Hyponatremia in intracranial disorders

Hyponatremia is a common electrolyte disturbance following intracranial disorders. Hyponatremia is of clinical significance as a rapidly decreasing serum sodium concentration as well as rapid correction of chronic hyponatremia may lead to neurological symptoms. Especially two syndromes leading to hyponatremia in intracranial disorders need to be distinguished, as they resemble each other in many, but not all ways. These are the syndrome of inappropriate ADH secretion (SIADH) and the cerebral salt wasting syndrome (CSW). The syndrome of inappropriate ADH secretion is characterized by water retention, caused by inappropriate release of ADH, leading to dilutional hyponatremia. The cerebral salt wasting syndrome on the other hand, represents primary natriuresis, leading to hypovolemia and sodium deficit. SIADH should be treated by fluid restriction, whereas the treatment of CSW consists of sodium and water administration. However, in the literature there is abundant evidence that hyponatremia in intracranial diseases is mostly caused by CSW. Therefore, treatment with fluid and salt supplementation seems indicated in patients with intracranial disorders who develop hyponatremia and natriuresis.     

Inappropriate secretion of antidiuretic hormone:a rare complication after common bile duct exploration

BACKGROUND:The syndrome of inappropriate secretion of antidiuretic hormone(SIADH)as a dilutional hyponatremia is due to a pathological increase of antidiuretic hormone(ADH).It is characterized by hyponatremia and decreased serum osmolarity as well as an increase in urinary osmolarity.The most common etiological factors of this syndrome include diseases or trauma of the central nervous system and malignant tumor or inflammation of the lung.SIADH following abdominal surgery is rare. METHODS:We report the case...     

Drug-induced syndrome of inappropriate diuresis or of antidiuretic hormone secretion?

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (Bartter and Schwartz, 1967) is defined as low effective plasma osmolality due to impaired renal water dilution together with impaired thirst center regulation once effective hypovolemia and corticotropin deficiency are ruled out (Robertson, 2006).Impaired water dilution is encountered following stimulation of voloreceptors triggering ADH (i.e., vasopressin) secretion through brain circumventricular organ stimulation [including notably the subfornical organ (SFO)] (Bichet, 2019). This condition is reversed as soon as volemia is restored: hyponatremia is corrected within hours, unlike withdrawal of drugs inducing SIADH, in which optimal water dilution recovery usually takes several days or weeks. Therefore, diuretics will be beyond the scope of this review.     

Carbamazepine-induced hyponatremia

Treatment with some drugs may lead to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), the presence of which is more likely in some populations, including people who are elderly or who take diuretics. Resulting drug-induced hyponatremia is often mild and usually resolves following water restriction and withdrawal of the drug. In some patients, however, it may be a potentially fatal condition that is typically asymptomatic until it becomes severe. In this article, we describe the case of a 59-year-old man with arterial hypertension, already treated with hydrochlorothiazide, who presented with hyponatremia after starting administration of carbamazepine. After excluding other common causes of hyponatremia, a diagnosis of SIADH was established, carbamazepine was withdrawn and SIADH treatment introduced. Our study shows that routine assessment of blood electrolytes is reasonable not only in patients receiving diuretics but also in patients treated with other drugs affecting vasopressin secretion.     

The syndrome of inappropriate antidiuretic hormone secretion (SIADH): pathophysiologic mechanisms in solute and volume regulation.

1. Studies on eight patients were performed to clarify the mechanism(s) of altered sodium metabolism and volume regulation in SIADH. The mechanism controlling water excretion was also studied to determine whether there is evidence that altered osmoregulation may be the basis for inappropriate ADH secretion in some patients. 2. These studies show that cumulative sodium balance and aldosterone secretion rates in patients with SIADH are negatively correlated with water intake. There is also a negative correlation between aldosterone secretion and urinary sodium excretion. In the absence of normal urine diluting ability, this increased excretion of sodium becomes a mechanism that allows an increased quantity of water to be excreted despite the persistence of an ADH effect on the renal tubules. 3. Within the range of hyponatremia observed in our studies, changes in serum sodium concentration were accounted for by changes in solute and water balance. One patient, who was potassium deficient during the studies, retained large quantities of sodium and potassium that could not be accounted for by an increase in either serum osmolality or body weight. These observations suggest that intracellular osmotically active solute is either lost or "inactivated" in some manner as intracellular potassium is replenished. 4. Marked impairment of urine diluting ability was demonstrated in all patients. However, two patients with SIADH associated with pulmonary tuberculosis exhibited graded responses to water loading, which suggests that ADH secretion may have been suppressed as serum osmolality was progressively reduced. Whether this can be attributed to a basic alteration or "re-setting" or osmoreceptor function, or is merely an indication that greater than normal reductions of serum osmolality are required to inhibit potent nonosmotic stimuli, remains to be determined.     

