Hyponatremia (low blood sodium) is very rare during dDAVP therapy of uncomplicated CDI, provided the patient drinks only when truly thirsty. However, hyponatremia is the rule when dDAVP is used to treat DI that is due to or associated with an abnormality in the thirst mechanism.

The dDAVP tablets are less well absorbed than the nasal spray but that problem is overcome simply by taking more of the drug. The tablets sometimes work less consistently than the nasal spray, but because they are also more convenient it would be worthwhile to try them.

It is unclear whether a lack of vasopressin, which is CDI, also results in increased loss of water via perspiration and/or respiration. Even if it does, however, the problem also should be corrected by treatment with dDAVP. Water intoxication is not a risk of dDAVP therapy if the thirst mechanism is normal and fluid intake is limited to times when thirst is present.

If the patient has a low serum sodium (hyponatremia), he should not be taking desmopressin (DDAVP) since he probably has some abnormality in fluid intake.

Hyponatremia (low serum sodium) in a patient taking DDAVP is always due to excessive intake of water. The reason for the excessive intake varies from patient to patient. Sometimes it is due to an abnormality in thirst, but often it has another cause such as the highly publicized and widespread misconception that a high fluid intake is healthy. Identifying the cause and appropriately treating for the excessive intake may be as simple as a thorough history or as complex as a series of tests of the posterior pituitary and the thirst mechanism. The latter is best undertaken by physicians with particular experience/expertise in this area.

It is very unlikely that poor memory or inability to lose weight is due to CDI or to the wrong dose of dDAVP. If these problems developed after the surgical removal of a pituitary tumor, they are probably due to some other effect of the surgery. Depending on how large the tumor was and the approach used to remove it, these complications include damage to the appetite center in the hypothalamus, hypothyroidism, and the treatment for adrenal insufficiency if it is present. The first problem can be treated only by rigorous dieting, but the last two problems could be corrected easily by adjusting hormone replacement therapy.

Familial CDI, which seems to be the type that runs in your family, has no appreciable effect on GFR unless lack of treatment leads to permanent bladder distention, incomplete drainage, infections, and chronic pyelonephritis. This complication is uncommon, however, even in patients who are not treated for their CDI. Desmopressin has no direct effect on GFR that I am aware of. It may increase it indirectly by increasing total body water but this effect is probably quite small.

Drinking a gallon of liquids per day is obviously highly abnormal for a 16-month-old child. It indicates that he has some form of severe polydipsia and polyuria. Any further conclusion would require more specific information about which tests were performed under what conditions and if “negative” means “normal.” If it does and diabetes mellitus (sugar diabetes) has been excluded by measurements of blood or urine glucose, it is very likely that the child has some type of DI. In this case, the fluid deprivation tests would be appropriate. If urine osmolality was measured and was found to rise above 300, this result is not necessarily “negative” in the sense that it excludes CDI or NDI or indicates primary polydipsia (see guidelines for interpreting fluid deprivation tests at www.diabetesinsipidus.org/water_deprivation_protocol.htm) because it is also consistent with a partial defect in vasopressin secretion or action. The child’s age, response to dDAVP, and associated defect in growth hormone secretion also suggests CDI. Other tests may be needed to establish the diagnosis. I suggest that these issues be discussed with the child’s pediatrician who may wish to consult the DiF web site (www.diabetesinsipidus.org).

Hyponatremia (low serum sodium) in someone taking dDAVP is always due to excessive intake of water. The reason for the excessive intake varies from patient to patient. Sometimes it is due to an abnormality in thirst but often it has another cause such as the highly publicized and widespread misconception that a high fluid intake is healthy. Identifying the cause and appropriately treating the excessive intake may be as simple as a thorough history or as complex as a series of tests of the posterior pituitary and the thirst mechanism. The latter is best undertaken by physicians with particular experience/expertise in this area.

CDI has not been associated with hypochondroplasia or any other form of skeletal dysplasia. However, it is not inconceivable, since defects in other CNS functions have been observed and the growth or function of the posterior pituitary could also be affected if the sella turcica were malformed like some other parts of the skeleton.

