Diabetes Insipidus (Arginine Vasopressin Deficiency or Resistance)

A new name: AVP deficiency and resistance

In 2022, international endocrine and kidney societies recommended renaming diabetes insipidus to avoid confusion with diabetes mellitus:

• Central diabetes insipidus is now arginine vasopressin deficiency (AVP-D)
• Nephrogenic diabetes insipidus is now arginine vasopressin resistance (AVP-R)

You will still see both names in use.

How water balance normally works

The hypothalamus in the brain makes arginine vasopressin (AVP, also called antidiuretic hormone), which is stored in and released from the posterior pituitary gland. When you are short of water, AVP tells the kidneys to reabsorb water, producing small amounts of concentrated urine. In DI, this system fails, so water is lost in large volumes of urine.

Types and causes

Symptoms

• passing large volumes of pale, watery urine: more than 3 liters (about 100 oz) a day in adults, sometimes much more
• frequent urination day and night (nocturia), disturbing sleep
• extreme thirst, often with a strong preference for ice-cold water
• tiredness from broken sleep
• dehydration if water intake cannot keep up: dry mouth, dizziness, headache, confusion

In infants and young children: heavy, very wet diapers, irritability, poor feeding, vomiting, fever, constipation and slow growth. Bedwetting may be the first sign in older children.

Diabetes insipidus vs diabetes mellitus

Both cause thirst and frequent urination, which is the only reason for the shared name. See diabetes for the blood sugar condition.

Diagnosis

1. Confirm a high urine volume: a 24-hour urine collection over 3 liters (or more than 50 ml/kg).
2. Rule out other causes: blood sugar, calcium, potassium and kidney function.
3. Paired blood and urine tests: in DI, the urine is dilute (low osmolality) while blood sodium is normal-high or high.
4. Copeptin testing: copeptin is released alongside vasopressin and is easier to measure. A level after stimulation with hypertonic saline or arginine helps separate central DI from primary polydipsia, and a high baseline level suggests nephrogenic DI.
5. Water deprivation test: in a supervised setting, fluids are withheld to see whether the urine concentrates, then desmopressin is given. Central DI responds to desmopressin; nephrogenic DI does not.
6. MRI of the pituitary and hypothalamus in central DI, to look for a cause.

Treatment

Central DI (AVP deficiency)

• Desmopressin: a synthetic form of vasopressin, taken as tablets, melts, nasal spray or injection. It reduces urine output and thirst.
• Avoiding low sodium: the main risk of desmopressin is water retention and low sodium (hyponatremia), causing headache, nausea and confusion. Drink only to thirst, and many people are advised to have a short daily "breakthrough" period when the medicine wears off. Sodium levels are checked regularly.
• Treat the underlying cause, such as a pituitary tumor.

Nephrogenic DI (AVP resistance)

• Treat the cause: stop or adjust lithium if possible, correct calcium and potassium.
• Thiazide diuretics paradoxically reduce urine volume, sometimes with an NSAID or amiloride (especially with lithium).
• Low-salt, moderate-protein diet to reduce urine output.
• Free access to water.

Gestational DI

Desmopressin is effective because it is not broken down by the placental enzyme. The condition usually resolves within weeks after birth.

Living with diabetes insipidus

• always have access to water, including when traveling
• wear medical ID, particularly if you have central DI, so emergency staff manage fluids and desmopressin correctly
• tell doctors before surgery, as fluid management must be planned
• people with central DI from pituitary disease may have other hormone deficiencies, including cortisol, that need replacing

With treatment, most people with DI lead normal lives.

Frequently asked questions

What are the symptoms of diabetes insipidus?

The main symptoms are passing very large amounts of pale urine (more than 3 liters a day in adults), getting up repeatedly at night to urinate, and intense thirst, often for cold water. Dehydration can cause tiredness, headache and confusion.

Is diabetes insipidus the same as diabetes?

No. Diabetes insipidus is a problem with the water-balancing hormone vasopressin, and blood sugar is normal. Diabetes mellitus is a problem with insulin and blood sugar. To avoid confusion, DI is now being renamed AVP deficiency or AVP resistance.

What causes diabetes insipidus?

Central DI is caused by damage to the hypothalamus or pituitary from surgery, head injury, tumors, inflammation or genetics. Nephrogenic DI is caused by kidneys not responding to vasopressin, most often due to lithium, high calcium, low potassium or inherited mutations.

How is diabetes insipidus treated?

Central DI is treated with desmopressin, a synthetic vasopressin, while avoiding excess water to prevent low sodium. Nephrogenic DI is treated by addressing the cause, thiazide diuretics, a low-salt diet and plenty of water.