A case of 'essential' hypernatraemia due to resetting of the osmostat

We describe a 24-year-old short, obese girl who has bizarre episodic neurological abnormalities related to hyperosmolality due to hypernatraemia. Investigation of osmoregulation by water loading and infusion of hypertonic saline revealed (i) hypodipsia with thirst onset raised to plasma osmolality of 332 mmol/kg and (ii) elevation of the threshold for vasopressin release (plasma osmolality 320 mmol/kg) but normal slope of the plasma vasopressin-plasma osmolality curve. Baroregulated vasopressin release was also grossly subnormal. Other hypothalamo-pituitary investigations showed deficiencies of releasing hormones for gonadotrophins and growth hormone, but prolactin response to combined hypoglycaemia and TRH was blunted She demonstrated other anomalies including hyperlipoproteinaemia and defective lymph drainage of the legs. Skull X-rays, together with computerized tomography and nuclear magnetic resonance scans of the hypothalamo-pituitary region and the rest of the brain were normal. We believe that this is the first case of essential hypernatraemia documented with direct evidence of resetting of the osmostat.