Rarely does imitation truly occur in a patient and I am always skeptical when I hear this diagnosis. How was a diagnosis made? The only true way to make a diagnosis of DI and to determine what type (CDI or NDI) it is would be to use the water deprivation test; there is a protocol for conducting this test on DiF’s web site at www.diabetesinsipidus.org/water_deprivation_protocol.htm.

If the dDAVP is given by injection, a problem with technique is the most likely cause of a variable effect. Review the injection technique with your doctor to be sure you are always getting the medication beneath the skin and not in it. Also, be sure that the medication has been stored properly and is not old or outdated. Another cause of an inconstant effect is variations in the amount of solutes such as salt or glucose in the urine. These variations can result from changes in diet or a separate problem, such as diabetes mellitus (sugar diabetes). It is also conceivable that a person has developed antibodies to the dDAVP, but that is extremely rare.

I am not sure why you experience heavy pressures in your chest before and after your doses of dDAVP. It may be due to rapid shifts in body water, particularly if you are taking the drug in such a way as to allow the effects of one dose to wear off before taking the next dose. If so, you should talk with your doctor about the possibility of taking the dDAVP on a more regular schedule that prevents intermittent breakthrough. This should not produce excessive retention of water if your thirst mechanism is normal and you remember to drink only when you are truly thirsty.

As far as we know, there is no chemical difference in the generic and brand name, but there could be a difference in the vehicle (solution in which it is dissolved) that affects stability or the absorption of the drug. If you are having problems with variable effectiveness, you might try the brand name or switch to a different route of administration.

Many patients with CDI take dDAVP instead of chlorpropamide because their doctors do not know how effective the latter can be. Chlorpropamide can lower blood sugar. Usually this does not have any consequences except for a slight increase in appetite, sometimes weight gain, and occasionally irritability. However, the low blood sugar can be more severe if the patient goes on a strict diet or engages in heavy physical exercise. The drug should not be taken during pregnancy since we do not know if it affects the fetus. As far as we know, the chlorpropamide has no significant long term side effects and it is a good deal less expensive than dDAVP. I would recommend it to patients who do not respond well or cannot afford dDAVP.

Do you mean that your DI sometimes stops even when you do not take dDAVP? That is very unusual for CDI and, if present, it would suggest that you are a smoker or have a second problem such as postural hypotension or adrenal insufficiency, any one of which can mask DI. However, if you mean by your question whether you should take dDAVP in doses sufficient to prevent breakthrough of your DI, the answer is “yes” unless you have an associated abnormality in your thirst mechanism or developed water intoxication for some other reason during treatment.

DDAVP has few side effects in patients with uncomplicated CDI. It may produce water intoxication if the thirst mechanism is abnormal or if the patient does not remember to restrict his or her drinking to times when he or she is truly thirsty.

The dose of dDAVP required to control CDI should not change over time, unless the patient is a growing child, in which case it may increase gradually in proportion to size. If the dose of dDAVP required to control CDI does increase significantly, it is usually because the efficiency of absorption has decreased (for example, when a patient using the nasal spray develops hay fever or a cold). Occasionally, the dose requirements increase because the patient develops antibodies to dDAVP, but this is very rare. Incidentally, the dose of dDAVP should be determined by its effects on urine output, NOT by its effect on plasma sodium. The latter is determined primarily by the rate of fluid intake, which can and should be regulated separately. In most cases, the thirst mechanism will adequately regulate fluid intake without any interference from care givers. Occasionally, however, in patients who are very young, unconscious, or lack a normal thirst mechanism, it is necessary to regulate fluid intake for them. This can be difficult to do and requires the help of an expert.

DDAVP is absorbed into the bloodstream and taken directly to the kidneys where it acts to concentrate the urine and, thereby, reduce urine output.

The dose of dDAVP required to control CDI should not change over time, unless the patient is a growing child, in which case it may increase gradually in proportion to size. If the dose of dDAVP required to control CDI does increase significantly, it is usually because the efficiency of absorption has decreased (for example, when a patient using the nasal spray develops hay fever or a cold). Occasionally, the dose requirements increase because the patient develops antibodies to dDAVP, but this is very rare. Incidentally, the dose of dDAVP should be determined by its effects on urine output NOT by its effect on plasma sodium. The latter is determined primarily by the rate of fluid intake, which can and should be regulated separately. In most cases, the thirst mechanism will adequately regulate fluid intake without any interference from care givers. Occasionally, however, in patients who are very young, unconscious, or lack a normal thirst mechanism, it is necessary to regulate fluid intake for them. This can be difficult to do and requires the help of an expert.

