Diabetes Insipidus

Abstract

Diabetes insipidus (DI) is characterized by polydipsia and polyuria with a dilute urine having a specific gravity less than 1.010, hypernatremia, and dehydration. It results either from a deficiency of arginine vasopressin (AVP), termed central DI (CDI), or from renal resistance to the action of AVP, called nephrogenic DI (NDI). The prevalence of DI is 1:25,000, with fewer than 10% of cases from hereditary forms. Intact thirst protects selfsufficient patients against severe hypernatremic dehydration, putting infants and neurologically compromised patients more at risk for clinically significant dehydration.Water balance is tightly regulated by AVP, which stimulates both water reabsorption by the kidneys and the ingestion of water in response to thirst. AVP is principally synthesized in the hypothalamic paraventricular, and supraoptic nuclei, and then is stored in the posterior pituitary before it is secreted into the systemic circulation in response to increasing plasma osmolality. In the kidneys, AVP, through binding to the vasopressin V2 receptor in the basolateral membrane of the collecting ducts, activates a series of reactions that allows water to move freely across an osmotic gradient back from a relatively dilute urine into the systemic circulation in response to the plasma's rising osmolality.Decreased production or release of AVP results in CDI, which can present at any age. Underlying mechanisms of CDI include mutations in the AVP gene, anatomical hypothalamic or pituitary defects, trauma, neoplasms, infections, autoimmune disease, or infiltrative processes affecting the AVP neurons or fiber tracts (Table 1). Familial, autosomal dominant CDI results from any of multiple different mutations in the coding region of the AVP gene, with variable severity within a family, and it usually presents after the first year after birth. Another cause of genetically acquired CDI is Wolfram syndrome, a rare autosomal dominant disorder characterized by diabetes mellitus, CDI, optic nerve atrophy, and sensorineural hearing loss. CDI may also manifest as a component of septo-optic dysplasia, which includes optic nerve hypoplasia, an abnormal septum pellucidum, and pituitary hormone deficiencies. CDI associated with septo-optic dysplasia puts patients at particular risk for dehydration due to dysfunction of the osmo-regulated thirst mechanism. Slightly more than half of patients with a craniopharyngioma have accompanying CDI, either before or, particularly, after resection. Typically, a triphasic response follows neurosurgery, with CDI first manifesting 1 to 2 days postoperatively, giving way to the syndrome of inappropriate antidiuretic hormone 2 to 10 days postoperatively, and then converting back to CDI, either transiently or permanently.AUTHOR DISCLOSURE Drs Weiner and Vuguin have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Nephrogenic diabetes insipidus in children (Review)

“…In neonates and infants, the main theme should be early phenotypic and genetic recognition. Therefore, in the presence of mild fever, feeding intolerance, irritability and later, an increased appetite (polydipsia), polyuria plus modified laboratory tests (persistent hypernatremia, increased plasma osmolality, low urine osmolality, low FENa levels) as well as a positive family history, inherited NDI should be suspected (13,23,24).…”

“…NDI is characterized by a lack of response to the vasopressin test (low urine osmolality <200 mOsm/kg H 2 O and low urine gravity). Summary of laboratory results characteristic for NDI are: UOP >4 ml/kg/h, serum sodium >170 mmol/l, serum osmolality >300 mOsm/kg, urine osmolality <300 mOsm/kg, and a urine specific gravity <1,005 (23).…”

“…High plasma vasopressin levels indicate NDI while lower levels indicate CDI. Due to the short half-life of AVP, it makes it difficult to be measured (23). Copeptin (CT-proAVP) has proven to be a more stable marker of AVP (23).…”

“…Due to the short half-life of AVP, it makes it difficult to be measured (23). Copeptin (CT-proAVP) has proven to be a more stable marker of AVP (23). Therefore copeptin levels may be measured as a further confirmation of the diagnosis.…”

“…NDI can be acquired at any time (2,3,5,6). A particular group of NDI is represented by those who do not have acquired NDI but, rather, NDI due to secondary genetic disease, similar to patients with renal disorders as well as in the context of autoimmune disease (Sjögren's syndrome) (13,23). A list of potential etiologies of acquired and secondary NDI is presented in Table II.…”