Diabetes Insipidus

Abstract

Diabetes insipidus (DI) is a clinical syndrome characterized by the excretion of large volumes of dilute urine. The polyuria is accompanied by a commensurate increase in fluid intake (polydipsia) and minor changes in total body water, plasma osmolarity, and plasma sodium. DI can result from any of four fundamentally different defects; (1) a deficiency in posterior pituitary production of the antidiuretic hormone, arginine vasopressin(AVP), a disorder known variously as pituitary, cranial, neurogenic, hypothalamic, or central DI; (2) increased degradation of AVP during pregnancy by an enzyme made by the placenta, known as gestational DI; (3) decreased sensitivity of the kidneys to the antidiuretic effect of AVP, known as nephrogenic DI; and suppression of AVP secretion by excessive fluid intake, known as primary polydipsia. Differentiation between these four types of DI is essential for effective and safe management as well as a properly focused search for the underlying cause be it acquired or genetic. In some cases, most notably gestational DI, differentiation is possible from the clinical setting. Often, however, it is ambiguous and traditional fluid deprivation tests are unreliable particularly when the defect in AVP secretion or action is partial. These problems in differential diagnosis have now been virtually eliminated by the development of a sensitive and specific radio-immunoassay for plasma AVP when it is used with either a fluid deprivation test or brain MRI to indicate the presence or absence of the normal posterior pituitary bright spot. In pituitary and gestational DI, the polyuria, thirst, and polydipsia can be eliminated completely and safely by treatment with desmopressin, a synthetic analogue of AVP. However, it should not be used in primary polydipsia because it eliminates the polyuria but not the polydipsia resulting in water intoxication with hyponatremia. The polyuria and polydipsia of nephrogenic DI are not altered by standard doses of desmopressin but they can be reduced considerably by administration of a thiazide diuretic with or without indomethacin or other prostaglandin synthetase inhibitor. If DI of the pituitary or nephrogenic type began early in life, occurs in other family members or cannot be traced to an acquired disorder, analysis of either the AVP gene or the AVP receptor 2 gene to look for a mutation may reveal the cause and provide information useful for family counseling.