One of the most prevalent indications of water-electrolyte imbalance is edema. Aquaporins (AQPs) are a protein family that can function as water channels. Osmoregulation and body water homeostasis are dependent on the regulation of AQPs. Human kidneys contain nine AQPs, five of which have been demonstrated to have a role in body water balance: AQP1, AQP2, AQP3, AQP4, and AQP7. Water imbalance is connected with AQP dysfunction. Hyponatremia with elevated AQP levels can accompany edema, which can be caused by disorders with low effective circulating blood volume and systemic vasodilation, such as congestive heart failure (CHF), hepatic cirrhosis, or the syndrome of incorrect antidiuretic hormone secretion (SIADH). In CHF, upregulation of AQP2 expression and targeting is critical for water retention. AQP2 is also involved in aberrant water retention and the formation of ascites in cirrhosis of the liver. Furthermore, water retention and hyponatremia in SIADH are caused by increased expression of AQP2 in the collecting duct. Fluid restriction, demeclocycline, and vasopressin type-2 receptor antagonists are widely utilized to treat edema. The relationship between AQPs and edema is discussed in this chapter.

The diagnosis of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) relies on an adequate assessment of a hyponatremic state (that is a serum sodium level <136 mmol/l) and on the exclusion of other causative conditions leading to an adequate secretion of antidiuretic hormone (ADH). The understanding of mechanisms involved in pathological ADH secretion is essential for diagnosis and therapy. Although some forms are due to dysregulation in central nervous system regulations, other forms are dependent on diseases in peripheral organs and structures including ADH-producing/secreting neuroendocrine tumors, while others are induced by medical compounds. ADH regulation is closely linked to other systems such as the sympathetic tone, baroreflex regulation. Patients with hyponatremia should be carefully clinically (neurological symptoms) assessed and be classified according to volume status, also with respect for the need of intensive care monitoring. In parallel, laboratory findings of blood and urine must be analyzed appropriately. It is important to demonstrate true hyponatremia, which is paralleled by a decrease in serum osmolality. Mandatory laboratory diagnostic steps comprise the determination of blood and urine electrolytes and serum and urine osmolality, analysis of thyroid, adrenocortical, and kidney function as well as uric acid. Different test results such as a high fractional uric acid excretion may hint to an existing SIADH. Assessment of urine osmolality and urine sodium / potassium concentrations in view of kidney disorders, diuretic use and intravasal volume level allow for further discrimination and may be indicative for a specific underlying disease, covering SIADH. Brain volume changes (“hydrocephalus ex vacuo”) may depend on age rendering the elderly more tolerant to acute or chronic serum sodium changes. The course of an incident hyponatremia, if documented, may affect therapy. A serum sodium drop within less than 48 hours is considered as acute hyponatremia. A rapid bolus of 100 to 150 ml of intravenous 3% hypertonic saline is appropriate to avoid catastrophic outcomes in severe cases of acute symptomatic hyponatremia.

Long-term neurocognitive deficits after human herpesvirus-6 (HHV-6) infection are common in stem-cell transplant recipients, but SIADH (Syndrome of inappropriate antidiuretic hormone secretion) with persistent hyponatremia is rare. A 51-year-old woman presented with somnolence, hyponatremia (121 mmol/L) and HHV-6 viremia (80,330 copies/ml) on day +22 post umbilical cord blood transplant (UCBT). With waterrestriction, tolvaptan and combination of foscarnet and ganciclovir, patient's hyponatremia and HHV-6 viremia improved. On day +94 UCBT, hyponatremia and HHV-6 viremia recurred. Foscarnet was restarted and continued until day +269 UCBT due to multiple HHV-6 recurrences with persistent hyponatremia. At day +712, patient remains on water-restriction, tolvaptan for continuous hyponatremia from SIADH.

