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We present a case of severe hyponatraemia due to syndrome of inappropriate antidiuretic hormone (SIADH) in a patient with respiratory syncytial virus (RSV) infection. A retrospective analysis of all patients admitted to our hospital with RSV in the preceding 3-year period revealed hyponatraemia in 41 (28%) cases, of which 13 (8.9%) were moderate or severe. SIADH was explored and confirmed in five (3.4%) patients, raising this as an important, previously unrecognised, complication of RSV infection in adults. Physician awareness of SIADH as a potential complication of RSV will facilitate early diagnosis and treatment of this potentially fatal disorder.

The precise mechanism of hyponatremia in Kawasaki disease (KD) remains elusive because assessment of volume status based on serial changes in body weight is lacking in previous reports.Seventeen patients who were diagnosed with KD and hyponatremia (serum sodium levels135 mmol/L) were analyzed. Volume status was assessed based on serial changes in body weight. Plasma arginine vasopressin (ADH), urine electrolytes, and serum cytokine levels were measured on diagnosis of hyponatremia. An increase in body weight by3% was defined as hypervolemia and a decrease in body weight by3% was defined as hypovolemia.The volume status was hypervolemic in three patients (18%), euvolemic in 14 (82%), and hypovolemic in none (0%). Five (29%) patients were diagnosed with "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH) and no patients were diagnosed with hypotonic dehydration. The contribution of decreased total exchangeable cations (salt loss) to hyponatremia (5.9% [interquartile range, 4.3%, 6.7%]) was significantly larger than that of increased total body water (-0.7% [-1.8%, 3.1%]) (P = 0.004). Serum interleukin-6 levels were elevated in all of the nine patients who were evaluated. Among the 12 (71%) patients who did not meet the criteria of SIADH and hypotonic dehydration, plasma ADH levels were inappropriately high in ten patients. These patients were also characterized by euvolemic or hypervolemic hyponatremia and salt loss, which might be compatible with a diagnosis of SIADH.Our study shows that hyponatremia in KD is euvolemic or hypervolemic and is associated with nonosmotic secretion of ADH and salt loss in the majority of patients.

Background Gastric cancer ranks as a leading cause of cancer deaths worldwide. Information of prognostic factors related to gastric cancer are limited. Aim This study aimed to gather clinical data and prevalence of prognostic factors related to gastric adenocarcinoma in Thailand. Methods and results This retrospective cohort study was conducted at Thammasat University Hospital, Thailand between January 2010 and July 2018. Gastric adenocarcinoma patients were enrolled and followed up for at least 5 years. Total of 210 gastric tumor patients were enrolled. One hundred patients were diagnosed with gastric adenocarcinomas (57 men and 43 women, mean age = 61.1 years). The leading presenting symptoms were weight loss (65%), followed by dyspepsia (54%) and UGI bleeding. Common clinical manifestations were thrombocytosis (26%), followed by syndrome of inappropriate antidiuretic hormone (SIADH; 15%). Eosinophilia was present in early cancer (25.0% vs 6.5%, P = .123), while SIADH and thrombocytosis were more common in advanced stages (16.3% vs 0%, P = .602, and 28.3% vs 0%, P = .108, respectively). SIADH was significantly related to reduced 1‐year survival rate compared to normal serum sodium levels (21.4% vs 71.4%, OR 0.109, 95% CI 0.024‐0.497, P = .004). Five‐year survival rates were worse in patients with SIADH, but better in patients with eosinophilia compared to patients without these conditions (0% vs 27.8%, P = .058 and 20.0% vs 7.8%, P = .375, respectively). Conclusion Thrombocytosis and SIADH were common in gastric cancer. SIADH was significantly correlated with poor 1‐year survival. These clinical manifestations might be useful for predicting gastric cancer prognosis.

