Endocrine Abstracts

A 53-year-old man was referred for assessment of diabetes insipidus. He had been treated with intranasal desmopressin from18 months of age on the basis of an extensive family history but without confirmatory testing. The current referral was because of hyponatraemia in a similarly affected relative, which had raised uncertainty about diagnosis and treatment.

The family history included 11 affected individuals across four generations and suggested autosomal dominant transmission. Each of the 11 had presented in early childhood with thirst and polyuria which responded to small doses of desmopressin.

On assessment he was asymptomatic with no evidence of anterior pituitary dysfunction and normal vision. Desmopressin was withheld prior to a water deprivation test. He had a maximal urine osmolality of 88mOsm/kg with associated serum osmolality of 311 mOsm/kg and inappropriately low plasma AVP of 1.9 pmol/l. There was a good response to administration of intramuscular desmopressin confirming cranial diabetes insipidus. Anterior pituitary function was normal and MRI demonstrated a normal pituitary bright spot.

Genetic analysis revealed a c.160G>A point mutation in exon 2 of the AVP preprohormone gene. This results in the amino acid substitution Gly54Arg leading to cytotoxic accumulation of mutant protein in neurons.

Familial CDI is a rare condition caused by mutations of the gene encoding the precursor hormone. In most cases the condition is not present at birth but develops in early childhood due to a progressive decline in AVP secretion and selective degeneration of AVP producing neurons. Genetic confirmation enables predictive testing and family counselling.