CDI does not cause neuropathy. However, a few of the diseases that can cause CDI could, in theory, also cause neuropathy.

The dose of dDAVP required to control CDI should not change over time, unless the patient is a growing.

I assume the blood value for vasopressin was obtained because of your urinary frequency, but associated with “little volume.” All forms of DI, by definition, have large urine volumes (at least 3 or 4 liters a day for an adult) with the urine being dilute. You have not provided any evidence that you have DI, and therefore, there is no need for vasopressin levels to be obtained or followed up by an endocrinologist, except perhaps for your problem of lactation. I would suggest that you ask your nephrologist about your urinary frequency. After that you might have to see a urologist.

If the thirst mechanism is damaged, it cannot be used as a reliable guide to fluid intake. This kind of damage is very unusual in ordinary CDI, but is the rule when the hypothalamic osmoreceptor rather than the pituitary itself is damaged. This is much less common than ordinary CDI and is characterized by elevations in serum sodium (hypernatremia) without thirst. If this defect is present, fluid intake must be regulated by other methods, such as constant monitoring of body weight or serum sodium (by equipment now available for use in the home).

Growth hormone should not affect the treatment of CDI.

Was the patient thirsty when he had a serum sodium of 181? If he was mentally alert and not thirsty, he has a severe problem called adipsic DI. Patients like these must be monitored continually with intakes matched to output, including urine volume, estimated losses in perspiration, and frequent checks of blood for sodium levels. With the passage of time, the patient and the caregiver may notice some personality changes when the serum sodium is increased or decreased, thus making it somewhat easier to adjust the fluid intake to the output. The amount of dDAVP nasal spray or pills to keep the patient from urinating excessively and thus having to drink excessively has to be worked out between the patient and his physician. Remember that there are no side effects from dDAVP itself. Side effects are from taking too much or too little fluids in relation to the urine output and other fluid losses. Too much fluid intake in relation to fluid losses causes decreased serum sodium level and too little intake in relation to fluid losses causes hypernatremia, as this patient seems to have. Why was the serum potassium low? My guess is that it is from concomitant therapy with diuretics. This is an inappropriate use of diuretics, which may be helpful and the only effective treatment in some patients with NDI, but it is not indicated for the treatment of CDI.

This observation is a very interesting one. It is well known that people tend to get dehydrated upon acute exposure to high altitude. For that reason, one would think that a HIGHER dose of dDAVP might help the problem by retaining water in the body; yet, you find that a LOWER dose gives relief -- and I’m sure that your observation is correct -- at least as it concerns yourself. One possible explanation is that you are aware of the dehydration problem at high altitude; therefore, you deliberately drink more than your thirst demands; you can’t excrete the extra water you drink because of your normal dose of dDAVP; and goes into hyponatremia (also known as mild to moderate water intoxication). Continue to reduce your dose of dDAVP when your ski or is at high altitude for some other reason. If it works for you, you should keep it up. Even though you don’t purposely drink more while skiing, if you continued your regular dosage of dDAVP, you would/might go into slight water intoxication. This condition, as you probably know, is manifested as hyponatremia (low sodium concentration in the blood or serum). One might be able to nail down my suspicion by your not reducing the dosage of dDAVP and having your physician friend or someone else take a blood sample for sodium analysis. But I don’t really advocate that, since it would make you feel lousy. Better, just keep up your current practice.

Diffuse neurological abnormalities are very rare in patients with CDI. The only two instances that I recall from my own experience were in patients with diffuse brain damage due either to eosinophilic granuloma or anoxic encephalopthy. Multiple sclerosis can also produce diffuse, fluctuating neurological abnormalities and DI but the DI is always of the dipsogenic type (abnormal thirst). It also responds to dDAVP but, unlike CDI, it will result in water intoxication unless the treatment is given so as to allow complete escape at least once a day.