Transsphenoidal surgery is the first-line treatment for many clinically significant pituitary tumors and sellar lesions. Although complication rates are low when performed at high-volume centers, disorders of salt and water balance are relatively common postoperatively. Both, or either, central diabetes insipidus (recently renamed arginine vasopressin deficiency - AVP-D), caused by a deficiency in production and/or secretion of arginine vasopressin, and hyponatremia, most commonly secondary to the syndrome of inappropriate antidiuresis, may occur. These conditions can extend hospital stay and increase the risk of readmission. This article discusses common presentations of salt and water balance disorders following pituitary surgery, the pathophysiology of these conditions, and their diagnosis and management.

We report a case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after total proctocolectomy followed with ileal pouch-anal anastomosis (TPC-IPAA) for ulcerative colitis (UC). The patient was a 46-year-old woman. She was diagnosed with UC of pancolitis in 2000. High grade dysplasia was detected in the transverse colon after a surveillance colonoscopy in 2021. She underwent laparoscopy-assisted TPC-IPAA. On the sixth postoperative day, she had a decreased level of consciousness that worsened on the following day. Her laboratory data showed a serum sodium level of 108 mEq/L and the plasma osmolality was 234 mOsm/kg. We did not find any other abnormalities in the laboratory examination that could cause hyponatremia. Computed tomography scan showed no central nervous system disturbances such as a pituitary tumor, antidiuretic hormone-producing tumors, or pulmonary diseases. The patient was diagnosed with Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) caused by surgical invasion. We started to administer 3% sodium chloride slowly to improve the hyponatremia. Her serum sodium level became normal and stable. Although it is rare for SIADH to be caused by abdominal surgery, if hyponatremia is observed after surgery, the possibility of postoperative SIADH should be considered.

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare multisystem necrotizing vasculitis that involves small- to medium-sized blood vessels. We report a rare case of syndrome of the inappropriate antidiuretic hormone (ADH) secretion (SIADH) secondary to EGPA. A 53-year-old man applied with complaints of pain in the large joints and morning stiffness in knee for 2 months. The patient had the history of impaired fasting glucose, asthma, nasal polyps, and urticaria. Physical examination revealed intrinsic muscle atrophy and weakness in the right hand. Peripheral eosinophil count was 9.78 × 109/L (0.02-0.5), erythrocyte sedimentation rate 39 mm/h (0-20), and C-reactive protein 5.77 mg/dL (0-0.5). Migratory ground-glass pulmonary opacities had been reported in previous chest computed tomography scans. Echocardiography revealed findings compatible with eosinophilic involvement. Electroneuromyographic evaluation showed acute distal axonal neuropathy of right ulnar nerve. EGPA was considered. Oral methylprednisolone treatment was initiated. Intravenous immunoglobulin (IVIG) and cyclophosphamide treatment and gradual tapering of oral steroids were planned. In 24-h urine analysis, sodium was 387 mEq, creatinine was 1156 mg, and volume was 3000 mL. When his medical records were investigated, it was observed that hyponatremia was present for nearly 2 years. While serum osmolality was 270, urine osmolality was 604 mOsm/kg H2O. So, SIADH diagnosis was made. Fluid intake was restricted. Although the patient's sodium level did not return to normal, it rose up to 130 mEq/L. After second cycle of EGPA treatment (cyclophosphamide and IVIG), serum sodium was normal. There is only four other documented cases of SIADH associated with EGPA. We hypothesized that blood supply to the hypothalamus and/or posterior hypophysis might be affected from EGPA vasculitis. Here, in this case, with effective treatment of EGPA, SIADH was resolved which implies a causality between two conditions.

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

The neurohypophysis (pars posterior) is a structure that is located at the base of the brain and is the posterior lobe of the pituitary gland. Its embryological origin is from the neuroectodermal layer called the infundibulum. The neurohypophysis is divided into two regions; the pars nervosa and the infundibular stalk. Sometimes the pars intermedia and the median eminence are included. It secretes oxytocin and vasopressin; vasopressin is also called antidiuretic hormone (ADH) due to its function of preventing diuresis. These hormones are produced at the magnocellular neurosecretory cells in the hypothalamus, specifically, from the paraventricular nuclei and supraoptic nuclei of the hypothalamus. These cells are neurons that project axons to the neurohypophysis. The hormones are transported from the hypothalamus to the neurohypophysis where they are stored and later released into the neurohypophyseal capillaries, which then carry the hormones into the systemic circulation.[1] Dysfunction of the posterior pituitary affects the hormonal homeostasis, which causes diabetes insipidus (DI), and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Disorders caused by oxytocin deficiency are rare, but most are related to pregnancy and lactation problems. The posterior pituitary contains pituicytes that function in the pars nervosa like glial cells for support and modulation of the release of the hormones. A  tumor formed from the pituicytes is called pituicytoma.

