Diabetes insipidus

Diabetes insipidus is an endocrine disease caused by the lack of antidiuretic hormone (ADH) or by a renal resistance to the action of ADH.

The lack of functional antidiuretic hormone (ADH) prevents the normal reabsorption of water by the kidneys and cause an excessive urine production.

The body requires a fluid and electrolyte balance. The balance of water and electrolytes dissolved (sodium, potassium, etc.) is necessary to maintain organ function.

Osmolality refers to the concentration of dissolved chemicals in the blood (plasma). Plasma osmolality is regulated by the antidiuretic hormone (ADH), also called vasopressin or arginine vasopressin, which is produced by the pituitary, a small gland located at the base of the brain.

When there is very little fluid compared to the concentration of solute, the pituitary will increase ADH production. The ADH hormone induces the kidneys to retain more water and to decrease the amount of urine produced.

On the contrary, when the fluid content of the blood is high in comparison to the concentration of solute, ADH production will decrease and the kidneys will produce an increased amount of urine allowing the plasma osmolality to return to normal.

Diabetes insipidus occurs when:

• The pituitary cannot produce enough amount of antidiuretic hormone (ADH), what is called central diabetes insipidus.
• Kidney response to antidiuretic hormone (ADH) is defective, what is called nephrogenic diabetes insipidus.

The person affected by diabetes insipidus produces a huge amount of urine each day accompanied by intense thirst.

The causes of diabetes insipidus depend on the type. They are different if it is due to a lack of ADH (central DI) or due to a renal resistance to ADH (nephrogenic).

Central diabetes insipidus may be caused by:

• Idiopathic or unknown cause (more than 50% of cases)
• Injury to the head
• After a brain surgery
• Tumors that spread to the pituitary gland (leukemia, lymphoma or lung cancer)
• Sarcoidosis
• Hypoxic encephalopathy (oxygen deprivation to the brain)
• Drugs that decrease the ADH production such as phenytoin (antiepileptic drug)
• Pregnancy or after delivery
• Wolfram syndrome
• Langerhans cell histiocytosis or hand-Schüller-Christian disease
• Congenital disorders

Nephrogenic diabetes insipidus may be due to:

• Medication containing lithium
• Patients with hypercalcemia (a high level of calcium in the blood)
• Pregnancy
• Sometimes it can be congenital and hereditary due to mutations in the gene AVPR2 on chromosome X or in the gene AQP2 on chromosome 12

Diabetes insipidus has a prevalence of 1 in 25,000-40,000 and occurs more frequently in males than in females.

The two most common symptoms of diabetes insipidus are:

• Polydipsia or extreme thirst (with a special desire to drink cold water)
• Polyuria or excessive urination (sometimes reaching 10 or more liters each day) and nocturia (excessive urination at night)

When the amount of intake water is not enough to replace the water excreted into the urine, the patient may begin to suffer symptoms of dehydration that may include:

• Weakness and fatigue
• Fever
• Low blood pressure
• Increased heart rate
• Dizziness and confusion

The diagnosis is suspected from the symptoms, but may be followed by a urine test. The urine will be very dilute with values of specific gravity below 1.005 and very close to 1.000. The urine will be mostly water with no solute. On the contrary, blood will be very concentrated, high in solute and low in fluid volume.

There are also some specific tests to confirm the diagnosis such as the water deprivation test or desmopressin (DDAVP) stimulation test.

Treatment depends on the type of diabetes insipidus. Some of the medication used to try to decrease the amount of water that the kidneys excrete in the urine.

For central diabetes insipidus the recommended treatment is:

• Vasopressin injected or desmopressin (an ADH analog that replaces the missing anti-diuretic hormone) given subcutaneously, orally, or as a nasal spray.
• Antidiuretic drugs (such as chlorpropamide, clofibrate or carbamazepine).

Patients with nephrogenic diabetes insipidus need special diets that restrict the amount of salt and proteins. These patients are also treated with thiazide diuretics (hydrochlorothiazide).