More About Laboratory Tests: How To Interpret Them

In my last entry I discussed the rather contentious topic of how physicians order/should order laboratory tests.  I say “contentious” because lately there has been intense scrutiny by governmental agencies, physician specialty groups, and the like, to  cut down on the extraordinary health care costs in the U.S.  Anyway, just the other day, it was brought to my attention that I had not addressed the question of what to with the test result.  Last weekend, I was grading medical student tests (one of my least favorite pastimes).  At our medical school, the curriculum is so-called “problem-based.”  This means that for the most part, teaching is tied to problem-solving rather than to the classic approach of mostly lectures for the first 2 years and then, exposure to patients and their problems.  I think the curriculum is good but in my opinion, its one serious downfall is that even the tests are problem-based, that is, essay questions about a clinical problem.  So there I was last weekend, grading 300 long essays.   The details of the case are not important- the patient likely had a stroke.   The clinical documentation included a brief medical history, a physical examination, and results of the initial laboratory tests ordered in the emergency room.  The results for 2 of the many ordered tests (I believe most of the tests were ordered appropriately) were abnormal;  the serum sodium level was just below the lower limit of normal while the serum calcium level was just above the upper limit of normal.  I was fascinated by the different approaches students took in problem-solving the 2 minimally abnormal test results.  About 25% of the students (these were end of third year students who are  supposed to be pretty savvy) acknowledged the abnormal calcium and sodium results but noted that the results were barely out of the normal range and that they would probably just repeat the tests at some point and that these findings were not likely related to the patient’s primary problem.   A few of the students, never mentioned the test results while most of the rest gave the sodium and calcium results the kind of attention one would give an EKG that showed a serious cardiac arrhythmia- they wrote and wrote what the tests results might mean and what further testing they were going to do.  So how come, only about 25% of the students knew how to approach the sodium and calcium results correctly but the rest were way off course?  That’s what I want to discuss a bit in this entry.

What Does a “Normal Range” Mean?

I do not want to get all technical here, but what goes into establishing a normal range (really called ” reference interval) is rather complicated and is heavy into statistics.  I will try to keep it simple.  Basically, every laboratory is supposed to establish its own  reference interval for every laboratory test it performs.  Every pathologist and clinical chemist knows how this is supposed to be done.  One takes x number  of people (usually 50-100) who are presumably normal with respect to the test in question, and performs the test on them.  A mean value is calculated as is the normal range (usually the mean +/- 2 standard deviations or SD).  If the test values follow a “normal” distribution (you know the familiar bell-shaped curve), then the mean +/- 2 SD comprises about 95% of values in a healthy population.  In statistical terms, this means that out of 100 normal people, 5 individuals are likely to have their test results either above or below the 2 SD reference interval.  I told you this was complicated.  All you need to know is that people who are entirely normal have a reasonable chance of having a laboratory test result that is outside the reference interval.

Do All Laboratories Calculate Their Own  Reference Intervals?

Many laboratories actually do not calculate their own  reference intervals although as far as I know, all large commercial laboratories do this.  It is quite a bit of work and a small laboratory in a hospital or in doctor’s office is not going to want to mess with it.  Instead, they use either the  reference interval that comes in the packaging with the test kit they use or use some published reference interval.  Unfortunately, even if the laboratory does a great job in performing the test, the test results may not fit so well with the reference interval the laboratory uses.  For example, if the published serum free thyroxine level normal reference interval is 1.1 ng/dl +/- 0.5 (mean +/- 2 SD) but if the laboratory normal reference interval is actually 1.3 ng/dl +/- 0.5, many reports will be interpreted by the ordering physician as either normal or abnormal when the opposite is true.  Another important example is HbA1c, the test that quantifies average plasma glucose over the previous 2-3 months and is now widely used to screen for/diagnose diabetes or glucose intolerance.  A level 6.5% or greater is considered diagnostic for diabetes but only if the test is performed in a laboratory that has test results aligned (basically standardized) to those in the Diabetes Control and Complications Trial (DCCT) Reference Laboratory.  That approach obviates the need for the laboratory to establish its own reference interval (I still think it is a good idea for the laboratory to do that if it is at all practical).  I didn’t even mention the fact that for many laboratory tests there are age and sex differences in the  reference interval.  If this is not appreciated by the physician, serious errors in interpretation of the test result can be made.  For example, serum alkaline phosphatase is much higher in growing children than in adults.  In a child, a serum alkaline phosphatase of 300 U/L might be just fine, while in an adult it likely means either liver or bone disease.

Back to the Slightly Elevated Serum Calcium and the Slightly Low serum Sodium

In the “real” world, not the world of medical student tests, physicians must frequently figure out what do do with a test result that is outside the reference interval.  First, as I discussed in my earlier entry, no test should be ordered without a good reason.  Second, the test result must be reviewed and interpreted; some physicians are so busy that they often do not even look over the tests they have ordered or just scan them, looking for the test results listed as “out of range.”  Sometimes a test result is abnormal yet it falls just inside the reference interval.  Remember, just because a test result is outside the reference interval it is not always abnormal, that is, related to some medical problem.  In much the same way, just because a test result is inside the reference interval, that does not mean all is well.  Borderline low and high test results need to be scrutinized.  Maybe they mean something and maybe not.  That is more of the art and science of medicine.  How do medical students learn about these things?  I am not sure.  Based on the test I just graded, maybe we do not do such a good job in teaching them either how to order tests in an artful and scientific way and in figuring out what to do with the test results.

The Most Important Part of Sorting Out Test Results

In my opinion, arguably the most important part of interpreting laboratory test results is sharing the information with the patient and discussing what the results might or might not mean.  In this age of electronic medical records, e-mail, etc., I am amazed at how many otherwise excellent physicians do not have a systematic method of keeping track of what tests they have ordered for their patients and what the test results turn out to be.  Worst of all, they do not have a systematic way of getting in touch with their patients to let them know what the test results are and what it all means.  All patients deserve to be “in the loop.”


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