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A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis
Journal
Best Practice and Research Clinical Endocrinology and Metabolism
Volume
30
Number
2
Pages / Article-Number
219-233
Abstract
The syndrome of inappropriate antidiuretic hormone secretion (SIADH), also referred to as syndrome of inappropriate antidiuresis (SIAD), is the most common cause of hyponatremia characterized by extracellular hypotonicity and impaired urine dilution in the absence of any recognizable nonosmotic stimuli for the antidiuretic hormone arginine vasopressin (AVP). Hyponatremia in SIADH is primarily the result of excessive water retention caused by a combination of inappropriate antidiuresis and persistent fluid intake in the presence of impaired osmoregulated inhibition of thirst. It is sometimes aggravated by a sodium deficiency caused by a decreased intake or a secondary natriuresis in response to elevated extracellular volume. Inappropriate antidiuresis usually results from endogenous production of AVP that can be either ectopic (from a malignancy) or eutopic (from the hypothalamus/neurohypophysis). Regardless of its origin, different types of osmotic dysregulation of AVP have been reported with possibly fundamental deviations in treatment need and efficacy. A recent quantitative analysis of 50 patients with SIADH, which underwent serial measurements of copeptin during hypertonic saline infusion, revealed five distinct types of osmoregulatory defect ("type A to E") without affiliation to specific underlying diseases. In addition to apparently impaired osmoregulated inhibition of AVP release in the majority of patients, 12% of patients showed an AVP-independent mechanism of inappropriate antidiuresis, whilst 20% of them presented a reverse relation between hormone release and serum osmolality, presumably related to interrupted nonosmotic inhibitory pathways. The interference of these different types of SIAD with clinical presentation and therapy response will be a relevant subject for future research.