Hyponatremia is a common electrolyte disorder in cancer patients and has been associated with poor prognosis. A frequent cause of cancer‐related hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH). This study was a post hoc subgroup analysis of the SALT‐1 (Study of Ascending Levels of Tolvaptan in Hyponatremia) and SALT‐2 clinical trials. Hyponatremic subjects with SIADH and cancer received the oral selective vasopressin V2‐receptor antagonist tolvaptan (n = 12) or matching placebo (n = 16) once‐daily for 30 days. The initial tolvaptan dose (15 mg) was titrated over 4 days to 30 or 60 mg per day, as needed, according to serum sodium level and tolerability. Baseline serum sodium levels in the SIADH/cancer cohort of the SALT trials was 130 and 128 mEq/L for tolvaptan and placebo, respectively. Mean change from baseline in average daily serum sodium AUC for tolvaptan relative to placebo was 5.0 versus −0.3 mEq/L (P

SummaryObjective The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia. Data on SIAD are mainly derived from retrospective studies, often with poor ascertainment of the minimum criteria for the correct diagnosis. Reliable data on the incidence of adrenal failure in SIAD are therefore unavailable. The aim of the study was to describe the aetiology of SIAD and in particular to define the prevalence of undiagnosed adrenal insufficiency. Design Prospective, single centre, noninterventional, observational study of patients admitted to Beaumont Hospital with euvolaemic hyponatraemia (plasma sodium ≤ 130 mmol/l) between January 1st and October 1st 2015. Patients A total of 1323 admissions with hyponatraemia were prospectively evaluated; 576 had euvolaemic hyponatraemia, with 573 (43·4%) initially classified as SIAD. Main outcome measures (i) Aetiology of SIAD, defined by diagnostic criteria; (ii) Incidence of adrenal insufficiency. Results Central nervous system diseases were the commonest cause of SIAD (n = 148, 26%) followed by pulmonary diseases (n = 111, 19%), malignancy (n = 105, 18%) and drugs (n = 47, 8%). A total of 22 patients (3·8%), initially diagnosed as SIAD, were reclassified as secondary adrenal insufficiency on the basis of cortisol measurements and clinical presentation; 9/22 cases had undiagnosed hypopituitarism; 13/22 patients had secondary adrenal insufficiency due to exogenous steroid administration. Conclusions In a large, prospective and well-defined cohort of euvolaemic hyponatraemia, undiagnosed secondary adrenal insufficiency co-occurred in 3·8% of cases initially diagnosed as SIAD. Undiagnosed pituitary disease was responsible for 1·5% of cases presenting as euvolaemic hyponatraemia.

AIM: Using fluid restriction to treat syndrome of inappropriate antidiuretic hormone secretion (SIADH) in infants is potentially hazardous, as fluid and caloric intake are connected. Antagonists for the type 2 vasopressin receptor have demonstrated efficacy in adult patients with SIADH, but evidence in children is lacking. We reviewed our experience from two cases in the UK. METHODS: This was a retrospective review of the clinical data on two patients diagnosed with SIADH in infancy and treated with tolvaptan, an oral vasopressin receptor antagonist. RESULTS: Persistent hyponatraemia was noted in both patients in the first month of life and eventually led to SIADH diagnoses. Initial salt supplementation in one patient resulted in severe hypertension, treated with four anti-hypertensive drugs. Tolvaptan was commenced at two and four months of age, respectively, and was associated with normalisation of plasma sodium values and blood pressure without the need for anti-hypertensive treatment. There was transient hypernatraemia in one patient, which was normalised with a dose reduction. Tolvaptan was administered by crushing the tablet and mixing it with water. CONCLUSION: Tolvaptan provided effective treatment for SIADH in both infants and could be administered orally.

The syndrome of inappropriate antidiuretic hormone (SIADH) consists of a number of key features, namely hyponatraemia, inappropriate urinary concentration and clinical euvolaemia or hypervolaemia. It is caused by inappropriate secretion of the antidiuretic hormone (ADH), which activates the vasopressin type 2 receptor (AVPR2) in the principal cells of the collecting duct of the kidney and leads to increased reabsorption of water through aquaporin 2 channels. Common causes of SIADH in children include trauma, asphyxia, pain, stress, certain drugs and recent neurosurgery (1).

