Syndrome Of Inappropriate Antidiuretic Hormone Research Articles

A complex pheotype in a girl with a novel heterozygous missense variant (p.Ile56Phe) of the GNAS gene

BackgroundGNAS is a complex gene that encodes Gsα, a signaling protein that triggers a complex network of pathways. Heterozygous inactivating mutations in Gsα-coding GNAS exons cause hormonal resistance; on the contrary, activating mutations in Gsα result in constitutive cAMP stimulation. Recent research has described a clinical condition characterized by both gain and loss of Gsα function, due to a heterozygous de novo variant of the maternal GNAS allele.Patients and methodsWe describe a girl with a complex combination of clinical signs and a new heterozygous GNAS variant. For the molecular analysis of GNAS gene, DNA samples of the proband and her parents were extracted from their peripheral blood samples. In silico analysis was performed to predict the possible in vivo effect of the detected novel genetic variant. The activity of Gsα protein was in vitro analyzed from samples of erythrocyte membranes, recovered from heparinized blood samples.ResultsWe found a new heterozygous missense c.166A > T—(p.Ile56Phe) GNAS variant in exon 2, inherited from the mother that determined a reduced activity of 50% of Gsα protein function. The analysis of her parents showed a 20–25% reduction in Gsα protein activity in the mother and a normal function in the father. Clinically our patient presented a multisystemic disorder characterized by hyponatremia compatible with a nephrogenic syndrome of inappropriate antidiuresis, subclinical hyperthyroidism, subclinical hypercortisolism, precocious thelarche and pubarche and congenital bone abnormalities.ConclusionsThis is the first time that the new variant c.166A > T (p.Ile56Phe) on exon 2 of GNAS gene, originated on maternal allele, has been described as probable cause of a multisystemic disorder. Although the mutation is associated with a reduced activity of the function of Gsα protein, this unusual phenotype on the contrary suggests a mild functional gain.

Hydrocephalus-Associated Hyponatremia: A Review.

Hydrocephalus is the pathological accumulation of cerebrospinal fluid within the ventricles of the brain. Hydrocephalus may be broadly divided into three categories: congenital, acquired, or other. Hyponatremia, serum sodium level <135 meq/ml, may be caused by dilution (e.g. syndrome of inappropriate antidiuretic hormone (SIADH)), depletion (e.g. cerebral salt wasting (CSW)), or delusion (e.g. psychogenic water intake) etiologies. This review discusses “hydrocephalus-associated hyponatremia” as a clinical entity, distinct from SIADH and CSW.Some experts believe that in hydrocephalus patients, increased pressure on the hypothalamus leads to the release of antidiuretic hormone (ADH), which in turn causes hyponatremia. The true etiology of hyponatremia is critical to diagnose, as it will determine the treatment. So while both SIADH and CSW may result in hyponatremia, the former is treated with fluid restriction, while the latter requires fluid repletion; treating SIADH as CSW, and vice versa, will exacerbate the hyponatremia.The etiology and severity of hyponatremia will determine the management. For hydrocephalus-associated hyponatremia, treating the underlying problem (i.e. hydrocephalus) is the mainstay of therapy. Theoretically, treatment of hydrocephalus-related hyponatremia with CSF-diversion procedures should relieve the pressure on the hypothalamus, mitigating ADH production, which in turn will decrease sodium excretion and ameliorate the hyponatremia.

Routine postoperative fluid restriction to prevent syndrome of inappropriate antidiuretic hormone secretion after transsphenoidal resection of pituitary adenoma.

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

The management and outcome of hyponatraemia following transsphenoidal surgery: a retrospective observational study

