Introduction: An 18 day old term male baby presented with faltering growth and hyponatraemia. Extensive investigations suggested the cause of hyponatraemia was water excess which may result from either overproduction of Antidiuretic hormone (SIADH) or the nephrogenic syndrome of inappropriate antidiuresis (NSIAD). Genetic testing demonstrated a hemizygous mutation in the AVPR2 gene.
Case report: The infant presented with 8% weight loss and hyponatraemia (lowest Na: 114 mmol/l), serum osmolality was 233 mosm/kg with an inappropriately elevated urine osmolality of 629 mosm/kg. Endocrine investigations included a normal 17OHP (3.7 nmol/l), Synacthen test (peak cortisol 1013 nmol/l) and urine steroid profile. The plasma aldosterone was 1032 pmol/l with a suppressed plasma renin of <0.2 nmol/l per hr. Metabolic tests were normal apart from a heavy aminoaciduria. There was no evidence of proximal tubular dysfunction. The renal ultrasound scan and magnetic resonance imaging of the brain were normal. The results indicated excess free water secondary to SIADH or NSIAD. The Copeptin (marker of vasopressin levels) was in the low normal range at 2.9 pmol/l.
Treatment: Sodium supplements had minimal effect on the serum sodium. Fluid restriction increased the sodium to 126 mmol/l, however this resulted in inadequate calorie intake and poor weight gain. Addition of a vasopressin receptor antagonist (Tolvaptan) allowed some relaxation of the fluid restriction with unchanged sodium levels. The poor growth however persisted. Genetic tests confirmed a rare gain of function mutation in the AVPR2 gene leading to excessive water retention. Diuresis was achieved by providing an increased osmotic load by increasing dietary protein intake to 6 g/kg per day and subsequently giving oral urea. These measures normalized the serum sodium levels and the child is now thriving. The urinary aminoaciduria is improving.
Conclusions: Both SIADH and NSIAD respond to fluid restriction, but this is at the expense of nutritional intake. SIADH but not NSIAD respond to Tolvaptan. Measurement of copeptin levels and genetic testing can help differentiate between the two conditions. Osmotic diuresis with the introduction of a high protein diet and oral urea can normalize hyponatraemia in NSIAD.
07 - 09 Nov 2018
British Society for Paediatric Endocrinology and Diabetes