To study the effect of tolvaptan on non-acute, non-hypovolemic hyponatremia in inappropriate secretion of antidiuretic hormone (SIADH) syndrome in Chinese patients. Hyponatremic SIADH patients received placebo (N = 18) or tolvaptan (N = 19) at an initial dose of 15 mg/day with further titration to 30 mg/day and 60 mg/day based on serum sodium concentrations. Randomized, double-blind, placebo-controlled trial. Primary endpoint was the change of the serum sodium from baseline to days 4 and 7. Analysis of covariance (ANCOVA) was used for statistical analysis. At day 4, average daily changes in serum sodium levels from baseline was 1.9 ± 2.9 mmol/L (1.9 ± 2.9 mEq/L) in the placebo group and 8.1 ± 3.6 mmol/L (8.1 ± 3.6 mEq/L) in the tolvaptan group; at day 7, the values were 2.5 ± 3.9 mmol/L (2.5 ± 3.9 mEq/L) and 8.6 ± 3.9 mmol/L (8.6 ± 3.9 mmEq/L) for the placebo and tolvaptan groups (ANCOVA, P

Context Nephrogenic syndrome of inappropriate antidiuresis (NSIAD), resulting from activating mutations in the arginine vasopressin receptor type 2 (AVPR2), is a rare cause of hyponatraemia. However, its true prevalence may be underestimated and it should be considered in the investigation of unexplained hyponatraemia, with implications for management and targeted gene testing. Objective We describe a structured approach to the investigation of hyponatraemia in a young patient, which allowed a diagnosis of NSIAD to be made. We review current knowledge of NSIAD and use a structural modelling approach to further our understanding of the potential mechanisms by which the causative mutation leads to a constitutively active AVPR2. Design Clinical and biochemical investigation of hyponatraemia; a formal water load test with measurement of arginine vasopressin levels (AVP); sequencing of AVPR2; and computed structural modelling of the wild-type and constitutively activated mutant receptors. Results A 38-year-old man presented with intermittent confusion and nausea associated with hyponatraemia and a biochemical picture consistent with syndrome of inappropriate antidiuretic hormone (SIADH). Adrenocortical and thyroid function and an acute intermittent porphyria screen were normal. Cross-sectional imaging of the head, chest and abdomen did not identify an underlying cause and so we proceeded to a water load test. This demonstrated a marked inability to excrete a free water load (just 15% of a 20 ml/kg oral load by 240 min postingestion), with the onset of hyponatraemia (Na(+) 125 mmol/l, urine osmolality 808 mOsm/kg). However, AVP levels were low throughout the test (0·4-0·9 pmol/l), consistent with a diagnosis of NSIAD. AVPR2 sequencing revealed a previously described hemizygous activating mutation (p.Arg137Cys). Through structural modelling of AVPR2, we suggest that disruption of a hydrogen bond between residues Thr269 and Arg137 may promote stabilization of the receptor in its active conformation. Since diagnosis, the patient has adhered to modest fluid restriction and remained well, with no further episodes of hyponatraemia. Conclusion NSIAD should be considered in young patients with unexplained hyponatraemia. A water load test with AVP measurement is a potentially informative investigation, while AVPR2 sequencing provides a definitive molecular genetic diagnosis and a rationale for long-term fluid restriction.

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.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been reported as a paraneoplastic syndrome in many different types of malignancies. Several case reports of SIADH have been reported in patients with olfactory neuroblastoma (ONB), but the exact incidence is unknown. The purpose of this study was to review our experience with olfactory neuroblastoma and to identify all patients who had a history of SIADH prior to the diagnosis of ONB.Case series and chart review.Tertiary care university-affiliated medical center.A total of 21 patients presented to our institution with ONB between 1997 and 2009. All records were reviewed for a history of preoperative hyponatremia or SIADH.Three patients were identified who had a history of SIADH prior to the diagnosis of ONB. Immunohistochemical staining of the tumor specimens from the 3 patients with SIADH was positive for arginine vasopressin. SIADH resolved in all 3 patients after successful treatment of ONB.Although uncommon, SIADH can be the presenting symptom of ONB and should be considered during the workup for idiopathic SIADH.

Four patients are presented, all having pathologic responses in plasma vasopressin concentration to changes in plasma osmolality. Clinically, three of them had the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The fourth had diabetes insipidus associated with an increased threshold for plasma osmolality. Two of the patients with SIADH had lowered thresholds for ADH secretion and one of these also had increased sensitivity to increments in osmolality. The latter patient, like another earlier reported similar case, had a defective blood-cerebrospinal fluid barrier. The third SIADH patient had no response at all to changes in osmolality from 230 to 305 mOsm/kg and had a small cell carcinoma of the lung. These examples illustrate that both the setting and the sensitivity of osmoreceptors and AVP-secreting neurons probably are under complex control from the CNS, and that CNS diseases can affect one or several of these pathways thereby affecting the setting of the osmoreceptor-vasopressin system.

