In a healthy person, alcohol transiently increases urine output primarily by inhibiting secretion of the antidiuretic hormone. As far as I know, alcohol should have little or no effect in a patient with NDI because the antidiuretic hormone is unable to affect urine concentration or flow. Therefore, urine output is already high and cannot be increased further by inhibiting hormone secretion. The alcohol may cause what we call a ‘solute diuresis’ that could add to the water diuresis but the resultant increase in urine output would be so small that it probably would not be noticed.

Constipation is not a recognized side effect of NDI. However, there have been many anecdotal reports of young children with NDI who also have constipation. Constipation can be helped by increasing the fiber in his diet (prune juice or prunes).

Anorexia nervosa can be associated with DI and deficient secretion of the antidiuretic hormone, vasopressin (CDI). These deficiencies are slowly reversible if the patient regains and keeps her normal weight for six months or more. NDI has not been demonstrated in anorexia nervosa but it may also occur because some of the patients with DI do not have a vasopressin deficiency but do have hypokalemia (low potassium), which can interfere with the antidiuretic action of the hormone. It is also possible if not likely that some patients with anorexia nervosa have a form of dipsogenic DI due to a reversible abnormality in the thirst mechanism. Therefore, treatment with dDAVP or thiazide diuretics should be given very cautiously since they may produce water intoxication.

The primary treatment for NDI is restricting sodium intake (300 mg to 500 mg for young children) and administering a thiazide diuretic and amiloride or other potassium-sparing diuretic, with or without a prostaglandin inhibitor. There are several companies that make these drugs. Their names and addresses can be found in the Physicians Desk Reference, which is published by Medical Economics, Five Paragon Drive, Montvale NJ 07645-1742; 201-358-7500; www.pdr.net.

Certain types of DI (nephrogenic or dipsogenic) can be caused by drugs, such as lithium. Theophylline does increase urine out put, but the effect is usually mild and short and is not usually thought of as DI.

Lithium-induced NDI is very similar to other types of NDI except that it may stop if the lithium can be stopped. There is no reason why it cannot be treated with a low-sodium diet and a thiazide diuretic just like other forms of NDI. The pharmaceutical drugs used to treat bipolar disorder (which would be treated by lithium) are not known to interact negatively with the medications given to treat NDI, and should not prevent your using this treatment. The only thing you have to do is to continuously monitor your serum lithium levels, since the treatment for DI alters the urinary excretion of lithium and you may have to change the dose to keep a “therapeutic level.”

The only treatments for lithium-induced DI are:

1. to stop the lithium, which usually is not acceptable;

2. administer chlorothiazide or amiloride diuretics; and

3. eat a low-sodium diet.

The last is the most often overlooked and it can be quite effective particularly when combined with the thiazide. At best, however, it usually reduces urine volume by only between 50% to 75%, which, depending on how severe your DI was originally, may not be enough to completely eliminate the need to get up at night to urinate.

Lithium can cause DI in either of two ways. The most common is damage to the part of the kidney that is normally responsible for controlling urine output. This form of lithium-induced DI is called nephrogenic DI. Depending on how long the problem has been present, it may or may not be corrected by stopping the lithium. If it cannot be corrected by stopping lithium, it may be partially controlled by treatment with amiloride or thiazide diuretics as well as a low-sodium diet. The other way that lithium can cause DI is by damaging the thirst mechanism in the brain. It is called dipsogenic DI and is usually reversible if the lithium is stopped. If the lithium cannot be stopped, this type of DI should not be treated with diuretics or antidiuretic hormone since they will induce water intoxication. Determining which type of lithium-induced DI you have would require measurements of plasma vasopressin before and during a fluid deprivation test or a closely monitored therapeutic trial with dDAVP. Either test should be performed only under the supervision of a physician experienced in their use.

Lithium-induced NDI is relatively common. It is uncomfortable but not fatal, provided water intake is not restricted for too long. It can also be treated to reduce the symptoms. However, before starting any treatment, it is a good idea to be tested to verify that the DI is really NDI. These tests include a controlled water deprivation test with various blood and urine measurements as well as a closely monitored trial of treatment with dDAVP.

