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.     

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.     

Hyponatremia in patients with central nervous system disease: SIADH versus CSW.

The syndromes of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting (CSW) are two potential causes of hyponatremia is patients with disorders of the central nervous system. Distinguishing between these two causes can be challenging because there is considerable overlap in the clinical presentation. The primary distinction lies in the assessment of the effective arterial blood volume (EABV). SIADH is a volume-expanded state because of antidiuretic hormone-mediated renal water retention. CSW is characterized by a contracted EABV resulting from renal salt wasting. Making an accurate diagnosis is important because the treatment of each condition is quite different. Vigorous salt replacement is required in patients with CSW, whereas fluid restriction is the treatment of choice in patients with SIADH. Although most physicians are familiar with SIADH, they are much less familiar with CSW. This review emphasizes the need for CSW to be included in the differential diagnosis of hyponatremia in a patient with central nervous system disease. Distinguishing between these two disorders is of crucial importance because therapy indicated for one disorder but used in the other can result in negative clinical consequences.     

Cerebral salt wasting syndrome in bacterial meningitis

Subarachnoid hemorrhage is the most common cause of cerebral salt wasting syndrome. There are few reports of this condition in infectious meningitis. We describe a patient with hyponatremia and bacterial meningitis. Hyponatremia rapidly improved after administration of sodium chloride. The purpose of this report is to alert clinicians to the fact that hyponatremic patients with central nervous system disease do not necessarily have a syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but may have cerebral salt wasting syndrome. By contrast with SIADH, the treatment requires saline administration.     

中枢性低钠血症的诊治体会

目的探讨中枢性低钠血症的发病机制、诊断及治疗方法。方法对该院21例中枢性低钠血症患者的临床资料进行回顾性分析。结果19例低钠血症恢复正常;2例因合并颅内感染,高热不退,1例死亡,1例经控制感染后,低钠血症恢复正常,但仍昏迷不醒。结论低血钠、高尿钠和意识状态改变是中枢性低钠血症的诊断依据,抗利尿激素分泌不当综合征（SIADH）应限水治疗,脑性盐耗综合征（CSWS）则作水化和补盐治疗。     

低钠血症诊断思路

低钠血症(血清钠<135 mmol/L)是临床最常见的电解质紊乱之一，临床表现主要包括神经系统和肌肉系统表现两个方面。首先应该查血渗透压水平除外假性低钠血症，尿渗透压检查可以鉴别大量饮用低渗液体或其他肾外失钠的情况，容量判断有助于进一步鉴别低钠血症原因。利尿剂过量、脑耗盐综合征和盐皮质激素减少都能造成低容性低钠血症。而等容或高容性低钠血症则常常因为抗利尿激素不适当分泌综合征、甲状腺激素不足、糖皮质激素缺乏或心、肝、肾功能不全引起。     

Chronic hyponatremia in a patient with renal salt wasting and without cerebral disease: relationship between RSW,risk of fractures and cognitive impairment

Renal salt wasting syndrome (RSW) is defined as a renal loss of sodium leading to hyponatremia and a decrease in extracellular fluid volume (ECV). Differentiation of this disorder from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), a common cause of hyponatremia, can be difficult because both can present with hyponatremia and concentrated urine with natriuresis. Our clinical case about a 78-year-old woman with a recent fracture of the right femur not only confirms that this syndrome can occur in patients without intracranial pathologies (CT documented), but depicts how the hyponatremia caused by RSW can show a chronic, oscillating course. This is an interesting point of view because it suggests to us to consider RSW in the differential diagnosis of patients with chronic 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。     

Prevalence and clinical demographics of cerebral salt wasting in patients with aneurysmal subarachnoid hemorrhage

Hyponatremia is a frequent complication following subarachnoid hemorrhage (SAH), and is commonly attributed either to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome (CSW). The object of this study is to elucidate the clinical demographics and sequelae of hyponatremia due to CSW in subjects with aneurysmal SAH. Retrospective chart review of patients >18 years with aneurysmal SAH admitted between January 2004 and July 2007 was performed. Subjects with moderate to severe hyponatremia (serum sodium <130 mmol l⁻¹) were divided into groups consistent with CSW and SIADH based on urine output, fluid balance, natriuresis, and response to saline infusion. Clinical demographics were compared. Of 316 subjects identified, hyponatremia (serum sodium <135 mmol l⁻¹) was detected in 187 (59.2%) subjects and moderate to severe hyponatremia in 48 (15.2%). Of the latter group, 35.4% were categorized with SIADH and 22.9% with CSW. Compared to eunatremic subjects, hyponatremia was associated with significantly longer hospital stay (15.7 ± 1.9 vs. 9.6 ± 1.1 days, p < 0.001). Subjects with CSW had similar mortality and duration of hospital stay vs. those with SIADH. Though less common than SIADH, CSW was detected in approximately 23% of patients with history of aneurysmal SAH and was not clearly associated with enhanced morbidity and mortality compared to subjects with SIADH. Further studies regarding the pathogenesis and management, along with the medical consequences, of CSW are important.     

