clinical features which may indicate underlying SARS-CoV-2-related inflammation, such as gastrointestinal symptoms, are not uncommon. Hyponatremia can develop and may reflect underlying inflammation. Interferon-6 is an important pro-inflammatory cytokine involved in the pathogenesis of severe COVID-19 complications and may play a role in the inappropriately higher secretion of antidiuretic hormone leading to hyponatremia. This pathway is the so-called immuno-neuroendocrine interface. Hyponatremia in COVID-19 has been reported in a few case series of non-kidney transplant patients and only one reported kidney transplant recipient. However, the clinical course and prognostic value of hyponatremia in this population are not described in detail. We report a kidney transplant recipient who was infected with COVID-19 and exhibited severe hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. Hyponatremia is one of the clinical presentations of COVID-19, although less common, and may occur more frequently in kidney transplant recipients. Thus, the possible underlying immuno-neuroendocrine relationship related to the inflammatory process of COVID-19 leading to hyponatremia and its prognostic value are reviewed.

A 60-year-old man with a history of smoking was transferred to our hospital for consciousness disorder. A diagnosis of ALK-rearranged lung adenocarcinoma associated with a paraneoplastic electrolytic disorder was made following a cutaneous needle biopsy. Both the primary lung lesion and multiple metastases shrunk and his electrolytic disorder resolved after the introduction of a first-line molecular-targeted drug chemotherapy with crizotinib. We herein report a case of ALK-rearranged lung adenocarcinoma accompanied by SIADH, successfully treated with crizotinib.

Syndrome of inappropriate ADH (SIADH) secretion is a condition where there is an increase in the secretion of ADH resulting in retention of excess water in the body. ADH or Antidiuretic hormone (also called Vasopressin) is produced in the hypothalamus of the brain and released by the pituitary gland. The main biochemical abnormality is low plasma sodium or hyponatraemia. However hyponatraemia can occur for multiple reasons and it is important to diagnose the specific cause as the management can vary. SIADH is a cause for euvolaemic hyponatraemia and the management includes stopping the drug responsible for causing it, fluid restriction and using medications like Tolvaptan and Demeclocycline. The audit below is an attempt to find out if the prevailing Guidelines were considered during the management of SIADH in our hospital.

1,2,4-Triazole derivatives have been widely used in medical practice due to their wide spectrum of biological activities and low toxicity, as they have 1,2,4-triazole cycle in their structure. That makes 1,2,4-triazole derivatives a very promising and attractive class of organic compounds in research of their physical and chemical properties, and biological activity determining. In order to find new substances with potential biological activity 20 new compounds of 4-amino-5-methyl-4 H -1,2,4-tiazole-3-thion derivatives were synthesized, which have never been described in literature before. The objective of this study was the research of bioactivity of 4-amino-5-methyl-4 H -1,2,4-tiazole-3-thion derivatives. Materials and methods . Compounds of research were synthesized in Department of Toxicological and Inorganic Chemistry of ZSMU. Berchin method was used in order to estimate the effect of compounds on excretory function of kidneys. Results . Diuretic activities of 4-amino-5-methyl-4 H -1,2,4-tiazole-3-thion derivatives were studied. The compounds exhibit both diuretic and antidiuretic effects. It is worth noting that 4-((R-idene)amino)-5-methyl-4 H -1,2,4-triazole-3-thion derivatives demonstrated both moderate and high diuretic activity. In such way, introduction of 3,4-methoxybenzyl, 3,5-methoxybenzyl and 2-chloro-6-fluorobenzyl substituents into the structure of 4-((R-idene)amino)-5-methyl-4 H -1,2,4-triazole-3-thion slightly increased diuretic effect. Reduction of compounds 4-((4-bromobenzylidene)amino)-5-methyl-4 H -1,2,4-triazole-3-thion, 5-methyl-4-((thiophen-2-ylmethylene)amino)-4 H -1,2,4-triazole-3-thion, 4-((2-chloro-6-fluorobenzylidene)amino)-5-methyl-4 H -1,2,4-triazole-3-thion caused decline of diuretic activity. The most potent bioactivity was observed in 4-((4-methoxybenzyl)amino)-5-methyl-4 H -1,2,4-triazole-3-thion. Conclusion . Derivatives of 4-amino-5-methyl-4 H -1,2,4-tiazole-3-thion exhibit both diuretic and antidiuretic effects. “Structure – Effect” relation was shown. The most potent activity was observed in 4-((4-methoxybenzyl)amino)-5-methyl-4 H -1,2,4-triazole-3-thion.

Central diabetes insipidus (CDI) is a severe pathology of the hypothalamic-pituitary system, based on a deficit of antidiuretic hormone (ADH). The disease is a life threating condition for patients without adequate replacement therapy by various preparations of arginine vasopressin. This review presents the current concepts on etiology, pathogenesis, diagnostic proсedures, and treatment of CDI. The article gives comparative pharmacological characteristics of various desmopressin forms for the treatment of the central form of disease. When choosing a therapy for the treatment of CDI, the article highlights the long-term high efficiency and safety of the original sublingual form of desmopressin (Mininin Melt), which is confirmed by real clinical practice and clinical trials, including the comparison with other forms of desmopressin.