PurposeHyponatraemia is a common complication following transsphenoidal surgery. However, there is sparse data on its optimal management and impact on clinical outcomes. The aim of this study was to evaluate the management and outcome of hyponatraemia following transsphenoidal surgery.MethodsA prospectively maintained database was searched over a 4-year period between January 2016 and December 2019, to identify all patients undergoing transsphenoidal surgery. A retrospective case-note review was performed to extract data on hyponatraemia management and outcome.ResultsHyponatraemia occurred in 162 patients (162/670; 24.2%) with a median age of 56 years. Female gender and younger age were associated with hyponatraemia, with mean nadir sodium being 128.6 mmol/L on postoperative day 7. Hyponatraemic patients had longer hospital stay than normonatraemic group with nadir sodium being inversely associated with length of stay (p < 0.001). In patients with serum sodium ≤ 132 mmol/L, syndrome of inappropriate antidiuretic hormone secretion (SIADH) was the commonest cause (80/111; 72%). Among 76 patients treated with fluid restriction as a monotherapy, 25 patients (25/76; 32.9%) did not achieve a rise in sodium after 3 days of treatment. Readmission with hyponatraemia occurred in 11 cases (11/162; 6.8%) at a median interval of 9 days after operation.ConclusionHyponatraemia is a relatively common occurrence following transsphenoidal surgery, is associated with longer hospital stay and risk of readmission and the effectiveness of fluid restriction is limited. These findings highlight the need for further studies to better identify and treat high-risk patients, including the use of arginine vasopressin receptor antagonists.

Study on the Etiology of the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Among the Hospital Admitted Patient

Background: The syndrome of inappropriate antidiuretic hormone (SIADH) is a clinical illness that increases antidiuretic hormone (ADH) production or activity due to different disease processes. Normal release of ADH, or arginine vasopressin (AVP), occurs in the posterior lobe of the pituitary gland. SIADH, a hemodynamic disturbance, does not cause secretion of ADH. It is mediated through no osmotic receptors, resulting in water retention and dilutional hyponatremia. Materials methods: This was a cross-sectional observational study carried out by the Department of Medicine, Shaheed Ziaur Rahman Medical College Hospital, Bogura. Total 100 consecutive patients had hyponatremia due to SIADH. All patients were interviewed using standardized questionnaires. Data were analyzed using the statistical packages for social sciences (SPSS) for windows version 16. Results: Most of the patients (42%) in the study were older people &gt;60 years. The average age was 60.69 years. The male-female ratio was 1.43.1. The symptoms of hyponatremia were fever (32%), headache (34%), weakness (40%). confusion (48%), convulsion (19%) and coma (52%). Of them, 34% were hypertensive, and 51% of patients had a Glasgow coma scale of 3/15. It was observed that the most common etiology of SIADH was hemorrhagic stroke (46%) then ischemic (41%). Among the hemorrhagic strokes, 40% were intracerebral, 4% were subarachnoid hemorrhage, and 2% were brain stem hemorrhage. Another etiology was meningitis (4%). Encephalitis (4%). Pneumonia (3%) and pulmonary tuberculosis (2%). Serum Na+ &lt;120 mmol/L was seen in 38% patients. Total plasma osmolality was 260.40±8.51 (mmol/Kg), urinary Na+ was 13465±55.81 mmol/L, urinary osmolality was 408.05±157.02 mmol/L. S. creatinine was 1.06±1.02 m/dl, and S. uric acid was 3.35±0.75 mg/dl. Conclusions: The most common symptoms were Coma, confusion, weakness, headache, fever, and convulsion by hemorrhagic stroke and ischemic stroke. Meningitis, encephalitis, pneumonia, and pulmon

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

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

Covid-19, the thyroid and the pituitary — The real state of play

Thyroid and pituitary disorders linked to the coronavirus SARS-CoV-2, responsible for the COVID-19 epidemic, are mainly due to direct infection of the endocrine glands by the virus and to cell damage induced by the immune response. The two most frequent thyroid complications of COVID-19 are low T3 syndrome, or “non-thyroidal illness syndrome” (NTIS), and thyroiditis. Studies among in-patients with COVID-19 have shown that between one out of six and half of them have a low TSH level, related to NTIS and thyroiditis, respectively, sometimes found in the same patient. In NTIS, the decrease in free T3 concentration correlates with the severity of the infection and with a poor prognosis. Assessment of thyroid function in patients after a COVID-19 infection, shows normalization of thyroid function tests. Thyroiditis linked to COVID-19 can be divided into two groups, which probably differ in their pathophysiology. One is “destructive” thyroiditis occurring early in infection with SARS-CoV-2, with a severe form of COVID-19, usually observed in men. It is often asymptomatic and associated with lymphopenia. The other is subacute thyroiditis occurring, on average, one month after the COVID-19 episode, usually in clinically symptomatic women and associated with moderate hyperleukocytosis. Post-infection, one quarter to one third of patients remain hypothyroid. An Italian study demonstrated that low TSH in patients hospitalized for COVID-19 was associated with prolonged hospitalization and a higher mortality risk. Pituitary diseases associated with SARS-CoV-2 infection are much rarer and the causal relationship more difficult to ascertain. Several cases of pituitary apoplexy and diabetes insipidus during COVID-19 infection have been reported. Hyponatremia occurs in 20–50% of patients admitted to hospital for COVID-19. The prevalence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) amongst these hyponatremic cases is difficult to determine. These endocrine complications may influence the prognosis of infection with SARS-CoV-2. Although they rarely require specific treatment, it is important that endocrinologists recognize them to ensure appropriate management, particularly in the acute phase.

