The Management of Diabetes Insipidus in Adults

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Title: The Management of Diabetes Insipidus in Adults
Authors: Singer, Irwin; Oster, James R.; Fishman, Lawrence M.
Publisher: Archives of Internal Medicine
Date Published: June 23, 1997
Reference Number: 146
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The management of patients with diabetes insipidus can be confusing because of the disorder's variable pathophysiology, the numerous medications used, and the possible complications related to their use. Nevertheless, the primary care physician, rather than the subspecialist, will increasingly be called on to manage patients with such relatively uncommon conditions in the future. If a few basic facts and principles are kept in mind, the care of most patients with diabetes insipidus can be successful. A comprehensive, practical review of the short- and long-term therapy for patients with diabetes insipidus, including central diabetes insipidus, nephrogenic diabetes insipidus, and the "excessive vasopressinase syndrome," is presented. The use of single and multidrug regimens, and of the newly marketed oral formulation of desmopressin acetate, is described for common clinical settings.

This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

Diabetes insipidus (DI) is the excessive production of dilute urine. Dilute urine is urine with a very low solute to solvent ratio. Solutes are the particles in a solution (e.g., the salt in salt water). A solvent is the liquid part of a solution (e.g., the water in salt water). DI is characterized by polyuria (excessive volume of urine) and polydipsia (excessive fluid intake). There are several types of DI, and proper treatment depends on accurate diagnosis. In central DI (CDI), the neurohypophyseal system in the hypothalamus does not produce enough (or any) of the antidiuretic hormone, arginine vasopressin (AVP). AVP is necessary for the kidney to reasorb water normally. Thus, with a deficiency of AVP, the kidneys cannot optimally reabsorb water, so large amounts of dilute urine are excreted. In nephrogenic DI (NDI), there are adequate amounts of AVP, but the kidneys do not respond to it. Again, the result is excretion of large amounts of dilute urine. In yet another form of DI, excessive vasopressinase syndrome, enough AVP is produced, but it is destroyed inside the body. Sometimes a form of DI can develop during pregnancy where normal metabolic changes brought on by pregnancy alter the threshold for AVP release and thirst, accelerate AVP metabolism, and decrease responsiveness to AVP. This can sometimes cause a woman with preexisting stable DI or subclinical CDI or NDI to become symptomatic during and for a short time after pregnancy. Symptoms may range from mild to severe in all forms of DI.

In this article, Singer, et al., focus on the management of DI in adults. One goal for the treatment of DI includes correcting DI-caused water deficits. (The amount of fluid replacement required to correct the deficit may be determined by a formula that takes into account the patient's normal body weight and his or her baseline fluid and salt content.) A patient's blood pressure may have to be restored before correcting his or her water deficits. Other goals include reducing ongoing excessive urinary losses and lowering the patient's blood sodium levels if they are too high. Excessively high blood sodium levels --hypernatremia-- can cause a net flow of body water out of the cells resulting in dehydration of cells. Reversing hypernatremia and reducing ongoing water loss are important treatment goals. The water deficit formula mentioned does not take into account ongoing water losses, so frequent blood and urine determinations should be made, all water losses measured or estimated, and the administration rate of water adjusted accordingly. If the patient's blood sodium level needs to be reduced, more water must be given than lost.

There are several drugs that help decrease chronic water loss brought on by DI. Each has its strengths and weaknesses. Synthetic AVP is used mainly for confirming diagnoses, differentiating between NDI and CDI, and for emergency situations. Unfortunately, it often increases blood pressure and has too short a half-life for therapeutic purposes. Desmopressin (DDAVP) is the drug of choice for long-term use in CDI or the excessive vasopressinase syndrome. It is administered into the nasal passages either through a tube or by using a nasal spray pump. Dosages of DDAVP must be individualized and scheduled according to individual needs. DDAVP is not always absorbed fully and its side effects, which are uncommon and generally dose-related, include headache, nausea, nasal congestion and inflammation, flushing and abdominal cramping. At high doses in susceptible patients, it may cause angina or increased blood pressure.

Thiazide diuretics are the therapeutic mainstay for most forms of NDI. To work most effectively, thiazides should be used with a low sodium diet. Blood potassium levels of patients using thiazides should be monitored by their physician.

Both NDI and CDI can be either inherited or acquired. In some cases, such as after trauma to the head affecting the pituitary, CDI can be acute, though generally it is chronic. Treatment is different for the different types and forms of CDI. After the acute phase of post-traumatic or post-surgical CDI, it is possible for symptoms to partially or completely disappear, and physicians should monitor this process. Normally, chronic CDI is not life-threatening, though polydipsia and polyuria may be inconvenient. Some patients with mild partial CDI do not require drug therapy. Patients with complete CDI are generally given DDAVP, but the amount taken must be calibrated to avoid high or low blood sodium levels. To avoid low blood sodium levels, it is best to periodically curtail DDAVP and permit occasional polyuric episodes. Since DDAVP is usually self-administered, the patient must be properly trained to periodically halt DDAVP administration and allow the blood sodium level, if low, to return to normal.

NDI requires different drugs, sometimes depending on whether the disorder is acquired or inherited. If it was acquired through use of the drug lithium, then the drug amiloride can often alleviate the symptoms. As yet, inherited NDI can only be managed, not cured. A low-sodium diet and thiazide administration help control the disorder's symptoms. And sometimes the patient may benefit by using several types of drugs at the same time, for example a thiazide along with a nonsteroidal anti-inflammatory agent.

Sometimes a person may have both CDI and NDI. This usually requires treatment with both DDAVP and one or more of the drugs used in NDI. DDAVP is the ideal therapy for pregnancy-induced DI.

Patients can be responding well to therapy and then begin to experience problems. This generally happens either when the patient stops following the prescribed management program or has an unrelated medical emergency. Sometimes the prescribed drugs produce undesireable side-effects or stop being effective. To minimize these instances, the patient should be well-educated about the treatment program, the program should be convenient, and he or she should wear a DI identification tag in case there is a medical emergency.