In Europe, Dr. Soren Rittig in Aarhus Denmark may be able to sequence the AVP-NPII gene in patients with the autosomal dominant form of familial CDI. The gene responsible for the x-linked recessive form of familial CDI cannot be tested because it has not been identified. All that can be done at present is to perform linkage studies in the kindred in hopes of further localizing and identifying the gene.

It sounds like the patient has bladder neck spasm or perhaps an enlarged prostate gland. There are medications and behavioral techniques to treat the former and medications for the latter. Although it is possible that the patient has CDI as well as one of these other problems, the original diagnosis of CDI should be reconsidered.

Only if they are overhydrated with oral or IV fluids. It would be a good idea to have an endocrinologist or nephrologist involved to see to it that proper hydration is maintained.

Diabenese is often as effective in severe CDI as in partial CDI. The way it works is unclear. Dipsogenic DI is due to an abnormality in thirst, which causes excessive intake of fluids that suppresses release of antidiuretic hormone.

Most, but not all, people with CDI experience weight gain. That is one of the most common complaints. Ask your physician what you should experience to make sure that the CDI has gone away.

Patients with uncomplicated CDI and a normal thirst mechanism do not need to interrupt dDAVP treatment to release excess fluid if they always remember to limit their fluid intake to the amounts needed to satisfy thirst. That is because the thirst mechanism regulates intake to prevent overhydration (excess water). Interruption of treatment is necessary only if the thirst mechanism is damaged and not working properly or if the patients drinks excessive amounts for some other reason such as the belief, now widespread, that a high fluid intake improves health.

There is no evidence that CDI itself effects body temperature. However, some of the conditions that can be associated with CDI may have this effect. One is the ingestion of large volumes of cold water or other beverages, which can cause chilling. Another is damage to the part of the pituitary that regulates the thyroid. This can cause hypothyroidism, which can also result in a slight lowering of body temperature and “cold intolerance”. A third is damage to the thermoregulatory mechanism, which is located in the hypothalamus near the cells that make vasopressin.

DDAVP is used in relatively high doses to treat partial forms of hemophilia. The doses used to treat DI are much lower and probably do not affect clotting in any way although this question has not been completely investigated. Other drugs, most notably chlorpropamide, can be used to treat CDI, but they are sometimes less effective and may have other side effects. Therefore, I would be inclined to stick with the dDAVP, although the issue should be discussed with the physicians who are treating the Factor V disorder.

DDAVP tablet and dDAVP nasal spray work equally well overall, although certain patients do better on one than the other, probably because of individual differences in the efficiency of absorptions from the nose and gastrointestinal tract.

Food may affect the absorption of dDAVP in the gastrointestinal tract, so it is probably better to take the tablet on an empty stomach.

The dose of dDAVP required to control CDI does vary with the size of the patient. However, it cannot be specified exactly in terms of body weight because other factors, such as differences in absorption or metabolism, also exert a major influence. Therefore, the optimum dose varies quite widely from patient to patient and must be determined by trial and error. The dose also depends on the route of administration. When given by injection, it is usually necessary to give between 1 microgram to 2 micrograms once or twice a day. By nasal spray, the necessary dose can range from 5 micrograms to 20 micrograms twice or three times a day. By tablet, the usual dose is 100 micrograms to 200 micrograms two to three times a day.

In most patients with uncomplicated CDI, dDAVP should be given as often and in as large a dose as necessary to completely normalize the rate of urine output. This is usually achieved most conveniently by giving at least two doses, one in the morning and one at bedtime. If necessary, a third dose can be given in the late afternoon. It is not necessary to allow breakthrough from the antidiuresis except in very young infants whose diet is still largely liquid or in the uncommon patient who has a defect in the thirst mechanism in addition to CDI. Patients with dipsogenic DI should be given dDAVP only in small doses at bedtime to reduce the need to get up and urinate at night. If they take dDAVP in large doses or during the day, they will develop water intoxication.

