Polyuria-polydipsia syndrome: a diagnostic challenge

The main determinants for the maintenance of water homeostasis are the hormone arginine vasopressin (AVP) and thirst. Disturbances in these regulatory mechanisms can lead to polyuria-polydipsia syndrome, which comprises of three different conditions: central diabetes insipidus (DI) due to insufficient secretion of AVP, nephrogenic DI caused by renal insensitivity to AVP action and primary polydipsia due to excessive fluid intake and consequent physiological suppression of AVP. It is crucial to determine the exact diagnosis because treatment strategies vary substantially. To differentiate between the causes of the polyuria-polydipsia syndrome, a water deprivation test combined with desmopressin administration is the diagnostic 'gold standard'. Thereby, AVP activity is indirectly evaluated through the measurement of urine osmolality after prolonged dehydration. However, this test has several limitations and may fail to distinguish precisely between patients with primary polydipsia and mild forms of central and nephrogenic DI. The direct measurement of AVP during the water deprivation test, which was reported in the 1980s, has not been widely adopted due to availability, assay issues and diagnostic performance. Recently, copeptin, the c-terminal portion of the larger precursor peptide of AVP, has been evaluated in the setting of polyuria-polydipsia syndrome and appears to be a useful candidate biomarker for the differential diagnosis. A standardised method for the water deprivation test is presented as part of a joint initiative of the Endocrine Society of Australia, the Australasian Association of Clinical Biochemists and the Royal College of Pathologists of Australasia to harmonise dynamic endocrine tests across Australia.