Syndrome of inappropriate antidiuretic hormone secretion associated with acute myeloid leukemia with multilineage dysplasia

A patient having acute myeloid leukemia (AML) with multilineage dysplasia, developed hyponatremia and showed all symptoms of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) through a mechanism similar to tumor lysis. Retrospective immunohistochemical analysis of blast cells was positive for antidiuretic hormone (ADH) protein. According to us, this is the first case report of SIADH in an AML patient with multilineage dysplasia, showing blast cells immunostained for ADH, which clearly demonstrated that the tumor cells produced ADH.     

Syndrome of recurrent increased secretion of antidiuretic hormone following multiple doses of vincristine

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been recognized to occur following treatment with vincristine. None of the reports have provided information regarding its potential for recurrence on further challenge with vincristine (VCR), an agent generally required for repeated use in patients with malignancies. Symptomatic hyponatremia and SIADH that occurred 8 days following administration of VCR in a child with acute lymphatic leukemia was documented with specific radioimmunoassay of urinary ADH levels. The further occurrence of recurrent elevations in ADH excretion 8-10 days following repeated treatment with VCR was also observed. However, SIADH was prevented by prophylactic rigorous fluid restriction. The occurrence of SIADH following VCR therefore does not preclude the further safe usage of this drug.     

Behandlung der Hyponatriämie

Hyponatremia is encountered quite frequently in everyday clinical practice. The symptomatology mainly includes neurological manifestations. In addition, it has been noted in recent years that uncertain gait, falls, fractures, and osteoporosis are also associated with hyponatremia. Based on clinical and laboratory analyses, hyponatremia can be classified into three categories: hypovolemic (decreased volume), hypervolemic (with venous edema), and euvolemic. The severity of the neurological symptoms related to hyponatremia should serve to guide the therapeutic approach. Severe cerebral symptoms due to acute cerebral edema require a prompt and closely monitored course of action with administration of hypertonic saline solution. Milder and moderate symptoms as well as the syndrome of inappropriate ADH secretion (SIADH) can now also be managed with controlled use of the ADH antagonist tolvaptan, one of a new class of vaptans. Tolvaptan is a selective antagonist of the antidiuretic effect of vasopressin without primarily affecting blood pressure and depending on the dose leads to increased excretion of free water (aquaresis). Side effects predominantly concern thirst, polyuria, and hypernatremia. Under these conditions, vaptans represent a valuable asset to the therapeutic spectrum in SIADH. Further studies are needed to determine whether falls and fractures can also be beneficially influenced.     

Severe hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone developed as initial manifestation of human herpesvirus‐6–associated acute limbic encephalitis after unrelated bone marrow transplantation

Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell transplantation (allo‐SCT) recipients and >50% of cases of severe hyponatremia are caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we present a patient with rapidly progressive severe hyponatremia as an initial sign and symptom of human herpesvirus‐6–associated post‐transplantation acute limbic encephalitis (HHV‐6 PALE) after allo‐SCT. A 45‐year‐old woman with acute lymphoblastic leukemia received unrelated bone marrow transplantation from a one locus‐mismatched donor at the DR locus. On day 21, she developed a generalized seizure and loss of consciousness with severe hyponatremia, elevated serum antidiuretic hormone (ADH), and decreased serum osmolality. A high titer of HHV‐6 DNA was detected in cerebrospinal fluid. Treatment with foscarnet sodium and hypertonic saline was started with improvement of neurological condition within several days. Although an elevated serum ADH, low serum osmolality, and high urinary osmolality persisted for 2 months, she had no other recurrent symptoms of encephalitis. Our experience suggests that hyponatremia accompanied by SIADH should be recognized as a prodromal or concomitant manifestation of HHV‐6 PALE, and close monitoring of serum sodium levels in high‐risk patients for HHV‐6 PALE is necessary for immediate diagnosis and treatment initiation.     

A case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) with low plasma concentrations of antidiuretic hormone.