The dDAVP is absorbed into the bloodstream and taken directly to the kidneys where it acts to concentrate the urine and thereby reduce urine output. There is no need for extra fluid during or after the surgery if dDAVP is administered to prevent excessive water loss by the kidneys. In fact, extra fluid would be hazardous in this situation since the dDAVP would prevent normal excretion of the excess water. If dDAVP is not given during and after the surgery, extra fluid should be given to compensate for the loss. The amount that is required depends on the rate of urine output. It can be determined by keeping track of urine output and also the plasma sodium concentration.

Question # 0730 EWv7n2, 0301 EWv3n1, 0075 FAQ Keywords: ice water, DDAVP, CDI side effects

The difference is probably due to the amount of ice water consumed in the two situations. It is several times larger when the medication is not working because urine output and thirst are also increased several fold. At those times, the amount of ice water consumed may be so great as to lower body temperature 1 or 2 degrees. It is possible that this effect is aggravated by malfunction of the mechanism that regulates body temperature (the thermoregulatory center) because it is located in the brain near the cells that make vasopressin and may be damaged by the same pathologic process (for example, neurosarcoid). However, this type of “collateral” injury is unusual in CDI and, if it were present, body temperature should fluctuate up and down even without exposure to heat or cold. The chilling produced by drinking large amounts of ice water is uncomfortable, but is not hazardous unless body temperature falls more than 5 degrees Fahrenheit. If that is happening, there is a risk of heart malfunction and the patient should consult a physician about changing the treatment of the CDI.

DDAVP tablet and dDAVP nasal spray work equally well overall, although certain patients do better on one than the other, probably because of individual differences in the efficiency of absorption from the nose and gastrointestinal tract.

Research into a cure for CDI is being conducted, but there are no promising leads at present and it is unlikely that a cure will be available anytime soon. Fortunately, a good treatment (dDAVP) is available to control the disorder. A better treatment for NDI is also being actively investigated and, although the leads there are a little more promising, it will likely be some time before it is routinely available.

DDAVP has no known long-term effects and should not affect schoolwork in the future.

CDI is treated with dDAVP, a synthetic (manmade) form of the natural antidiuretic hormone, vasopressin. If another disease causes the DI it is treated separately. The method of treatment depends on what that disease is. It can be surgery, radiation, or drugs.

The symptoms you describe may be caused by a sudden increase in urine output that distends the ureters. However, you should discuss it with his physician to be sure that further investigations for another cause are not warranted.

Unless you also have an abnormality in your thirst mechanism, the only consequences of stopping your dDAVP treatment would be a return of the frequent urination, constant thirst, and increased fluid intake. Your electrolyte and water balance should remain within normal limits provided you drink enough to satisfy your thirst. If they do not, you probably have an associated abnormality in your thirst mechanism and will need to be treated differently than a patient with uncomplicated CDI. The other symptoms that you describe may or may not result from mild dehydration that results from stopping the dDAVP. The only other way to relieve them when you stop dDAVP is to drink enough fluid.

If your dDAVP treatment works poorly sometimes, the reason is probably poor absorption of the drug. If you are taking the dDAVP by mouth, you may be able to improve consistency by taking the tablet on an empty stomach or by increasing the size or frequency of the dose. If you are taking the nasal spray, try blowing your nose before each dose. If that does not help, consult your doctor about increasing the size or frequency of the dosing.

I am not sure why you experience heavy pressures in your chest before and after your doses of dDAVP. If may be due to rapid shifts in body water, particularly if you are taking the drug in such a way as to allow the effects of one dose to wear off before taking the next dose. If so, you should talk with your doctor about the possibility of taking the dDAVP on a more regular schedule that prevents intermittent escape. This should not produce excessive retention of water if your thirst mechanism is normal and you remember to drink only when you are truly thirsty. As far as we know, there is no chemical difference in the genetic and brand name dDAVP, but there could be a difference in the vehicle (solution in which it is dissolved) that affects stability or absorption of the drug. If you are having problems with variable effectiveness, you might try the brand name or switch to a different route of administration.

At effective doses, dDAVP tablets are not less expensive than dDAVP nasal spray. They are more convenient and often as effective as the spray. However, in some patients, their effects are more erratic owing to variations in absorption from the gut. This variability sometimes can be prevented or reduced by taking the tablets on an empty stomach, but other times it is necessary to go back to the nasal spray.

