Medical test results are usually interpreted based on their relation to a reference range

The "Normal" or Reference Range

"Your test was out of the normal range," your doctor says to you, handing you a sheet of paper with a set of test results, numbers on a page. Your heart starts to race in fear that you are really sick. But what does this statement mean, "Out of the normal range”? Is it cause for concern? The brief answer is that a result out of the normal range is a signal that further investigation is needed. The interpretation of any clinical laboratory test involves an important concept in comparing the patient’s results to the test’s “reference range." (It's also commonly called the “normal range” but today reference range is considered a more descriptive term.

What is a reference range?

Some tests provide a simple yes or no answer. A typical lab report will have your results followed by a normal or reference range. For example, your results for a Thyroid Stimulating Hormone (TSH) test might look something like: 2.0 m-IU/L, ref range 0.5 – 5.0 m-IU/L. The test results indicate that it falls within the “normal” range. How was that reference range established? The short answer is: by testing a large number of healthy people and observing what appears to be “normal” for them.

Effects of Age and Sex on the reference range

For many tests, there is no single reference range that applies to everyone because the tests performed may be affected by the age and sex of the patient, as well as many other considerations. Alkaline phosphatase is an enzyme found in the cells that make bone, so its concentration in the body rises in proportion to new bone cell production. In a child or adolescent, a high alkaline phosphatase level is not only normal but also desirable-the child should be growing healthy bones. But these same levels found in an adult are a sign of trouble-osteoporosis, metastatic bone disease (extra bone growth associated with tumors), or other conditions. So experience from testing large numbers of people has led to different reference ranges by age group. Hemoglobin and hematocrit (a red blood cell measure) both decline as a natural part of the aging process. The patient’s sex is another important consideration for many tests. Creatinine is produced as a natural by-product of muscle activity and then removed from your bloodstream by your kidneys. Because males have greater muscle mass than females, the reference range for males is higher than for females. As another example, blood loss through menstruation may cause lower hemoglobin and hematocrit levels in premenopausal women.

Other Factors Affecting Test Results

Laboratories will generally report your test results accompanied by a reference range keyed to your age and sex. Your physician then will still need to interpret the results based on personal knowledge of your particulars, including any medications or herbal remedies you may be taking. Additional factors that can affect your test results include your intake of caffeine, tobacco, alcohol, and vitamin C; your diet (vegetarian vs. non-vegetarian); stress or anxiety; or a pregnancy. Even your posture when the sample is taken can affect some results, as can recent heavy exertion. It’s important to comply with your doctor’s instructions in preparing for the test, such as coming in first thing in the morning, before you eat anything, to get your blood drawn. That compliance makes your sample as close as possible to others; it keeps you within the parameters of your reference group.

What does it mean if my test result is out of the reference range?

Based on the laws of probability, 1 out of 20 (or 5%) determinations will fall outside the established reference range, thus a single test value may mean nothing significant. Generally, the test value is only slightly higher or lower than the reference range. To put this in more perspective: If a doctor runs 20 different tests on you, there’s a good chance that one result will fall out of a reference range despite the fact that you are in good health. Of course, the result may indicate a problem. The first thing your doctor is likely to do is to re-run the test. Perhaps the analyte being measured happened to be high that day due to one of the reasons stated above, or perhaps something went awry with the sample (the blood specimen was not refrigerated, or the serum was not separated from the red cells, or it was exposed to heat). Laboratories will generally report the findings based on age and sex, and leave it to the physician to interpret the results based on factors such as diet, your level of activity, or medications you are taking.