A 61-year-old woman presented with a right mandibular tumor and was diagnosed with DLBCL clinical stage IIIA from the biopsy results of the tumor and CT examination. An initial rituximab was administrated a week after the first CHOP treatment. During the infusion of rituximab, she exhibited disorientation, seizure, and consciousness disturbance. Hyponatremia due to SIADH and hypertension were coincidentally observed. MRI revealed T2 and FLAIR hyperintense signals involving the bilateral occipital, parietal, frontal lobes and the cerebellum that were consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Her consciousness level recovered in parallel with corrections in serum sodium levels and blood pressure. Although she presented with transient cortical blindness, all neurological abnormalities disappeared 40 hours after the occurrence of seizure. She received a further 7 cycles of CHOP followed by 7 cycles of rituximab treatment with no relapse of RPLS. After irradiation for a residual abdominal tumor, she has maintained complete remission for 2 years. Although RPLS is a rare complication of rituximab-CHOP chemotherapy, it should be considered in patients with DLBCL who present with acute neurological deterioration.

A 69-year-old woman complained of diplopia and truncal titubation after upper respiratory infection. She presented with mydriasis and external opthalmoplegia of bilateral eyes, ataxia, hyporeflexia and cervical-brachial muscle weakness. The protein abnormally increased (49 mg/dl) in the cerebrospinal fluid, and the serum anti-GQ1b and anti-GT1a IgG antibodies were positive. The blood sodium level was 128 mmol/l indicating hyponatremia. She had low plasma osmolarity (251 mOsm/kg), high urine osmolarity (357 mOsm/kg) and high urine sodium level (129 mmol/l), while the blood level of antidiuretic hormone was not able to be measured. She was diagnosed to have Fisher syndrome (FS), pharyngeal-cervical-brachial variant of Guillain-Barré syndrome (PCB) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The hyponatremia improved with hyperosmotic saline infusion and restriction of water intake. Intravenous immunoglobulin therapy (IVIg) was effective only for ataxia, but the other symptoms mostly remained unchanged for a month. The serum anti-GQ1b IgG antibody was still positive even after one month. We performed high-dose intravenous steroid-pulse therapy. Then the mydriasis, external opthalmoplegia and cervical-brachial muscle weakness were immediately improved. This was a rare case of FS and PCB complicated with SIADH. IVIg, not steroid therapy, is generally chosen for FS since FS is considered as a variant of Guillain-Barré syndrome and steroid is not effective for Guillain-Barré syndrome as was proven by double-blind study. We suppose that the combined therapy of IVIg and steroid would be effective in patients with complicated symptoms and multiple antibodies.

Although various formulas predicting plasma sodium level ([Na]) are proposed for correction of hyponatremia, it seems that an anticipated [Na] frequently exceeds or falls below the measured [Na], especially in syndrome of inappropriate antidiuretic hormone secretion (SIADH). The causative factors of the fluctuation have never been investigated clearly. The aim of this study was to identify the determining factors for accurate prediction of [Na] by comparing data from previously proposed formulas and a novel osmotic compartment model (O-C model). The O-C model, which simulates the amounts of osmoles in extracellular and intracellular fluids, can estimate resultant osmotic water shift (OWS) and [Na]. The accuracy of representative formulas was verified in a point-to-point study using blood and urine samples obtained every 4 hours from 9 patients. Among 161 measurement points, a large fluctuation of urine volume and urine sodium level was observed. The gap between anticipated and measured [Na] in the widely used Adrogue-Madias formula was -0.5 ± 0.1 mEq/L/4 h (mean ± standard error), showing a marked tendency to underestimate [Na]. The gap in the O-C model including OWS was 0.1 ± 0.1 mEq/L/4 h, and that in the O-C model eliminating OWS was 1.9 ± 0.2 mEq/L/4 h, indicating that measurement of urine output and estimation of resulting OWS are essential for a superior prediction of [Na] in SIADH. A simulation study with the O-C model including OWS unveiled a distinctive correction pattern of [Na] dependent on the urine volume and urine sodium level, providing a useful choice for the proper type and rate of infusion.