I am not aware that dDAVP has damaged the sense of smell or taste in anyone. However, relatively few patients have been using the nasal spray as long as you have, so we cannot rule out the possibility that chronic, long-term exposure to the drug or vehicle has this effect in some people. If you have not already done so, I would suggest that you consult an ear, nose, and throat specialist to see if you have any scarring or inflammation of your nasal mucosa or sinuses that might explain your loss of smell and taste (much of what we call “taste” is actually dependent on the ability to detect subtle odors). If you do, it would not necessarily be attributable to dDAVP, but it would at least be a link or explanation and might lead to some effective treatment. The other thing you might do is try changing to the oral dDAVP to see if your sense of smell and taste improves.

An increase in the requirement for vasopressin (or dDAVP) is not necessarily a cause for alarm unless it gets way above the normal range. Usually, it only indicates that the drug has gone bad or is not being given or absorbed optimally. This can occur for a variety of reasons, and you should discuss this with your doctor or specialist. If that does not solve the problem and you are really taking vasopressin (and not the analogue dDAVP) in abnormally high doses, it is also possible that you have developed antibodies. If so, you may want to switch to dDAVP or chlorpropamide since they are usually not affected by the antibodies.

Cortef in the dose will interfere with dDAVP. In some people, dDAVP is not well absorbed from the gastrointestinal tract. Try taking it on an empty stomach. If that does not provide good control with reasonable doses (i.e., up to 0.2 mg three times a day), switch to the nasal spray.

You could either increase his morning dose or add a third dose around 4 p.m. If his thirst mechanism is working properly and he has not other stimulus to drink, it would be safe to experiment by increasing the size or frequency of the doses to determine how much is needed to completely control his urine output.

The hyponatremia may be responsible for your daughter’s symptoms. It is caused by the combination of dDAVP treatment and excessive fluid intake. From the information provided, I cannot tell why she is drinking water so much. I recommend that she stop the dDAVP and undergo further evaluation or education about CDI before proceeding.

Your symptoms may or may not be due to water intoxication induced by the dDAVP. The best way to tell is to measure your serum sodium. If it is low, you are developing water intoxication and should stop the dDAVP and undergo repeat evaluation as to the type of DI you have.

DDAVP reduces urine output by increasing urine concentration, an effect virtually identical to the natural hormone, vasopressin. This antidiuretic effect is not ‘all or none’. Its magnitude is directly proportional to the amount of dDAVP in the blood. At low blood levels, urine concentration (also called osmolality) is low and urine output is high. Conversely, at high blood levels, urine concentration is high and urine output is low. Even at very high blood levels, however, dDAVP does not stop urine output completely because there is a natural limit to the amount of urine concentration that it can produce. All it can do is reduce urine output to a minimum, which in humans is around 0.3 to 0.5 milliliters per minute or about 2 cups a day. However, even though dDAVP controls the rate of urine output, it does not regulate the amount of water in the body the way that the natural hormone does because the amount of dDAVP in the blood is not regulated by body water the way that the natural hormone is. It is determined solely by other factors such as the size and timing of the dose and the efficiency of absorption from the nose or gastrointestinal tract (if given by pill) and as a practical matter it is impossible to control these dosing factors with sufficient accuracy to regulate urine output in accordance with the body’s need for water. Fortunately, dDAVP does not need to do this because the normal thirst mechanism compensates by altering the rate of water intake. That is why we recommend those patients with uncomplicated CDI (i.e., a normal thirst mechanism) should take dDAVP in doses sufficient to maintain a fixed, uninterrupted level of antidiuresis and let their thirst mechanism do the rest.

The body does not store dDAVP, but it can accumulate if it is given faster than the body disposes of it. The half-life varies markedly from person to person but averages around 1 to 2 hours. The antidiuretic effect of the usual intranasal dose also lasts for variable periods of time not only because of variations in half-life but also in absorption of the drug. On average, however, it is about 8 to 12 hours, or 4 to 6 half lives, because the initial blood levels achieved are greater than necessary to produce antidiuresis. For the reasons outlined above, taking the drug more frequently does not lead to accumulation of water if thirst and water intake are regulated normally. Water retention occurs only if the thirst mechanism does not work normally or if the patient drinks excessively for other reasons (e.g., habit, nervousness, etc.)