Effect of hyponatremia normalization on osteoblast function in patients with SIAD.

Hyponatremia is associated with an increased risk of bone fragility and fractures. Many studies suggest that hyponatremia stimulates osteoclast activation, whereas other studies rather reveal a possible role of acute hyponatremia in impairing osteoblast function. We aimed to assess whether and how correction of hyponatremia in hospitalized patients with the syndrome of inappropriate antidiuresis (SIAD) has an impact on bone metabolism. This was a predefined secondary analysis of 88 hospitalized patients with SIAD undergoing a randomized treatment with SGLT-2 inhibitors or placebo for 4 days. Biochemical markers of bone resorption (CTX) and bone formation (PINP) were collected in serum at baseline and after the intervention (day 5). Bone formation index (defined as PINP/CTX) and its difference between day 5 and baseline were calculated. Patients with steroid therapy (n = 6), fractures (n = 10), or whose data were missing (n = 4) were excluded from the analysis. Out of 68 patients, 27 (39.7%) were normonatremic at day 5. These patients showed an increase in serum PINP (P = 0.04), whereas persistent hyponatremic patients did not (P = 0.38), with a relevant difference between these two subgroups (P = 0.005). Serum CTX increased similarly in the two groups (P = 0.43). This produced a 47.9 points higher PINP/CTX difference between discharge and admission in normonatremic patients (95% CI: 17.0-78.7, P = 0.003) compared to patients with persistent hyponatremia, independent of age, sex, BMI, smoking habits, randomization arm, and baseline cortisol levels. Our predefined post hoc analysis shows that correction of hyponatremia in hospitalized patients with SIAD might have a positive impact on osteoblast function.

Clinical analysis for osmotic demyelination syndrome in patients with chronic hyponatremia

Background: Although osmotic demyelination syndrome (ODS) has been well known to be associated with a rapid correction of sodium (Na+) in patients with chronic hyponatremia, its risk factors and clinical outcomes have not been examined in Taiwan. Aim: The aim of the study was to analyze the underlying causes and overlooked risk factors in patients with ODS. Methods: We retrospectively collected chronic hyponatremic patients developing ODS and analyzed their clinical characteristics. Results: Fourteen patients (7 males and 7 females) with a mean age of 62.7 ± 17.9 years old were enrolled. Their underlying causes included gastrointestinal illness with poor intake (n = 7), chronic use of diuretics (n = 2), syndrome of inappropriate antidiuretic hormone (n = 2), pneumonia (n = 2), and hypopituitarism (n = 1). Their serum Na+ was 107.2 ± 1.2 mmol/L with mild hypokalemia (potassium 3.1 ± 7 mmol/L), hypoalbuminemia (albumin, 3.4 ± 0.6 g/dL), and hypophosphatemia (phosphorus, 2.3 ± 1.0 mg/dL). Their mean Na+ correction rate was 8.4 ± 9 mmol/L/day and most patients (60%) developed ODS in first 3 days. Their manifestations included delirium, seizures, unstable gait, aphasia, and drowsy consciousness. Brain magnetic resonance imaging demonstrated that 42.8% had isolated central pontine myelinolysis. Totally, 43% of ODS patients had unfavorable outcome with death and disability. In addition, patients with rapid Na+ correction rate (>12 mmol/L/day, n = 4) usually exhibited significant hypokalemia (2.5 ± 0.4 vs. 3.5 ± 0.7 mmol/L, P < 0.05) as compared with those without. Conclusion: Nutritional status and concurrent electrolyte deficiencies such as hypokalemia are major risk factors in patients with ODS. Clinicians should timely recognize these potential risks of ODS and reduce Na+ correction rate to avoid catastrophic outcomes.

