Sarah D is an 8 year old female who had been in good health. She was successfully toilet-trained at age 3 years. Over the past 2 weeks, she had wet the bed on 4 separate occasions. There was no history of any day-time “accidents.” Sarah’s mother called the pediatrician’s office and scheduled a clinic visit.
The pediatrician, who had cared for Sarah since her birth, obtained a detailed medical history. In summary, the child had been quite healthy and the bed-wetting seemed to be the only problem. The “review of systems” revealed no history of excessive urination except for the night-time bed-wetting which is also called enuresis. There was no history of excessive thirst, fatigue, or any emotional problems that the patient’s mother could identify. There was no family history of members with childhood enuresis or with kidney diseases. The physical examination was unremarkable including a brief genital examination that revealed no evidence of inflammation except for slight erythema of the thighs, suggesting a mild “diaper dermatitis.”
So, what’s going on? What did the pediatrician think?
Sarah’s pediatrician scratched her head after obtaining the medical history and performing the physical examination. Clearly, the enuresis was not a normal variant- a finding that might be expected as part of the developmental process. Many normal children do take a long time to be consistently dry overnight and this is often genetic. But, to become completely dry for a number of years and then to start wetting the bed again was not normal. The physician’s first thought was to order some lab tests but she had the good sense to first put together a differential diagnosis.
She considered the following disorders as most likely: urinary tract infection or some other kidney or bladder problem; diabetes mellitus- a high blood sugar would lead to sugar in the urine which would “pull” water with it resulting in increased urination; psychogenic water drinking- a condition where an individual just consumes a large amount of liquid, as a habit or as the result of a psychological disorder; and diabetes insipidus- a disorder usually caused by a deficiency in the hypothalamic hormone vasopressin (stored in the pituitary gland), which controls water reabsorption by the kidneys; the kidneys filter the blood and if most of the water in the blood were not reabsorbed, it would mean rapid dehydration and death. Diabetes insipidus, or “DI” as it is commonly called can be caused by quite a number of medical conditions including head trauma, brain tumors, brain inflammatory processes, and for no apparent reason (in this instance it is called “idiopathic”). The pediatrician thought the most likely possibilities were a urinary tract infection or diabetes mellitus.
What did the pediatrician do?
After putting together a “rough” differential diagnosis, the pediatrician went back and obtained more medical history. Specifically, she found no history of head trauma, headaches, or other neurologic symptoms (findings that might suggest diabetes insipidus), no history of excessive fluid intake compared to other family members,and no history of urinary tract infections.
Next the pediatrician ordered a few simple laboratory studies including the following: routine urinalysis, blood chemistries to include electrolytes, BUN (a measure of a person’s state of hydration and kidney function). She also ordered a serum calcium because she remembered that a high serum calcium or a low serum potassium (obtained with the electrolytes) could mimic diabetes insipidus. She thought about but decided to wait on head imaging studies (e.g, MRI, CT scan) until the initial lab test results were in. A plasma glucose came with the blood chemistries but she knew that if the increased urination was from diabetes mellitus, the urinalysis would show glucose (normally, the urine is glucose-free).
What did the initial lab tests show?
The urinalysis was “clean,” with no evidence of a urinary tract infection or diabetes mellitus. The urine specific gravity (SpG) , a measure of the degree of concentration or dilution of the urine) was 1.002, a very low value, consistent with either normal kidney function, psychogenic water drinking, or diabetes insipidus. In DI the deficiency (or poor action) of vasopressin prevents the kidneys from concentrating the urine, excreting waste products while reabsorbing most of the water. A urine SpG of 1.010 is roughly equivalent to the concentration of blood. The maximum urine SpG is about 1.035 indicating kidney reabsorption of as much water as possible as well as plenty of vasopressin and normal kidney function. It would not be unusual for a normal person to have a urine SpG of 1.002 if he had been consuming a large amount of liquid.
The blood tests showed normal electrolytes except for a slightly high sodium (145 meq/L), slightly high BUN (25 mg/dL), normal calcium (9.3 mg/dL), and normal glucose (84 mg/dL).
What does all this mean and what should be done next?
