Diabetes Insipidus

What is Diabetes Insipidus?

A deficiency of vasopressin (also called antidiuretic hormone) causes diabetes insipidus, which is a water metabolism disorder characterized by excessive fluid intake and hypotonic polyuria. The disorder may start in childhood or early adulthood (median age of onset is 21) and is more common in men than in women. Incidence is slightly higher today than in the past.

In uncomplicated diabetes insipidus, with adequate water replacement, the prognosis is good and patients usually lead normal lives. However, in cases complicated by an underlying disorder, such as cancer, the prognosis varies.

Causes of Diabetes Insipidus

The most common cause of diabetes insipidus is failure of vasopressin secretion in response to normal physiologic stimuli (pituitary or neurogenic diabetes insipidus). A less common cause is failure of the kidneys to respond to vasopressin (congenital nephrogenic diabetes insipidus).

Normally, vasopressin is synthesized in the hypothalamus and then stored by the posterior pituitary gland (neurohypophysis). When released into the general circulation, vasopressin acts on the distal and collecting tubules of the kidneys, increasing their water permeability and causing water reabsorption. The absence of vasopressin in diabetes insipidus allows the filtered water to be excreted in the urine instead of being reabsorbed and results in the passage of large quantities of dilute fluid throughout the body.

There are two types of pituitary diabetes insipidus. Primary pituitary diabetes insipidus (50% of patients) is familial or idiopathic in origin. The primary form may occur in neonates as a result of congenital malformation of the central nervous system (CNS), infection, trauma, or tumor. Secondary pituitary diabetes insipidus results from intracranial neoplastic or metastatic lesions, hypophysectomy or other types of neurosurgery, a skull fracture, or head trauma, which damages the neurohypophyseal structures. The secondary form of this disease can also result from infection, granulomatous disease, or vascular lesions.

A transient form of diabetes insipidus also occurs during pregnancy, usually after the fifth or sixth month of gestation. The condition usually spontaneously reverses after delivery.

Signs & Symptoms of Diabetes Insipidus

Signs & Symptoms include:

• Excessive thirst that is difficult to satisfy.
• Passage of large amounts of diluted, colorless urine.
• Fatigue, lethargy
• Headache
• Irritability
• Low body temperature
• Muscle pains
• Rapid heart rate
• Weight loss
• Normal or high ADH levels
• The kidneys not making a more concentrated urine when the person is given ADH
• Dehydration, leading to rapid heart rate, low blood pressure and shock.

Diagnostic tests

To distinguish diabetes insipidus from other types of polyuria, urinalysis and a dehydration test may be ordered. Urinalysis reveals almost colorless urine of low osmolality (50 to 200 mOsm/kg of water, less than that of plasma) and of low specific gravity (less than 1.005).

The dehydration test (water deprivation test) is a simple, reliable way to diagnose diabetes insipidus and differentiate vasopressin deficiency from other forms of polyuria. It compares urine osmolality after dehydration with urine osmolality after vasopressin administration. Fluids are withheld long enough to result in stable hourly urine osmolality values (an hourly increase of 30 mOsm/kg of water for at least 3 successive hours). After the 3rd hour, the patient is given 5 units of aqueous vasopressin. Plasma osmolality is determined immediately before vasopressin administration, and urine osmolality is measured 30 and 60 minutes later. In diabetes insipidus, the increase in urine osmolality after vasopressin administration exceeds 9%. Patients with pituitary diabetes insipidus respond to exogenous vasopressin with decreased urine output and increased urine specific gravity. Patients who have nephrogenic diabetes insipidus show no response to vasopressin.

If a patient is critically ill, diagnosis shouldn't be delayed for more time-consuming tests; a diagnosis may be based on the following laboratory values:

• urine osmolality - 200 mOsm/kg
• urine specific gravity - 1.005
• serum osmolality - 300 mOsm/kg
• serum sodium - 147 mEq/L.

Treatment

Until the cause of the patient's diabetes insipidus is identified and eliminated, administration of various forms of vasopressin or a vasopressin stimulant can control fluid balance and prevent dehydration.

• Aqueous vasopressin is a replacement agent administered by subcutaneous injection in doses of 5 to 10 units. Its duration of action ranges from 3 to 6 hours. This drug is used in the initial management of diabetes insipidus after head trauma or a neurosurgical procedure.
• Desmopressin acetate, a synthetic vasopressin analogue, affects prolonged antidiuretic activity and has no pressor effects. It may be given orally, by nasal spray that is absorbed through mucous membranes, or by S.C. or I.V. injection. The duration of action of desmopressin acetate is 8 to 20 hours, depending on dosage.
• Chlorpropamide (Diabinese), a sulfonylurea agent used in diabetes mellitus, is also sometimes used to stimulate endogenous release of antidiuretic hormone and is effective if some pituitary function is present.
• Nephrogenic diabetes insipidus is treated with a low-sodium, high-protein diet and thiazide diuretics. The mild diuretic action reduces blood volume and enhances sodium and water reabsorption in the proximal tubule.

Prevention Tips

Many of the cases may not be preventable. Prompt treatment of infections, tumors and injuries may reduce risk.