Chronic Hypernatremia Derived from Hypothalamic Dysfunction

Impaired Secretion of Arginine Vasopressin and Enhanced Renal Water Handling

Abstract

We analyzed the disorder of water metabolism in a 32 year-old female with chronic hypernatremia. She had meningitis at 4 years, and ventriculo-peritoneal shunt operation at 13 years because of normal pressure ydrocephalus. At 14 years hypernatremia of 166mmol/l was initially found and thereafter hypernatremia ranging from 150 to 166mmol/l has been persisted for the last 18 years. Physical and laboratory findings did not show dehydration. Urine volume was 750-1700ml per day and urinary osmolality (Uosm) 446-984mmol/kg, suggesting no urinary concentrating defect. Plasma arginine vasopressin (AVP) levels ranged from 0.4 to 1.2 pmol/l despite hyperosmolality of 298 through 343mmol/kg under ad libitum water drinking. There was no correlation between plasma osmolality (Posm) and plasma AVP levels, but Uosm had a positive correlation with Posm (r=0.545, P<0.05). Hypertonic saline (5% NaCl) infusion after a water load increased Uosm from 377 to 679mmol/kg, and plasma AVP from 0.2 to 1.3pmol/l. There was a positive correlation between Posm and plasma AVP levels in the hypertonic saline test (r=0.612, P<0.05). In contrast, an acute water load (20ml/kg BW) verified the presence of impaired water excretion, as the percent excretion of the water load was only 8.5% and the minimal Uosm was as high as 710mmol/kg. Urinary excretion of aquaporin-2 remained low in concert with plasma AVP levels. No abnormality in pituitary-adrenocortical function was found. These results indicate that marked hypernatremia is derived from partial central diabetes insipidus and elevated threshold of thirst, and that enhanced renal water handling may contribute to maintenance of body water in the present subject.