As far as we know, alcohol does not negate the effect of dDAVP. It may slightly increase the rate of disposal but this effect is minimal. In normal people, ethanol produces an increase in urine output by inhibiting secretion of the natural hormone, vasopressin. This effect obviously would not occur with dDAVP.

As far as we know, stress does not affect dDAVP absorption, although it might increase the metabolism or disposition of the drug.

In some patients with CDI, the pituitary is able to produce small amounts of the hormone as, for example, when they smoke or become dehydrated. However, the variability in the duration of action of the dDAVP in you is probably due mainly to variability in the efficiency of adsorption. Colds, sinusitis, or even a little hay fever markedly impair the absorption of the drug from the nasal mucosa and result in much shorter durations of action.

Although caffeine does cause a mild diuresis (increased urine output) in normal people, it seems to have little or no noticeable effect in individuals taking dDAVP for CDI. Therefore, it does not increase the risk of dehydration and need not be avoided.

In the usual patient with uncomplicated CDI, there is no need or benefit to waiting for symptoms to appear before taking the next dose of dDAVP. It is preferable to take the drug in doses or with a frequency that prevents breakthrough because this regimen is not only more convenient, it minimizes fluctuations in hydration, which, in the long run, may have deleterious effects. If taking dDAVP this way results in water intoxication (typified by symptoms of headache, nausea, and dizziness and a fall in blood sodium to abnormally low levels), it is usually because the patient’s thirst mechanism is abnormal. This abnormality can occur in association with CDI or as an isolated defect that causes symptoms and signs closely resembling the other forms of DI. If water intoxication does develop with dDAVP, special methods of diagnosis and treatment can be used to resolve the situation.

Using dDAVP for a long time has not produced any bad effects that we know about.

When a patient with CDI stops taking dDAVP (or some other pharmaceutical drug), it is normal for polyuria (increased urination) to occur 2 to 3 hours before the thirst and polydipsia (increased drinking) set in. The more important question is why you have started to develop hyponatremia on dDAVP. It indicates that you are drinking excessively either because you have abnormal thirst or for some other reason. If the problem persists, you may want to switch from dDAVP to chlorpropamide, since the latter is less likely to induce hyponatremia. It is not clear why your dose requirements for dDAVP have decreased. It could be because you have developed hypothyroidism or hypoadrenalism. Therefore, you should have your plasma cordsol and thyroid hormone measured. If your MRI is really completely normal (i.e., the posterior pituitary bright spot is present), you do not have CDI and must have dipsogenic DI. The latter would be consistent with developing hyponatremia on dDAVP. Therefore, it is very important to determine if the posterior pituitary bright spot was seen. The other way to determine if you have dipsogenic or CDI is to measure plasma vasopressin during a fluid deprivation/hypertonic saline infusion test.

To my knowledge, dDAVP tablets do not cause gastrointestinal clamping, or stomach pains. The possibility that they do could be evaluated by switching, at least temporarily, to the intranasal form.

Regarding the correct dose of dDAVP for your son: he should be given enough that his CDI does not breakthrough. If you switch from the rhinal to the nasal spray, this probably could be accomplished by giving him 1 spray (10 mcg) every 8 hours or 2 sprays in the morning and one in the evening at bedtime. Apart from the unnecessary expense, you do not need to worry about giving him too much. Even higher doses of the drug should not result in water intoxication, provided his thirst mechanism is normal and he learns to drink only when he is thirsty. Both of these conditions are probably being met if all measurements of his serum sodium have been normal. If you go to a higher dose of dDAVP, continue to check his serum sodium weekly for a month and, if they are all normal, repeat them only if he develops symptoms of water intoxication.

A sudden gain of 13 pounds after starting dDAVP is almost certainly due to excessive water retention and indicates fluid intake is excessive, due either to an abnormality in the thirst mechanism or a lack of understanding about the need to avoid drinking unless thirst is present. She should ask her physician to check her plasma sodium concentration while she is on dDAVP. If it is low, she should learn to drink only when she is thirsty. If that does not eliminate the hyponatremia, she should stop treatment and be re-evaluated to determine if she has CDI or dipsogenic DI.