Electrolyte disorders are common and potentially fatal laboratory findings in emergency patients. Approximately 20 % of patients in the emergency department present with either hyponatremia or hypernatremia. Recently it was shown that disorders of serum sodium are not only an expression of the severity of the underlying disease but independent predictors for the outcome of patients. They directly influence patient daily life by causing not only gait and concentration disturbances but also an increased tendency to fall together with a reduced bone mass. Given these new data it is even more important to detect and adequately correct dysnatremia in patients in the emergency department. Acute, symptomatic dysnatremia should be corrected promptly by use of 3 % NaCl for hyponatremia and 5 % glucose for hypernatremia. A close monitoring of serum sodium concentration is, however, essential in any case of correction of hyponatremia or hypernatremia in order to avoid rapid overcorrection and subsequent complications. A profound knowledge of the mechanisms underlying the development of hyponatremia, e.g. diuretics, syndrome of inappropriate antidiuretic hormone secretion (SIADH), heart failure and cirrhosis of the liver and hypernatremia, e.g. dehydration, infusions, diuretics and osmotic diuresis is essential. The present article describes the epidemiology, etiology and correction of hyponatremia and hypernatremia on the basis of current knowledge with special emphasis on emergency department patients.

Neuroendocrine carcinomas of the colon and rectum comprise fewer than 1% of all colorectal cancers. These aggressive tumors generally have a poor prognosis compared to that associated with colorectal adenocarcinoma. We describe herein the case of a 68-year-old female presenting with a bleeding rectal mass involving the anal canal, which case was associated with hyponatremia due to inappropriate serum levels of antidiuretic hormone. The histopathological examination was consistent with a small-cell neuroendocrine tumor. She was treated with combination chemotherapy and radiation therapy. The Syndrome of Inappropriate Antidiuretic Hormone (SIADH) was managed with vasopressin antagonists. After the completion of therapy, endoscopic ultrasound revealed evidence of residual disease, for which she underwent an abdominoperineal resection (APR). The patient died 4 months later of disease progression. To our knowledge, this is the first report of a small-cell neuroendocrine tumor involving the rectum and anal canal that presented with the paraneoplastic syndrome, SIADH.

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a common and multifactorial cause of hyponatremia that is often overlooked. The common pathophysiological mechanism is the increased production and/or action of antidiuretic hormone within the kidney, resulting in hypotonic hyponatremia. Inadequate correction of hyponatremia may have fatal neurological consequences leading to central pontine myelinolysis. We report the case of a patient with a history of recent head trauma, who came to our observation for acute-onset mental confusion secondary to severe hyponatremia due to SIADH of combined etiology.

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is the most common form of hyponatremia in hospitalized patients. The available treatment options for SIADH are limited and not completely effective. A more recent and specific option for treatment of hyponatremia secondary to SIADH are the vasopressin-receptor antagonists. Conivaptan, an intravenous vasopressin-receptor antagonist, is Food and Drug Administration approved for the treatment of euvolemic and hypervolemic hyponatremia in adults; however, data regarding its use in pediatric patients are extremely limited. Conivaptan played an integral role in the treatment of hyponatremia in this situation when conventional treatment modalities were ineffective. This patient did not experience any adverse effects, and his sodium level corrected slowly over a 24-hour period, avoiding complications of rapid sodium correction.

Context:

Apelin and vasopressin levels are regulated in opposite directions to maintain body fluid homeostasis.