The aim of this work is to examine our experience in the use of urea in patients with SIADH. Observational retrospective analysis of 48 patients with SIADH that have been treated with urea in a third-level hospital. Pre-post analysis of serum sodium levels. The 48 patients with SIADH had a median age of 78.5 (range 26-97 years). The serum sodium nadir was 119.8 ± 5.0 mmoL/L and at the beginning of treatment 125.6 ± 4.1 mmoL/L. The patients continued the treatment for a mean time of 2.95 ± 6.29 months, being the treatment still active in 4 patients. In all patients there was an improvement in serum sodium, being the final serum sodium at the end of treatment 134.4 ± 4.9 mmoL/L (p < 0.01). This improvement was observed from the first week. Adverse events were only detected in 2 patients with mild digestive symptomatology and 2 patients refused the treatment due to the low palatability of the urea. There was an economic cost reduction of 87.9% in comparison with treatment with tolvaptan. Urea has shown to be a safe and cost-effective option for the treatment of hyponatremia caused by SIADH.

A 9-year-old girl with remarkable hyponatremia was diagnosed with SIADH that was likely secondary to varicella. Under appropriate treatment, her serum sodium returned to the normal level. There was no evidence of hyponatremia at a 3-month follow-up. We propose that medical professionals need to consider the existence of that SIADH when treating patients with varicella who present with severe hyponatremia.

Hyponatremia is the most frequent electrolytic disorder in hospitalized patients, and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), the most frequent cause of hiponatremia with clinically normal extracellular volume. It consists of a disorder of the regulation of body water that obeys to different causes, mainly cancer, pulmonary illnesses, disorders of the central nervous system and diverse drugs. As in any hiponatremia it a physiological knowledge of the regulation of body water and sodium is essential as well as the application of precise diagnostic criteria in order to manage the problem with an effective treatment. The available data until the moment show that the clinical diagnosis of SIADH made by professionals is mainly not supported on the established criteria drawn by experts and this lack of accuracy probably hits in the therapeutic result. The basis of the treatment of the SIADH is to correct its cause, water restriction, solutes (sodium chloride) and the use of vaptans in case of failure of the previous measures.

Ayahuasca is a psychedelic blend originating from South America that has been used for hundreds of years by local tribes in ritualistic ceremonies. For the last few decades, its usage has expanded to North America in various mindfulness retreats that can benefit from its hallucinogenic properties. In this case report, our patient had attended a satanic ritual where he had consumed copious amounts of Ayahuasca over three days. Upon his return, he continued having demonic hallucinations along with paranoid delusion with increasing bouts of nausea and vomiting. He was brought in by first responders due to suicidal ideations, and shortly after arrival, he became unresponsive with seizure-like activity. The patient was evaluated to be comatose with a Glasgow Coma Scale (GCS) score of 3, and upon securing the airway, was transferred to the critical care unit. Laboratory results showed a case of hypoosmolar hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH), and following the supportive care, he was able to recover within four days of admission. We theorize that due to the similarity in the pharmacodynamics of the active compound of Ayahuasca, and drugs such as monoamine oxidase inhibitors (MAOI) and 3,4-methylenedioxymethamphetamine (MDMA), it can result in SIADH in its users.

