Copeptin and its role in the diagnosis of diabetes insipidus and the syndrome of inappropriate antidiuresis

Abstract

Clinical Endocrinology. 2019;91:22-32. wileyonlinelibrary.com/journal/cen 1 | INTRODUC TI ON Arginine vasopressin (AVP) is the main regulating hormone of body fluid homeostasis. It is secreted from the posterior pituitary upon osmotic or nonosmotic stimuli, with the main osmotic stimulus being increased plasma osmolality and the main nonosmotic stimulus being hypovolaemia and promotes water reabsorption via V2 receptors in the kidney, thereby normalizing hypertonicity and vasomotor tone. Disorders of body fluid homeostasis are common and can be divided into hyper-and hypoosmolar circumstances: the classical AbstractCopeptin is secreted in an equimolar amount to arginine vasopressin (AVP) but can easily be measured in plasma or serum with a sandwich immunoassay. The main stimuli for copeptin are similar to AVP, that is an increase in osmolality and a decrease in arterial blood volume and pressure. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation.Copeptin has, therefore, been evaluated as diagnostic biomarker in vasopressin-dependent disorders of body fluid homeostasis. Disorders of body fluid homeostasis are common and can be divided into hyper-and hypoosmolar circumstances: the classical hyperosmolar disorder is diabetes insipidus, while the most common hypoosmolar disorder is the syndrome of inappropriate antidiuresis (SIAD). Copeptin measurement has led to a "revival" of the direct test in the differential diagnosis of diabetes insipidus. Baseline copeptin levels, without prior thirsting, unequivocally identify patients with nephrogenic diabetes insipidus. In contrast, for the difficult differentiation between central diabetes insipidus and primary polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is clearly superior to the classical water deprivation test. On the contrary, in the SIAD, copeptin measurement is of only little diagnostic value. Copeptin levels widely overlap in patients with hyponatraemia and emphasize the heterogeneity of the disease. Additionally, a variety of factors lead to unspecific copeptin elevations in the acute setting further complicating its interpretation. The broad use of copeptin as diagnostic marker in hyponatraemia and specifically to detect cancer-related disease in SIADH patients can, therefore, not be recommended. K E Y W O R D Scopeptin, diabetes insipidus, diagnosis, hypernatremia, hyponatraemia, primary polydipsia, SIAD This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Acute interstitial nephritis and nephrogenic diabetes insipidus following treatment with sulfamethoxazole‐trimethoprim and temozolomide

“…17 Recently, copeptin has been identified as a surrogate marker of secretion of antidiuretic hormone as is secreted in equimolar concentrations to ADH. 18 In addition, baseline concentrations of copeptin greater than 21.4 pmol/L can reliably diagnose nDI, 18 as was reported in our case. Central diabetes insipidus is treated by increasing blood concentrations of ADH through use of drugs such as desmopressin, carbamazepine and chlorpropamide.…”

Hyponatremia in the cancer patient

“…94 Copeptin, the C-terminal segment of the vasopressin precursor peptide, correlates with vasopressin concentrations and can be easily r e v i e w BT Workeneh et al: Hyponatremia in the onconephrology patient measured, providing a reliable surrogate marker for vasopressin. 95 SIAD can now be categorized into 5 different groups: type A, characterized by a markedly elevated copeptin level independent of plasma osmolality, suggesting an ectopic source; type B, in which copeptin increased linearly with rising plasma osmolality, but abnormally low osmotic thresholds for its release were seen; type C, with normal copeptin levels but independent of plasma osmolality, also suggesting an ectopic source but with lower secretory activity; type D, in which a suppressed copeptin level independent of osmolality was observed; and a new type of defect pattern termed type E or "barostat," characterized by a linear reduction in copeptin levels while plasma osmolality was increasing. In contrast to the prior classification, malignancy is more prominent in type A and type C defects in the new classification, with 80% of patients with a type-A defect suffering from lung cancer, and 32% of patients in type C suffering from solid tumors.…”

Use of Copeptin Levels to Predict the Resolution of Transient Postoperative SIADH

“…Attempts have been made using copeptin levels to help providers correctly differentiate patients with SIADH from those with other causes of hyponatremia. However, given the breadth of conditions leading to hyponatremia, developing a copeptin-based approach remains challenging [18]. The ratio of copeptin to urinary sodium may differentiate SIADH from other conditions of overall ineffective circulatory volume [6].…”