Approach to and management of abnormalities in plasma sodium.

The differential diagnosis between hypertonic, isotonic and hypotonic hyponatremia are presented. The help of some usual serum (urea, uric acid and TCO2) and urine parameters (mainly osmolality and sodium concentration) are discussed and help to determine the best treatment. Morbidity associated with untreated hyponatremia and with the different treatment available is also discussed. Who to prevent and treat ODS (osmotic demyelating syndrome) is recalled. The pathophysiology and treatment of hypernatremia are also discussed.

Mild water restriction with or without urea for the longterm treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH): Can urine osmolality help the choice?

BACKGROUND: Treatment options for chronic SIADH include water restriction (WR) and urea. The usefulness of urine osmolality to guide the choice of the treatment option is not clearly defined. We hypothesized that urine osmolality can indicate whether treatment with mild water restriction alone could be successful. METHODS: Retrospective Review of clinical and biochemical (blood and urine) data of patients with chronic SIADH treated for at least one year with mild WR (1.5-2l/day) either with or without urea. RESULTS: Twenty nine patients were included. Nine patients were treated by mild WR. Mean serum sodium (SNa) and mean Uosm were 129±2mEq/l and 274±78mOsm/kgH2O respectively before WR, and increased to 138.5±3mEq/l and 505±87mOsm/kgH2O (P<0.001). Eight patients were treated with mild WR and 15g urea daily, the SNa and Uosm before treatment were 127.5±3mEq/l and 340±100mOsm/kgH2O respectively and increased to 136.5±1mEq/l and 490±151mOsm/kgH2O (P<0.001). Four of the eight patients had a permanent low solute intake which contributed to hyponatremia. Twelve patients needed 30g urea daily combined with mild WR. The SNa and Uosm were respectively 126±2mEq/l and 595±176mOsm/kgH2O and increased to 136.5±2mEq/l and 698±157mOsm/kgH2O (P<0.05). Uosm increased in most of the treated patients. CONCLUSIONS: About 30% of patients could be treated by moderate WR alone. All these patients presented an initial urine osmolality lower than 400mOsm/kgH2O.

Hyperglycemia induces attention and gait deficits in diabetic mellitus patients.

AIMS: Patients with diabetes mellitus experience a large number of falls and bone fractures that are not related solely to complications of the disease. The purpose of our study was to determine whether transient hyperglycemia affects attentional functions and gait. METHODS: This was a case-control study. We asked 17 patients with type 1 or type 2 diabetes mellitus to perform three visual tests and one visual and auditory attention test (Phasic Alert A1-4 and A2-3, Go/No Go, Intermodal Comparison). Mean response time (ms) and total number of errors were assessed. Ten of the patients also performed a tandem gait test consisting of three steps. The total distance travelled (TDT, in mm) by the center of pressure was measured with a pressure-sensitive calibrated platform. Transient hyperglycemia was defined as blood glucose level greater than 13, 8 mmol/L at the time of the test. These same patients were retested 1-3 days later at a blood glucose level at least 5, 5 mmol/L lower than the initial values (T24-72h). Nineteen patients with diabetes mellitus were matched with the original participants and performed the same test under normoglycemic conditions. RESULTS: During transient hyperglycemia, the mean response time (ms) and the TDT were significantly longer. The mean response time for the four tests increased by 53, 5 ms (P < 0.001). There was no increase in the number of errors. The TDT of the center of pressure increased significantly by 102 mm (P < 0.001). CONCLUSIONS: Transient hyperglycemia alters attention and gait in patients with diabetes mellitus.

Long-term treatment of hyponatremic patients with nephrogenic syndrome of inappropriate antidiuresis: personal experience and review of published case reports.