急性脑血管疾病中的脑耗盐综合征：附29例临床分析

目的 :观察急性脑血管病病程中并发的脑耗盐综合征。方法 :依次从我院神经科 1年中收治的各种急性脑血管病中筛选出低钠血症病例 ;根据脑耗盐综合征的诊断标准确定该综合征的病例。结果 :在 6 36例各种急性脑血管疾病中发现低钠血症 38例 ,其中脑耗盐综合征 2 9例。结论 :急性脑血管疾病的低钠血症 ,大部分是脑耗盐综合征 ,妥善处理脑耗盐综合征 ,能提高急性脑血管病的疗效     

Syndrome d’antidiurèse inappropriée (sécrétion inappropriée d’hormone antidiurétique)

The syndrome of inappropriate antidiuresis (SIAD; formerly the syndrome of inappropriate secretion of antidiuretic hormone) is the most frequent cause of hyponatremia. A strong association exists between mortality and hyponatremia, which reflects the severity of the underlying disease. In SIAD, hyponatremia is associated with normovolaemia but the assessment of extracellular volume can be difficult. Clinical features are mainly neurological and can lead to death but mechanisms of adaptation can limit cerebral oedema. The notion of mild asymptomatic hyponatremia was questioned by the observation of subclinical neurocognitive impairment, a greater risk of falls and fractures. Aetiologies are classified into six groups: neurologic disorders, infections mainly cerebral, meningeal and pulmonary, drugs in particular antidepressants, tumors, genetic causes, and idiopathic. Symptomatic acute hyponatremia is a therapeutic emergency that is not specific of SIAD. When hyponatremia is asymptomatic, fluid restriction with salt intake is generally sufficient but urea can be an alternative. In chronic SIAD, there is currently no recommendation. Fluid restriction is not always feasible; urea has proved its efficacy, its good tolerance and its long-term harmlessness. Vaptans have demonstrated their good tolerance and their efficacy on the correction of hyponatremia from SIAD in studies subgroups, for moderate hyponatremia and asymptomatic patients. In the only study having compared vaptans and urea, efficacy and tolerance were similar. Because of the cost difference between vaptans and urea and while waiting for follow-up studies, urea appears at present as the first-line treatment of hyponatremia in SIAD.     

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.     

Urinary retention: a cause of hyponatremia?

BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia in elderly hospitalized patients; however in many patients the etiology remains unclear even after routine investigations. OBJECTIVE: To report our experience of the association of hyponatremia and urinary retention in elderly hospitalized patients. PATIENTS: Six patients with hyponatremia and urinary retention who were admitted to the geriatric department in our hospital during a four-year period (2001-2004). RESULTS: The mean age of the patients was 85 years. The mean serum sodium level was 120 mEq/l, average volume of retained urine was 933 ml (range 500-1,500 ml). All patients underwent a comprehensive work-up seeking a possible cause for the hyponatremia. The diagnostic work-up was negative. In 5 of the patients the laboratory findings fulfilled the criteria for SIADH. In all patients hyponatremia resolved following urinary catheterization and fluid restriction. All patients made a complete recovery. CONCLUSIONS: Potentially, urinary retention by itself may cause hyponatremia. The possible mechanism for this is SIADH, triggered by bladder distention or pain due to bladder distention. Urinary catheterization may be the key to treatment in these cases of hyponatremia.     

A case of pulmonary tuberculosis initially presented with syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

A 90-year old man was admitted to a hospital because of consciousness loss with hyponatremia. Although his symptom promptly improved with Na supply, his chest X-ray film showed pulmonary infiltration and direct microscopy of sputum smear was positive for acid-fast bacilli, then he was referred our hospital and was admitted. We made a clinical diagnosis of pulmonary tuberculosis with SIADH based on detailed examinations. But he should neither respiratory symptoms nor fever. He was medicated with the standard antituberculosis drugs with fluid restriction, and his tuberculosis and hyponatremia were improved gradually. We should be more careful about pulmonary tuberculosis irrespective of its severity as a cause of SIADH.     