A 66-year-old Japanese man presented with persistent hyponatremia without polydipsia and polyuria. Laboratory examination showed serum sodium of 117 mEq/l, plasma osmolality 239 mosm/kg, urine sodium 108 mEq/l, urine osmolality 577 mosm/kg, and normal levels (less than 2.0 pg/ml) of serum antidiuretic hormone (ADH). ADH release was regulated normally with changes in plasma osmolality. No obvious cause for the syndrome of inappropriate secretion of ADH (SIADH) could be detected. However, 20 months later, the patient had bouts of hematuria and was found to have cancer of the urinary bladder. Increased renal sensitivity to ADH was suspected as the underlying mechanism of SIADH.     

Recurrent hyponatremia after traumatic brain injury

Dysregulation of the neuroendocrine system is a frequent complication after traumatic brain injury (TBI). Symptoms of these hormonal abnormalities might be subtle and thus easily ignored. Hyponatremia usually indicates underlying disorders that disrupt fluid homeostasis. In most patients with TBI, hyponatremia is a feature of the syndrome of inappropriate antidiuretic hormone (SIADH) secretion due to pituitary dysfunction after head injury. Usually TBI-associated hyponatremia is transient and reversible. We report the case of a 48-year-old man with TBI-associated hyponatremia with delayed recovery and recurrent hyponatremia precipitated by subsequent surgery. In this report, we emphasize the importance of identifying patients with slow recovery of the injured brain, which could complicate with SIADH and acute hyponatremia. Differentiating TBI-associated SIADH from other important causes of hyponatremia such as cerebral salt wasting, and hypocortisonism are also reviewed. Prevention of its recurrence by avoiding further risk is mandatory in managing patients with TBI.     

提高抗利尿激素分泌异常综合征的诊治水平

抗利尿激素分泌异常综合征(SIADH)以稀释性低钠血症为主要表现,是住院患者等容量性低钠血症最常见的病因.SIADH的传统治疗包括限制液体入量、输注盐溶液及一些调节体液平衡的药物.由于各种原因,常规治疗的疗效欠佳.抗利尿激素受体拮抗剂是一种新型的药物,可以阻断抗利尿激素介导的受体活化,是针对SIADH的病因治疗.     

Drug-related disorders of water and electrolyte metabolism

Pharmacologic treatment may lead to diverse disturbances of water and electrolyte metabolism as adverse drug events. Diuretics are particularly likely to cause these complications typically including volume depletion, metabolic alkalosis, hyponatremia, and hypokalemia. Salt and water retention with edema formation is most frequently elicited by antihypertensives, steroid hormones, and nonsteroidal anti-inflammatory drugs. Drug-induced disorders of Na+ concentration may usually be attributed to altered antidiuretic hormone (ADH) effects, either as diabetes insipidus or as the syndrome of inappropriate ADH secretion. With hyper- and hypokalemia, redistribution between intra- and extracellular fluid as well as renal excretion play a role. Strategies to prevent these adverse drug reactions include careful consideration of risk factors and clinical and laboratory controls in the course of treatment.     

Occult pulmonary malignancy in syndrome of inappropriate ADH secretion with normal ADH levels

Although the syndrome of inappropriate ADH secretion (SIADH) has many causes, principally pulmonary, central nervous system or neoplastic disease, and drugs, patients may present with SIADH in whom the etiology is not readily evident. We measured serum ADH levels in such an individual in both the eunatremic and water-loaded states and found levels to be undetectable despite failure to dilute the urine. A small oat cell pulmonary carcinoma was ultimately diagnosed with lung tomograms and cytology. Following a partial response to water restriction, demeclocycline was effective in producing a water diuresis that restored the serum sodium concentration to normal. Patients with clinical SIADH but low serum ADH levels can harbor a malignant or benign process that, notwithstanding the low ADH levels, may still remain responsive to demeclocycline, suggesting either neoplastic production of a biologically-active, immunologically-inactive ADH-like peptide, or increased renal tubular sensitivity to ADH.     

Volumen- und Elektrolytstörungen bei medikamentöser Therapie

Pharmacologic treatment may lead to diverse disturbances of water and electrolyte metabolism as adverse drug events. Diuretics are particularly likely to cause these complications typically including volume depletion, metabolic alkalosis, hyponatremia, and hypokalemia. Salt and water retention with edema formation is most frequently elicited by antihypertensives, steroid hormones, and nonsteroidal anti-inflammatory drugs. Drug-induced disorders of Na+ concentration may usually be attributed to altered antidiuretic hormone (ADH) effects, either as diabetes insipidus or as the syndrome of inappropriate ADH secretion. With hyper- and hypokalemia, redistribution between intra- and extracellular fluid as well as renal excretion play a role. Strategies to prevent these adverse drug reactions include careful consideration of risk factors and clinical and laboratory controls in the course of treatment.     