A rare side effect (syndrome of inappropriate antidiuretic hormone) of a commonly used drug (Ramipril)

A rare side effect (syndrome of inappropriate antidiuretic hormone) of a commonly used drug (Ramipril)

Postrenal transplant disseminated cryptococcosis presenting as a syndrome of inappropriate antidiuretic hormone secretion - A case report

Cryptococcosis is the most common invasive fungal infection to involve the central nervous system in the posttransplant period. Cryptococcal meningitis, which constitutes disseminated cryptococcosis, can present with nonspecific signs and symptoms leading to a diagnostic challenge. There are case reports of cryptococcal meningitis presenting as a syndrome of inappropriate antidiuretic hormone secretion (SIADH). A 54-year-old male with autosomal dominant polycystic kidney disease was a live-related renal allograft recipient 1 year back and presented with complaints of generalized weakness and imbalance while walking. His serum sodium on admission was 117 mEq/L and investigations were suggestive of SIADH. He was given hypertonic saline and fluid restriction. However, he had a recurrence of symptomatic hyponatremia. He was evaluated for the cause of SIADH. Chest X-ray and computed tomography of the thorax revealed patchy consolidation. In view of persistent giddiness and imbalance, lumbar puncture was done and cerebrospinal fluid (CSF) analysis showed hypoglycorrhachia with elevated protein and cell counts. CSF cryptococcal antigen test was positive. He was thus diagnosed with disseminated cryptococcosis with meningitis and pulmonary involvement. He received amphotericin B deoxycholate for 4 weeks, followed by fluconazole. He improved symptomatically and serum sodium normalized thereafter. This is the first case of disseminated cryptococcosis presenting with SIADH in the postrenal transplant period with one prior case being reported after a liver transplant. This highlights the variable presentations of cryptococcosis and the need to evaluate the primary cause in posttransplant patients presenting with hyponatremia.

Hyponatremia in Melioidosis: Analysis of 10-year Data from a Hospital-Based Registry.

Introduction:Hyponatremia is a frequent finding in hospitalized patients and is associated with poor clinical outcomes. While hyponatremia is known to commonly occur in certain infections, its association with melioidosis has not been studied previously. We studied incidence and impact of hyponatremia on clinical outcomes in melioidosis.Methods:This was a retrospective analysis of a single-center hospital registry of culture-positive patients with melioidosis hospitalized during a 10-year period (January 01, 2010, through January 31, 2021). Hyponatremia was defined as serum sodium of <135 mmol/L, and severe hyponatremia as serum sodium <120 mmol/L. The association of hyponatremia with in-hospital mortality, need for intensive care unit (ICU) stay and mechanical ventilation was studied.Results:Of 201 patients with melioidosis, 169 (84.1%) had hyponatremia, with severe hyponatremia in 35 (17.4%) patients. Older age (adjusted odds ratios [OR] 1.03, 95% confidence intervals [CI]: 1.00–1.06; P = 0.049) and acute kidney injury (AKI) (adjusted OR 3.30, 95% CI: 1.19-9.19; P = 0.02) were independently associated with hyponatremia. Twenty-two patients had been evaluated for cause of hyponatremia and of these, 11 (50%) had syndrome of inappropriate antidiuresis. Severe hyponatremia was associated with in-hospital mortality (adjusted OR 3.75, 95% CI: 1.37–10.27; P = 0.01), need for ICU stay (adjusted OR 7.04, 95% CI: 2.88–17.19; P < 0.001) and mechanical ventilation (adjusted OR 3.99, 95% CI: 1.54–10.32; P = 0.004).Conclusion:Hyponatremia occurs in 84.1% of hospitalized patients with melioidosis. Older age and AKI are associated with a higher incidence of hyponatremia. The presence of severe hyponatremia is an independent predictor of in-hospital mortality, need for mechanical ventilation and ICU stay.

