Vasopressin-Dependent Disorders: What Is New in Children?

Abstract

Arginine vasopressin (AVP)–mediated osmoregulatory disorders, such as diabetes insipidus (DI) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are common in the differential diagnosis for children with hypo- and hypernatremia and require timely recognition and treatment. DI is caused by a failure to concentrate urine secondary to impaired production of or response to AVP, resulting in hypernatremia. Newer methods of diagnosing DI include measuring copeptin levels; copeptin is AVP’s chaperone protein and serves as a surrogate biomarker of AVP secretion. Intraoperative copeptin levels may also help predict the risk for developing DI after neurosurgical procedures. Copeptin levels hold diagnostic promise in other pediatric conditions, too. Recently, expanded genotype and phenotype correlations in inherited DI disorders have been described and may better predict the clinical course in affected children and infants. Similarly, newer formulations of synthetic AVP may improve pediatric DI treatment. In contrast to DI, SIADH, characterized by inappropriate AVP secretion, commonly leads to severe hyponatremia. Contemporary methods aid clinicians in distinguishing SIADH from other hyponatremic conditions, particularly cerebral salt wasting. Further research on the efficacy of therapies for pediatric SIADH is needed, although some adult treatments hold promise for pediatrics. Lastly, expansion of home point-of-care sodium testing may transform management of SIADH and DI in children. In this article, we review recent developments in the understanding of pathophysiology, diagnostic workup, and treatment of better outcomes and quality of life for children with these challenging disorders.

Fluid management in hospitalized pediatric patients

“…Lastly, a formal water deprivation test challenges a child's urine concentrating ability and is the current gold standard to diagnose DI. Further work is being done to normalize copeptin levels, a carrier protein of AVP, serving as a marker of AVP levels systemically, to help decrease the need for ongoing water deprivation testing 73 …”

“…Although etiologies of hypovolemic hyponatremia include GI loss, sepsis with acute sequestration, and severe burns, these tend to be readily apparent, and it is more challenging to diagnose SIADH from other causes of hyponatremia, such as cerebral salt wasting. Much work has been done to better characterize SIADH from cerebral salt wasting, including polyuria, elevated potassium excretion, copeptin level assessment, and elevated fractional uric acid secretion 73,86,87 …”

“…Further work is being done to normalize copeptin levels, a carrier protein of AVP, serving as a marker of AVP levels systemically, to help decrease the need for ongoing water deprivation testing. 73 Once the diagnosis of DI has been made, deamino-8-Darginine (dDAVP) can differentiate central DI from nephrogenic DI. Children with central DI increase their urine osmolality in response to dDAVP administration.…”

“…Much work has been done to better characterize SIADH from cerebral salt wasting, including polyuria, elevated potassium excretion, copeptin level assessment, and elevated fractional uric acid secretion. 73,86,87…”

Endocrine Disorders in Children with Brain Tumors: At Diagnosis, after Surgery, Radiotherapy and Chemotherapy

“…Hypernatremia and polyuria due to diabetes insipidus requires treatment with desmopressin, an ADH analogue with prolonged antidiuretic and reduced vasoactive effect. The starting dose needs to be cautiously individualized and titrated with the lowest possible dose until stable euvolemic status and normal sodium levels throughout the day are achieved [ 33 , 37 , 38 , 39 , 40 ]. As central diabetes insipidus can be transient, at first only a single and low dose of desmopressin should be administered, and further doses are only given if there is evidence for persisting or recurring polyuria (breakthrough polyuria) [ 33 ].…”