SUMMARY Surgery for craniopharyngioma is often followed by swinging changes in serum sodium. Four children were managed postoperatively with strictly controlled fluid input, matched to output hour by hour, in an attempt to keep total body water constant and to avoid hypernatraemia secondary to dehydration and dilutional hyponatraemia. Three of the children had an episode of hyponatraemia, two, five and seven days after the last dose of pitressin, occurring six to eight days postoperatively and preceded by a sudden increase in urinary sodium excretion. These episodes clinically resembled the syndrome of inappropriate antidiuretic hormone secretion. RESUME Craniopharyngiome de l'enfance: nature et traitement des perturbations precoces postoperatoires des liquides et des electrolytes La chirurgie des craniopharyngiomes est souvent suivie de variations en dents de scie du sodium serique. Quatre enfants ont ete traites post-operatoirement par un controle stricte de l'apport liquidien, adapte aux pertes heure par heure, dans le but de maintenir constante l'eau corporelle totale et d'eviter une hypernatremie secondaire a la deshydratation ou encore une hyponatremie de dilution. Trois des enfants presenterent un episode d'hyponatremie, deux, cinq et sept jours apres la derniere dose de vasopressine survenant six a huit jours apres l'operation et precede d'une augmentation brutale de l'excretion sodee urinaire. Ces episodes mimaient cliniquement le syndrome d'une secretion inappropriee de l'hormone antidiuretique. ZUSAMMENFASSUNG Craniopharyngiom im Kindesalter: Ursache und Behandlung der fruhen postoperativen Wasser- und Elektrolytstorungen Nach Craniopharyngiomoperationen kommt es haufig zu Storungen der Natriumspiegel im Serum. Bei vier Kindern wurde postoperativ die Flussigkeitszufuhr streng nach der stundlich gemessenen Ausfuhr bilanziert in der Vorstellung, das Gesamtflussigkeitsvolumen des Korpers konstant zu halten und sowohl eine Hypernatriaemie infolge einer Dehydratation als auch eine Hyponatriaemie durch Uberwasserung zu vermeiden. Drei der Kinder hatten eine kurzfristige Hyponatriaemie 2, 5 und 7 Tage nach der letzten Pitressingabe, die sechs bis acht Tage nach der Operation auftrat und der ein plotzlicher Anstieg der Natriumausscheidung im Urin vorausging. Diese Phasen waren klinisch vergleichbar mit dem Schwartz-Bartter-Syndrom. RESUMEN Craniofaringioma en la infancia: naturaleza y tratamiento de las alteraciones precoces postoperatorias de liquidos y electrolitos La cirugia del craniofaringioma se sigue a menudo de cambios alternativos en el sodio serico. Cuatro ninos fueron tratados postoperatoriamente con un ingreso de liquidos estrictamente controlados, de acuerdo con la enumeracion de cada hora, en un intento de mantener constante la cantidad total de agua corporal y evitar la hipernatremia secundaria a la deshidratacion y la hipoanatremia dilucional. Tres de los ninos tenian un episodio de hiponatremia, a los 2, 5 y 7 dias despues de la ultima dosis de pitresina, ocurriendo seis o siete dias despues de la operacion y siendo precedidos por un aumento subito en la excrecion urinaria de sodio. Estos episodios se asemejan clinicamente al sindrome de secrecion inapropiada de hormona antidiuretica.

