ESPE Abstracts

Introduction: Arginine vasopressin (AVP) and thirst are the main determinants of water homeostasis maintenance, and dysregulation leads to polyuria-polydipsia syndrome. This comprises of three key conditions: CDI due to insufficiently secreted AVP; NDI, due to renal AVP insensitivity and Primary Polydipsia (PP), caused by excessive fluid intake resulting in physiological suppression of AVP. Differentiating between these three conditions is important, as the treatment strategies differ and incorrect treatment can be dangerous. The standard water deprivation test has been the “gold-standard” for differentiating these entities, but relying on this has its limitations, with difficulty in reliably differentiating between CDI and NDI. In addition the long duration of the test and sampling requirements make this test difficult to perform. Measuring AVP upon osmotic stimulation would theoretically overcome the limitations of the water deprivation test, but it is not used in clinical practice due to technical limitations of the AVP assay. Copeptin on the other hand is secreted in equimolar ratio to AVP in response to osmotic, haemodynamic and stress-related stimuli. It has been shown to be a reliable, stable and easily measured marker which is useful in the differential diagnosis of these states.

Case presentation: Our patient presented at 14 months of age with failure to thrive, with all growth parameters below 0.4th centile. There was also a history of polyuria, polydipsia and some concerns regarding mild developmental delay. Routine blood tests had shown hypernatremia (160-170mmol/L). His plasma osmolality was high (316 mosm/kg) and paired urine osmolality low (110 mosm/kg). The neurohypophyseal bright signal was absent on MRI scan, suggesting a diagnosis of CDI. However, he failed to respond to treatment with increasing doses of desmopressin (10mcg-240 mg twice daily). His baseline Copeptin results showed very high levels (285.6 pmol/l), confirming the diagnosis of NDI and he was commenced on appropriate treatment with Cholrothiazide. The results of cytogenetic investigations are awaited.

Discussion: The MRI findings in this child were suggestive of a diagnosis of CDI. It is hypothesised that the posterior pituitary bright signal is due to the presence of AVP in the neurosecretory granules. It is possible that in NDI, due to hypersecretion of AVP, the neurosecretory granules are depleted of AVP, leading to loss of the bright spot in the posterior pituitary on MRI scan. This case highlights the ease and reliability of using Copeptin in differentiating NDI and CDI.