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.     

Hypouricemia, inappropriate secretion of antidiuretic hormone, and small cell carcinoma of the lung

The hospital records of 106 patients with small cell carcinoma of the lung were reviewed to determine if hypouricemia accompanied hyponatremia (less than 130 mmole/L) and if coexistent hypouricemia and hyponatremia were predictive of the presence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Thirty-seven patients were excluded because of insufficient data or factors that would affect the uric acid level. Six of eight patients with SIADH had hypouricemia. The coexistence of hypouricemia and hyponatremia predicted SIADH reliably (6/6 patients), but hypouricemia alone had a low predictive value (46%) since it was seen in seven of 61 patients without SIADH.     

Esophageal small-cell carcinoma with syndrome of inappropriate secretion of antidiuretic hormone

Small-cell carcinoma (SCC) of the esophagus is rare, and its clinical characteristics remain poorly understood. A 54-year-old man was given a diagnosis of esophageal SCC and underwent esophagectomy. Four months after surgery, he was admitted to our hospital because of rapidly developing hyponatremia. Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) due to extensive recurrence of SCC was diagnosed. Combined chemotherapy with irinotecan and cisplatin has dramatically reduced metastatic tumors, and it was concomitantly effective for SIADH. This case demonstrates that esophageal SCC could induce SIADH as a paraneoplastic syndrome and that the above combined chemotherapy was feasible and effective.     

Syndrome of inappropriate antidiuretic hormone secretion in a patient with cryptococcal meningoencephalitis: a hidden mediastinal small cell carcinoma

We report a 59-year-old man with cryptococcal meningoencephalitis who presented with typical features of syndrome of inappropriate antidiuretic hormone secretion (SIADH). There was no evidence of lung disease or drugs causing SIADH. Studies for endocrine functions and tumor markers were normal. The patient's hyponatremia was refractory to treatment (Na 120-125 mmol/L) after resolution of the cryptococcal infection. Three months after completion of antifungal treatment, a radiograph of the chest disclosed widening of the mediastinum. Computed tomography revealed a mediastinal mass. A tentative diagnosis of extrapulmonary cryptococcoma or a tumor was made. Positron emission tomography using F-fluorodeoxy glucose demonstrated an intense uptake mass in the mediastinum without lesions elsewhere in the body. A biopsy of the mass clearly showed small cell carcinoma (SCC) with positive immunoreactivity for arginine vasopressin and atrial natriuretic peptide. The hyponatremia completely resolved and tumor size dramatically decreased after chemotherapy. To the best of our knowledge, this is the first case of mediastinal SCC associated with SIADH. Patients with otherwise unexplained SIADH should be meticulously scrutinized for a possible malignancy.     

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.     

Acute psychosis, polydipsia, and inappropriate secretion of antidiuretic hormone

A relationship between acute psychosis, water ingestion, and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been reported. This syndrome was observed in a psychotic patient who ingested massive amounts of water and became symptomatically hyponatremic with seizures. Although he had been taking haloperidol, the SIADH responded to fluid restriction alone. SIADH was clearly established, and a temporal relationship to his acute exacerbation of psychosis and polydipsia could be shown. This case illustrates that psychosis, polydipsia, and SIADH are often associated as a triad, and that psychiatric history must be considered in the evaluation of this syndrome.     

HIGH MOLECULAR WEIGHT VASOPRESSIN: DETECTION OF A LARGE AMOUNT IN THE PLASMA OF A PATIENT

Using a sensitive and specific radioimmunoassay for arginine-vasopressin, we have searched for the presence of high molecular weight (HMW) vasopressin in the plasma of a patient with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and an oat cell carcinoma of the lung. After incubation in 8 mol/l urea, one millilitre of the plasma from this patient was fractionated on a Sephadex G-50 column and the immunoreactive vasopressin content was evaluated before and after trypsin treatment of the eluted fractions. A wide peak of apparent mol. wt. 2500-6000 daltons was revealed only after tryptic digestion of each fraction. This peak contained the equivalent of 1900 pg of vasopressin. A tryptic digest of this peak, rechromatographed on Sephadex G-25, gave two small peptides the major one eluting at a position identical to vasopressin. These results demonstrate the presence of a large amount of HMW vasopressin in the plasma of a patient with SIADH and oat cell carcinoma of the lung.     

