Challenging case of hypernatraemia in infancy

Arch Dis Child Educ Pract Ed. 2024 Aug 28:edpract-2024-327310. doi: 10.1136/archdischild-2024-327310. Online ahead of print.

Abstract

A 1-month-old male infant presented unwell with a fever and shock. Blood tests showed hypernatraemia, hyperchloraemia and raised urea and creatinine. Initially, he was treated for dehydration secondary to sepsis. However, high urine output combined with low urine osmolality and high plasma osmolality was suggestive of a disorder of arginine vasopressin (AVP), previously called diabetes insipidus (DI). On further endocrine testing, thyroxine (T4) level was low with an inappropriately normal thyroid-stimulating hormone level with no other anterior pituitary hormone abnormalities, a normal MRI head and ophthalmological assessment. Desmopressin, a synthetic form of AVP, was commenced, however, there was an inadequate response despite dose escalation, leading to a diagnosis of AVP resistance (previously nephrogenic DI) rather than AVP deficiency (previously cranial DI). Copeptin, an AVP precursor peptide and surrogate marker, was significantly elevated. A renal tubulopathy genetic screen demonstrated a likely pathogenic hemizygous variant in the AVP receptor 2 gene, which has previously been associated with X-linked vasopressin resistance. This case demonstrates the challenge of differentiating between AVP deficiency and resistance in infancy and the value of copeptin and genetic testing in confirming diagnosis. We outline an approach to fluid management in AVP disorders.

Keywords: Endocrinology; Genetics; Nephrology; Paediatrics.