Diabetes Insipidus

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 self-sufficient 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 …