A 61-year-old man had hyponatremia (serum Na 112 mmol/L), which was associated with disturbance of consciousness. Therefore, administration of hypertonic saline was commenced. Eventually he was diagnosed with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Hypertonic saline was continued for 45 days, and plasma Na concentration rose to 138 mmol/L. At that time we were consulted regarding further administration of hypertonic saline. At the time of the consultation marked edema had developed affecting the whole body. The cardiothoracic ratio was increased and pleural effusion was evident on the chest X-ray. Administration of hypertonic saline was discontinued to prevent further worsening of the edema. Furthermore, water restriction (500 mL/day) was started. Body weight decreased by 4.3 kg in 7 days and the edema was diminished. However, plasma Na concentration decreased to 117 mmol/L. At that stage, we needed to balance the treatment of hyponatremia to the increased extracellular fluid volume (ECF). To normalize the ECF, we carried out ultrafiltration (UF) three times. Resolution of edema by using an extracorporeal UF method allowed the control of plasma Na concentration. In this case increased ECF volume hindered the adjustment of plasma Na concentration. The infusion of hypertonic saline is now used commonly by physicians. It is necessary to consider the potential risks of such treatment.

Background: Hyponatraemia is associated with substantial morbidity and mortality. Identification of the risk factors associated with the development of symptomatic hyponatraemia is important in determining preventive strategies. Methods: A retrospective analysis of the risks factors associated with the development of severe, symptomatic hyponatraemia requiring hospital admission over the past 3 years at our institution was carried out. Results: Forty-seven patients (26 women, 21 men) with a hospital admission serum sodium

An autopsy case of primary small cell carcinoma (SCC) of the prostate in a 68-year-old man is reported. The patient was admitted to hospital because of a bloody stool and suspected rectal cancer. However, a diagnosis of prostate cancer was made on the basis of a digital rectal examination, the serum level of prostate-specific antigen, and a needle biopsy of the prostate. The patient also experienced a syndrome of inappropriate secretion of antidiuretic hormone. He died 29 days after admission. At autopsy, the tumor had invaded the rectum, bladder and pelvic peritoneum. Metastases to the heart, vertebrae and lymph nodes were observed. Microscopically, the tumor was composed of small round cells that showed a solid growth pattern. Rosette formations were observed. Immunohistochemically, the tumor cells were positive for a prostatic epithelial marker and neuroendocrine markers. A high level of antidiuretic hormone was detected in the tumor tissue. To our knowledge, this is the first reported case of SCC of the prostate in which both a prostatic epithelial marker and neuroendocrine markers have been found in the same tumor. This finding supports the hypothesis that SCC of the prostate originates from a multipotential stem cell of the prostatic epithelium.

Rifabutin is increasingly critical for treatment of atypical mycobacterial infections. One of its serious adverse effects is leukopenia. When encountering rifabutin-induced leukopenia, clinicians are faced with the dilemma of whether to lower the dosage of rifabutin or discontinue it because existing literature does not indicate whether rifabutin-induced leukopenia is dose related or idiosyncratic. We report the first established case of idiosyncratic rifabutin-induced leukopenia in an immunocompetent man treated for pulmonary Mycobacterium avium complex infection. The patient also developed rifabutin-induced syndrome of inappropriate antidiuretic hormone (SIADH), which also has not been previously reported.

Objective The syndrome of inappropriate secretion of antidiuretic hormone is a rare disorder in dogs characterised by hypo-osmolality and persistent arginine vasopressin production in the absence of hypovolaemia and/or hypotension. The study describes the efficacy and safety of the nonpeptide selective arginine vasopressin V-2 receptor antagonist OPC-31260 in a dog with the naturally occurring syndrome. Design The detailed case history of a dog with spontaneous syndrome of inappropriate secretion of antidiuretic hormone that received long-term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC-31260 and of a dose administered after a continuous dosing period of 12 days are reported. Procedure Packed cell volume, plasma sodium, total protein, arginine vasopressin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasma osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. Results Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma sodium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevated throughout the study. Results were similar when the trial procedure was repeated after a stabilisation period of 12 days. Long-term therapy with OPC-31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-year follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. Conclusions Treatment of a dog with naturally occurring syndrome of inappropriate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body weight orally every 12 h resulted in marked aquaresis and significant palliation of clinical signs with no discernible side-effects detected over a 3-year period. Thus, OPC-31260 appears to offer a feasible medical alternative to water restriction for treatment of dogs with syndrome of inappropriate secretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome.

A 72-year-old woman with the syndrome of inappropriate secretion of antidiuretic hormone of unknown cause during more than one year of observation is reported. Plasma vasopressin levels were excessively elevated, even during a water load test. Her serum electrolyte abnormalities and general state were ameliorated after fluid restriction. During treatment with demeclocycline the patient was able to increase fluid intake without deterioration.

