Diabetes insipidus

Diabetes insipidus (DI) is a disease characterized by excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced. It denotes inability of the kidney to concentrate urine. DI is caused by a deficiency of antidiuretic hormone, or by an insensitivity of the kidneys to that hormone. more...

Signs and symptoms

Excessive urination and extreme thirst (especially for cold water) are typical for DI. Symptoms of diabetes insipidus are quite similar to those of severely deranged diabetes mellitus, with the distinction that the urine is not sweet and there is no hyperglycemia (elevated blood glucose). Blurred vision is a rarity.

The extreme urination continues throughout the day and the night. In children, DI can interfere with appetite, eating, weight gain, and growth as well. They may present with fever, vomiting, or diarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is drunk to offset the urinary losses. However, there is a continuous risk of dehydration.

Diagnosis

In order to distinguish DI from other causes of excess urination, blood glucose, bicarbonate and calcium need to be tested. Electrolytes can show substantial derangement; hypernatremia (excess sodium levels) are common in severe cases. Urinalysis shows low electrolyte levels, and measurement of urine osmolarity (or specific gravity) is generally low.

A fluid deprivation test helps determine whether DI is caused by:

1. excessive intake of fluid
2. a defect in ADH production
3. a defect in the kidneys' response to ADH

This test measures changes in body weight, urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH during this test is also necessary.

To distinguish between the main forms, desmopressin stimulation is also used; desmopressin can be taken by injection, a nasal spray, or a tablet. While taking desmopressin, a patient should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in central DI. If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient, and the kidney responds normally. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.

If central DI is suspected, testing of other hormones of the pituitary, as well as magnetic resonance imaging (MRI), is necessary to discover if a disease process (such as a prolactinoma) is affecting pituitary function.

Pathophysiology

Electrolyte and volume homeostasis is a complex mechanism that balances the body's requirements for blood pressure and the main electrolytes sodium and potassium. In general, electrolyte regulation precedes volume regulation. When the volume is severely depleted, however, the body will retain water at the expense of deranging electrolyte levels.

The regulation of urine production is the hypothalamus, which produces antidiuretic hormone (ADH or vasopressin) in the posterior lobe of the pituitary gland. In addition, it regulates the sensation of thirst as perceived by the cortex.

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