I apologize for not having an entry for about a month- a busy time with the holidays. Best wishes to all for 2008. I want to start out the new year with a case scenario. I promise it won’t be as esoteric as one of Dr. House’s cases (for those of you who don’t watch TV, Dr. House is a rather unconventional medical sleuth).
The patient is an 18 year old white male named Chad with a history of type 1 diabetes diagnosed at age 10 years. He had generally done well with the diabetes over the years; hemoglobin A1c values had been consistently in the 7-7.5% range (hemoglobin A1c is a blood test that can provide an index of the average blood glucose over the previous 3-4 months). That’s pretty good for a teenager. The patient saw me for a routine checkup in September 2007. Things seemed fine except that I noted a 5 lb. weight loss from the previous visit. There was no change in diet or activity that might explain the weight loss. I suggested that the patient monitor his weight and notify me if he lost as much as another 5 lbs. I scheduled a follow-up clinic visit for December 2007, sooner than I would have normally done so.
Note: Since the patient seemed quite healthy based on my medical history and physical examination, I elected to carry out no special studies at the time of the visit. Some physicians might have done some detective work at that time but I was comfortable to wait and watch.
Two Months Later
I saw Chad for his scheduled follow-up visit in mid-December. He had not contacted me in the interim (I encourage patients to contact me by e-mail whenever they have questions or need something done such as a prescription refill- it works very well and even in my mostly rural state of Missouri, about 90% of families have internet access). The medical history was more or less unchanged except for, perhaps, somewhat less well controlled diabetes. Again, there was no history of anything of concern; specifically, no fatigue, no gastrointestinal symptoms, no change in appetite, no history of drug or alcohol use. The physical examination was unremarkable except for another 7 lbs. weight loss. Now the patient was beginning to look a bit underweight. I was puzzled and concerned.
The Differential Diagnosis
Now it was a question of getting serious about finding out what the problem might be. Eighteen year old males do not lose substantial amounts of weight for no reason. I first decided not to “accept” as fact my medical history. Thus I felt a “fresh” look at the problem was necessary. I first considered if the weight loss was somehow related to the diabetes. Teenage girls with diabetes all know that skipping some of their insulin injections (or turning off their insulin pumps) is the quickest and easiest way to trim down- high blood glucose levels result in large glucose losses in the urine. Every gram of glucose lost is 4 calories lost. It’s not a healthy way to lose weight but it happens. Anyway, I was satisfied that Chad’s weight loss was not from poor diabetes control (a clue would have been the presence of ketone bodies, fat breakdown products, in his urine- urine ketone tests were consistently negative). Next, I wondered about disorders associated with diabetes that might be responsible for the weight loss. Type 1 diabetes is an autoimmune disease and certain other autoimmune diseases are more common in people with type 1 diabetes than in the general population. Chronic lymphocytic thyroiditis causing hypothyroidism is the most common associated autoimmune disorder but I couldn’t have accounted for the weight loss. Hyperthyroidism from Graves Disease is another autoimmune disease slightly more common in people with diabetes than in the general population and this disorder could cause weight loss from an increased metabolic rate. Against the diagnosis was the absence of an enlarged thyroid gland, normal pulse and blood pressure, and absolutely no history of anxiety, poor sleeping, or other typical hyperthyroidism signs and symptoms. Finally I thought about celiac disease, an autoimmune disease of the small bowel caused by intolerance to gluten, a major component of wheat. Celiac disease is currently “in vogue” and recent studies have documented that it is much more common in people with diabetes and in the general population than was previously known; studies show that the prevalence of celiac disease in the general population ranges from about 0.1-1% depending on the study population. The disorder is particularly common in people with northern European backgrounds- Finland has a prevalence of 1-2%. In people with type 1 diabetes, the prevalence is 2-3 fold higher than in the general population but it varies widely depending on the criteria for diagnosis and the characterisitcs of the patient population studied. Patients with celiac disease may have no signs or symptoms pointing to the diagnosis, but a variety of gastrointestinal symptoms are common. Weight loss on the basis of decreased appetite and/or malabsorption is fairly common (remember, Chad had no gastrointestinal symptoms).
