Inappropriate secretion of antidiuretic hormone and systemic lupus erythematosus.
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Biomedical subjects
Publications and source records attributed to G Decaux.
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In order to determine if the neurologic manifestations in chronic hyponatraemia result partly from brain oedema, we measured the cerebral ventricular volume before and after correction of hyponatraemia in eight patients with central nervous system manifestations. Only the three patients with seizures showed a clear change in the ventricular size and probably had brain oedema.
We present 1 patient with hypouricemia and hyperuricosuria. Serum uric acid level ranged between 1.5 and 1.9 mg/dl and uric acid fractional excretion between 20 and 28%. Apart from that the renal function was normal. The pyrazinamide suppression test gave a normal response showing nearly complete suppression of urate excretion. The uricosuric response to sulfinpyrazone was normal too. The renal tubular response to extracellular fluid volume contraction induced by furosemide indicated a normal tubular sensitivity to extracellular fluid volume variations. From these results we conclude that our patient has a specific tubulopathy characterized by uric acid hypersecretion.
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The clinical significance of hypouricemia in hospitalized patients was studied retrospectively and prospectively. Two thousand two hundred patients routinely screened for serum uric acid were reviewed: 88 (4%) had serum uric acid levels below 2.5 mg/dl and 23 (1%) below 2 mg/dl. We found that 32 (36.4%) patients with serum uric acid below 2.5 mg/dl were patients treated with forced diuresis. Thereafter, to confirm the importance of perfusions in the evaluation of serum uric acid levels, 20 suicide-attempt patients and 7 patients with renal colic all treated with forced diuresis, were prospectively studied. Our results show that perfusions significantly increased the fractional excretion of uric acid that was responsible for the observed decrease of serum uric acid level.
Seven out of nine patients with chronic inappropriate secretion of antidiuretic hormone were successfully treated with 40 mg frusemide daily. One patient needed 80 mg, and the remaining patient achieved only a small increase in diuresis after 40 mg frusemide; this was probably related to his low creatinine clearance. In order to maintain a salt intake high enough to compensate for the loss of urine electrolytes 3 to 6 g sodium chloride was added as tablets to the sodium-free diet in six patients. Hypokalaemia occurred in five patients but was easily corrected with either supplements of potassium chloride or a potassium-sparing diuretic. These findings add further weight to evidence that Frusemide is a good alternative for the treatment of patients with inappropriate secretion of antidiuretic hormone who cannot tolerate water restriction.
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When red cell mean corpuscular volume (MCV) is determined by use of the Coulter counter, the blood sample is first diluted in a solution with fixed osmolality (Isoton). Therefore we studied the interference of blood osmolality with MCV measured by this method. In 14 patients with hyposmolality, the correction of osmolality was accompanied by an increase in MCV of 4.7% (p less than 0.001) and a decrease in mean corpuscular hemoglobin concentration (MCHC) of 4.8% (p less than 0.001). In 9 patients with hyperosmolality the decrease in MCV was of 5% (p less than 0.001) and the rise in MCHC of 4% (p less than 0.001) after osmolality correction. Before correction of hyposmolality, 1 patient had false microcytosis and 3 had masked macrocytosis. In the hypertonic group 3 patients has initially false macrocytosis. Red blood cells (RBC) from hypotonic patients probably shrink when they are acutely placed in the Isoton which is a hypertonic solution (330 mosm/kg H2O). Conversely RBC from patients with severe hyperosmolality swell in the same conditions. The patients osmolality must be considered to interpret the MCV measured by the Coulter counter correctly, as a 10-mosm/kg H2O change in serum osmolality is responsible for an artefactual change in MCV of 1 fl.
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Since urea and uric acid clearance are affected by the effective intravascular volume, we measured the fractional urea and uric acid excretion in cirrhosis. High urea and uric acid clearances were observed in 30 and 55 percent, respectively, of 20 consecutive cirrhotic patients with normal renal function. In seven patients with a high fractional uric acid excretion, 5 mg of isosorbide dinitrate every four hours for 24 hours induced a significant increase in the serum uric acid level (from 3.7 +/- 0.8 mg/dl to 4.4 +/- 0.8 mg/dl; less than 0.001) with a concomitant decrease in the fractional uric acid excretion (from 14.0 +/- 3.2 percent to 8.8 +/- 3.1 percent; less than 0.02). During the same test, the blood urea level increased from 3.3 +/- 1.1 mmol/liter to 4.1 +/- 1.2 mmol/liter (p less than 0.005) with a decrease in fractional excretion from 51 +/- 4.5 percent to 39 +/- 5 percent (p less than 0.001). The oral intake of sulfinpyrazone in six of these patients induced a normal uricosuric response. In two cirrhotic patients with ascites, 40 mg of furosemide associated with a 24-hour severe water restriction was also shown to normalize the high fractional excretion of both urea and uric acid. In nine patients with ascites, we observed a significant increase in blood urea and uric acid concentration despite the absence of change in creatinine clearance once ascites was removed by diuretics. On the basis of these findings, we believe that the high fractional excretion of both urea and uric acid frequently observed in cirrhosis is related to an increase in the effective vascular volume.
Mild hypocalcemia was observed in 6 out of 12 patients with SIADH associated hyponatremia, this was in fact related to low albumin levels resulting partly from body fluid dilution. In the 7 SIADH patients where it was measured, we observed an increased fractional calcium excretion (3.2 +/- 1.7%) as long as the patients were hyponatremic. This was corrected by water restriction (0.73 +/- 0.4%, p less than 0.01). We suggest that volume expansion was responsible for the increased calcium clearance, and not hyponatremia by itself, since in volume depletion hyponatremia, calcium clearance was within the normal range. Mild hypocalcemia and hypercalciuria is a common finding in SIADH-associated hyponatremia.
The efficacy of oral urea in producing a sufficiently high osmotic diuresis was tested in seven patients with the syndrome of inappropriate secretion of antidiuretic hormone. In all patients urea corrected the hyponatraemia despite a normal fluid intake. Five patients were controlled (serum sodium concentration greater than 128 mmol(mEq)/1) with a dose of 30 g urea daily, and two with 60 g daily. The patients who needed 30 g drank 1-2 1 of fluid daily, while those who needed 60 g drank up to 3.1 per day. No major side effects were noted, even after treatment periods of up to 270 days. These findings suggest that urea is a safe and efficacious treatment of the syndrome of inappropriate secretion of antidiuretic hormone.
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Explore the source record for details and available documents.
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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 less than 0.01). In one patient with an oat cell carcinoma and SIADH-induced hyponatremia, we observed the same positive correlation (r = 0.80; p less than 0.01) but also a negative one between the excreted fraction of filtered sodium and urinary urea (r = -0.67; p less than 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 (less than 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 presented with persistent hyponatremia despite the restriction of water intake.
Three cases of central nervous system complications of Mycoplasma pneumoniae infections are reported. There were several atypical findings: the first patient presented with an acute disseminated encephalitis with normal cerebrospinal fluid and hypogammaglobulinaemia. The second patient presented with a left sixth nerve palsy followed six weeks later by choreoathetoid movements and an acute psychosis. The third patient presented with an acute encephalitis associated with acute renal failure secondary to rhabdomyolysis and was the only patient who did not completely recover; he was discharged akinetic and mute, but with normal renal function. The diagnosis of complications of Mycoplasma pneumoniae may be difficult. In two of the three cases a raised red blood cell volume secondary to a high titre of cold agglutinins rapidly led to the correct diagnosis.