Objective:

We thus assessed plasma apelin to copeptin ratios, with plasma copeptin concentrations as a reliable index of vasopressin secretion, in pathological states combining high levels of vasopressin secretion with hyponatremia. Design, Participants, and

Setting:

We carried out a cross-sectional study including 113 healthy subjects, 21 hyponatremic patients with the syndrome of inappropriate antidiuretic hormone (SIADH), and 16 normonatremic and 16 hyponatremic patients with chronic heart failure (CHF) in an academic hospital. Outcome Measures: Individual apelin to copeptin ratios were plotted against natremia and compared with those of 10 healthy subjects of a previous study acutely challenged by water loading or hypertonic saline infusion. We calculated the percentage of SIADH/CHF patients whose apelin to copeptin ratio for a given natremia lies outside the 95% prediction limits of the physiological relationship.

Results:

In healthy subjects, median (interquartile range) plasma apelin and copeptin concentrations were 254 fmol/mL (225-311) and 4.0 fmol/mL (2.6-6.9), respectively. Sex- and age-adjusted plasma apelin concentrations were 26% higher in SIADH and normonatremic and hyponatremic CHF patients than in healthy subjects. Sex- and age-adjusted plasma copeptin concentration was 75%, 187%, and 207% higher in SIADH and normonatremic and hyponatremic CHF patients, respectively, than in healthy subjects. During an acute osmotic challenge, the plasma apelin to copeptin ratio decreased exponentially with natremia. Apelin to copeptin ratios as a function of natremia were outside the 95% predicted physiological limits for 86% of SIADH patients and 81% of hyponatremic CHF patients.

Conclusion:

Inappropriate apelin concentrations and apelin to copeptin ratios as a function of natremia in SIADH and CHF patients suggest that the increase in plasma apelin secretion cannot compensate for the higher levels of vasopressin release and may contribute to the corresponding water metabolism defect.

Hyponatremia is the most common electrolyte disorder encountered in clinical practice and represents a clinical, social, and economic burden. Conventional treatments of hyponatremia present some pitfalls, such as suboptimal efficacy, risk of overly rapid correction, and adverse effects. Vasopressin receptor antagonists, known as vaptans, represent a new and interesting class of drugs for the treatment of the euvolemic and hypervolemic forms of hyponatremia.This review is based on a PubMed search with the following terms: "vaptans," "vasopressin receptor antagonists," "tolvaptan," "conivaptan," "vasopressin receptor antagonists and SIADH," "vasopressin receptor antagonists and congestive heart failure," "vasopressin receptor antagonists and cirrhosis," and "vasopressin receptor antagonists and polycystic kidney disease."Overall, the studies reported in this review indicate that vaptans effectively correct hyponatremia in euvolemic and hypervolemic patients. In the latter group, vaptans generally had favorable effects on fluid balance also. To date two vaptans, ie, conivaptan and tolvaptan, have been marketed in the United States for the treatment of euvolemic and hypervolemic hyponatremia, whereas tolvaptan has been marketed in Europe with the limitation of euvolemic hyponatremia. Although these drugs have a good safety profile, caution should be used, and treatment should be initiated in a hospital setting in order to closely monitor patients and avoid overly rapid correction or overcorrection.Vaptans can be considered a new effective tool for the treatment of euvolemic and hypervolemic hyponatremia. Nevertheless, more comparative research of vaptans vs other therapies on clinical grounds is needed to more accurately assess the value of these drugs in the treatment of hyponatremia.

Hyponatraemia is a very common electrolyte abnormality with varied presenting features depending on the underlying cause. The authors report the case of a 75-year-old, previously fit, gentleman who presented with weight loss, lethargy and blackouts. He required four admissions to the hospital over an 8-month period. Investigations revealed persistent hyponatraemia consistent with a diagnosis of syndrome of inappropriate antidiuretic hormone secretion, macrocytic anaemia and partial hypopituitarism. Unfortunately, all other investigations that were performed failed to identify the underlying cause and a diagnosis of intravascular large B-cell lymphoma was only confirmed following postmortem studies. The authors recommend that endocrinologists should be involved at the outset in the management of patients with persistent hyponatraemia and that intravascular large B-cell lymphoma should be considered in the differential diagnosis of hyponatraemia.