BACKGROUND: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a disorder of water balance linked to gain-of-function mutation of arginine vasopressin receptor type 2 (AVPR2) resulting in free water reabsorption and episodes of hyponatremia. AIMS: To review the long-term treatment of NSIAD. METHODS: In the first part of this paper, we report 3 cases of male patients presenting with hyponatremia due to NSIAD. The second part consists of a comprehensive review of all published case reports. RESULTS: In our experience, long-term fluid restriction (FR) and treatment with low doses of urea are efficient and well tolerated. Episodic intake of urea seems sufficient in some patients. Treatment data were available for 13 of the 16 hyponatremic patients reported in the literature. Each of these 13 patients had regulated fluid intake. Six of the patients received urea with no reported failure to correct hyponatremia and 5 received NaCl supplementation with varying efficacy. The AVPR2 antagonists tolvaptan and satavaptan (prescribed before the diagnosis of NSIAD was made) showed no efficacy in 1 patient. CONCLUSIONS: NSIAD is quite easy to treat with FR and urea in adults as well as in children, with good compliance and efficacy. Of note, FR is well tolerated, suggesting that NSIAD may differ from other causes of syndrome of inappropriate antidiuretic hormone secretion by reduction of thirst intensity due to lower levels of AVP (which stimulates thirst). In eventual refractory cases, furosemide (associated with NaCl supplementation) would represent a valuable therapeutic option by analogy of its efficacy in syndrome of inappropriate antidiuretic hormone secretion.

Inefficacy of intravenous immunoglobulins and infliximab in Degos' disease.

We report the case of a 60-year-old man who presented with sudden visual loss, a history of postprandial abdominal pain, malabsorption, and skin lesions typical of systemic Degos' disease. Despite anti-aggregants and prednisone the patient's status did not improve. On the basis of the hypothetical dysimmune origin of this disease, we attempted treatment with intravenous immunoglobulins, without success. We then administered infliximab (Remicade), but 2 months after the third injection the patient developed mesenteric infarction and died. We therefore believe that both intravenous immunoglobulins and antiTNFalpha are ineffective for the treatment of Degos' disease.

An atypical case of Whipple's disease: case report and review of the literature.

We report the case of a 57-year-old man, presenting with bilateral panuveitis, bilateral sacroiliitis, intermittent pyrexia and a pulmonary nodule. The patient had been under immunosuppressive treatment for 2 years for Behçet's disease. However, he did not fulfill the diagnostic criteria of Behçet's disease. Blood analysis showed a very high C reactive protein (CRP at 34 mg/dl). In view of severe intra-ocular inflammation, the anterior chamber was punctured. Polymerase chain reaction (PCR) on the aqueous humour and on the blood revealed the presence of Tropheryma whippelii DNA, an agent responsible for Whipple's disease. The patient was treated with ceftriaxone followed by trimethoprim-sulfamethoxazol for 1 year with good clinical and biological evolution. This case illustrates the difficulty to diagnose an atypical Whipple's disease. In cases of uveitis with atypical signs and/or not responding to the treatment, the internist must consider to perform an analysis of the ocular fluids.

Mild hyponatremia and risk of fracture in the ambulatory elderly.

BACKGROUND: Mild hyponatremia is the commonest electrolyte imbalance in the older population and has been shown to be associated with gait and attention deficits resulting in higher frequency of falls. The association of mild hyponatremia and bone fracture is still unknown. OBJECTIVE: To determine if mild hyponatremia is associated with increased risk of bone fracture in ambulatory elderly. DESIGN, SETTING AND PARTICIPANTS: Case control study of 513 cases of bone fracture after incidental fall in ambulatory patients aged 65 or more in general university hospital. Controls were age and sex matched randomly selected ambulatory patients without history of bone fracture. MAIN EXPOSURE MEASURES: Odds ratio (OR) of bone fracture after incidental fall associated with presence of hyponatremia. RESULTS: Prevalence of hyponatremia (serum sodium <135 mEq/l,) in patients with bone fracture and in controls patient was, respectively, 13.06% and 3.90%. Hyponatremia was mild and asymptomatic in all patients (mean serum sodium 131 mEq/l) and was found to be associated with bone fracture after incidental fall in ambulatory elderly (unadjusted OR: 3.47, 95% CI: 2.09-5.79, and adjusted OR: 4.16 95% CI: 2.24-7.71). Hyponatremia was either drug induced (36% diuretics, 17% selective serotonin reuptake inhibitors) or resulted from idiopathic syndrome of inappropriate antidiuretic hormone secretion (37%). Hyponatremia was associated with 9.20% of all bone fractures. CONCLUSION: Mild asymptomatic hyponatremia is associated with bone fracture in ambulatory elderly and avoiding iatrogenic hyponatremia or treating hyponatremia may decrease the number of bone fractures in this population.

Myopericarditis revealing adult-onset Still's disease.