One study from Italy published several years ago ( Cerutti et. al., Diabetes Care 2004;27:1294-98) followed 4322 children with type 1 diabetes ages 4-11 years. The investigators found a prevalence of biopsy-proven celiac disease in 6.8% of the children. Risks for celiac disease were increased 3-fold if the diabetes was diagnosed before age 4 years. In 90% of cases, the diabetes was diagnosed prior to the diagnosis of celiac disease.
Back to the detective work- I next considered systemic disorders- medical conditions that could cause weight loss, particularly those without obvious signs and/or symptoms. Thus I considered, inflammatory and infectious conditions (e.g., regional enteritis, tuberculosis, AIDS, other chronic infectious processes); I considered neoplasia (e.g, lymphoma); I considered illicit drug use; I considered an eating disorder (e.g., anorexia nervosa); I considered a chronic anemia- as a primary problem or secondary to another diagnosis.
Moving from Differential Diagnosis to Diagnosis
Next, I needed to take my differential diagnosis and then order appropriate laboratory tests. This is the tricky part. Should I order every imaginable test, just a few, or do one at a time, waiting for results from one before I move to the next? Doing tests one at a time would not have been very practical here- it would have been the least expensive approach but one with the likely possibility of many, many needle sticks and return visits over several weeks. I elected to focus on the most important diagnoses and ordered the following tests: a blood count, blood inflammation tests (erythrocyte sedimentation rate and c-reactive protein) blood chemistries including tests of liver function, a drug screen, HIV testing, thyroid function testing, a chest x-ray, and a celiac test panel (this includes several tests carried out at the same time). So it was one blood stick and one chest x-ray.
I should mention that I discussed with Chad why I ordered the tests that I did, including the drug screen and the HIV tests (he readily gave permission for me to order those tests). Next it was time to wait. The results started to come in and one by one they were all completely normal until I was waiting on only the celiac test panel. So he didn’t have a drug problem, AIDS, a hidden infection, hyperthyroidism, etc. What could it be?
Finally, after a week or so the celiac panel came back wildly positive for celiac disease. We had a diagnosis and one that could explain his weight loss. Why he had no gastrointestinal symptoms (other than weight loss), I don’t know. It is interesting that the simple celiac antibody tests (anti-gliadin IgA and IgG) were normal; the more specific anti-endomysial IgA was positive as was the very specific anti-human tissue transglutaminase test (>100 U/ml with normal < 4 U/ml). The Next Step
So, we had a diagnosis and the next step was referral to a gastrointestinal specialist for maybe a small bowel biopsy and certainly a gluten-free diet. If the diagnosis is correct (with respect to the reason for his weight loss), Chad will begin gaining weight on the gluten-free diet. This last step in diagnosis is important. We want to be certain we have identified the cause of Chad’s weight loss.
Note: Some would argue that we should have screened Chad for celiac disease even before he had any weight loss, given the increased prevalence of the disorder in patients with type 1 diabetes. I have smart colleagues who screen all patient with type 1 diabetes for celiac disease and other equally smart ones who do not. Celiac panels are very expensive and usually “negative.” I would generally screen all patient with type 1 diabetes under age 5 years for celiac disease but not older patients unless there are some signs or symptoms suggesting the diagnosis. I do recommend autoimmune thyroid disease screening for all patients with type 1 diabetes since the prevalence of thyroid disease is 30-40% in patients with type 1 diabetes, the testing is relatively inexpensive, and most patients who will ever develop autoimmune thyroid disease, have “positive” thyroid antibodies at the time they are diagnosed with the diabetes. Maybe, I’ll change my mind about all this next year? That’s clinical medicine- still lots of room for “clinical judgment.”
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