Diabetes Insipidus: Arginine Vasopressin Deficiency and Arginine Vasopressin Resistance

Diabetes insipidus is a clinical syndrome of dysregulated free water balance. It results either from vasopressin deficiency, usually due to inadequate secretion of vasopressin from the posterior pituitary gland (central diabetes insipidus), or from an impaired renal response to the antidiuretic effect of vasopressin (nephrogenic diabetes insipidus). During the past decade, there have been proposals to retire the term diabetes insipidus and to refer instead to the diagnoses of arginine vasopressin deficiency (AVP-D) and arginine vasopressin resistance (AVP-R). In the absence of vasopressin-mediated urinary concentration, increased excretion of dilute urine (polyuria) leads to a loss of free water. Increased thirst will stimulate increased water intake (polydipsia), but if not replenished, the free water deficit leads to a hyperosmolar state characterized by plasma hypernatremia. Thus, the clinical hallmarks of diabetes insipidus are polyuria of inappropriately dilute urine and hyperosmolarity. In some patients with these findings, the diagnosis of diabetes insipidus will be clear. In many patients, the diagnosis may need to be confirmed with provocative testing. Central diabetes insipidus may result from a wide variety of causes, including genetic and other congenital anomalies, pituitary injury (from trauma, surgery, or tumors), and systemic diseases that may disrupt vasopressin secretion. Nephrogenic diabetes insipidus can result from genetic and congenital disorders involving the kidneys, systemic conditions affecting renal function, and many drugs. An extensive evaluation may be required to determine the etiology of diabetes insipidus in a particular patient. Vasopressin and its analog desmopressin (also called dDAVP) are the specific therapies for central diabetes insipidus. Treatment of nephrogenic diabetes insipidus typically depends upon reversal of the underlying cause, but pharmacological treatment can be successful. Treating infants and postoperative patients with diabetes insipidus can be particularly challenging and requires additional management strategies and special care.