Korean Society of Nephrology 2022 Recommendations on Controversial Issues in Diagnosis and Management of Hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Postoperative hyponatremia in neonates with esophageal atresia and tracheoesophageal fistula receiving restricted hypotonic fluids

BackgroundDuring the postoperative course following neonatal surgery, several stimuli like respiratory distress, pain, and stress cause the release of the antidiuretic hormone which can induce hyponatremia. This hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) in neonates can lead to neurologic impairment and in severe cases can cause significant morbidity and mortality. Lung involvement in neonates undergoing TEF makes this subset of patients vulnerable to this entity because most of them are sick and require ventilation in the postoperative period. The incidence of postoperative hyponatremia following neonatal surgery has not been studied vastly. To the best of our knowledge, this is the first prospective study that has analyzed the incidence of postoperative hyponatremia in this vulnerable population.MethodsProspective observational study to assess the incidence of postoperative hyponatremia in neonates with esophageal atresia and tracheoesophageal fistula (EA and TEF) receiving restricted hypotonic fluids. As per the unit policy N/4 5% D is given in the postoperative period. Most neonatal units follow a protocol in which fluid is hiked daily to reach 150 ml/kg/day in 5–7 days. However, in our neonatal surgical unit a protocol to restrict the maintenance fluid at 100 ml/kg/day irrespective of day of life is followed.ResultsOut of a total of 90 neonates (270 sodium measurements), we identified 16 with hyponatremia (11%). Most of the neonates had mild hyponatremia(130–135 meq/l). The incidence of moderate and severe hyponatremia was low.ConclusionPostoperative restriction of fluids especially in neonates who are at a high risk for developing SIADH can lead to decreased incidence of severe hyponatremia.

SIADH (Syndrome of Inappropriate ADH Secretion): Perplexing Look of Dengue Fever

Dengue is a mosquito-borne disease (female mosquitoes of the Aedes genus, principally Aedes aegypti) caused by any one of four closely related dengue viruses. It is endemic in tropical and subtropical continent. World health organization (WHO) currently estimates there may be 50 -100 million dengue infections worldwide every year with over 2.5 billion people at risk of dengue. Symptomatic dengue virus infection may manifests as undifferentiated fever, classical dengue fever (with or without unusual hemorrhages), and dengue hemorrhagic fever (with or without shock). Isolated organopathy or expanded dengue syndrome (EDS) was coined by WHO in the year 2012 to describe cases, which do not fall into either dengue shock syndrome or dengue hemorrhagic fever. The atypical manifestations noted in expanded dengue are multisystemic and multifaceted with organ involvement, such as liver, brain, heart, kidney, central/peripheral nervous system, gastrointestinal tract, lympho reticular system. Dengue virus has long been considered as a non-neurotropic virus, as animal studies have shown that virus does not cross blood brain barrier. Hyponatremia may be found in association with dengue fever and is thought to be caused by peripheral fluid extravasation and resulting intravascular hypovolaemia. But hyponatremia due to syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) in Dengue fever is rare. We report a 40 years old male who was diagnosed as Dengue fever (Dengue Ns1Ag positive) with thrombocytopenia and hyponatremia. He was admitted and further investigations revealed SIADH. He responded well to cautious sodium replacement and addition of tolvaptan. He recovered completely and was discharged after one week. Thus, all clinicians should keep in mind the possibility of SIADH as a part of expanded dengue syndrome.

Mirtazapine Risk of Hyponatremia and Syndrome of Inappropriate Antidiuretic Hormone Secretion in Adult and Elderly Patients: A Systematic Review.

Hyponatremia is the most common fluid and electrolyte imbalance in hospitalized patients. Among hyponatremia causes, syndrome of inappropriate antidiuretic hormone secretion is a condition characterized by excessive release of antidiuretic hormone from the pituitary gland or nonpituitary sources. One of the most common drugs associated with hyponatremia is selective serotonin reuptake inhibitors, especially in elderly patients. Therefore, distinct therapeutic alternatives are essential for patients having risk factors for hyponatremia or syndrome of inappropriate antidiuretic hormone secretion development. The present article aims to review the available literature evaluating mirtazapine-induced hyponatremia or syndrome of inappropriate antidiuretic hormone secretion in adult or elderly patients in order to determine the incidence of these adverse effects and analyze the existence of any correlation between the administered dose of mirtazapine and serum sodium levels. A systematic search was conducted, using key terms from the research topic, their synonyms, and Boolean/logic operators. From this evidence pool, inclusion and exclusion criteria were applied. We abstracted population characteristics and clinical endpoints. Relevant data from selected studies was abstracted and subject to statistical analysis. A total sample size of 30,851 patients treated with mirtazapine was included. Mirtazapine-induced hyponatremia incidence was 3.26% (95% CI 3.06-3.45%), with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) the most probable underlying cause. Among case series and case reports evaluated (n=7), hyponatremia and SIADH were more frequent in female patients (71.4%) and the most frequent clinical manifestations included confusion (57%), somnolence (42%), and altered speech (28%). Mean serum sodium levels were (117 mEq/L, ranging from 113-130 mEq/L). The average time lapse between mirtazapine administration and clinical findings was 34 days. The Spearman's rank correlation coefficient between mirtazapine dosage and serum sodium levels was -0.3181 with a p-value >0.05. In conclusion, mirtazapine presents a moderate risk of hyponatremia and should be considered as an alternative therapy in patients requiring antidepressants with risk factors for this preventable adverse effect.