We report the case of a 33 year-old man presenting with fever, arthralgias, sore throat, dyspnea and chest pain. Myopericarditis was diagnosed on the basis of electrocardiogram, echocardiography and cardiac magnetic resonance imaging (MRI). The dramatic increase in ferritinemia suggested the diagnosis of adult-onset Still's disease (AOSD), which could be established according to criteria of Yamaguchi. Rapid improvement occured under corticosteroids. Myocarditis is very rare in AOSD, pericarditis being more frequent. We report herein the first description of AOSD associated myocarditis evidenced by cardiac MRI.

Positive octreotide scintigraphy and determination of lanreotide activity in Paget's disease of bone associated with phosphate diabetes: a case report.

A patient with Paget's disease developed phosphate diabetes (phosphate: 1.6 mg/dl (2.5-4.4 mg/dl), with 29 ml/min phosphate clearance (Nl<15ml/min) and a 65% phosphate reabsorption rate (Nl>85%). As previously demonstrated in tumor-induced osteomalacia, we hypothesized that osteoblasts might manifest somatostatin receptor activity. The patient underwent an octreotide scan which demonstrated increased uptake localized in affected bone. Under lanreotide treatment (40 mg i.m.), the patient's bone pain improved with a concomitant decrease in phosphate alkaline level. Phosphate clearance and tubular readsorption rate of phosphate did not change significantly. We reviewed previously reported cases of associated Paget's bone disease and phosphate diabetes.

Low plasma bicarbonate level in hyponatremia related to adrenocorticotropin deficiency.

Patients with hyponatremia related to adrenocorticotropic deficiency are not easily distinguished by routine laboratory studies from patients with nonendocrine inappropriate secretion of antidiuretic hormone (SIADH). We wanted to investigate whether, in the routine biological analysis of such patients, some parameters could help to better identify this subgroup of hyponatremic patients. The biochemical profiles of 13 consecutive patients with hyponatremia related to ACTH deficiency were analyzed and compared with 30 consecutive patients with classical SIADH. Patients with adrenocorticotropic deficiency presented low uric acid and urea levels as in nonendocrine SIADH, but their total carbon dioxide was significantly lower (total CO(2), 20.5 +/- 3 vs. 25.5 +/- 2.4 mmol/liter; P < 0.001). Nine of the 13 patients presented a value lower than 22 mmol/liter, although this was not observed in the nonendocrine SIADH patients (P < 0.001). Arterial blood gas analysis was available in eight patients and showed a compensated respiratory alkalosis in most of them (pH 7.42 +/- 0.02; PCO(2), 30 +/- 5 mm Hg; HCO(3)(-), 20 +/- 2 mmol/liter; base excess, -3.4 +/- 1.8 mmol/liter). Aldosterone levels were much lower in ACTH deficiency patients during the hyponatremic state (33 +/- 40 pg/ml) when compared with the nonendocrine SIADH (120 +/- 60 pg/ml; P < 0.01). Correction of hyponatremia by cortisone therapy normalized total CO(2) and aldosterone levels. Low carbon dioxide level is a frequent observation in hyponatremia related to ACTH deficiency and could help to differentiate it from classical SIADH.

Solute loss plays a major role in polydipsia-related hyponatraemia of both water drinkers and beer drinkers.

BACKGROUND: Polydipsia-related hyponatraemia is generally considered an acute dilutional state. AIM: To determine whether solute loss plays a role in the pathogenesis of polydipsia-related hyponatraemia. DESIGN: Prospective uncontrolled study. METHODS: We studied routine biochemical volume-related parameters before and after 2 l isotonic saline infusion over 24 h, in 10 consecutive hyponatraemic polydipsia patients (mean age 55 +/- 11 years; 6 beer drinkers and 4 compulsive water drinkers) with initial urinary osmolality <220 mosm/kg H(2)O. In five of these patients, we measured balance data over 24 h. RESULTS: Mean initial plasma protein concentration in the 10 studied polydipsia patients was 7 +/- 0.7 g/dl, unexpectedly high for an acute dilutional state. Mean plasma sodium concentration increased from 126 +/- 5 mmol/l before saline, to 135 +/- 5 mmol/l after infusion of 2 l isotonic saline (p < 0.01). Balance data in five polydipsia patients showed a mean decrease of 1.6 kg of their initial body weight and a mean salt retention of 406 mosm. DISCUSSION: Polydipsia-related hyponatraemia is a mixed disorder, in which about half of sodium decrease is due to solute loss. This explains the apparent paradox of a normal plasma protein concentration, despite the increase in body weight due to water intoxication.