Diabetes Insipidus: Rare Disease Update

With an estimated incidence of 1 in 25,000, diabetes insipidus (DI) is considered a rare disease. Research shows that it is approximately equally common in men and women.

In this Q&A with Consult QD, endocrinologist Leann Olansky, MD, in Cleveland Clinic’s Department of Endocrinology, Diabetes and Metabolism, provides an update on the diagnosis and management of DI.

What are the main causes of DI?

There are two main congenital defects that lead to diabetes insipidus: one is the inability of kidneys to respond to the antidiuretic hormone (ADH) — vasopressin, which helps the body retain water. This defect causes nephrogenic DI. The other is ADH deficiency — the inability of the body to make vasopressin. This latter defect leads to central DI.

How are these two forms of DI diagnosed?

The clinical manifestations – thirst and increased urine output — are the same in both forms, but the laboratory findings are different. The water deprivation test is used to definitively diagnose DI. After a period of fluid restriction, the urine output, serum sodium levels, as well as the weight of the patient are monitored. At the end of the test, when urine concentration has been constant for over 2 hours, the patients are given a dose of either vasopressin or a synthetic analog of vasopressin called desmopressin (DDAVP). If they are then able to concentrate the urine, then we know they have ADH deficiency. If they are not able to concentrate the urine, then we know that the cause of their symptoms is the lack of responsiveness to ADH (nephrogenic DI).

Are there any recognized triggers of DI?

No. DI is either a congenital problem or it is caused by a deficiency associated with other kinds of damage to the hypothalamus. The damage can be autoimmune, traumatic or due to a condition such as sarcoidosis or a hypothalamic tumor called craniopharyngioma.

How are patients with nephrogenic and central DI managed?

Nephrogenic DI does not respond to the only drug that mimics the action of vasopressin, DDADP. It only can only be treated by keeping patients on a low-salt diet, so that they do not produce too much urine. Central diabetes insipidus is managed by hormone replacement; patients are given either vasopressin or DDAVP that serves the same purpose. Thus, central DI is more treatable than nephrogenic DI.

Which situations can complicate the management of DI?

There is a thirst center in the hypothalamus very close to where vasopressin is made. Damage to the nuclei that make vasopressin can be accompanied by damage to the nuclei that trigger the thirst mechanism. A certain amount of regulation happens when patients who are losing excess water get thirsty and drink more water to compensate. If the patients lack that thirst mechanism, then they need to be given a certain amount of water and a certain amount of ADH replacement. If the balance between those two is off, then they will either have high or low serum sodium levels. Both of those situations inhibit normal brain function and could potentially be fatal. Matching the water intake to the medication dose in a patient that lacks a thirst mechanism is very difficult.

How is DI managed in patients undergoing prolonged surgeries such as a face transplant?

Up until the surgery, the patient undergoing a face transplant at Cleveland Clinic was managed using a synthetic analog of ADH, however, during the surgery that lasted 28 hours, DDAVP was not an option because it has a long half-life. Naturally occurring vasopressin was used because it is a short-acting hormone and it was titrated to maintain a urine volume that is neither too low nor too high. During surgery, the patient’s serum sodium was kept in a very tight normal range so that she would not experience any neurologic problems.

Is DI reversible?

In pregnancy, an enzyme made by the placenta called vasopressinase breaks down some of the vasopressin, which leads to transient DI. In those cases, women can use DDAVP which cannot be broken down by vasopressinase during their pregnancy. Once they deliver, they do not usually need it. That’s about the only reversible type of DI there is.

What is the overall outlook for patients with DI?

If patients are able to maintain their replacement, they can do very well. They either have to take it twice or three times a day, depending on whether the hormone replacement effects last 12 or 8 hours. If patients have a normal thirst mechanism, then they can compensate for any slight imbalance in the needed dose.