The pediatrician reviewed the laboratory test results and concluded that Sarah might well have diabetes insipidus but definitely not diabetes mellitus or a urinary tract infection. The physician next sent me an e-mail to discuss the case and to ask if I would carry out the necessary studies to confirm the diagnosis and to initiate treatment. Thus, I scheduled the patient for admission to hospital for a water deprivation test. This test is exactly what its name implies- the patient is deprived of water until he shows an ability to concentrate the urine or that he definitely has diabetes insipidus. Since the goal of the water deprivation test is to induce some degree of dehydration, the test can be dangerous. Thus, I generally admit patients to hospital for the test. I generally admit the patient under a category called “23 hour observation status” which means the patient will not be charged for a hospital day if I can discharge them from hospital in less than 24 hours (I have no idea how many hospitals offer this option).
The water deprivation test
So, I admitted the patient to hospital late one afternoon. I obtained my own medical history and performed my own physical examination which added nothing to the pediatrician’s initial assessment. I then ordered baseline laboratory tests which included a urine specimen for SpG and osmolality (a more specific test for urine concentration- it ranges from about 200-1200 mOsm/kg water, roughly equivalent to urine SpG ranging from 1.001-1.035), blood chemistries, and serum osmolality (normal is 280-290 mOsm/kg water; a level of 300 or more without highly concentrated urine would confirm a diagnosis of diabetes insipidus). As part of the physical examination, I had a baseline body weight.
The test results showed about what the pediatrician had found; the serum BUN and serum sodium levels were borderline elevated. The serum osmolality was slightly elevated (300 mOsm/kg water) while the urine value was low (300 mOsm/kg water). Since the patient did not normally drink any liquids after going to bed, I restricted all food and drink after supper, at which time the water deprivation test formally began. The patient was to be supervised at all times. We repeated the body weight. We did not insert a urinary catheter even though we thought the patient might wet the bed- we suggested that she be encouraged to urinate in a collection bottle every 4 hours or so during the night (if we had been desperate to collect all urine, we would have inserted a urinary catheter). If the patient had given a history of drinking liquids throughout the night at home, we would have allowed this because of the risk of dehydration.
In the morning, the patient was feeling well but a bit thirsty. She had urinated (in the bottle) about 1000 ml , about a quart. Her body weight was down about 2 pounds (consistent with the urine loss). The urine SpG was 1.005 and the urine osmolality was 300 mOsm/kg water. Blood chemistries showed definitely elevated serum sodium and BUN levels. The serum osmolality was 310 mOsm/kg water. We had a diagnosis!
The next step
First, the patient was given access to water but asked to drink no more than 1 liter or so over the next hour. The patient was then given a subcutaneous injection of aqueous vasopressin, called pitressin. We continued to collect urine. Within 1 hour, the urine SpG had risen to 1.025 and the osmolality to almost 1200 mOsm/kg water. Thus, we learned that the patient not only had diabetes insipidus but was responsive to vasopressin. The test was discontinued. A synthetic form of vasopressin called d-desamino arginine vasopressin or dDAVP was prescribed to be given as one nasal squirt at bedtime (the medication dosage depends on the degree of vasopressin deficiency and weight but can range from 1 squirt per 24 h to as many as 3 or 4).
The next step
The patient responded well to the dDAVP and the enuresis did not recur. In retrospect, the parents noted that the Sarah drank much less liquid after starting the dDAVP nasal spray. Unfortunately, our work was not done; we needed to determine why Sarah had diabetes insipidus. Neurology and ophthalmology consultations were ordered. Head imaging studies were ordered (MRI and CT scan). To make a long story short, no specific cause for the DI could be identified and the disorder was classified as “idiopathic.” Idiopathic DI occurs in about 10% of childhood DI cases, at least based on the medical literature. In my experience, about 25% of cases fall into the idiopathic category. What does this mean? It means that we can’t explain why the patient has DI but that we need to monitor the patient long-term to be certain none of the rather nasty causes becomes evident. I try hard never to forget that one of my former students defined idiopathic as “the idiots just don’t know the pathology.” So right he was.
This interesting “real-life” case teaches us several things. First, that primary care physicians are to key to timely diagnosis of medical conditions. Second, that knowledgeable primary care physicians can greatly facilitate the evaluation of patients with complex medical conditions. Finally, that step by step thoughtful evaluations solve medical diagnostic dilemmas as well or better than the “order as many tests as possible now and think later” approach used by some.
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