Hyponatremia in Cirrhosis and End-Stage Liver Disease: Treatment with the Vasopressin V2-Receptor Antagonist Tolvaptan

Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance. The primary cause is increased release of arginine vasopressin. Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients. Clinical evidence suggests that adding serum sodium to model for ESLD (MELD) scoring identifies patients in greatest need of liver transplantation by improving waiting list mortality prediction. Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant. Vasopressin receptor antagonists, which act to increase free water excretion (aquaresis) and thereby increase serum sodium concentration, have been evaluated in patients with hypervolemic hyponatremia (including cirrhosis and heart failure) and euvolemic hyponatremia (SIADH). Tolvaptan, a selective vasopressin V₂-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia. The SALT trials showed that tolvaptan treatment rapidly and effectively resolved hyponatremia in these settings, including cirrhosis, and it has been shown that this agent can be safely and effectively used in long-term treatment. Fluid restriction should be avoided during the first 24?h of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely.     

The syndrome of inappropriate secretion of antidiuretic hormone and fluid restriction in meningitis--how strong is the evidence?

In patients with meningitis, fluid restriction is recommended to counter the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and to reduce cerebral oedema. However, any effects of an increased plasma level of ADH upon cerebral oedema would be due not to fluid retention but to hypoosmolality. In a literature review of fluid and electrolyte disturbances and the effect of fluid therapy in bacterial/tuberculous meningitis, the prevalence of hyponatraemia, hypoosmolality and SIADH varied considerably; apparently, non-osmotic stimuli for the secretion of ADH, e.g. intracranial hypertension and hypovolaemia, were present in most patients. Neither clinical nor experimental studies have confirmed that fluid restriction reduces the cerebral oedema in meningitis. Furthermore, compared with maintenance therapy, fluid restriction did not improve outcome in a randomized controlled study. Thus, we find no evidence to support the use of fluid restriction in patients with meningitis. Fluid therapy in acute bacterial meningitis should aim at avoiding hypovolaemia and hypoosmolality based on the assumptions that (i) ADH is increased by non-osmotic stimuli; (ii) elevated ADH is less important for cerebral oedema than severe hypoosmolality, which may in itself induce or aggravate oedema; (iii) maintenance fluid therapy aiming at isoosmolality will not worsen neurological outcome; and (iv) hypovolaemia is difficult to detect, and detrimental for cerebral perfusion, in these patients.     

Central salt-wasting diuresis syndrome as a cause of hyponatremia in patients at the internal medicine department

Hyponatremia is a common electrolyte disorder related to central nervous system diseases and is often attributed to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and on the other hand to the cerebral salt wasting syndrome (CSWS). This syndrome is characterized by hyponatremia due to excessive renal sodium excretion resulting from a centrally mediated process. Given the divergent nature of the treatment it is of paramount importance for a clinician to be able to recognize and differentiate between these two entities. Thus the monitoring of renal function tests, which are needed for earlier diagnosis of effective osmolality disorders, is important to do in intensive care units, which are caring for patients with central nervous system lesons. Two patients successfully treated for CSW due to ischemic stroke caused by arterial embolism from heart cavities are described.     

Symptomatic hyponatremia in association with a low-iodine diet and levothyroxine withdrawal prior to I131 in patients with metastatic thyroid carcinoma

BACKGROUND: Strategies to improve I131 uptake in thyroid carcinoma include levothyroxine (LT4) withdrawal or thyrotropin (TSH) administration along with a low-iodine diet. We report five patients with papillary or follicular thyroid carcinoma who developed symptomatic hyponatremia during LT4 withdrawal and low-iodine diet. RESULTS: Four patients had pulmonary and/or brain metastases. All had restricted iodine intakes during LT4 withdrawal. Presenting complaints included weakness, dizziness, fainting spells, lethargy, and/or nausea. Baseline serum sodium levels while on LT4 suppression were normal. During presentation all were hypothyroid and serum sodium ranged from 110 to 121 mmol/L (normal 135-148). Despite hyponatremia, the plasma renin activity and serum aldosterone levels were suppressed, indicating volume expansion. The hyponatremia responded to fluid restriction and normalized after LT4 replacement. Low sodium intake, inappropriate antidiuretic hormone secretion syndrome (SIADH)-like disorder secondary to hypothyroidism and/or lung or cerebral metastases may have contributed to hyponatremia. CONCLUSIONS: The development of hyponatremia during LT4 withdrawal and low-iodine diet in otherwise healthy patients with thyroid carcinoma is extremely rare. However, elderly patients with metastatic thyroid carcinoma need observation during LT4 withdrawal combined with a low-iodine diet and should receive instruction to take iodine-free sodium chloride. Free water restriction may be necessary in some patients.