SIADH as the initial manifestation of acute intermittent porphyria: A case report

Acute intermittent porphyria (AIP) is a rare autosomal dominant and the most severe form of the inherited hepatic porphyrias, affecting mainly young women. We present the case of an 18-year-old female who presented with severe abdominal pain, purple urine, autonomic dysfunction, and severe hyponatremia, seizures on further evaluation came out to be a case of AIP. This case report is a reminder to keep AIP among the differentials in young female patients with a classic constellation of abdominal urine discoloration syndrome of inappropriate secretion of antidiuretic hormone and autonomic dysfunction.

Triphasic dysnatremia complicated by generalized convulsions following craniopharyngioma resection in a pediatric patient

Craniopharyngiomas are benign epithelial tumors arising from craniopharyngial duct. Although rare, these are the most common suprasellar, non-glial tumors in children constituting about 50% of all sellar / suprasellar tumors. The management of these tumors can be very challenging not only periopratively but also in postoperative phase as it can lead to extremes of dysnatremias ranging from central diabetes incipidus (CDI), syndrome of inappropriate anti diuretic hormone (SIADH) to cerebral salt wasting syndrome (CSWS). We present a triphasic sodium imbalance following craniopharyngioma resection complicated by generalized convulsions.

Elderly with refractory chronic severe hyponatremia and anesthesia management dilemma: a case report with literature review

Hyponatremia is a common electrolyte disorder, especially in the frail elderly population. With the increasing number of surgeries in the aging population, hyponatremia is frequently encountered by anesthesiologists and surgeons. Unfortunately, management of hyponatremia is often complex in the elderly population as it is often multifactorial, and they are physiologically susceptible. While it is well known that preoperative hyponatremia is associated with increased perioperative morbidity and mortality, a lack of recommendations or guidelines adds to the dilemma in managing such cases. The most common cause of chronic hyponatremia in the elderly is the syndrome of inappropriate antidiuretic hormone (SIADH), which can be resistant to conventional treatment. On the other hand, paraneoplastic SIADH leading to hyponatremia is rare, and surgery may be the only option available for its correction. We present a case of a 78- years-gentleman to highlight such a dilemma. He was diagnosed with renal cell carcinoma and had chronic refractory severe hyponatremia despite treatment with fluid restriction, low dose hydrocortisone, tolvaptan, and 3% sodium chloride.

Updates and Perspectives on Aquaporin-2 and Water Balance Disorders.

Ensuring the proper amount of water inside the body is essential for survival. One of the key factors in the maintenance of body water balance is water reabsorption in the collecting ducts of the kidney, a process that is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and impermeable to ions or other small molecules. Impairments of AQP2 result in various water balance disorders, including nephrogenic diabetes insipidus (NDI), which is a disease characterized by a massive loss of water through the kidney and consequent severe dehydration. Dysregulation of AQP2 is also a cause of water retention with hyponatremia in heart failure, hepatic cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Antidiuretic hormone vasopressin is an upstream regulator of AQP2. Its binding to the vasopressin V2 receptor promotes AQP2 targeting to the apical membrane and thus enables water reabsorption. Tolvaptan, a vasopressin V2 receptor antagonist, is effective and widely used for water retention with hyponatremia. However, there are no studies showing improvement in hard outcomes or long-term prognosis. A possible reason is that vasopressin receptors have many downstream effects other than AQP2 function. It is expected that the development of drugs that directly target AQP2 may result in increased treatment specificity and effectiveness for water balance disorders. This review summarizes recent progress in studies of AQP2 and drug development challenges for water balance disorders.