Patients with NDI must restrict their sodium intake and take thiazides and/or other diuretics all their life if they want to reduce the level of urine output. Dehydration is the most serious risk and is greatest during infancy. However, dehydration can also pose a risk for adults if they become separated from an unlimited supply of fresh water. Hypertrophy (overgrowth) of the bladder (floppy bladder) and ureters can also occur and cause stasis and chronic urinary infection. I cannot tell if the problem is so advanced in your son’s case that it cannot be controlled by standard treatment and truly requires the drastic approach of self-catheterization. However, I would be inclined to wait to see if it does not gradually improve when your son returns to appropriate treatment for his NDI.

There are many drugs that can cause NDI. The most common offenders are lithium and demeclocycline.

Probably any major university medical center in western Europe can diagnose and treat NDI, as well as major medical centers in North America. In Europe, the one with which I am most familiar are in Denmark (Aarhus University, Dr. Soren Rittig), but there are others in Holland and Germany. You can find a list at the Nephrogenic Diabetes Insipidus Foundation’s web site at www.ndif.org.

NDI disrupts sleep by causing frequent awakenings to empty the bladder, which fills up quickly with urine. NDI is not associated with any allergies or respiratory problems although the latter two problems are common and may occur independent of NDI. NDI is not known to be associated with acid reflux disease. However, many young boys with NDI vomit frequently, sometimes twice or three-times daily, until the ages of 3 or 4 years.

One form of familial NDI is due to a recessive mutation that is carried by females but causes DI only in males. Therefore, it is possible, if not likely, that your son inherited the disease from his mother, even though she is not affected. It is also possible that he has a “de novo” mutation (which means that it occurred in the fertilized egg from which he developed) or that he has another type of recessive mutation that does not affect either male or female carriers and causes the disease only when an offspring inherits a gad gene from each parent (neither of whom is affected themselves). If you have not already had a genetic analysis performed, you should consider having this done.

Yes, it is common for children with NDI to have poor appetite and problems with taking adequate nutrition on their own. Children with NDI need at least 100% of their caloric requirements (RDA) to maintain growth and between 120% and 140% of RDA to achieve catch-up growth. This can often be achieved in the first few years of life only by using various protein, lipid, or carbohydrate modulers. These children probably do not use calories any differently; the problem is getting, and keeping, the calories in them.

* What diet should he be following?

Thiazide and amiloride therapy is most effective when combined with a low-sodium diet. His nosebleeds are probably not caused by his NDI or the treatment for it. They might be due to something that also causes his DI, although this too is very unlikely if he has the inherited (genetic) form.

There are three medications that may reduce urine output and thirst in NDI. The most effective are the thiazide diuretics (e.g., Diuril or hydrochlorothiazide). Their efficacy is greatest when used in conjunction with a low-sodium diet. Indomethacin and amiloride may also be used with a low-sodium diet (300 mg - 500 mg for small children; 500 mg - 600 mg for adults), but they are often less effective than thiazide diuretics. The alcohol in the suspension form of indomethacin is too dilute to have any effect on the body, but if you are concerned about it your son could be changed to the capsules. The indomethacin itself is probably also safe, but the manufacturer does not recommend its use in children younger than 14 because its safety in that age group has not been established. Therefore, you might consider replacing it with tolmetin sodium, a related drug that is known to be safe in children and has much the same effects on DI. You do not mention the cause of the NDI in your son, but the very early age of diagnosis suggests it may be due to an inherited genetic defect. If he has not already had genetic testing, you should do so because it will determine if there is a risk of passing the disease to other children, and if so, make it possible to tell at birth if the defect is present.

Ibuprofin will cause gastric irritations in many individuals. Has a urinary infection been ruled out? Unrelated to NDI, many infants have “colic” due to standard formulas, and do better on a soy formula such as Prosobee or a hypoallergenic formula such as Neutramagin.