Hyponatremia is the most common electrolyte disorder, which can occur in outpatients and hospitalized patients, so both first-contact doctors and specialists must keep up-to-date on the prevention, recognition, diagnosis and management of this complication. A 68-year-old male patient presents to Dos de Mayo National Hospital Emergency Department. He was diagnosed as COVID-19 pneumonia and hospitalized for management of acute respiratory failure. The patient had neurological impairment associated with poor oral tolerance. Initial laboratory examinations were C-reactive protein in 363.5 mg/L, serum sodium of 128.42 mmol/L and urine sodium was 83 meq/L. Osmolality in plasma was 266.15 mOsm/Kg and urine osmolality was 420 mOsm/Kg. Thyroid function tests as well as cortisol levels were in normal range. Our patient was diagnosed as SIAD by hyponatremia, osmolality in plasma 100 mOsm / kg, urine sodium > 40 mEq / l, euvolemic state and exclusion of cortisol and thyroid hormone deficiency. Treatment of hyponatremia was initiated and rapidly elevate plasma sodium by 4 meq/l in the first 6 hours. There was clinical improvement. Blood sodium levels ranged from 115 to 135 mmol/L with bolus therapy of hypertonic solutions in 72 hours. Intravenous boluses of hypertonic saline should be administered to rapidly elevate plasma sodium by 4 to 6 mEq/L in the first 6 hours. The data shows that fluid bolus therapy is more effective in acutely elevating plasma sodium than traditional low-dose hypertonic saline infusion that may lead to avoidable deaths according to recent guidelines. In this case a strategy based with bolus therapy for reversal of hyponatremia was used effectively. A number of cases of COVID-19 pneumonia are associated with SIAD. The presence of SIAD could be a clue to diagnosing COVID-19. SIAD is a major complication of COVID-19 and could be the first and only manifestation. In cases of SIAD without a clear etiology we should suspect COVID-19 in a patient with respiratory distress in the current pandemic. Syndrome of inappropiate antidiuresis (SIAD) should be assessed in every patient with COVID-19 as their treatment and early identification decreases mortality. The association between COVID-19 pneumonia and SIAD should be further identified, requiring doctors to be aware of this condition. Additional studies are required to determine the incidence and pathogenesis of SIAD in patients with COVID-19.

Background: Central diabetes insipidus (CDI) as a complication of acute myeloid leukemia (AML) is rare, occurring in less than 0.6% of AML cases. The mechanism is thought to involve leukemic infiltration in or around the pituitary gland, not always seen on imaging. In one study, as many as 61.4% of patients with CDI due to AML had no abnormalities on MRI, and at autopsy 46% of AML patients had perihypohyseal leukemic infiltration in the absence of overt CDI. CDI is also associated with AML in cases that involve monosomy 7 and inversion 3q21q26, both of which result in ectopic viral integration site 1 (EVI-1) overexpression. It is postulated that EVI-1 overexpression interferes with hypothalamic secretion of antidiuretic hormone (ADH) or may lead to its inactivation. We present a case of adipsic CDI due to AML in a patient with monosomy 7. Case: A 70-year-old female presented for routine follow-up and was found to have a white blood cell count of 2.6 K/µL with 29% blasts, anemia (Hgb 10.3 g/dL) and normal platelets (300 K/µL). She was diagnosed with AML and molecular evaluation showed del (3)(q21),-7,add(17(p13) consistent with monosomy 7. She was admitted for induction chemotherapy with cytarabine, daunorubicin and intrathecal methotrexate. She denied thirst. On physical exam she was euvolemic and visual fields were full on confrontation. Her admission sodium was 146 mmol/L, urine osmolality was 149 mOsm/kg H2O, urine sodium 14 mmol/L. Urine output was 5.1 L over the first 24 hours. She underwent a 6 hour water deprivation test, during which her urine output averaged 250 cc/hr. Her sodium increased to 158 mmol/L, serum osmolality 331 mOsm/kg H2O, urine osmolality 146 mOsm/kg H2O. She was then administered 100 µg of DDAVP PO and her serum sodium and osmolality decreased to 155 mmol/L and 326 mOsm/kg H2O, respectively, while her urine osmolality nearly doubled to 292 mOsm/kg H2O. Urine output decreased to 50-100 cc/hr. At no point during her testing did she report thirst. The patient’s pituitary laboratory profile did not show any other abnormalities. Her pituitary MRI revealed subtle thickening of the proximal infundibulum and hypothalamus but no definitive intra-sellar pathology. She was discharged on twice daily DDAVP with a sodium of 142. Unfortunately, her AML was refractory to treatment. She was transitioned to comfort care and died peacefully. Conclusion: CDI as a complication of AML is very rare and is a poor prognostic marker. Based on her MRI findings, the most likely mechanism in this case was infundibular/hypothalamic infiltration. Her adypsia is interesting and may point to more generalized hypothalamic involvement including thirst center. Her monosomy 7 mutation may have also played a role. We present this case to bring awareness to this etiology of DI and its proposed mechanisms.