Systematic evaluation of 8 arginine vasopressin and neurophysins plasma levels in 10 patients with oat cells carcinoma of the lung (author's transl)]

Plasma AVP level, neurophysins and osmolality have been measured in 10 patients with oat cell carcinoma of the lung but without any biological signs of syndrome of inappropriate secretion of ADH (SIADH), before and 15 mn after an intravenous injection of Ethanol. No statistically significant difference was noted in the AVP, neurophysins and osmolality values between 10 patients with asymptomatic oat cell carcinoma and control population (10 normal volunteers, 12 patients with non neoplasic lung pathology and 10 patients with different lung carcinoma). We concluded that AVP and neurophysins cannot be considered as a good tumoral marker in the detection of oat cell carcinoma of the lung.     

Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by urea

Recent data have shown the role of urea in the urinary concentrating mechanism. We studied the effects of exogenous urea administration in hyponatremia associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In 20 patients with SIADH, we observed a positive correlation between serum sodium and blood urea levels (r = 0.65; p < 0.01). In one patient with an oat cell carcinoma and SIADH-induced hyponatremia, we observed the same positive correlation (r = 0.80; p < 0.01) but also a negative one between the excreted fraction of filtered sodium and urinary urea (r = -0.67; p < 0.001). The short-term administration of low doses of urea (4 to 10 g) resulted in correcting the “salt-losing” tendency of this patient. Longer term administration of high doses of urea (30 g/day) was attempted with the same patient as well as with a healthy volunteer subject with Pitressin^®-induced SIADH. In both patients, urea treatment lowered urinary sodium excretion as long as hyponatremia was significant (< 130 meq/liter). Urea treatment also induced a persistent osmotic diuresis, allowing a normal daily intake of water despite SIADH. This was clearly shown during the long-term treatment of a third patient with SIADH who was taking 30 g urea/day during 11 weeks.It is concluded that urea is a good alternative in the treatment of patients with SIADH who present with persistent hyponatremia despite the restriction of water intake.     

A case of interstitial pneumonia accompanying SIADH]

A 75-year-old man was transferred to our hospital on November 28, 2003 because of acute aggravation while being treated for interstitial pneumonia superimposed on pneumoconiosis at a local hospital. Upon admission, oxygen inhalation therapy and antimicrobial chemotherapy were started for the interstitial pneumonia. In addition, since he showed hyponatremia from admission, a saline load was administered and the clinical course was observed. However, disturbance of consciousness developed on January 5, 2004. At that time, the serum sodium was 115mEq/l. Since secretion of antidiuretic hormone (SIADH) had continued despite a low plasma osmolarity, we diagnosed syndrome of inappropriate secretion of antidiuretic hormone (SIADH). We initiated treatment with water restriction and saline load, but no remarkable improvement was observed. From February 7, 40mg /day prednisolone was started because of aggravation of interstitial pneumonia. As a result, the respiratory status and image findings improved, and serum sodium level was normalized. This case was considered to be SIADH secondary to interstitial pneumonia. Among respiratory tract diseases, SIADH is often caused by small cell lung carcinoma, although it may also occur concurrently with other respiratory tract diseases. Since hyponatremia may manifest grave disturbance of consciousness, investigation of the cause is important.     

Syndrome of inappropriate ADH secretion attributed to the serotonin re-uptake inhibitors,venlafaxine and paroxetine

We report on 2 patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) which developed a few weeks after they had started treatment with venlafaxine and paroxetine, respectively. Due to the temporal relationship and the exclusion of other potential causes, a causal relationship between the use of the antidepressants and SIADH seems likely. Diagnostic criteria for SIADH and the role of drugs, especially serotonin re-uptake inhibitors, are discussed.     

Human neurophysins in carcinoma of the lung: relation to histology, disease stage, response rate, survival, and syndrome of inappropriate antidiuretic hormone secretion

At diagnosis, 65% of 103 patients with small cell carcinoma of the lung were found to have elevated plasma concentrations of vasopressin-associated human neurophysin (VP-HNP), oxytocin-associated human neurophysin (OT-HNP), or both, which were thought to be related to tumor secretion of these proteins. The remainder of patients were designated as nonsecretors (24%) or possible secretors (11%), depending upon plasma concentration of the neurophysins prior to therapy. There was a significantly higher percentage of secretors among patients with extensive disease (82%) than among those with limited disease (40%) (P = 0.001). However, within each stage group, there was no correlation between secretory status and response to therapy, survival, or histologic subtype. In addition, patients who initially were nonsecretors or possible secretors maintained this status throughout the course of disease remission and subsequent relapse. These findings suggest the possibility of biochemical differences between tumors which present as limited disease and those which present as extensive disease. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was infrequent in limited disease but was present in 33% of patients with extensive disease. SIADH was not seen without VP-HNP elevation; however, with extensive disease, 49% of patients with elevated VP-HNP had SIADH. In contrast, elevated plasma concentrations of the neurophysins were seen in only 19.6% of 56 patients with non-small cell carcinoma of the lung. The levels were in general lower than those in patients with small cell carcinoma and were seen at approximately equal frequencies in each major cellular subtype.     

