Patient Education

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 sick. However, 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.

Tests results—all medical data—can only be understood once all the pieces are together. 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. Was the culture positive for strep throat? Did the test find antibodies to a virus that indicates an infection?

However, for many more tests, the meaning of the results depends on their context. A typical lab report will have your results followed by a normal or reference 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.

The term "reference range" is preferred over "normal range" because the reference population can be clearly defined. Rather than implying that the test results are being compared with some ill-defined concept of "normal," the reference range means the results are being considered in the most relevant context. When you examine test results from different populations, you quickly discover that what is "normal" for one group is not necessarily normal for another group. For example, pregnancy changes many aspects of the body's chemistry; so pregnant women have their own set of reference ranges.

Effects of Age and Sex

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.

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:

• Creatine is produced as a natural by-product of muscle activity and them removed from your bloodstream by your kidneys. It is often measured as a gauge of how well your kidneys are functioning. Because males have greater muscle mass than females, the reference range for males is higher than for females.
• The form of the enzyme creatine kinase called CK-MB presents a similar situation. It is released in the bloodstream by damaged muscles, and a high level of CK-MB indicates damage to the heart muscle, so this enzyme is used to diagnose heart attacks. Because of their greater muscle mass, men tend to have higher CK levels. When the test first came into use, many elderly women demonstrated considerably lower levels of CK-MB, and, thus, did not pass the threshold level believed to indicate a heart attack, so heart attacks were often missed in this age group of women.

As another example, blood loss through menstruation may cause lower hemoglobin and hematocrit levels in premenopausal women. These are examples of tests with reference ranges keyed to both age and sex.

• 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. A plethora of additional factors can affect your test results: your intake of caffeine, tobacco, alcohol, and vitamin C; your diet (vegetarian vs. carnivorous); stress or anxiety; or a pregnancy. Even your posture when the sample is taken can affect some results, as can recent heavy exertion. For example, albumin and calcium levels may increase when shifting from lying down to an upright position.

Such exotic factors as occupation, altitude, and distance from the ocean have been known to affect results. Regular exercise can also affect values—in particular, levels of creatine phosphokinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) will increase. Additionally, testosterone, luteinizing hormone (LH), and platelet levels can increase in people who participate for months and years in strenuous exercise such as distance running and weightlifting.

All these considerations underscore the significance of taking blood or urine samples in a standardized fashion for performing and interpreting laboratory tests (and home tests as well). 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.

When Normal Doesn't Matter

For tests such as cholesterol, rather than worrying about the "normal" range, the vast majority of people need only be concerned if their cholesterol level falls into the high-risk range. If, as studies have shown, a cholesterol level of 200 milligrams per deciliter is the cut-off where heart disease risk should trigger medical intervention, then it doesn't really matter if this result falls into a statistically "normal" range.

There are additional tests for which the "normal" range is irrelevant. In testing for the amount of a drug in the blood of an unconscious person, for example, the doctor will interpret the result in terms of the likely effects of the drug at the tested level, not in terms of a reference range.

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.

If you know of any special circumstances that could affect a test, mention them to your doctor; don't assume your doctor has thought of every possible circumstance.