Hypouricaemia has been observed in patients with the syndrome of inappropriate secretion of antidiuretic hormone (IADH). Accordingly, 69 patients with untreated bronchogenic small cell carcinoma were examined for IADH. Serum urate was also measured. IADH was proven in 25 (35%) of the 69 patients. The median serum concentration of urate in these patients was 0.26 mmol/l (range 0.13-0.50), compared to 0.36 mmol/l (0.21-0.60) in the 44 patients without IADH. The difference is statistically significant (p less than 0.01), but serum urate--when used alone--is lacking in both sensitivity and specificity for the diagnosis of IADH.

Objective. The study determines the incidence of SSRI-induced hyponatraemia due to SIADH in an elderly psychiatric inpatient population. Design. A retrospective case-note study. Setting. An acute old age psychiatry ward. Sample. Patients admitted from January 1 to December 31, 1996. Measures. Demographics, medication, psychiatric diagnoses, plasma sodium level and physical comorbidity were collected. Patients on SSRIs were selected and those developing hyponatraemia due to SIADH were identified. Results. Of 32 patients taking SSRIs, four developed symptomatic hyponatraemia due to SIADH (12.5%). A further four developed asymptomatic hyponatraemia following introduction of an SSRI (12.5%), although laboratory confirmation of SIADH was lacking. Conclusions. The incidence of SSRI-induced hyponatraemia due to SIADH has not previously been established. This study shows a high incidence in elderly patients of this potentially dangerous complication. Clinical practice in the prescription of SSRIs to elderly people must change to include monitoring of electrolytes for early detection and reduction of morbidity. © 1998 John Wiley & Sons, Ltd.

OBJECTIVE: To determine the prevalence of hyponatremia in a nursing home population and to identify clinical factors that increase the risk for development of hyponatremia. DESIGN: Retrospective and prospective record review. SETTING: A Veterans Affairs nursing home care unit. PATIENTS: One hundred nineteen residents, who ranged in age from 60 to 103 years. Sixty ambulatory patients, 62 to 91 years of age, who attended a geriatric medicine outpatient clinic served as a reference population. MEASUREMENTS: Most recent serum sodium, creatinine, BUN, and all serum sodium determinations during the preceding 12 months; clinical diagnoses, diet, medications, and significant events at the time of recorded hyponatremic episodes; response to acute water loading in a subset of patients; number of deaths in the 12 months following entry into the study. RESULTS: In the 119 nursing home patients, ages 60 years or older, the most recent serum sodium identified 18% who were hyponatremic, compared with a prevalence of 8% in similarly aged ambulatory patients. When all serum sodium determinations for the previous 12 months were examined, 53% of the nursing home patients had at least one episode of hyponatremia during this time period. There was a high incidence of central nervous system (CNS) and spinal cord disease in the total nursing home population. Episodes of hyponatremia were frequently associated with an increased intake of fluids, given either orally or intravenously, and with tube feeding. Water load testing revealed abnormal water handling consistent with the syndrome of inappropriate antidiuretic hormone (ADH) secretion in 18 of 23 patients who had a history of hyponatremia. Seventeen percent of the patients with hyponatremia died over the following 12 months, compared to a death rate of 21% in the normonatremic patients. CONCLUSIONS: Hyponatremia is a common occurrence in nursing home residents and may be a consequence of abnormal ADH secretion resulting from CNS disease. Exposure to increased fluid intake, or to a low sodium tube-feeding diet, can lead to the onset of hyponatremia or to a worsening of an already present low-serum sodium concentration.

