Endocrine Abstracts (2017) 50 CC06 | DOI: 10.1530/endoabs.50.CC06

Activating mutation in the arginine vasopressin receptor AVPR2 resulting in nephrogenic syndrome of inappropriate antidiuresis in a female

Mohamed Ashif Majeed1, Jennifer Hague2, Andrew S Powlson3, Julia Hale1, Ruth Casey1, Sue Oddy4, Mark Gurnell3, Soo-Mi Park2 & Helen Simpson5


1Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals, Cambridge, United Kingdom; 2Department of Clinical genetics, Cambridge University Hospitals, Cambridge, United Kingdom; 3Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom; 4Department of Clinical Biochemistry, Cambridge University Hospitals, Cambridge, United Kingdom; 5Department of Diabetes and Endocrinology, UCLH NHS Foundation Trust, London, United Kingdom.


Introduction: Hyponatraemia is the commonest electrolyte disturbance, but is not common in young people. Here, we describe a female subject, with recurrent unexplained symptomatic hyponatraemia in whom we considered the possibility of an activating mutation in the arginine vasopressin receptor type 2 (AVPR2) as a rare cause of Syndrome of Inappropriate Anti-Diuresis (SIAD).

Case: A 39 year old woman had a history of unexplained hyponatraemia (serum sodium typically 125 mmol/l) from the age of 16 years, clinically and biochemically consistent with SIAD(H). Adrenocortical and thyroid function, an acute intermittent porphyria screen and relevant imaging were normal and there were no culprit drugs. A water load test was performed which was suggestive of SIAD as she could excrete only 40% of a 20 ml/kg oral load by 240 min post-ingestion. Normal subjects excrete 78–82% of the water load in 4 hours. However, concentrations of copeptin, a stable and easily measured peptide which can be used as a surrogate marker of AVP release were low throughout the test (T, p.(Arg137Cys). Her mother was identified as a gene carrier and retrospectively she also gave a history of intermittent asymptomatic hyponatraemia. The proband is currently managed with fluid restriction of between 1.0 and 1.5 L/day preventing further admissions.

Conclusion: Unexplained hyponatraemia in young subjects should be investigated thoroughly and activating AVPR2 mutations considered in the differential diagnosis. This is an X-linked recessive disorder and all reported adult index cases to date have been males. Although two affected female carriers have been described presenting acutely in the neonatal period, this case represents the first reported adult female proband. A plausible explanation for this unusual presentation in a female could be skewed X-inactivation. Further genetic testing is awaited.