Hyponatremia and syndrome of inappropriate antidiuretic hormone secretion complicating stem cell transplantation

Hyponatremia is a common electrolyte disorder in hospitalized patients. Although there are a few case reports of hyponatremia following stem cell transplantation (SCT), no reports concerning the incidence are currently available. We describe the occurrence of hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following SCT. In a single center analysis of 140 patients, hyponatremia and SIADH were observed in 40 and 11.4% of patients, respectively, following SCT. Risk factors for SIADH included young age, transplantation from an HLA-mismatched or unrelated donor, cord blood transplantation, and graft-versus-host disease prophylaxis with methyl prednisolone. Multivariate analysis revealed that transplantation from an HLA-mismatched donor and performance of SCT in a child below 4 years of age were risk factors for SIADH. For patients who underwent SCT from an HLA-mismatched or unrelated donor, those with SIADH showed a significantly higher overall survival rate (90.9 vs 40.2%) and event-free survival rate (77.8 vs 33.8%) compared to those without SIADH. Overall, our data show that hyponatremia and SIADH are relatively common complications following SCT, especially in children below 4 years of age and after SCT from an HLA-mismatched donor.     

Case report of hypopituitarism with suspected syndrome of inappropriate VP secretion (SIADH) due to a large aneurysm of the internal carotid in the sellar region

Hypopituitarism and hyponatremia, especially when severe, are infrequent findings particularly when the cause of hypopituitarism at presentation is unknown and untreated. Interestingly, hyponatremia is usually seen in elderly patients with hypopituitarism due to various causes. We present a case with unrecognized and untreated hypopituitarism due to a large aneurysm of the internal carotid artery in the sellar region causing the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).     

Syndrome of inappropriate secretion of antidiuretic hormone associated with localized herpes zoster ophthalmicus

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with localized herpes zoster is rarely reported and may be under-appreciated. We describe two diabetic men with herpes zoster ophthalmicus (HZO) who developed hyponatremia (114 and 116 mmol/L) during acute illness. Both were euvolemic and had elevated urine osmolality (435 and 368 mmol/kg.H₂O) and sodium (Na⁺) concentration (61 and 63 mmol/L) along with normal cardiac, renal, liver, and endocrine function consistent with the diagnosis of SIADH. Thorough investigation for other causes of SIADH, including detailed physical examination, laboratory studies, and computed tomography of the brain, chest, and abdomen, were negative. Despite antiviral therapy (acyclovir) for herpes zoster, ophthalmoplegia, keratitis, and post-herpetic neuralgia (PHN) developed. Even with fluid restriction and high salt diet, SIADH lasted for 3 to 4 months and resolved concomitantly with resolution of PHN, suggesting an association between SIADH and HZO. These two cases raise the potential for herpes zoster infection, especially HZO, to involve the regulatory pathway of ADH secretion, contributing to SIADH. The presence of PHN, which reflects greater neural damage may, at least in part, explain the prolonged ADH secretion and hyponatremia.     

Is polydipsia sometimes the cause of oxcarbazepine-induced hyponatremia?

Hyponatremia is a commonly encountered clinical problem with potentially severe complications. Among the underlying implicated etiologies are medications such as oxcarbazepine, which has been well documented and attributed to the syndrome of inappropriate antidiuretic hormones (SIADH). We report the case of a 28-year-old woman with a diagnosis of secondary antiphospholipid syndrome who presented with asymptomatic hyponatremia secondary to excessive water intake after oxcarbazepine ingestion, suggesting a new mechanism for oxcarbazepine-induced hyponatremia.     

脑耗盐综合征的研究进展

中枢神经系统疾病如动脉瘤引起的蛛网膜下腔出血、头部创伤等常可致低钠血症。除医源性因素外,脑耗盐综合征（CSWS）和抗利尿激素分泌不当综合征是引起上述低钠血症的常见原因。CSWS可引起液体和钠盐的丢失,尿钠排出增多。关于心房利钠肽、脑钠肽在CSWS发病机制中的作用尚存在争议。CSWS患者伴随的低钠血症和血容量不足会加重神经系统症状,故适时的液体和钠盐补充治疗十分重要,必要时可予氟氢考的松以增加肾小管对钠盐的重吸收。