Lack of appropriate investigations in making a diagnosis of syndrome of inappropriate antidiuretic hormone

The syndrome of inappropriate antidiuretic hormone (SIADH) is reported as the most common cause of hyponatraemia. This retrospective cross‐sectional study evaluated the diagnosis of SIADH in 110 hospitalised patients in an Australian tertiary hospital with reference to recently published clinical guidelines. Investigation of SIADH was incomplete in all but 20% of cases. Adrenal insufficiency and hypothyroidism were not excluded in a significant number of cases.     

SIADH consecutive to ciprofloxacin intake

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is often drug-induced. We describe the first case, to our knowledge, of SIADH consecutive to ciprofloxacin administration. On two occasions, a 70-year-old patient, known for post-actinic bladder with repeated episodes of hematuria, was given ciprofloxacin and developed severe hyponatremia with seizures. On both occasions, the patient's condition improved rapidly after withdrawal of the drug. As all organic diseases likely to cause SIADH were excluded, and because the drug rechallenge was positive, we suggest that ciprofloxacin be added to the list of drugs prone to induce SIADH.     

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.     

Chlorambucil-induced inappropriate antidiuresis in a man with chronic lymphocytic leukemia

 The syndrome of inappropriate antidiuretic hormone (SIADH) has been described in patients suffering from leukemia or lymphoma involving the central nervous system. Several alkylating agents have also been associated with this syndrome. We describe a patient with chronic lymphocytic leukemia, without evidence of central nervous system involvement, who suffered from SIADH presumably caused by small doses of chlorambucil. Received: May 15, 1998 / Accepted: August 31, 1998     

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.     

Systemic lupus erythematosus and the syndrome of inappropriate secretion of antidiuretic hormone

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been reported rarely in systemic lupus erythematosus (SLE) with central nervous system disease. Previous case reports linking SIADH with lupus have either not documented clearly that SLE was the sole cause of the problem, or have not demonstrated a correlation between indicators of lupus activity and the onset and resolution of antidiuretic hormone secretion. We describe a case in which SLE was the sole contributor to the initiation of SIADH and where other evidence of lupus activity correlated temporally with inappropriate antidiuretic hormone secretion.     

The syndrome of inappropriate secretion of antidiuretic hormone associated with SCT: clinical differences following SCT using cord blood and BM/peripheral blood

Previously, we reported the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) as an underestimated complication associated with SCT. In the present report, we analyzed detailed data on a larger number of patients with SIADH following SCT and found different SIADH clinical features following cord blood SCT (CBSCT) and BMT/PBSCT. The median onset of SIADH following CBSCT and BMT/PBSCT was 19 and 46 days after SCT, respectively, and the median numbers of WBC at the onset of SIADH were 1.0 and 3.1 x 10(9)/l, respectively. Furthermore, severe symptoms such as seizures, somnolence and rigidity of limbs were observed only in patients with CBSCT (8/15 vs 0/10). These differences were statistically significant (P<0.01). Although the precise basis for SIADH following SCT still remains unknown, the different features of SIADH observed following CBSCT and BMT/PBSCT may provide important clues to the disease mechanism following SCT. Additionally, we confirmed our previous results that patients with SIADH showed a higher overall survival and event-free survival rates. However, we first suggested that they had some neurological disorders and that neurological sequelae such as developmental delay and seizures would consequently occur.     

Usefulness of FDG-PET in detecting an ADH-secreting tumor: a case report

We report a case of a 41-year-old woman who was diagnosed as having the syndrome of inappropriate secretion of ADH (SIADH). There was no evidence of any disorders of the central nervous system, lung diseases, or drugs causing SIADH. Positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) was performed and indicated a tumor of the uterine cervix. After resection of the tumor, both serum sodium level and serum osmolarity were normalized concomitantly with a decrease in serum ADH level. This is the first case report suggesting the usefulness of a FDG-PET scan to detect an occult cancer responsible for SIADH. It seems plausible that FDG-PET may be helpful in the diagnosis of other ectopic hormone-producing tumors such as ectopic ACTH-producing tumors that cause Cushing's syndrome.