What Is the Most Common Cause of Diabetes Insipidus?

Causes of nephrogenic diabetes insipidus include kidney disease or hereditary.

Diabetes insipidus is a rare condition in which the body produces too much urine. 

There are two main forms of diabetes insipidus: 

• Central diabetes insipidus (also called neurogenic, pituitary, or neurohypophyseal), in which the body does not make enough of the antidiuretic hormone (ADH) vasopressin to maintain a balance of fluids in the body
• Nephrogenic diabetes insipidus, in which the body produces adequate amounts of the antidiuretic hormone, but the kidneys do not respond to it

Diabetes insipidus is not the same as diabetes mellitus (usually simply referred to as “diabetes”) which is a metabolic condition characterized by high levels of blood sugar in the body. 

The main symptoms of diabetes insipidus include:

• Urinating more than usual/frequent urination (polyuria)
• Thirst
• Waking at night to urinate (nocturia)

Other symptoms of may include: 

• Excessive fatigue
• Decreased sex drive 
• Impotence (erectile dysfunction)
• Headache
• Dry skin
• Hair loss
• Kidney swelling due to buildup of urine (hydronephrosis), characterized by pelvic fullness, side pain or tenderness, or pain radiating to the testicle or genital area
• Bladder enlargement 
• Dehydration if the thirst mechanism is impaired or there is inadequate fluid intake

Infants with diabetes insipidus may exhibit the following symptoms:

• Crying
• Irritability
• Overheating
• Growth retardation
• Weight loss

Children with diabetes insipidus may exhibit the following symptoms:

• Bedwetting 
• Loss of appetite 
• Linear growth defects
• Fatigability

The cause of diabetes insipidus is problems with antidiuretic hormone (vasopressin). Either the body does not make enough which affects the balance of fluids in the body, or the body produces adequate amounts but the kidneys do not respond to it.

The cause of most cases of central diabetes insipidus is unknown. Possible causes of central diabetes insipidus include:

• Cancers (most often due to lung cancer, leukemia, lymphoma, or tumors in the brain)
• Infiltrative diseases (such as Langerhans cell histiocytosis) 
• Neurosurgery
• Trauma to the hypothalamus and posterior pituitary 
• Genetic disorders
  • Familial CDI
  • Wolfram syndrome
  • Congenital hypopituitarism 
  • Septo-optic dysplasia
• Hypoxic encephalopathy  
• Post-supraventricular tachycardia 
• Anorexia nervosa 

Causes of nephrogenic diabetes insipidus include:

• Hereditary nephrogenic diabetes insipidus
• Lithium toxicity due to treatment with chronic lithium therapy
• High blood calcium levels (hypercalcemia)
• Low blood potassium (hypokalemia)
• Kidney disease 
• Certain drugs such as lithium, cidofovir, foscarnet, vasopressin V2 receptor antagonists, amphotericin B, demeclocycline, ifosfamide, ofloxacin, orlistat, and didanosine 
• Pregnancy 
• Craniopharyngioma surgery 
• Bardet-Biedl syndrome 
• Bartter syndrome
• Other inherited disorders such as nephronophthisis, cystinosis, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and chronic hypokalemia

Laboratory tests are performed to diagnose diabetes insipidus, including:

• 24-hour urine collection to determine urine volume
• Serum electrolyte concentrations and glucose level
• Urinary specific gravity
• Simultaneous plasma and urinary osmolality
• Plasma ADH level
• Water deprivation (Miller-Moses) test to ensure adequate dehydration and maximal stimulation of ADH for diagnosis
• Pituitary studies, including magnetic resonance imaging (MRI) and measurement of circulating pituitary hormones other than ADH

Many patients can drink more fluids to replace fluid lost through excess urination. When oral intake of fluids is insufficient, intravenous (IV) fluid replacement may be needed.

Additional treatment for diabetes insipidus may include:

• Following a diet low in salt and protein to help control symptoms. 
• Medications 
  • Desmopressin (DDAVP, Stimate), available as a nasal spray, a pill, or as a shot under the skin is the medication of choice for central diabetes insipidus to replace the body’s missing anti-diuretic hormone 
  • Synthetic vasopressin
  • Chlorpropamide
  • Thiazide diuretics
  • Carbamazepine (rarely used; last resort)

Treatment for patients who have nephrogenic diabetes insipidus may also include:

• Treating any underlying kidney problems
• Stopping medications that may be causing symptoms (do not stop taking any medication without first talking to your doctor)
• Certain medicines, including blood pressure drugs, may help
• Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (used only when no better options exist)

The main complications of diabetes insipidus include:

• Dehydration
• Electrolyte imbalances

The outlook for patients with diabetes insipidus is generally excellent, and deaths are rare in adults as long as they have adequate fluid intake. Death can occur in children and elderly patients and those with complicating illnesses. 

Factors that can contribute to a poor prognosis include: 

• Severe dehydration
• Excess blood sodium (hypernatremia)
• Fever
• Cardiovascular collapse