The first clinical case of a patient with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was presented by Schwartz et al. in 1957 (Am J Med 1957; 23: 529-42), describing two patients with lung cancer who developed hyponatraemia associated with continued urinary sodium loss. They postulated that the tumours led to the inappropriate release of antidiuretic hormone (ADH), later discovered to consist of arginine-vasopressin (AVP). This suggestion was later confirmed in several studies. The clinical description of the syndrome has changed little since the original observation, and the cardinal findings of SIADH are as follows: (i) hyponatraemia with corresponding hypo-osmolality of the serum and extracellular fluid, (ii) continued renal excretion of sodium. (iii) absence of clinical evidence of fluid volume depletion, (iv) osmolality of the urine greater than that appropriate for the concomitant osmolality of the plasma, i.e. urine less than maximal diluted, and (v) normal function of kidneys, suprarenal glands and thyroid glands. Measurement of AVP in plasma is not a part of the definition of SIADH. SIADH may be caused by a variety of malignant tumours, but may also be caused by various other conditions, such as disorders involving the central nervous system, intrathoratic disorders such as infections, positive pressure ventilation and conditions with decrease in left atrial pressure. Also, a large number of pharmaceutical agents have been shown to produce SIADH, including a number of cytotoxic drugs such as vincristine, vinblastine, cisplatin, cyclophosphamide, and melphalan. A broad spectrum of malignant tumours has been reported to cause SIADH; however, most of these observations have been in case reports including very few patients. This includes a number of primary brain tumours, haematologic malignancies, intrathoracic non-pulmonary cancers, skin tumours, gastrointestinal cancers, gynaecological cancer, breast-and prostatic cancer, and sarcomas. Larger series of patients have revealed that SIADH occurs in 3% of patients with head and neck cancer (47 cases out of 1696 patients), in 0.7% of patients with non-small-cell lung cancer (three cases out of 427 patients), and in 15% of cases of small-cell lung cancer (214 cases out of 1473 patients). The optimal therapy for SIADH is to treat the underlying malignant disease. If this is not possible, or if the disease has become refractory, other treatment methods are available such as water restriction, demeclocycline therapy, or, in severe cases, infusion of hypertonic saline together with furosemide during careful monitoring.

The syndrome of inappropriate antidiuretic hormone (SIADH), the most common cause of euvolemic hyponatremia, is due to nonphysiologic release of arginine vasopressin from the posterior pituitary. Hyponatremia induced by SIADH can be caused by several conditions, such as central nervous system disorders, malignancies, various nonmalignant lung diseases, hypoadrenalism, and hypothyroidism. A 67-year-old man developed hyponatremia consistent with SIADH. Although common comorbid conditions associated with SIADH were excluded as possible causes, his medical history and drug regimen were extensive. However, he had been taking spironolactone, amiodarone, and simvastatin for less than 3 months. Amiodarone was discontinued based on a case report suggesting that this drug can cause SIADH-induced hyponatremia. The patient's serum sodium level began to rise within 3 days of discontinuation and returned to normal within 1 month. Although SIADH-induced hyponatremia occurs only rarely, it should be recognized as a possible adverse effect of amiodarone.

Plasma levels of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) were measured in 15 patients with schizophrenic or schizoaffective disorders and 15 healthy volunteers during oral water loading at 20 ml/kg. In the patient group, plasma AVP was secreted even when plasma osmolality was below 270 mosmol/kg, although the sensitivity of AVP secretion response to osmolality was lower than in the controls. The ANP level was higher in the group of patients than in the controls. There was a negative correlation between plasma ANP and osmolality in the patients. We speculate that the volume expansion caused by inappropriate AVP secretion stimulated plasma ANP release and that the natriuresis resulting from the elevated plasma ANP level might contribute to hyponatremia.

Hyponatraemia (HN) can result from a wide range of mechanisms, and therapy must be individualized. Two theories of the origin of HN in acute brain disease have prevailed. The first is the cerebral salt wasting syndrome (CSWS), where excessive natriuresis caused by some unknown cerebral natriuretic factor lowers the total sodium pool of the body and hence the plasma concentration. The second theory is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), where an increase in total body water is caused by unphysiological secretion of ADH, lowering the concentration of sodium in the plasma. A third possibility is 'sodium shift', i.e. a displacement of sodium from the extracellular to the intracellular space with a simultaneous movement of potassium in the opposite direction. The morbidity and mortality associated with HN only arise in cases where the rate of development of HN was 0.5 mmol h-1 or more. Symptoms respond promptly when the HN is quickly corrected with furosemide and 3% sodium chloride.