Syndrome of inappropriate anti-diuretic hormone release (SIDAH) is a condition characterized by an unregulated release of anti-diuretic hormone (ADH) resulting in increased water retention and decreased plasma osmolarity. Without regulation, ADH release will cause a significant decrease in plasma sodium concentration and can present with cramping, nausea, vomiting, and in severe cases, seizures, and potentially falling into a comatose state. The causes of SIADH are variable and range from infections, some malignancies to some medications. We report a rare case of SIADH resulting from a single cycle of doxorubicin and cyclophosphamide chemotherapy in a 66-year-old female with left and right, estrogen receptor positive breast cancer who experienced seizures resulting from a dramatic drop in sodium levels.

Hyponatremia is the most common electrolyte abnormality in patients with decompensated cirrhosis on Liver Transplantation (LT) waiting list. Most of these patients have dilutional or hypervolemic hyponatremia secondary to splanchnic vasodilatation. Excessive secretion of the antidiuretic hormone also plays an important role. Hypervolemic hyponatremia is commonly associated with refractory ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy. Although uncommon, the use of diuretics and laxatives can cause hypovolemic hyponatremia that is characterized by the striking absence of ascites or pedal edema. Clinical features are often nonspecific and depend on the acuity of onset rather than the absolute value of serum sodium. Symptoms may be subtle, including nausea, lethargy, weakness, or anorexia. However, rarely patients may present with confusion, seizures, psychosis, or coma. Treatment includes discontinuation of diuretics, beta-blockers, and albumin infusion. Hypertonic saline (3%) infusion may be used in patients with very low serum sodium (<110 mmol/L) or when patients present with seizures or coma. Short-term use of Vasopressin (V2) receptor antagonists may also be used to normalize sodium levels prior to LT. However, all these measures may be futile, and LT remains the definite treatment in these patients to improve survival. In this review, we describe the classification, pathogenesis of hyponatremia, and its clinical implications in patients with cirrhosis. Approach to these patients along with management will also be discussed briefly.

Syndrome of inappropriate antidiuretic hormone ADH release (SIADH) is a condition defined by the unsuppressed release of antidiuretic hormone (ADH) from the pituitary gland or nonpituitary sources or its continued action on vasopressin receptors. The condition was first detected in two patients with lung cancer by William Schwartz and Frederic Bartter in 1967. They developed the classic Schwartz and Bartter criteria for the diagnosis of SIADH, which has not changed. SIADH is characterized by impaired water excretion leading to hyponatremia with hypervolemia or euvolemia.[1][2][3]

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.

Two postmenopausal women with breast cancer developed acute confusion and seizures, less than 24 hours after the first cycle of neoadjuvant chemotherapy with fluorouracil, epirubicin and low-dose cyclophosphamide. They were found to have severe, life-threatening hyponatraemia with sodium levels of 113 and 115 mEq/L, respectively. Both women made a full recovery within 24 hours of admission with slow correction of sodium levels. Following investigational workup, the most likely diagnosis was cyclophosphamide-associated syndrome of inappropriate antidiuretic hormone secretion (SIADH). Aprepitant - a commonly used antiemetic and moderate cytochromeP450 3A4 inhibitor was identified as the precipitating factor. Aprepitant was discontinued and both women were successfully re-challenged with full dose cyclophosphamide in an outpatient setting with no subsequent adverse events. This is a typical case of a rare cause of a common medical problem. A systematic approach to diagnosis and treatment of hyponatraemia in an oncology patient requires awareness of toxicities of systemic anticancer agents.

In the general population, the prevalence of mild, usually asymptomatic hyponatremia ranges from 1,7-7,7 %. With increasing age, it rises to 11,6 % in > 75-year-olds. The prevalence is much higher in nursing home residents and hospital patients. Hyponatremia thus represents the most common electrolyte disturbance in the elderly. Despite the existing evidence on the acute as well as chronic effects of hyponatremia, too little attention is paid to it in clinical practice. An algorithm has proven to be useful for the diagnosis of hyponatremia, which enables the cause to be identified in a few simple steps and at the same time leads to the correct therapeutic steps. The goal must be a serum sodium within the normal range. This is the only way to improve the prognosis and functionality of elderly patients. For SIADH, we have a potent substance available in tolvaptan. In order to be able to recognize the danger of overcorrection in time, the adjustment should take place in the inpatient setting.