1998 Global Conference Proceeding

March 02 - 04, 1998

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Conference: 1998 Global Conference
Title: Pitfalls in the Differential Diagnosis of Nephrogenic Diabetes Insipidus.
Author: Robertson, Gary
Institution: Northwestern University Medical School
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Gary RobertsonDiabetes insipidus (DI) is a disorder characterized by chronic thirst, increased fluid intake and excretion of abnormally large volumes of dilute urine. There are 3 different causes: (1) a deficiency of the antidiuretic hormone, arginine vasopressin (AVP) due either to deficient secretion (pituitary, central or neurohypophyseal DI) or abnormally rapid destruction of the hormone during pregnancy (gestational DI); (2) resistance of the kidneys to the antidiuretic effect of AVP (nephrogenic DI); and (3) excessive intake of water (primary polydipsia) caused either by a defect in thirst (dipsogenic DI) or by mental illness (psychogenic polydipsia). Each type of DI can be due to an inherited genetic defect or an acquired disease and must be treated differently. Thus, accurate diagnosis of the type of DI is essential for optimum care. These distinctions are usually easy when the deficiency of AVP is so severe that the patient is unable to concentrate his or her urine during a dehydration test. In this case, primary polydipsia is excluded and determining the change in urine concentration after injecting the AVP analogue, DDAVP, will usually distinguish pituitary from nephrogenic DI. However, if the dehydration test results in concentration of the urine, the distinction is more difficult because the patient can have either primary polydipsia or a partial defect in AVP secretion or action and the subsequent response to a conventional diagnostic dose of DDAVP does not differentiate between them. Sometimes the family or medical history will help in the differential diagnosis but this information can also be misleading or ambiguous. For example, an X-linked recessive mode of inheritance with concentration of the urine during a dehydration test as well as after a diagnostic dose of DDAVP is consistent with familial DI of either the pituitary or the nephrogenic type. Similarly, an autosomal dominant mode of inheritance with the same response to dehydration and DDAVP injection is consistent with familial DI of either the pituitary or dipsogenic type. In either situation, the type of DI usually can be determined by 4 additional tests: (1) an MRI of the brain to determine if the posterior pituitary 'bright spot' is present; (2) a 2 day therapeutic trial of parenteral DDAVP to determine if it abolishes thirst and polydipsia as well as polyuria without inducing water intoxication; (3) measurement of plasma AVP before and during a dehydration test to determine its relationship to plasma and urine osmolality; and (4) sequencing of the AVP and AVP receptor-2 genes.

Diabetes insipidus (DI) is characterized by chronic thirst, increased fluid intake and excessive urination. There are different types and causes of DI. Pituitary or Central DI is caused by a deficient secretion of the antidiuretic hormone, arginine vasopressin (AVP). Gestational DI occurs when there is a rapid destruction of AVP during pregnancy. Nephrogenic DI occurs when the kidneys are resistant to the antidiuretic effect of AVP. Dipsogenic DI is caused by an excessive intake of water (primary polydypsia) due to a defect in thirst. Each type of DI can be inherited or acquired; each must be treated differently; therefore, each must be diagnosed accurately for optimum care.

Diagnosing which type of DI a patient has is easier when the patient's urine has a low particle to liquid ratio after a period of restricted liquid intake. If this is so, it excludes the possibility of polydipsia, and the patient's response to an injection of synthetic AVP, as measured by urine concentration, will distinguish whether the DI is nephrogenic or pituitary. Diagnosis becomes more difficult when the patient's urine shows a high particle to liquid ratio after restricted water intake because the patient could have either primary polydipsia or a partial defect in AVP secretion or action, and the patient's response to synthetic AVP will not differentiate between them. In this case, the DI type can usually be determined by four additional tests:

  1. an MRI brain scan,
  2. a two day trial of synthetic AVP,
  3. measurement of AVP levels before and during a water deprivation period,
  4. analysis of the genetic sequencing of AVP and the AVP receptor-2 genes (inherited or familial forms of DI).