A young woman with acute intermittent porphyria (AIP) and juvenile myoclonic epilepsy began to have generalized tonic-clonic seizures (GTCs) at age 13. Subsequently, she had myoclonic seizures, which were often precipitated by visual stimulation, tended to occur in the morning, and sometimes evolved into GTCs. Valproate (VPA) resulted in a worsening of latent AIP, and treatment with a combination of phenytoin (PHT), carbamazepine (CBZ), and clonazepam (CZP) led to severe neuropathy of AIP and an electrolyte imbalance. These conditions were improved by water restriction, infusion of high doses of carbohydrates, and discontinuation of all antiepileptic drugs (AEDs) except for CZP. CZP appeared to be effective both in improving GTCs and myoclonic seizures and did not induce any symptoms of AIP. CZP may be porphyrogenic but can be used safely at a low dose for treatment of epilepsy in patients with AIP.

A 65-year-old man who had muscle weakness and dysarthria was admitted for investigation of motor neuron disease. He had lost 12 kg of weight in 6 months. Neurological findings disclosed upper and lower motor neuron disturbances with normal sensory nerve function, and needle electromyography showed a neurogenic pattern. Laboratory findings on admission demonstrated dilutional hyponatraemia due to an excessive secretion of antidiuretic hormone (ADH). Based on these findings, the patient was diagnosed as having the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with amyotrophic lateral sclerosis (ALS). During the night of first hospital day, the patient complained of severe dyspnoea, and mechanical ventilation was commenced. Following the mechanical ventilation, plasma ADH levels and serum sodium concentration were normalized. We propose that respiratory failure secondary to the atrophy of respiratory muscle might be responsible for the development of SIADH.

We describe a case of amiodarone induced hyponatremia consistent with the syndrome of inappropriate antidiuretic hormone (SIADH) that developed during amiodarone loading, similar to three prior reports. The hyponatremia improved after a lower maintenance dose was initiated. This episode was reported online to the FDA (http://www.fda.gov/medwatch), and future amiodarone labeling will include SIADH as a potential side effect (personal communication, Wyeth Medical Science). Clinicians should be aware of this rare but serious complication, especially in light of the neurological effect of profound hyponatremia. Amiodarone induced SIADH may develop during the loading phase, and may respond to dose reduction without termination of drug.

We report two patients with acute lymphoblastic leukaemia (ALL) who were entered into the current MRC adult ALL trial (UKALL XII) in whom unusually severe vincristine induced neurotoxicity developed. This appeared to be the result of an interaction with itraconazole suspension.

Acute percutaneous salicylate intoxication is a rare event in children but can happen with a skin disease where salicylic acid, used as a keratolytic ointment, can be absorbed transcutaneously. Until now, few cases of transcutaneous salicylate intoxication have been reported in the literature. Our case report is about a 5-year-old girl with lamellar ichthyosis and an acute salicylate transcutaneous intoxication after the application of a skin ointment. The child had a fever, hyperpnoea with respiratory alkalosis, comatose state and oculogyric crisis. We would like to emphasize the danger of applying salicylic acid in children with extensive skin diseases and, therefore, it is advisable to measure the plasma salicylic levels so as to prevent eventual salicylate toxicity.

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a disorder in which a sustained release of antidiuretic hormone occurs because of certain diseases, pharmacological agents, or trauma. Fluid volume expands with a resultant hyponatremia which, depending on the degree, may be asymptomatic or result in death. This case report describes a 38-year-old male in whom SIADH was strongly suspected secondary to Tegretol therapy to control a seizure disorder. Medical consultation is imperative for these patients before administering a fluid challenge during general anesthesia.

A fullterm infant had fetal distress and stained amnion. He underwent an exchange blood transfusion at 12 hours after birth because of hyperbilirubinemia. He developed oliguria combined with high urine osmolality during the first 27 hours of life despite normal creatinine clearance. The diagnosis of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was made on the basis of high urine osmolality, low plasma osmolality and elevated plasma arginine vasopressin (AVP) concentration. We determined the plasma atrial natriuretic peptide (ANP) concentration for the first 4 days of life. After 27 hours after birth, urine volume increased while plasma AVP concentration remained high. On the other hand, plasma ANP concentration gradually increased after 27 hours of life. We speculate that ANP may play an important role in producing the spontaneous diuresis in the newborn infant with SIADH.